The DOI matches its Crossref record; 94 of the 96 references it cites were found in a registry or an index; 6 of the 223 sources its claims cite were checked for support.
Current and Future Treatments in Alzheimer Disease: An Update
Open accessAbstract
Disease-modifying treatment strategies for Alzheimer disease (AD) are still under extensive research. Nowadays, only symptomatic treatments exist for this disease, all trying to counterbalance the neurotransmitter disturbance: 3 cholinesterase inhibitors and memantine. To block the progression of the disease, therapeutic agents are supposed to interfere with the pathogenic steps responsible for the clinical symptoms, classically including the deposition of extracellular amyloid β plaques and intracellular neurofibrillary tangle formation. Other underlying mechanisms are targeted by neuroprotective, anti-inflammatory, growth factor promotive, metabolic efficacious agents and stem cell therapies. Recent therapies have integrated multiple new features such as novel biomarkers, new neuropsychological outcomes, enrollment of earlier populations in the course of the disease, and innovative trial designs. In the near future different specific agents for every patient might be used in a “precision medicine” context, where aberrant biomarkers accompanied with a particular pattern of neuropsychological and neuroimaging findings could determine a specific treatment regimen within a customized therapeutic framework. In this review, we discuss potential disease-modifying therapies that are currently being studied and potential individualized therapeutic frameworks that can be proved beneficial for patients with AD.
Overview
AI snapshot
Written from the paper’s full text.
TL;DR
This narrative review summarizes current FDA-approved symptomatic treatments for Alzheimer disease and the 2019 pipeline of disease-modifying and symptomatic agents. It emphasizes that no disease-modifying therapy is approved and that future treatment may move toward biomarker-guided precision medicine.
Key findings
Current approved pharmacotherapy remains symptomatic: the 3 AChEIs donepezil, galantamine, and rivastigmine plus the NMDA antagonist memantine; no new FDA drug for AD has been approved since 2003 and there are no approved DMTs.
- A clinicaltrials.gov search accessed August 19, 2019 found 165 recruiting or active-but-not-recruiting phase 1–3 AD trials; the February 2019 pipeline review cited found 132 agents in 156 trials (28 drugs in 42 phase 3 trials, 74 drugs in 83 phase 2 trials, and 30 drugs in 31 phase 1 trials), classified as 73% DMTs, 13% symptomatic cognitive enhancers, and 11% for BPSD.
- Anti-amyloid failures include semagacestat, bapineuzumab, solanezumab, and the BACE inhibitors lanabecestat, verubecestat, and atabecestat; BACE inhibitors reduced CSF Aβ42 dose-dependently but without cognitive or functional benefit.
- Tau-directed agents remain earlier-stage: only 1 tau-related agent was in phase 2/3, 10 in phase 2, and 5 in phase 1; other DMT mechanisms include neuroprotection, anti-inflammatory effects, growth factor promotion, metabolic effects, and stem cell therapies.
Methods
Design: narrative review of current nonpharmacological and pharmacological AD management, FDA-approved medications, BPSD treatments, and phase 1–3 investigational agents.
- Data/sample: literature review plus a clinicaltrials.gov search for recruiting or active-but-not-recruiting phase 1–3 AD trials accessed August 19, 2019 (165 outcomes), and citation of the February 2019 AD drug development pipeline review (132 agents in 156 trials).
- Analysis: narrative synthesis and classification of agents by proposed mechanism—amyloid-related, tau-related, other DMT mechanisms, and symptomatic—without a formal systematic review or meta-analysis described.
Limitations
Stated: no effective treatment options and no approved DMTs exist; many trial failures are attributed to starting therapy too late, inappropriate drug doses, wrong treatment targets, inadequate understanding of AD pathophysiology, and variability in diagnostic markers and endpoints.
- Evident from the text: this is a narrative review without a stated systematic search strategy, inclusion/exclusion criteria, or risk-of-bias assessment.
- Evident from the text: pipeline findings are a cross-sectional 2019 snapshot and efficacy claims for many agents are brief, based on cited trials or conference reports rather than independent quantitative synthesis.
Model-written summary. Check it against the paper before relying on it.
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Claims the paper makes
171 Not checked yet · 4 Own interpretation · 3 Sources not found · 2 Partly supported · 1 Supported so far · 1 Own result · 1 No basis given · accuracy not yet measured
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“A number of additional pathogenic mechanisms have been described, possibly overlapping with Aβ plaques and NFT formation or induced by them, including inflammation, oxidative damage, iron deregulation, and cholesterol metabolism blood-brain barrier (BBB) dysfunction or α-synuclein toxicity.9-13”
§ Current and Future Treatments in Alzheimer Disease: An Update > Introduction
What the sources say
- Partly supportedcites [9] Bondi MW Edmonds EC Salmon DP Alzheimer’s disease: past, present, and future. J Int Neuropsychol Soc. 2017; 23: 818- 831. 29198280 PMC5830188 sourceExperimental — accuracy not yet measured
In “THE FUTURE” (page unavailable), the paper identifies blood–brain barrier dysfunction and α-synuclein as possible pathologies interacting with abnormal amyloid and tau. Our copy does not identify inflammation, oxidative damage, iron deregulation, or cholesterol metabolism as additional mechanisms in this context, nor does it say the listed pathologies are induced by plaques or tangles. (LLM, conf=0.87)
- Not checked yetcites [10] Atri A Current and future treatments in Alzheimer’s disease. Semin Neurol. 2019; 39: 227- 240. 30925615 source
- Partly supportedcites [11] Cummings J Morstorf T Lee G Alzheimer’s disease drug development pipeline: 2016. Alzheimers Dement. 2016; 2: 222- 232. PMC5651348 29067309 sourceExperimental — accuracy not yet measured
The Methods and Discussion describe AD drug targets beyond amyloid and tau, including neuroprotection and metabolic mechanisms. The Phase II and III tables also list antioxidant and anti-inflammatory agents. Our copy does not describe iron deregulation, blood–brain barrier dysfunction, or α-synuclein toxicity as pathogenic mechanisms, nor does it establish that the listed mechanisms overlap with or are induced by plaques or neurofibrillary tangles. (LLM, conf=0.84)
- Partly supportedcites [12] Cummings J Lee G Mortsdorf T Ritter A Zhong K Alzheimer’s disease drug development pipeline: 2017. Alzheimers Dement. 2017; 3: 367- 384. PMC5651419 29067343 sourceExperimental — accuracy not yet measured
The Methods section identifies anti-inflammatory and metabolic mechanisms among Alzheimer’s disease drug targets, and the Phase II table lists an antioxidant agent. These passages support parts of the list, but the paper does not establish iron deregulation, blood-brain barrier dysfunction, or α-synuclein toxicity as pathogenic mechanisms, or explain how the listed mechanisms overlap with or are induced by plaques and neurofibrillary tangles. Page numbers are unavailable in our copy. (LLM, conf=0.83)
- Partly supportedcites [13] Cummings J Lee G Ritter A Zhong K Alzheimer’s disease drug development pipeline: 2018. Alzheimers Dement. 2018; 4: 195- 214. PMC6021548 29955663 sourceExperimental — accuracy not yet measured
The Methods section identifies anti-inflammatory and metabolic mechanisms beyond amyloid and tau, and the Results (Phase II; page unavailable) lists therapies targeting oxidative stress and cholesterol synthesis. The copy does not establish iron deregulation, blood-brain barrier dysfunction, or α-synuclein toxicity as mechanisms, nor does it establish the claimed relationship of these mechanisms to plaque or tangle formation. (LLM, conf=0.84)
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Partly supported
The sources with a verdict support this claim; the rest weren’t checked yet, have no full text we could read, or their verdicts aren’t rated yet.
In the paper
“However, the clinical trials with the BACE inhibitors lanabecestat,32 verubecestat,33 and atabecestat34 have been recently discontinued due to unexpected difficulties.”
§ Current and Future Treatments in Alzheimer Disease: An Update > Current Landscape in Treatment Research for AD > Currently studied DMTs for AD
What the sources say
- Not checked yetcites [32] Burki T Alzheimer’s disease research: the future of BACE inhibitors. Lancet. 2018; 391: 2486. 29976459 source
- Supportedcites [33] Egan MF Kost J Voss T, et al Randomized trial of verubecestat for prodromal Alzheimer’s disease. N Engl J Med. 2019; 380: 1408- 1420. 30970186 PMC6776078 source
The Results (Patient Characteristics) state that the verubecestat trial was stopped in February 2018 on the data and safety monitoring committee’s recommendation because neither dose was expected to show superiority over placebo. This supports the verubecestat portion of the sentence, to which this citation is attached; it does not need to establish what happened in the separately cited lanabecestat and atabecestat trials. (LLM, conf=0.93)
- Not checked yetcites [34] Henley D Raghavan N Sperling R Aisen P Raman R Romano G Preliminary results of a trial of atabecestat in preclinical Alzheimer’s disease. N Engl J Med. 2019; 380: 1483- 1485. 30970197 source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“One of them, compound γ-AA26, seems almost 100-fold as efficient as the compound 18 of the KLVFF in the inhibition of the aggregation of Aβ42.52”
§ Current and Future Treatments in Alzheimer Disease: An Update > Current Landscape in Treatment Research for AD > Currently studied DMTs for AD
What the sources say
- Partly supportedcites [52] Nimmagadda A Shi Y Cai J γ-AApeptides as a new strategy for therapeutic development. Curr Med Chem. 2019; 26: 2313- 2329. 29110596 PMC5936681 sourceExperimental — accuracy not yet measured
Section 6 reports that γ-AA26 was almost 100-fold as potent as KLVFF at inhibiting Aβ aggregation. It describes screening and binding tests with Aβ40, but does not specify Aβ42 for the inhibition comparison; it also calls the comparator P4 (KLVFF), not “compound 18.” (LLM, conf=0.88)
hedgeddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Partly supported
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“A search for phases 1, 2, and 3 “recruiting” or “active but not recruiting” clinical trials for AD in clinicaltrials.gov (accessed August 19, 2019) showed 165 outcomes.”
§ Current and Future Treatments in Alzheimer Disease: An Update > Current Landscape in Treatment Research for AD
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
None of the sources cited for this claim have been checked yet.
In the paper
“However, despite all arduous research efforts, at the moment, there are no effective treatment options for the disease.3,4”
§ Current and Future Treatments in Alzheimer Disease: An Update > Introduction
What the sources say
- Not checked yetcites [3] Scheltens P Blennow K Breteler MMB, et al Alzheimer’s disease. Lancet. 2016; 388: 505- 517. 26921134 source
- Not checked yetcites [4] Cummings J Lee G Ritter A Sabbagh M Zhong K Alzheimer’s disease drug development pipeline: 2019. Alzheimers Dement. 2019; 5: 272- 293. PMC6617248 31334330 source
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
In the paper
“Initiation of AChEI treatment as soon as possible after the diagnosis is preferred as patients who started the AChEI 6 months later showed more rapid cognitive decline than those who started the drug immediately.17”
§ Current and Future Treatments in Alzheimer Disease: An Update > Introduction > Current management of AD
What the sources say
- Not checked yetcites [17] Farlow M Anand R Messina J Hartman R Jr Veach J A 52-week study of the efficacy of rivastigmine in patients with mild to moderately severe Alzheimer’s disease. Eur Neurol. 2000; 44: 236- 241. 11096224 source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
In the paper
“The elements of the cascade include local inflammation, oxidation, excitoxicity (excessive glutamate), and tau hyperphosphorylation.5”
§ Current and Future Treatments in Alzheimer Disease: An Update > Introduction
What the sources say
- Not checked yetcites [5] Yiannopoulou KG Papageorgiou SG Current and future treatments for Alzheimer’s disease. Ther Adv Neurol Disord. 2013; 6: 19- 33. 23277790 PMC3526946 source
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
In the paper
“Progressive neuronal destruction leads to shortage and imbalance between various neurotransmitters (eg, acetylcholine, dopamine, serotonin) and to the cognitive deficiencies seen in AD.5”
§ Current and Future Treatments in Alzheimer Disease: An Update > Introduction
What the sources say
- Not checked yetcites [5] Yiannopoulou KG Papageorgiou SG Current and future treatments for Alzheimer’s disease. Ther Adv Neurol Disord. 2013; 6: 19- 33. 23277790 PMC3526946 source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
In the paper
“The basic pathophysiology and neuropathology of AD that drives the current research suggests that the primary histopathologic lesions of AD are the extracellular amyloid plaques and the intracellular Tau neurofibrillary tangles (NFTs).5”
§ Current and Future Treatments in Alzheimer Disease: An Update > Introduction
What the sources say
- Not checked yetcites [5] Yiannopoulou KG Papageorgiou SG Current and future treatments for Alzheimer’s disease. Ther Adv Neurol Disord. 2013; 6: 19- 33. 23277790 PMC3526946 source
hedged- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
None of the sources cited for this claim have been checked yet.
In the paper
“All 3 AChEIs have proved their treatment benefits in delaying decline, stabilizing, or even improving cognition and activities of daily living in randomized placebo-controlled trials up to 52 weeks duration.10,18”
§ Current and Future Treatments in Alzheimer Disease: An Update > Introduction > Current management of AD
What the sources say
- Not checked yetcites [10] Atri A Current and future treatments in Alzheimer’s disease. Semin Neurol. 2019; 39: 227- 240. 30925615 source
- Not checked yetcites [18] Rountree SD Atri A Lopez OL Doody RS Effectiveness of antidementia drugs in delaying Alzheimer disease progression. Alzheimers Dement. 2013; 9: 338- 345. 23102979 source
boosteddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- It may state two separate claims as one. 78
- Probably not a substantial claim. 16
- The quote only partly states this claim. 1
None of the sources cited for this claim have been checked yet.
In the paper
“Thus, AChEIs are contraindicated in conditions including severe cardiac arrhythmias, especially bradycardia or syncope. They are also contraindicated in active peptic ulcer or gastrointestinal bleeding history and uncontrolled seizures.”
§ Current and Future Treatments in Alzheimer Disease: An Update > Introduction > Current management of AD
What the sources say
- Not checked yetcites [17] Farlow M Anand R Messina J Hartman R Jr Veach J A 52-week study of the efficacy of rivastigmine in patients with mild to moderately severe Alzheimer’s disease. Eur Neurol. 2000; 44: 236- 241. 11096224
- Not checked yetcites [18] Rountree SD Atri A Lopez OL Doody RS Effectiveness of antidementia drugs in delaying Alzheimer disease progression. Alzheimers Dement. 2013; 9: 338- 345. 23102979 source
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“It is the forming of amyloid oligomers to which neurotoxicity is mainly attributed and initiates the amyloid cascade.”
§ Current and Future Treatments in Alzheimer Disease: An Update > Introduction
What the sources say
- Not checked yetcites [5] Yiannopoulou KG Papageorgiou SG Current and future treatments for Alzheimer’s disease. Ther Adv Neurol Disord. 2013; 6: 19- 33. 23277790 PMC3526946 source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“Memantine binds preferentially to open NMDA receptor–operated calcium channels blocking NMDA-mediated ion flux and ameliorating the dangerous effects of pathologically elevated glutamate levels that lead to neuronal dysfunction.8”
§ Current and Future Treatments in Alzheimer Disease: An Update > Introduction
What the sources say
- Not checked yetcites [8] Matsunaga S Kishi T Iwata N Memantine monotherapy for Alzheimer’s disease: a systematic review and meta-analysis. PLoS ONE. 2015; 10:e0123289. PMC4393306 25860130
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“Further decline occurs, but even temporary discontinuation of these drugs results in rapid decline and is associated with greater risk of nursing home placement.16”
§ Current and Future Treatments in Alzheimer Disease: An Update > Introduction > Current management of AD
What the sources say
- Not checked yetcites [16] Howard R McShane R Lindesay J, et al Nursing home placement in the donepezil and memantine in moderate to severe Alzheimer’s disease (DOMINO-AD) trial: secondary and post-hoc analyses. Lancet Neurol. 2015; 14: 1171- 1181. 26515660
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“Memantine is a noncompetitive low-affinity NMDA-receptor open-channel blocker and affects glutamatergic transmission.5”
§ Current and Future Treatments in Alzheimer Disease: An Update > Introduction > Current management of AD
What the sources say
- Not checked yetcites [5] Yiannopoulou KG Papageorgiou SG Current and future treatments for Alzheimer’s disease. Ther Adv Neurol Disord. 2013; 6: 19- 33. 23277790 PMC3526946 source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“Donepezil and rivastigmine have been approved by FDA for mild, moderate, and severe AD, whereas galantamine for mild and moderate AD.18”
§ Current and Future Treatments in Alzheimer Disease: An Update > Introduction > Current management of AD
What the sources say
- Not checked yetcites [18] Rountree SD Atri A Lopez OL Doody RS Effectiveness of antidementia drugs in delaying Alzheimer disease progression. Alzheimers Dement. 2013; 9: 338- 345. 23102979 source
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Thus, AChEIs enhance central cholinergic neurotransmission and finally tend to mitigate decline in cognition at least during the first year of treatment.”
§ Current and Future Treatments in Alzheimer Disease: An Update > Introduction > Current management of AD
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“Although in the amyloid hypothesis, tau hyperphosphorylation was thought to be a downstream event of Aβ deposition, it is equally probable that tau and Aβ act in parallel pathways causing AD and enhancing each other’s toxic effects.3”
§ Current and Future Treatments in Alzheimer Disease: An Update > Introduction
What the sources say
- Not checked yetcites [3] Scheltens P Blennow K Breteler MMB, et al Alzheimer’s disease. Lancet. 2016; 388: 505- 517. 26921134 source
hedgeddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“According to the “amyloid hypothesis” Aβ production in the brain initiates a cascade of events leading to the clinical syndrome of AD.”
§ Current and Future Treatments in Alzheimer Disease: An Update > Introduction
What the sources say
- Not checked yetcites [5] Yiannopoulou KG Papageorgiou SG Current and future treatments for Alzheimer’s disease. Ther Adv Neurol Disord. 2013; 6: 19- 33. 23277790 PMC3526946 source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
None of the sources cited for this claim have been checked yet.
In the paper
“Pharmacokinetic characteristics differ among AChEIs: the primary route of elimination for donepezil and galantamine is hepatic metabolism, whereas for rivastigmine is liver and intestine metabolism.”
§ Current and Future Treatments in Alzheimer Disease: An Update > Introduction > Current management of AD
What the sources say
- Not checked yetcites [10] Atri A Current and future treatments in Alzheimer’s disease. Semin Neurol. 2019; 39: 227- 240. 30925615 source
- Not checked yetcites [17] Farlow M Anand R Messina J Hartman R Jr Veach J A 52-week study of the efficacy of rivastigmine in patients with mild to moderately severe Alzheimer’s disease. Eur Neurol. 2000; 44: 236- 241. 11096224
- Not checked yetcites [18] Rountree SD Atri A Lopez OL Doody RS Effectiveness of antidementia drugs in delaying Alzheimer disease progression. Alzheimers Dement. 2013; 9: 338- 345. 23102979 source
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“From this point of view, AD could be prevented or effectively treated by decreasing the production of Aβ and tau; preventing aggregation or misfolding of these proteins; neutralizing or removing the toxic aggregate or misfolded forms of these proteins; or a combination of these modalities.7”
§ Current and Future Treatments in Alzheimer Disease: An Update > Introduction
What the sources say
- Not checked yetcites [7] Hampel H Mesulam MM Cuello AC, et al The cholinergic system in the pathophysiology and treatment of Alzheimer’s disease. Brain. 2018; 141: 1917- 1933. 29850777 PMC6022632 source
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“The AChEIs increase the availability of acetylcholine at synapses and have been proven clinically useful in delaying the cognitive decline in AD.7”
§ Current and Future Treatments in Alzheimer Disease: An Update > Introduction
What the sources say
- Not checked yetcites [7] Hampel H Mesulam MM Cuello AC, et al The cholinergic system in the pathophysiology and treatment of Alzheimer’s disease. Brain. 2018; 141: 1917- 1933. 29850777 PMC6022632 source
boosteddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“Donepezil and galantamine inhibit selectively and reversibly the acetylcholinesterase, whereas rivastigmine is a “pseudo-irreversible” inhibitor of acetylcholinesterase and butyrylcholinesterase.”
§ Current and Future Treatments in Alzheimer Disease: An Update > Introduction > Current management of AD
What the sources say
- Not checked yetcites [10] Atri A Current and future treatments in Alzheimer’s disease. Semin Neurol. 2019; 39: 227- 240. 30925615 source
- Not checked yetcites [17] Farlow M Anand R Messina J Hartman R Jr Veach J A 52-week study of the efficacy of rivastigmine in patients with mild to moderately severe Alzheimer’s disease. Eur Neurol. 2000; 44: 236- 241. 11096224
- Not checked yetcites [18] Rountree SD Atri A Lopez OL Doody RS Effectiveness of antidementia drugs in delaying Alzheimer disease progression. Alzheimers Dement. 2013; 9: 338- 345. 23102979 source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“The AChEIs may also trigger bradycardia and increase the risk of syncope.”
§ Current and Future Treatments in Alzheimer Disease: An Update > Introduction > Current management of AD
What the sources say
- Not checked yetcites [17] Farlow M Anand R Messina J Hartman R Jr Veach J A 52-week study of the efficacy of rivastigmine in patients with mild to moderately severe Alzheimer’s disease. Eur Neurol. 2000; 44: 236- 241. 11096224
- Not checked yetcites [18] Rountree SD Atri A Lopez OL Doody RS Effectiveness of antidementia drugs in delaying Alzheimer disease progression. Alzheimers Dement. 2013; 9: 338- 345. 23102979 source
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“The most popular and broadly accepted explanations for the multiple failures of clinical trials of DMT agents for AD include the too late starting of therapies in disease development, the inappropriate drug doses, the wrong main target of the treatment, and mainly an inadequate understanding of the pathophysiology of AD.35”
§ Current and Future Treatments in Alzheimer Disease: An Update > Current Landscape in Treatment Research for AD
What the sources say
- Not checked yetcites [35] Gauthier S Albert M Fox N, et al Why has therapy development for dementia failed in the last two decades. Alzheimers Dement. 2016; 12: 60- 64. 26710325
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“The DMT agents were further separated into small molecules or biologics (monoclonal antibodies [mAbs] and other immunotherapies).”
§ Current and Future Treatments in Alzheimer Disease: An Update > Current Landscape in Treatment Research for AD
What the sources say
- Not checked yetcites [4] Cummings J Lee G Ritter A Sabbagh M Zhong K Alzheimer’s disease drug development pipeline: 2019. Alzheimers Dement. 2019; 5: 272- 293. PMC6617248 31334330 source
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
In the paper
“The DMT agents were also classified according to their potential MOA as amyloid targeting, as tau-related targeting, and as having other MOA such as anti-inflammatory or metabolic protection, neuroprotection, and growth factor support.4”
§ Current and Future Treatments in Alzheimer Disease: An Update > Current Landscape in Treatment Research for AD
What the sources say
- Not checked yetcites [4] Cummings J Lee G Ritter A Sabbagh M Zhong K Alzheimer’s disease drug development pipeline: 2019. Alzheimers Dement. 2019; 5: 272- 293. PMC6617248 31334330 source
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
In the paper
“Symptomatic agents are supposed to show symptomatic benefits over weeks to many months in cognition improvement or BPSD elimination.10”
§ Current and Future Treatments in Alzheimer Disease: An Update > Current Landscape in Treatment Research for AD
What the sources say
- Not checked yetcites [10] Atri A Current and future treatments in Alzheimer’s disease. Semin Neurol. 2019; 39: 227- 240. 30925615 source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
In the paper
“In addition, the use of clinical trial simulators, Bayesian statistics, and modifiable trial designs is strongly suggested.4”
§ Current and Future Treatments in Alzheimer Disease: An Update > Current Landscape in Treatment Research for AD
What the sources say
- Not checked yetcites [4] Cummings J Lee G Ritter A Sabbagh M Zhong K Alzheimer’s disease drug development pipeline: 2019. Alzheimers Dement. 2019; 5: 272- 293. PMC6617248 31334330 source
boosted- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
In the paper
“Given the fact that longer trial durations increase the probability of detecting a significant effect but at the same time increase tremendously the costs, the proposed solution seems to be the use of clinical trial simulators.28”
§ Current and Future Treatments in Alzheimer Disease: An Update > Current Landscape in Treatment Research for AD
What the sources say
- Not checked yetcites [28] Anderson RM Hadjichrysanthou C Evans S Wong MM Why do so many clinical trials of therapies for Alzheimer’s disease fail? Lancet. 2017; 390: 2327- 2329. 29185425 source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“A novel approach to the problem seems more technical and mathematical than biological and suggests that the selected trials’ clinical endpoint may be extremely premature, and additionally, the variability in diagnostic markers and end points may result in inaccurate diagnosis of patients’ disease state and is finally a definite source of errors.28”
§ Current and Future Treatments in Alzheimer Disease: An Update > Current Landscape in Treatment Research for AD
What the sources say
- Not checked yetcites [28] Anderson RM Hadjichrysanthou C Evans S Wong MM Why do so many clinical trials of therapies for Alzheimer’s disease fail? Lancet. 2017; 390: 2327- 2329. 29185425 source
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. It may state two separate claims as one.
In the paper
“They can also help in the perfecting of the design of the study; hence, they may augment the probability of success of estimated new drugs or save invaluable time and resources, by indicating earlier the forthcoming failure of any inappropriate therapy.37”
§ Current and Future Treatments in Alzheimer Disease: An Update > Current Landscape in Treatment Research for AD
What the sources say
- Not checked yetcites [37] Hadjichrysanthou C Ower AK de Wolf F Anderson RM The development of a stochastic mathematical model of Alzheimer’s disease to help improve the design of clinical trials of potential treatments. PLoS ONE. 2018; 13:e0190615. PMC5788351 29377891
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“The crucial step in AD pathogenesis is the production of amyloid (Aβ), which forms SPs (insoluble and proteolysis-resistant fibrils).”
§ Current and Future Treatments in Alzheimer Disease: An Update > Current Landscape in Treatment Research for AD > Currently studied DMTs for AD
What the sources say
- Not checked yetcites [5] Yiannopoulou KG Papageorgiou SG Current and future treatments for Alzheimer’s disease. Ther Adv Neurol Disord. 2013; 6: 19- 33. 23277790 PMC3526946 source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“Selective serotonin reuptake inhibitors are preferred for treating depression and anxiety.”
§ Current and Future Treatments in Alzheimer Disease: An Update > Introduction > Current management of AD
What the sources say
- Not checked yetcites [21] Bessey LJ Walaszek A Management of behavioral and psychological symptoms of dementia. Curr Psychiatry Rep. 2019; 21: 66. 31264056
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
In the paper
“The tested agents are classified as DMTs (73%), symptomatic cognitive enhancers (13%), and symptomatic for the treatment of BPSDs (11%).4”
§ Current and Future Treatments in Alzheimer Disease: An Update > Current Landscape in Treatment Research for AD
What the sources say
- Not checked yetcites [4] Cummings J Lee G Ritter A Sabbagh M Zhong K Alzheimer’s disease drug development pipeline: 2019. Alzheimers Dement. 2019; 5: 272- 293. PMC6617248 31334330 source
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“The APP cleavage by α-secretase leads to nonamyloidogenic pathway, whereas APP cleavage by β-secretase (BACE1) leads to amyloidogenic pathway.”
§ Current and Future Treatments in Alzheimer Disease: An Update > Current Landscape in Treatment Research for AD > Currently studied DMTs for AD
What the sources say
- Not checked yetcites [5] Yiannopoulou KG Papageorgiou SG Current and future treatments for Alzheimer’s disease. Ther Adv Neurol Disord. 2013; 6: 19- 33. 23277790 PMC3526946 source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“These simulators are constructed with mathematical, computational, and statistical tools and can predict the likelihood that a strategy and clinical end point selection of a given trial are proper or not, before the initiation of the trial.36”
§ Current and Future Treatments in Alzheimer Disease: An Update > Current Landscape in Treatment Research for AD
What the sources say
- Not checked yetcites [36] Romero K Ito K Rogers JA, et al The future is now: model-based clinical trial design for Alzheimer’s disease. Clin Pharmacol Ther. 2015; 97: 210- 214. 25669145 PMC6463482
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“No new drug has been approved by FDA for AD since 2003 and there are no approved DMTs for AD, despite many long and expensive trials.22,28”
§ Current and Future Treatments in Alzheimer Disease: An Update > Current Landscape in Treatment Research for AD
What the sources say
- Not checked yetcites [22] Hukins D Macleod U Boland JW Identifying potentially inappropriate prescribing in older people with dementia: a systematic review. Eur J Clin Pharmacol. 2019; 75: 467- 481. 30610274
- Not checked yetcites [28] Anderson RM Hadjichrysanthou C Evans S Wong MM Why do so many clinical trials of therapies for Alzheimer’s disease fail? Lancet. 2017; 390: 2327- 2329. 29185425 source
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“The National Institute on Aging and the Alzheimer’s Association (NIA-AA) proposed a new framework for research,39 which requires the application of amyloid, tau, and neurodegeneration biomarkers to clinical trials, succeeds in precise classification of patients in AD stages, and can be used to assist clinical trials design.”
§ Current and Future Treatments in Alzheimer Disease: An Update > Current Landscape in Treatment Research for AD
What the sources say
- Not checked yetcites [39] Jack CR Jr Bennett DA Blennow K, et al NIA-AA research framework: toward a biological definition of Alzheimer’s disease. Alzheimers Dement. 2018; 14: 535- 562. 29653606 PMC5958625 source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“Consequently, current guidance provided by the FDA for AD clinical trials further includes use of fluid or neuroradiological biomarkers in disease staging for preclinical and prodromal AD trials and of a single primary outcome in prodromal AD trials.”
§ Current and Future Treatments in Alzheimer Disease: An Update > Current Landscape in Treatment Research for AD
What the sources say
- Not checked yetcites [4] Cummings J Lee G Ritter A Sabbagh M Zhong K Alzheimer’s disease drug development pipeline: 2019. Alzheimers Dement. 2019; 5: 272- 293. PMC6617248 31334330 source
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“The last annual review of the drug development pipeline for AD examined clinicaltrials.gov in February, 2019 (132 agents in 156 trials) and provides information and conclusions available at that time: 28 drugs in 42 clinical trials in phase 3 trials, 74 drugs in 83 phase 2 trials, and 30 drugs in 31 phase 1 trials.4”
§ Current and Future Treatments in Alzheimer Disease: An Update > Current Landscape in Treatment Research for AD
What the sources say
- Not checked yetcites [4] Cummings J Lee G Ritter A Sabbagh M Zhong K Alzheimer’s disease drug development pipeline: 2019. Alzheimers Dement. 2019; 5: 272- 293. PMC6617248 31334330 source
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“Their combination benefits patients with usually additive effects, without any increase in adverse effects.14,15”
§ Current and Future Treatments in Alzheimer Disease: An Update > Introduction > Current management of AD
What the sources say
- Not checked yetcites [14] Na R Yang JH Yeom Y, et al A systematic review and meta-analysis of nonpharmacological interventions for moderate to severe dementia. Psychiatry Investig. 2019; 16: 325- 335. PMC6539264 31132836
- Not checked yetcites [15] Kishita N Backhouse T Mioshi E Nonpharmacological interventions to improve depression, anxiety, and quality of life (QoL) in people with dementia: an overview of systematic reviews. J Geriatr Psychiatry Neurol. 2019; 33: 28- 41. 31203712 source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“Two BACE inhibitors are still elaborated: elenbecestat (E2609) in phase 2 and umibecestat (CNP520) in phase 3.4”
§ Current and Future Treatments in Alzheimer Disease: An Update > Current Landscape in Treatment Research for AD > Currently studied DMTs for AD
What the sources say
- Not checked yetcites [4] Cummings J Lee G Ritter A Sabbagh M Zhong K Alzheimer’s disease drug development pipeline: 2019. Alzheimers Dement. 2019; 5: 272- 293. PMC6617248 31334330 source
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“The phase 3 lanabecestat trial was discontinued due to lack of efficacy, whereas verubecestat and atabecestat trials were ceased due to ineffectiveness, as well as safety reasons (rash, falls, liver toxicity, and neuropsychiatric symptoms).10,32-34”
§ Current and Future Treatments in Alzheimer Disease: An Update > Current Landscape in Treatment Research for AD > Currently studied DMTs for AD
What the sources say
- Not checked yetcites [10] Atri A Current and future treatments in Alzheimer’s disease. Semin Neurol. 2019; 39: 227- 240. 30925615 source
- Not checked yetcites [32] Burki T Alzheimer’s disease research: the future of BACE inhibitors. Lancet. 2018; 391: 2486. 29976459 source
- Not checked yetcites [33] Egan MF Kost J Voss T, et al Randomized trial of verubecestat for prodromal Alzheimer’s disease. N Engl J Med. 2019; 380: 1408- 1420. 30970186 PMC6776078 source
- Not checked yetcites [34] Henley D Raghavan N Sperling R Aisen P Raman R Romano G Preliminary results of a trial of atabecestat in preclinical Alzheimer’s disease. N Engl J Med. 2019; 380: 1483- 1485. 30970197 source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“APH-1105 is delivered intranasally and is assessed in mild to moderate AD.4”
§ Current and Future Treatments in Alzheimer Disease: An Update > Current Landscape in Treatment Research for AD > Currently studied DMTs for AD
What the sources say
- Not checked yetcites [4] Cummings J Lee G Ritter A Sabbagh M Zhong K Alzheimer’s disease drug development pipeline: 2019. Alzheimers Dement. 2019; 5: 272- 293. PMC6617248 31334330 source
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“Etazolate is currently evaluated in animal studies for its preventive effect in post-traumatic stress disorder.49”
§ Current and Future Treatments in Alzheimer Disease: An Update > Current Landscape in Treatment Research for AD > Currently studied DMTs for AD
What the sources say
- Not checked yetcites [49] Alzoubi KH Al Subeh ZY Khabour OF Molecular targets for the interactive effect of etazolate during post-traumatic stress disorder: role of oxidative stress, BDNF and histones. Behav Brain Res. 2019; 369:111930. 31047921
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
In the paper
“Aβ42 is the most aggregation-prone form and has the tendency to cluster into oligomers.”
§ Current and Future Treatments in Alzheimer Disease: An Update > Current Landscape in Treatment Research for AD > Currently studied DMTs for AD
What the sources say
- Not checked yetcites [5] Yiannopoulou KG Papageorgiou SG Current and future treatments for Alzheimer’s disease. Ther Adv Neurol Disord. 2013; 6: 19- 33. 23277790 PMC3526946 source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“Etazolate (EHT0202) stimulates the nonamyloidogenic α-secretase pathway acting as a selective modulator of GABA receptors.”
§ Current and Future Treatments in Alzheimer Disease: An Update > Current Landscape in Treatment Research for AD > Currently studied DMTs for AD
What the sources say
- Not checked yetcites [48] Vellas B Sol O Snyder PJ, et al EHT0202 in Alzheimer’s disease: a 3-month, randomized, placebo-controlled, double-blind study. Curr Alzheimer Res. 2011; 8: 203- 212. 21222604 source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“The KLVFF compound that mainly prevents the aggregation of Aβ42 and can also dissolve the oligomerics to a limited extend is the final compound 18, which is resilient in proteolytic decomposition.51”
§ Current and Future Treatments in Alzheimer Disease: An Update > Current Landscape in Treatment Research for AD > Currently studied DMTs for AD
What the sources say
- Not checked yetcites [51] Stark T Lieblein T Pohland M, et al Peptidomimetics that inhibit and partially reverse the aggregation of Aβ1-42. Biochemistry. 2017; 56: 4840- 4849. 28841311 source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“A phase 2 clinical trial in patients with AD did not provide evidence to support a clinical benefit of ELND005 while severe toxicity issues (infections) forced the cessation of the study.”
§ Current and Future Treatments in Alzheimer Disease: An Update > Current Landscape in Treatment Research for AD > Currently studied DMTs for AD
What the sources say
- Not checked yetcites [50] Salloway S Sperling R Keren R, et al; ELND005-AD201 Investigators. A phase 2 randomized trial of ELND005, scyllo-inositol, in mild to moderate Alzheimer disease. Neurology. 2011; 77: 1253- 1262. 21917766 PMC3179648 source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“Aβ38 is soluble, present in the vasculature of patients with sporadic and familial AD.”
§ Current and Future Treatments in Alzheimer Disease: An Update > Current Landscape in Treatment Research for AD > Currently studied DMTs for AD
What the sources say
- Not checked yetcites [5] Yiannopoulou KG Papageorgiou SG Current and future treatments for Alzheimer’s disease. Ther Adv Neurol Disord. 2013; 6: 19- 33. 23277790 PMC3526946 source
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“This fact is probably responsible for recent failures in clinical trials with γ-secretase inhibitors: semagacestat29 was associated with worsening of activities in daily leaving and increased rates of infections and skin cancer, avagacestat41 was associated with higher rate of cognitive decline and adverse dose-limiting effects (skin cancer) and tarenflurbil which showed low brain penetration.42”
§ Current and Future Treatments in Alzheimer Disease: An Update > Current Landscape in Treatment Research for AD > Currently studied DMTs for AD
What the sources say
- Not checked yetcites [29] Doody RS Raman R Farlow M, et al A phase 3 trial of semagacestat for treatment of Alzheimer’s disease. N Engl J Med. 2013; 369: 341- 350. 23883379 source
- Not checked yetcites [41] Coric V Salloway S van Dyck CH, et al Targeting prodromal Alzheimer disease with avagacestat: a randomized clinical trial. JAMA Neurol. 2015; 72: 1324- 1333. 26414022 source
- Not checked yetcites [42] Muntimadugu E Dhommati R Jain A Challa VG Shaheen M Khan W Intranasal delivery of nanoparticle encapsulated tarenflurbil: a potential brain targeting strategy for Alzheimer’s disease. Eur J Pharm Sci. 2016; 92: 224- 234. 27185298
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“KLVFF is a peptide sequence that resembles the hydrophobic central part of the Aβ and gradually replaces natural polypeptides.”
§ Current and Future Treatments in Alzheimer Disease: An Update > Current Landscape in Treatment Research for AD > Currently studied DMTs for AD
What the sources say
- Not checked yetcites [51] Stark T Lieblein T Pohland M, et al Peptidomimetics that inhibit and partially reverse the aggregation of Aβ1-42. Biochemistry. 2017; 56: 4840- 4849. 28841311 source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“Major sites of γ-secretase cleavage usually occur in positions 40 and 42 of Aβ, thus Aβ40 and Aβ42 oligomers are the main products of the sequential APP cleavage, as the amyloidogenic pathway is favored in neurons because of the greater plentifulness of BACE1.”
§ Current and Future Treatments in Alzheimer Disease: An Update > Current Landscape in Treatment Research for AD > Currently studied DMTs for AD
What the sources say
- Not checked yetcites [5] Yiannopoulou KG Papageorgiou SG Current and future treatments for Alzheimer’s disease. Ther Adv Neurol Disord. 2013; 6: 19- 33. 23277790 PMC3526946 source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“Aβ40 usually constitutes more than 50% of total detected Aβ.”
§ Current and Future Treatments in Alzheimer Disease: An Update > Current Landscape in Treatment Research for AD > Currently studied DMTs for AD
What the sources say
- Not checked yetcites [5] Yiannopoulou KG Papageorgiou SG Current and future treatments for Alzheimer’s disease. Ther Adv Neurol Disord. 2013; 6: 19- 33. 23277790 PMC3526946 source
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
None of the sources cited for this claim have been checked yet.
In the paper
“Restricted, nowadays, knowledge assumes that α-secretase activation is promoted through the phosphatidylinositol 3-kinase (PI3K)/Akt pathway and may be through γ-aminobutyric acid (GABA) receptor signaling; thus, agents that activate the PI3K/Akt pathway or act as selective GABA receptor modulators are suggested as potential therapeutic drugs for AD.47,48”
§ Current and Future Treatments in Alzheimer Disease: An Update > Current Landscape in Treatment Research for AD > Currently studied DMTs for AD
What the sources say
- Not checked yetcites [47] Cho WH Park JC Kim DH, et al ID1201, the ethanolic extract of the fruit of Melia toosendan ameliorates impairments in spatial learning and reduces levels of amyloid beta in 5XFAD mice. Neurosci Lett. 2014; 583: 170- 175. 25281546 source
- Not checked yetcites [48] Vellas B Sol O Snyder PJ, et al EHT0202 in Alzheimer’s disease: a 3-month, randomized, placebo-controlled, double-blind study. Curr Alzheimer Res. 2011; 8: 203- 212. 21222604 source
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. It may state two separate claims as one.
In the paper
“Aβ40 is somewhat aggregation-prone and it is mostly found in the cerebral vasculature as a main component of “cerebral amyloid angiopathy.””
§ Current and Future Treatments in Alzheimer Disease: An Update > Current Landscape in Treatment Research for AD > Currently studied DMTs for AD
What the sources say
- Not checked yetcites [5] Yiannopoulou KG Papageorgiou SG Current and future treatments for Alzheimer’s disease. Ther Adv Neurol Disord. 2013; 6: 19- 33. 23277790 PMC3526946 source
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
In the paper
“All agents showed significant and dose-dependent result of reducing CSF Aβ42, but without cognitive or functional benefit while many of them were poorly tolerated and some of them failed in subjects with prodromal AD.”
§ Current and Future Treatments in Alzheimer Disease: An Update > Current Landscape in Treatment Research for AD > Currently studied DMTs for AD
What the sources say
- Not checked yetcites [46] Panza F Lozupone M Solfrizzi V, et al BACE inhibitors in clinical development for the treatment of Alzheimer’s disease. Expert Rev Neurother. 2018; 18: 847- 857. 30277096
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“Unluckily, concerning γ-secretase, in addition to APP, this particular enzyme acts on many other substances and cleaves different transmembrane proteins. Notch receptor 1, which is essential for control of normal cell differentiation and communication, is among them.5”
§ Current and Future Treatments in Alzheimer Disease: An Update > Current Landscape in Treatment Research for AD > Currently studied DMTs for AD
What the sources say
- Not checked yetcites [5] Yiannopoulou KG Papageorgiou SG Current and future treatments for Alzheimer’s disease. Ther Adv Neurol Disord. 2013; 6: 19- 33. 23277790 PMC3526946 source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“ID1201 is a fruit extract of melia toosendan and also induces α-secretase activation. It is evaluated in mild AD.47”
§ Current and Future Treatments in Alzheimer Disease: An Update > Current Landscape in Treatment Research for AD > Currently studied DMTs for AD
What the sources say
- Not checked yetcites [47] Cho WH Park JC Kim DH, et al ID1201, the ethanolic extract of the fruit of Melia toosendan ameliorates impairments in spatial learning and reduces levels of amyloid beta in 5XFAD mice. Neurosci Lett. 2014; 583: 170- 175. 25281546 source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“Consequently, it is possible that effective AD immunotherapies must be able to simultaneously target both ptau and Aβ pathologies.56”
§ Current and Future Treatments in Alzheimer Disease: An Update > Current Landscape in Treatment Research for AD > Currently studied DMTs for AD
What the sources say
- Not checked yetcites [56] Wisniewski T Goñi F Immunotherapeutic approaches for Alzheimer’s disease. Neuron. 2015; 85: 1162- 1176. 25789753 PMC4366618 source
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Overall, Aβ-targeted strategies seem promising if used very early in the progression of the disease, before the presence of any symptoms; thus, they are developed in current trials in preclinical AD.”
§ Current and Future Treatments in Alzheimer Disease: An Update > Current Landscape in Treatment Research for AD > Currently studied DMTs for AD
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“CAD106 is an active Aβ immunotherapeutic agent, is studied in preclinical AD under the umbrella of the Alzheimer prevention initiative generation program, which comprises 2 phase 3 studies that evaluate simultaneously the safety and efficacy of CAD106 and umibecestat in asymptomatic individuals at risk of developing AD (60-75 years of age, APOE4 homozygotes, or APOE4 heterozygotes with elevated Am”
§ Current and Future Treatments in Alzheimer Disease: An Update > Current Landscape in Treatment Research for AD > Currently studied DMTs for AD
What the sources say
- Not checked yetcites [45] Lopez Lopez C Tariot PN Caputo A, et al The Alzheimer’s Prevention Initiative Generation Program: study design of two randomized controlled trials for individuals at risk for clinical onset of Alzheimer’s disease. Alzheimers Dement; 5: 216- 227. PMC6562315 31211217 source
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“A metal protein–attenuating compound, PBT2, has recently progressed in phase 2 AD treatment trials, as it demonstrated promising efficacy data in preclinical studies.54”
§ Current and Future Treatments in Alzheimer Disease: An Update > Current Landscape in Treatment Research for AD > Currently studied DMTs for AD
What the sources say
- Not checked yetcites [54] Krishnan HS Bernard-Gauthier V Placzek MS Metal protein-attenuating compound for PET neuroimaging: synthesis and preclinical evaluation of [11C]PBT2. Mol Pharm. 2018; 15: 695- 702. 29298483
boosteddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“Antigen-presenting cells present the immunogens to B cells. Use of Ab or ptau peptides will produce antibodies to Ab or ptau epitopes, respectively. Use of pBri will produce antibodies to both Aβ and ptau epitopes.56”
§ Current and Future Treatments in Alzheimer Disease: An Update > Current Landscape in Treatment Research for AD > Currently studied DMTs for AD
What the sources say
- Not checked yetcites [56] Wisniewski T Goñi F Immunotherapeutic approaches for Alzheimer’s disease. Neuron. 2015; 85: 1162- 1176. 25789753 PMC4366618 source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“ABvac40 is evaluated in a phase 2 study, as the first active vaccine against the C-terminal end of Aβ40.”
§ Current and Future Treatments in Alzheimer Disease: An Update > Current Landscape in Treatment Research for AD > Currently studied DMTs for AD
What the sources say
- Not checked yetcites [59] Lopez Lopez C Tariot PN Caputo A, et al The Alzheimer’s Prevention Initiative Generation Program: study design of two randomized controlled trials for individuals at risk for clinical onset of Alzheimer’s disease. Alzheimers Dement. 2019; 12: 216- 227. PMC6562315 31211217 source
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“ABri is a rare hereditary amyloidosis associated with a mutation that results in the production of a highly amyloidogenic protein with a unique carboxyl terminus that has no homology to any other human protein.”
§ Current and Future Treatments in Alzheimer Disease: An Update > Current Landscape in Treatment Research for AD > Currently studied DMTs for AD
What the sources say
- Not checked yetcites [57] Goñi F Herline K Peyser D, et al Immunomodulation targeting of both Aβ and tau pathological conformers ameliorates Alzheimer’s disease pathology in TgSwDI and 3xTg mouse models. J Neuroinflammation. 2013; 10: 150. 24330773 PMC3878790
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
In the paper
“In a 3-month phase 2 study, PBT2 succeeded in a 13% reduction of CSF Aβ and an executive function improvement in a dose-related pattern in patients with early AD.55”
§ Current and Future Treatments in Alzheimer Disease: An Update > Current Landscape in Treatment Research for AD > Currently studied DMTs for AD
What the sources say
- Not checked yetcites [55] Villemagne VL Rowe CC Barnham KJ, et al A randomized, exploratory molecular imaging study targeting amyloid β with a novel 8-OH quinoline in Alzheimer’s disease: the PBT2-204 IMAGINE study. Alzheimers Dement. 2017; 3: 622- 635. PMC5702880 29201996
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“GV1001 peptide (tertomotide) was previously studied as a vaccine against various cancers, whereas now it is evaluated in a phase 2 study for AD.60”
§ Current and Future Treatments in Alzheimer Disease: An Update > Current Landscape in Treatment Research for AD > Currently studied DMTs for AD
What the sources say
- Not checked yetcites [60] Lacosta AM Pascual-Lucas M Pesini P, et al Safety, tolerability and immunogenicity of an active anti-Aβ40 vaccine (ABvac40) in patients with Alzheimer’s disease: a randomised, double-blind, placebocontrolled, phase I trial. Alzheimers Res Ther. 2018; 10: 12. 29378651 PMC5789644 source
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
In the paper
“Immunotherapeutic approaches have dominated in the past 15 years with negative results until now.”
§ Current and Future Treatments in Alzheimer Disease: An Update > Current Landscape in Treatment Research for AD > Currently studied DMTs for AD
What the sources say
- Not checked yetcites [56] Wisniewski T Goñi F Immunotherapeutic approaches for Alzheimer’s disease. Neuron. 2015; 85: 1162- 1176. 25789753 PMC4366618 source
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“UB-311, a synthetic peptide used as Aβ vaccine, has been advanced into an ongoing phase 2 study in patients with mild and moderate AD. In phase 1, it induced a 100% responder rate in patients with AD. The usual adverse effects were swelling in the injection site and agitation. A slower cognitive decline rate was observed in patients with mild AD.62”
§ Current and Future Treatments in Alzheimer Disease: An Update > Current Landscape in Treatment Research for AD > Currently studied DMTs for AD
What the sources say
- Not checked yetcites [62] Hull M Sadowsky C Arai H, et al Long-term extensions of randomized vaccination trials of ACC-001 and QS-21 in mild to moderate Alzheimer’s disease. Curr Alzheimer Res. 2017; 14: 696- 708. 28124589 PMC5543567 source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“Monoclonal Abs to Ab, ptau, or b sheet epitopes are systemically and adequately for BBB penetration infused. As antibodies cross the BBB, they act to clear, degrade, or alternatively disaggregate or neutralize their targets.56”
§ Current and Future Treatments in Alzheimer Disease: An Update > Current Landscape in Treatment Research for AD > Currently studied DMTs for AD
What the sources say
- Not checked yetcites [56] Wisniewski T Goñi F Immunotherapeutic approaches for Alzheimer’s disease. Neuron. 2015; 85: 1162- 1176. 25789753 PMC4366618 source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“Furthermore, the design of the studies became more specific and targeted: the characteristics of amyloid-related imaging abnormalities were associated with the dose of antibodies and APOε4 genotyping, higher dosing necessity was recognized, and accurate measures for specific targets, such as reduction of Aβ plaque burden on amyloid PET, were required.10”
§ Current and Future Treatments in Alzheimer Disease: An Update > Current Landscape in Treatment Research for AD > Currently studied DMTs for AD
What the sources say
- Not checked yetcites [10] Atri A Current and future treatments in Alzheimer’s disease. Semin Neurol. 2019; 39: 227- 240. 30925615 source
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“The pBri peptide corresponds to this terminus and induces an immune response that recognizes Aβ and ptau.”
§ Current and Future Treatments in Alzheimer Disease: An Update > Current Landscape in Treatment Research for AD > Currently studied DMTs for AD
What the sources say
- Not checked yetcites [57] Goñi F Herline K Peyser D, et al Immunomodulation targeting of both Aβ and tau pathological conformers ameliorates Alzheimer’s disease pathology in TgSwDI and 3xTg mouse models. J Neuroinflammation. 2013; 10: 150. 24330773 PMC3878790
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“ACC-001 (vanutide cridificar), an Aβ vaccine, was studied in phase 2a extension studies in subjects with mild to moderate AD. It was administered with QS-21 adjuvant. Long-term therapy with this combination was very well tolerated and produced the highest anti-Aβ IgG titers compared with other regimens.61”
§ Current and Future Treatments in Alzheimer Disease: An Update > Current Landscape in Treatment Research for AD > Currently studied DMTs for AD
What the sources say
- Not checked yetcites [61] Kim H Seo EH Lee SH Kim BJ The telomerase-derived anticancer peptide vaccine GV1001 as an extracellular heat shock protein-mediated cell-penetrating peptide. Int J Mol Sci. 2016; 17: E2054. PMC5187854 27941629
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“Strict inclusion criteria were applied, such as biomarker proof of “amyloid positivity” and enrollment of individuals with preclinical stages of the disease.”
§ Current and Future Treatments in Alzheimer Disease: An Update > Current Landscape in Treatment Research for AD > Currently studied DMTs for AD
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“A phase 1 study was conducted with patients with mild to moderate AD aged 50 to 85 years. Neither incident vasogenic edema nor microhemorrhages were identified. Specific anti-Aβ40 antibodies were developed in the 92% of the individuals receiving injections of ABvac40.59”
§ Current and Future Treatments in Alzheimer Disease: An Update > Current Landscape in Treatment Research for AD > Currently studied DMTs for AD
What the sources say
- Not checked yetcites [59] Lopez Lopez C Tariot PN Caputo A, et al The Alzheimer’s Prevention Initiative Generation Program: study design of two randomized controlled trials for individuals at risk for clinical onset of Alzheimer’s disease. Alzheimers Dement. 2019; 12: 216- 227. PMC6562315 31211217 source
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“and crenezumab,70 gantenerumab, and solanezumab71 in studies for preclinical or at-risk populations”
§ Current and Future Treatments in Alzheimer Disease: An Update > Current Landscape in Treatment Research for AD > Currently studied DMTs for AD
What the sources say
- Not checked yetcites [70] Logovinsky V Satlin A Lai R, et al Safety and tolerability of BAN2401–a clinical study in Alzheimer’s disease with a protofibril selective Aβ antibody. Alzheimers Res Ther. 2016; 8: 14. 27048170 PMC4822297
- Not checked yetcites [68] Sevigny J Chiao P Bussière T, et al The antibody aducanumab reduces Aβ plaques in Alzheimer’s disease. Nature. 2016; 537: 50- 56. 27582220 source
- Not checked yetcites [71] Yang T Dang Y Ostaszewski B, et al Target engagement in an Alzheimer trial: crenezumab lowers amyloid β oligomers in cerebrospinal fluid. Ann Neurol. 2019; 86: 215- 224. 31168802 PMC6771589 source
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“Eleven of them are studied in phase 3: 3 cognitive intensifiers and 8 acting on BPSD.”
§ Current and Future Treatments in Alzheimer Disease: An Update > Current Landscape in Treatment Research for AD > Currently studied DMTs for AD
What the sources say
- Not checked yetcites [4] Cummings J Lee G Ritter A Sabbagh M Zhong K Alzheimer’s disease drug development pipeline: 2019. Alzheimers Dement. 2019; 5: 272- 293. PMC6617248 31334330 source
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“Twenty symptomatic agents are in phase 2: 14 cognitive intensifiers and 6 acting on BPSD.”
§ Current and Future Treatments in Alzheimer Disease: An Update > Current Landscape in Treatment Research for AD > Currently studied DMTs for AD
What the sources say
- Not checked yetcites [4] Cummings J Lee G Ritter A Sabbagh M Zhong K Alzheimer’s disease drug development pipeline: 2019. Alzheimers Dement. 2019; 5: 272- 293. PMC6617248 31334330 source
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“Only 1 agent with tau-related mechanism is evaluated in phase 2/3, whereas 10 agents that target tau as one of their mechanisms are evaluated in phase 2, and 5 more agents with tau-related mechanism are assessed in phase 1 studies.4”
§ Current and Future Treatments in Alzheimer Disease: An Update > Current Landscape in Treatment Research for AD > Currently studied DMTs for AD
What the sources say
- Not checked yetcites [4] Cummings J Lee G Ritter A Sabbagh M Zhong K Alzheimer’s disease drug development pipeline: 2019. Alzheimers Dement. 2019; 5: 272- 293. PMC6617248 31334330 source
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“NPT088 reduced Aβ and ptau aggregates and improved cognition in aged Tg2576 mice.”
§ Current and Future Treatments in Alzheimer Disease: An Update > Current Landscape in Treatment Research for AD > Currently studied DMTs for AD
What the sources say
- Not checked yetcites [77] Levenson JM Schroeter S Carroll JC, et al NPT088 reduces both amyloid-β and tau pathologies in transgenic mice. Alzheimers Dement. 2016; 2: 141- 155. PMC5651359 29067301
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“patients treated with ANAVEX 2-73 had high levels of 2 gut microbiota families, Ruminococcaceae and Porphyromonadaceae, which were associated with improved activities of daily living.”
§ Current and Future Treatments in Alzheimer Disease: An Update > Current Landscape in Treatment Research for AD > Currently studied DMTs for AD
What the sources say
- Not checked yetcites [81] Parmentier F Etcheto A Missling CU, et al Exploring Gut Microbiota as a Source of Potential Biomarkers: Initial Results from the ANAVEX®2-73 Alzheimer’s Disease Clinical Study [O4-02-04]. AAIC; 2019 http://www.arianapharma.com/wp-content/uploads/2019/07/Anavex-Microbiota-Presentation-AAIC-July-2019-FINAL-1.pdf.
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“There are also 2 cognitive intensifiers being studied in phase 1.4”
§ Current and Future Treatments in Alzheimer Disease: An Update > Current Landscape in Treatment Research for AD > Currently studied DMTs for AD
What the sources say
- Not checked yetcites [4] Cummings J Lee G Ritter A Sabbagh M Zhong K Alzheimer’s disease drug development pipeline: 2019. Alzheimers Dement. 2019; 5: 272- 293. PMC6617248 31334330 source
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
The quote only partly states this claim.
In the paper
“A monotherapy trial with MB on mild and moderate AD (NCT00515333) has demonstrated some clinical benefit in moderate, but not mild AD.82”
§ Current and Future Treatments in Alzheimer Disease: An Update > Current Landscape in Treatment Research for AD > Currently studied DMTs for AD
What the sources say
- Not checked yetcites [82] Wischik CM Staff RT Wischik DJ, et al Tau aggregation inhibitor therapy: an exploratory phase 2 study in mild or moderate Alzheimer’s disease. J Alzheimers Dis. 2015; 44: 705- 720. 25550228 source
boostedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“the first completed phase 3 trial of IVIg as a treatment for AD demonstrated good tolerability but lack of efficacy of the agent on clinical stability or delay of cognitive or functional decline of participants with mild and moderate AD.74”
§ Current and Future Treatments in Alzheimer Disease: An Update > Current Landscape in Treatment Research for AD > Currently studied DMTs for AD
What the sources say
- Not checked yetcites [74] Schwarz AJ Sundell KL Charil A, et al Magnetic resonance imaging measures of brain atrophy from the EXPEDITION3 trial in mild Alzheimer’s disease. Alzheimers Dement. 2019; 5: 328- 337. PMC6675941 31388559
boosted- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“TNF-α signaling has been proved to exacerbate both Aβ aggregation and tau phosphorylation in vivo,90”
§ Current and Future Treatments in Alzheimer Disease: An Update > Current Landscape in Treatment Research for AD > Currently studied DMTs for AD
What the sources say
- Not checked yetcites [90] Alam Q Alam MZ Mushtaq G, et al Inflammatory process in Alzheimer’s and Parkinson’s diseases: central role of cytokines. Curr Pharm Des. 2016; 22: 541- 548. 26601965
boosteddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“AGB101 (low-dose extended-release levetiracetam) is an SV2A modulator that is assessed in a phase 3 clinical trial as a repurposed agent (approved for use in another indication, not epilepsy but MCI due to AD).”
§ Current and Future Treatments in Alzheimer Disease: An Update > Current Landscape in Treatment Research for AD > Currently studied DMTs for AD
What the sources say
- Not checked yetcites [4] Cummings J Lee G Ritter A Sabbagh M Zhong K Alzheimer’s disease drug development pipeline: 2019. Alzheimers Dement. 2019; 5: 272- 293. PMC6617248 31334330 source
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“Overall, there are 33 symptomatic agents in current trials: 19 agents aim to improve cognition and 14 target BPSD.”
§ Current and Future Treatments in Alzheimer Disease: An Update > Current Landscape in Treatment Research for AD > Currently studied DMTs for AD
What the sources say
- Not checked yetcites [4] Cummings J Lee G Ritter A Sabbagh M Zhong K Alzheimer’s disease drug development pipeline: 2019. Alzheimers Dement. 2019; 5: 272- 293. PMC6617248 31334330 source
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“COR388 targets a periodontal pathogen acting as bacterial protease inhibitor that reduces neuroinflammation and consequently hippocampal degeneration and is currently assessed in a phase 3 clinical trial (NCT03823404).4”
§ Current and Future Treatments in Alzheimer Disease: An Update > Current Landscape in Treatment Research for AD > Currently studied DMTs for AD
What the sources say
- Not checked yetcites [4] Cummings J Lee G Ritter A Sabbagh M Zhong K Alzheimer’s disease drug development pipeline: 2019. Alzheimers Dement. 2019; 5: 272- 293. PMC6617248 31334330 source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“NDX-1017 is an hepatocyte growth factor with the role to regenerate neurons, which is studied in a phase 1 clinical trial (NCT03298672).4”
§ Current and Future Treatments in Alzheimer Disease: An Update > Current Landscape in Treatment Research for AD > Currently studied DMTs for AD
What the sources say
- Not checked yetcites [4] Cummings J Lee G Ritter A Sabbagh M Zhong K Alzheimer’s disease drug development pipeline: 2019. Alzheimers Dement. 2019; 5: 272- 293. PMC6617248 31334330 source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“BHV4157 (troriluzole) is a glutamate modulator that reduces synaptic levels of glutamate and is assessed in a phase 3 clinical trial (NCT03605667).4”
§ Current and Future Treatments in Alzheimer Disease: An Update > Current Landscape in Treatment Research for AD > Currently studied DMTs for AD
What the sources say
- Not checked yetcites [4] Cummings J Lee G Ritter A Sabbagh M Zhong K Alzheimer’s disease drug development pipeline: 2019. Alzheimers Dement. 2019; 5: 272- 293. PMC6617248 31334330 source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“Losartan plus amlodipine plus atorvastatin plus exercise is a combination repurposed agent suggested to succeed significant reduction of the vascular risk capable of preserving cognitive function. It is assessed in a phase 3 clinical trial (NCT02913664).4”
§ Current and Future Treatments in Alzheimer Disease: An Update > Current Landscape in Treatment Research for AD > Currently studied DMTs for AD
What the sources say
- Not checked yetcites [4] Cummings J Lee G Ritter A Sabbagh M Zhong K Alzheimer’s disease drug development pipeline: 2019. Alzheimers Dement. 2019; 5: 272- 293. PMC6617248 31334330 source
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“Masitinib acts on mast cells as a selective tyrosine kinase inhibitor and a modulator of neuroinflammation. It is assessed in a phase 3 clinical trial (NCT01872598).4”
§ Current and Future Treatments in Alzheimer Disease: An Update > Current Landscape in Treatment Research for AD > Currently studied DMTs for AD
What the sources say
- Not checked yetcites [4] Cummings J Lee G Ritter A Sabbagh M Zhong K Alzheimer’s disease drug development pipeline: 2019. Alzheimers Dement. 2019; 5: 272- 293. PMC6617248 31334330 source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“AstroStem is currently assessed in a phase 2 study (NCT03117738), whereas hMSCs (human mesenchymal stem cells) treatment is assessed in a phase 1 study (NCT02600130).4”
§ Current and Future Treatments in Alzheimer Disease: An Update > Current Landscape in Treatment Research for AD > Currently studied DMTs for AD
What the sources say
- Not checked yetcites [4] Cummings J Lee G Ritter A Sabbagh M Zhong K Alzheimer’s disease drug development pipeline: 2019. Alzheimers Dement. 2019; 5: 272- 293. PMC6617248 31334330 source
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“Candesartan, an angiotensin receptor blocker; formoterol, a β2 adrenergic receptor agonist; and intranasal insulin glulisine, which rises brain insulin signaling, are currently studied in phase 2 clinical trials (NCT02646982, NCT02500784, NCT02503501, respectively), whereas intranasal insulin aspart is assessed in a phase 1 clinical study.4”
§ Current and Future Treatments in Alzheimer Disease: An Update > Current Landscape in Treatment Research for AD > Currently studied DMTs for AD
What the sources say
- Not checked yetcites [4] Cummings J Lee G Ritter A Sabbagh M Zhong K Alzheimer’s disease drug development pipeline: 2019. Alzheimers Dement. 2019; 5: 272- 293. PMC6617248 31334330 source
plain- Asserted: passes — The authors put it forward as true.
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In the paper
“Icosapent ethyl is the eicosapentaenoic acid (EPA) omega-3 fatty acid in a purified form. It is supposed to protect neurons from disease pathology and is assessed in a phase 3 clinical trial (NCT02719327).4”
§ Current and Future Treatments in Alzheimer Disease: An Update > Current Landscape in Treatment Research for AD > Currently studied DMTs for AD
What the sources say
- Not checked yetcites [4] Cummings J Lee G Ritter A Sabbagh M Zhong K Alzheimer’s disease drug development pipeline: 2019. Alzheimers Dement. 2019; 5: 272- 293. PMC6617248 31334330 source
plainconditional- Asserted: passes — The authors put it forward as true.
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It may state two separate claims as one.
In the paper
“There are also 2 biologics and 24 small molecules with neuroprotection as one of their mechanisms4 assessed in phase 2 clinical studies and 8 small molecules in phase 1 clinical trials.4”
§ Current and Future Treatments in Alzheimer Disease: An Update > Current Landscape in Treatment Research for AD > Currently studied DMTs for AD
What the sources say
- Not checked yetcites [4] Cummings J Lee G Ritter A Sabbagh M Zhong K Alzheimer’s disease drug development pipeline: 2019. Alzheimers Dement. 2019; 5: 272- 293. PMC6617248 31334330 source
plain- Asserted: passes — The authors put it forward as true.
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It may state two separate claims as one.
In the paper
“Elderberry Juice improves the mitochondrial function acting as powerful antioxidant rich in anthocyanins (NCT02414607) and GRF6019, a human plasma protein fraction administered with infusions, based on the hypothesis that brain neuroinflammation can be counteracted by young blood parabiosis (NCT03520998, NCT03765762).4”
§ Current and Future Treatments in Alzheimer Disease: An Update > Current Landscape in Treatment Research for AD > Currently studied DMTs for AD
What the sources say
- Not checked yetcites [4] Cummings J Lee G Ritter A Sabbagh M Zhong K Alzheimer’s disease drug development pipeline: 2019. Alzheimers Dement. 2019; 5: 272- 293. PMC6617248 31334330 source
plaindirect- Asserted: passes — The authors put it forward as true.
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Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
In the citing paper
“Donepezil, galantamine, and rivastigmine are the cholinesterase inhibitors that are most frequently prescribed [102,103,104,105,106].”
From Recent Advances in Therapeutics for the Treatment of Alzheimer’s Disease (2024) · cites this paper as [102]
In the citing paper
“Monotherapy has shown beneficial effects in the short and long term in patients with moderate to severe AD, improving their quality of life, cognition, and behavioral and psychological symptoms of neurodegenerative diseases [33,34]”
From Multi-Target Mechanisms of Phytochemicals in Alzheimer’s Disease: Effects on Oxidative Stress, Neuroinflammation and Protein Aggregation (2022) · cites this paper as [34]
In the citing paper
“In fact, in preclinical models, decreasing tau protein levels via ASO strategies185,186 and recently by engineered zinc-finger transcription factors187 was shown to be durable and to reverse tau pathology.”
From PROTAC targeted protein degraders: the past is prologue (2022) · cites this paper as [186]
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Each contradiction between two passages listed here was confirmed by an independent check.
Rated minor: it would not touch a result — a value no result rests on, a p-value that stays on the same side of the significance level, or a conflict that is clerical, resolved elsewhere in the paper, or outside its own findings.
In the paper
§ Current and Future Treatments in Alzheimer Disease: An Update > References
“45. Lopez Lopez C Tariot PN Caputo A, et al The Alzheimer’s Prevention Initiative Generation Program: study design of two randomized controlled trials for individuals at risk for clinical onset of Alzheimer’s disease. Alzheimers Dement; 5: 216- 227. PMC6562315 31211217”
§ Current and Future Treatments in Alzheimer Disease: An Update > References
“59. Lopez Lopez C Tariot PN Caputo A, et al The Alzheimer’s Prevention Initiative Generation Program: study design of two randomized controlled trials for individuals at risk for clinical onset of Alzheimer’s disease. Alzheimers Dement. 2019; 12: 216- 227. PMC6562315 31211217”
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- Yiannopoulou KG, 2009, Primary Psychiatry, 16, 29
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Cited by
Sorted by citations
PROTAC targeted protein degraders: the past is prologue
Békés, M., Langley, D. R., & Crews, C. M. (2022) · Nature Reviews Drug Discovery · doi:10.1038/s41573-021-00371-6 · Cited by 3,395
Comprehensive Review on Alzheimer’s Disease: Causes and Treatment
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“Targeting these pathways may give potential therapeutic agents for AD [6].”
BackgroundPhosphorylated Tau in Alzheimer’s Disease and Other Tauopathies
Rawat, P., Sehar, U., Bisht, J., Selman, A., Culberson, J., & Reddy, P. H. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms232112841 · Cited by 509
“The use of lysine acetylation inhibitors might be a possible therapeutic approach for AD [221].”
BackgroundKent, S. A., Spires-Jones, T. L., & Durrant, C. S. (2020) · Acta Neuropathologica · doi:10.1007/s00401-020-02196-w · Cited by 446
Economic burden of Alzheimer disease and managed care considerations
Winston Wong, P. (2020) · The American Journal of Managed Care · doi:10.37765/ajmc.2020.88482 · Cited by 436
Neuroinflammation in Alzheimer’s Disease
Onyango, I. G., Jauregui, G. V., Čarná, M., Bennett, J. P., & Stokin, G. B. (2021) · Biomedicines · doi:10.3390/biomedicines9050524 · Cited by 330
“While new TNF-α inhibitors that are able to cross BBB are being developed [359], the use of the above compounds is limited to peripheral targeting of TNF-α as they are not able to readily cross the BBB [345].”
BackgroundTherapeutic Approach to Alzheimer’s Disease: Current Treatments and New Perspectives
Pardo-Moreno, T., González-Acedo, A., Rivas-Domínguez, A., García-Morales, V., García-Cozar, F. J., Ramos-Rodríguez, J. J., & Melguizo-Rodríguez, L. (2022) · Pharmaceutics · doi:10.3390/pharmaceutics14061117 · Cited by 239
“In one phase 3 clinical trial, participants with mild and moderate AD showed good tolerability, but no decrease in cognitive and functional impairment [75].”
BackgroundInfluentialNeuroprotective Natural Products for Alzheimer’s Disease
Chen, X., Drew, J., Berney, W., & Lei, W. (2021) · Cells · doi:10.3390/cells10061309 · Cited by 236
“With the substantial amount of evidence indicating that the primary causative factor in the pathogenesis of AD is the accumulation of Aβ [27], decreasing Aβ has become the major strategy in developing new therapeutics for AD [28].”
BackgroundGlial Cell-Mediated Neuroinflammation in Alzheimer’s Disease
Al-Ghraiybah, N. F., Wang, J., Alkhalifa, A. E., Roberts, A. B., Raj, R., Yang, E., & Kaddoumi, A. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms231810572 · Cited by 217
“Current medications such as the cholinesterase inhibitors donepezil, galantamine, and rivastigmine, and the NMDA antagonist memantine provide symptomatic relief such as improving memory and ability to perform daily functions without curing the disease [13,14]; and the recently approved immunotherapy aducanumab, which…”
BackgroundSafiri, S., Jolfayi, A. G., Fazlollahi, A., Morsali, S., Sarkesh, A., Sorkhabi, A. D., Golabi, B., Aletaha, R., Asghari, K. M., Hamidi, S., et al. (2024) · Frontiers in Medicine · doi:10.3389/fmed.2024.1474043 · Cited by 273
Buccellato, F. R., D’Anca, M., Fenoglio, C., Scarpini, E., & Galimberti, D. (2021) · Antioxidants · doi:10.3390/antiox10091353 · Cited by 179
The State of The Art on Acetylcholinesterase Inhibitors in the Treatment of Alzheimer’s Disease
Vecchio, I., Sorrentino, L., Paoletti, A., Marra, R., & Arbitrio, M. (2021) · Journal of Central Nervous System Disease · doi:10.1177/11795735211029113 · Cited by 189
Alzheimer’s Disease: Exploring the Landscape of Cognitive Decline
Tenchov, R., Sasso, J. M., & Zhou, Q. A. (2024) · ACS Chemical Neuroscience · doi:10.1021/acschemneuro.4c00339 · Cited by 170
Grimm, H. P., Schumacher, V. L., Schäfer, M. K.-H., Imhof-Jung, S., Freskgård, P., Brady, K., Hofmann, C., Rüger, P., Schlothauer, T., Göpfert, U., et al. (2023) · mAbs · doi:10.1080/19420862.2023.2261509 · Cited by 180
“7,8 Therapeutic proteins offer access to fundamentally different modes of action; for example, by engaging the brain’s immune system in fighting the disease.”
BackgroundA Systematic Review of Glucose Transport Alterations in Alzheimer's Disease
Kyrtata, N., Emsley, H. C. A., Sparasci, O., Parkes, L. M., & Dickie, B. R. (2021) · Frontiers in Neuroscience · doi:10.3389/fnins.2021.626636 · Cited by 171
“However, attempts to stabilize cognitive function through modification of Aβ and tau in the clinical setting have been unsuccessful to date (Congdon and Sigurdsson, 2018; Yiannopoulou and Papageorgiou, 2020).”
BackgroundPayne, A., Nahashon, S. N., Taka, E., Adinew, G. M., & Soliman, K. F. A. (2022) · Biomolecules · doi:10.3390/biom12030371 · Cited by 174
“Regarding AD, there have been no new FDA-approved drugs since 2003 and no authorized disease-modified treatment (DMT), although there have been many extensive clinical trials [32,33,128].”
BackgroundRecent Advancements of Nanomedicine in Neurodegenerative Disorders Theranostics
Mukherjee, S., Madamsetty, V. S., Bhattacharya, D., Roy Chowdhury, S., Paul, M. K., & Mukherjee, A. (2020) · Advanced Functional Materials · doi:10.1002/adfm.202003054 · Cited by 152
Predicting dementia from spontaneous speech using large language models
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“Given its prevalence and still no cure available for AD treatment [2], there is an urgent need for the early diagnosis of dementia, which would yield clear benefits in improving quality of life for individuals with dementia.”
BackgroundPhysiology and pharmacology of amyloid precursor protein
Cho, Y., Bae, H., Okun, E., Arumugam, T. V., & Jo, D. (2022) · Pharmacology & Therapeutics · doi:10.1016/j.pharmthera.2022.108122 · Cited by 150
The Neurovascular Unit Dysfunction in Alzheimer’s Disease
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“short and long term in patients with moderate to severe AD, improving their quality of life, cognition, and behavioral and psychological symptoms of neurodegenerative diseases [33,34], It is normally well-tolerated without the adverse effects presented by the AChEI at the gastrointestinal level, which are the most sev…”
BackgroundAn update on the novel and approved drugs for Alzheimer disease
Alhazmi, H. A., & Albratty, M. (2022) · Saudi Pharmaceutical Journal · doi:10.1016/j.jsps.2022.10.004 · Cited by 122
“AChEIs action on the gastro-intestinal tract (git) causes the most common side effects, which include diarrhea, nausea, and vomiting (Yiannopoulou et al., 2020).”
Regulated cell death: discovery, features and implications for neurodegenerative diseases
Cui, J., Zhao, S., Li, Y., Zhang, D., Wang, B., Xie, J., & Wang, J. (2021) · Cell Communication and Signaling · doi:10.1186/s12964-021-00799-8 · Cited by 130
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The Kappa Opioid Receptor: A Promising Therapeutic Target for Multiple Pathologies
Dalefield, M. L., Scouller, B., Bibi, R., & Kivell, B. M. (2022) · Frontiers in Pharmacology · doi:10.3389/fphar.2022.837671 · Cited by 130
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“The drug classes currently approved include acetylcholinesterase inhibitors (Donepezil, Rivastigmine, and Galantamine), NMDA receptor antagonists (Memantine), and monoclonal antibodies (Aducanumab and Lecanemab) (Yiannopoulou and Papageorgiou, 2020; Haddad et al., 2022; van Dyck et al., 2022).”
BackgroundNeuroinflammation in Neurodegenerative Disorders: Current Knowledge and Therapeutic Implications
Giri, P. M., Banerjee, A., Ghosal, A., & Layek, B. (2024) · International Journal of Molecular Sciences · doi:10.3390/ijms25073995 · Cited by 129
“The elevated level of acetylcholine promotes cholinergic neurotransmission and subdues cognitive impairment [27].”
BackgroundAdvances in developing therapeutic strategies for Alzheimer's disease
Nguyen, T. T., Nguyen, T. T. D., Nguyen, T. K. O., Vo, T. K., & Giau, V. V. (2021) · Biomedicine & Pharmacotherapy · doi:10.1016/j.biopha.2021.111623 · Cited by 108
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“Alzheimer's disease (AD) is a progressive neurodegenerative disorder that poses a growing threat to healthcare systems around the world (Yiannopoulou & Papageorgiou, 2020).”
BackgroundInfluentialAPOE Genotype and Alzheimer’s Disease: The Influence of Lifestyle and Environmental Factors
Angelopoulou, E., Paudel, Y. N., Papageorgiou, S. G., & Piperi, C. (2021) · ACS Chemical Neuroscience · doi:10.1021/acschemneuro.1c00295 · Cited by 109
Self-citationA Potential Link Between Visceral Obesity and Risk of Alzheimer’s Disease
Al-Kuraishy, H. M., Al-Gareeb, A. I., Alsayegh, A. A., Hakami, Z. H., Khamjan, N. A., Saad, H. M., Batiha, G. E., & WAARD, M. M. D. (2022) · Neurochemical Research · doi:10.1007/s11064-022-03817-4 · Cited by 106
“1 3 N-methyl-D-aspartate (NMDA) antagonists like memantine are used in treating cognitive deficits in AD patients [15, 16].”
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“The third therapeutic target is aimed at boosting Aβ clearance by active or passive immunotherapy [104].”
BackgroundPsychobiotics: the Influence of Gut Microbiota on the Gut-Brain Axis in Neurological Disorders
Oroojzadeh, P., Bostanabad, S. Y., & Lotfi, H. (2022) · Journal of Molecular Neuroscience · doi:10.1007/s12031-022-02053-3 · Cited by 109
“Researches show that the primary manifestations of AD are associated with the production of intracellular Tau neurofibrillary tangles (NFTs) and extracellular amyloid plaques (Yiannopoulou and Papageorgiou 2020).”
BackgroundIliyasu, M. O., Musa, S. A., Oladele, S. B., & Iliya, A. I. (2023) · Frontiers in Neuroscience · doi:10.3389/fnins.2023.1081938 · Cited by 106
“Nevertheless, diarrhea, nausea, and vomiting are some of the typical negative effects of AChEIs on the digestive system (Yiannopoulou and Papageorgiou, 2020).”
BackgroundBiomaterials in Neurodegenerative Disorders: A Promising Therapeutic Approach
Bordoni, M., Scarian, E., Rey, F., Gagliardi, S., Carelli, S., Pansarasa, O., & Cereda, C. (2020) · International Journal of Molecular Sciences · doi:10.3390/ijms21093243 · Cited by 99
“, donepezil, galantamine, and rivastigmine) that increase the availability of acetylcholine at synapses, and the noncompetitive N-methyl-d-aspartate (NMDA) receptor antagonist memantine, which modulates the opening of the calcium channel [14].”
BackgroundFranco, G. A., Interdonato, L., Cordaro, M., Cuzzocrea, S., & Paola, R. D. (2023) · International Journal of Molecular Sciences · doi:10.3390/ijms24087318 · Cited by 103
“The acetylcholinesterase inhibitors (AChEIs) improve the availability of acetylcholine at synapses and have been shown clinically to slow cognitive deterioration in AD [59].”
BackgroundWang, L., Bharti, Kumar, R., Pavlov, P. F., & Winblad, B. (2021) · European Journal of Medicinal Chemistry · doi:10.1016/j.ejmech.2020.112915 · Cited by 92
Acetyl-L-Carnitine in Dementia and Other Cognitive Disorders: A Critical Update
Pennisi, M., Lanza, G., Cantone, M., D’Amico, E., Fisicaro, F., Puglisi, V., Vinciguerra, L., Bella, R., Vicari, E., & Malaguarnera, G. (2020) · Nutrients · doi:10.3390/nu12051389 · Cited by 87
“However, tolerance and compliance to these drugs are variable and studies showed that they cannot delay or halt the disease progression [8].”
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Action Mechanisms of Curcumin in Alzheimer’s Disease and Its Brain Targeted Delivery
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“However, these drugs only provide symptomatic relief [9,37].”
BackgroundMethodSong, S., Lee, J. U., Jeon, M. J., Kim, S., & Sim, S. J. (2022) · Biosensors and Bioelectronics · doi:10.1016/j.bios.2021.113864 · Cited by 88
Hashmi, S., Khan, S., Shafiq, Z., Taslımı, P., Ishaq, M., Sadeghian, N., Karaman, H. S., Akhtar, N., Islam, M. F., Asari, A., et al. (2020) · Bioorganic Chemistry · doi:10.1016/j.bioorg.2020.104554 · Cited by 85
Statins Use in Alzheimer Disease: Bane or Boon from Frantic Search and Narrative Review
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“Nevertheless, these agents provide symptomatic relief without affecting the etiopathologic progression of AD [21,22].”
BackgroundCurrent Pharmacotherapy and Multi-Target Approaches for Alzheimer’s Disease
Cheong, S. L., Tiew, J. K., Fong, Y. H., Leong, H. W., Chan, Y. M., Chan, Z. L., & Kong, E. W. J. (2022) · Pharmaceuticals · doi:10.3390/ph15121560 · Cited by 94
“Intracellular neurofibrillary tangles and extracellular amyloid β plaques are the hallmark characteristics found in the cortical and limbic areas of the brain that are associated with AD [4].”
BackgroundInfluentialBehaviour Hallmarks in Alzheimer’s Disease 5xFAD Mouse Model
Pádua, M. S., Guil‐Guerrero, J. L., & Lopes, P. A. (2024) · International Journal of Molecular Sciences · doi:10.3390/ijms25126766 · Cited by 87
“Despite the substantial progress in AD knowledge since the first report by Alois Alzheimer in 1907 [14], there is still no effective treatment to fully reverse the underlying causes of this disorder [6,7,20].”
BackgroundNaturally Occurring Antioxidant Therapy in Alzheimer’s Disease
Collins, A. E., Saleh, T. M., & Kalisch, B. E. (2022) · Antioxidants · doi:10.3390/antiox11020213 · Cited by 93
“The currently available treatments for AD are ineffective in preventing, delaying progression, or curing disease [351].”
BackgroundMethodRole of glucagon-like peptide-1 receptor agonists in Alzheimer’s disease and Parkinson’s disease
Hong, C.-T., Chen, J.-H., & Hu, C.-J. (2024) · Journal of Biomedical Science · doi:10.1186/s12929-024-01090-x · Cited by 78
García‐Casares, N., Fuentes, P. G., Barbancho, M. Á., Lopez-Gigosos, R. M., Garcı́a-Rodrı́guez, A., & Gutiérrez‐Bedmar, M. (2021) · Journal of Clinical Medicine · doi:10.3390/jcm10204642 · Cited by 81
“Nevertheless, disease-modifying treatments are still under research [5], and for that reason, giving scientific evidence in possible risk and protective factors for AD assume high significance.”
BackgroundDanger-Sensing/Patten Recognition Receptors and Neuroinflammation in Alzheimer’s Disease
Chiarini, A., Armato, U., Hu, P., & Prà, I. D. (2020) · International Journal of Molecular Sciences · doi:10.3390/ijms21239036 · Cited by 77
“Clearly, the clarification of such neuroinflammatory mechanisms and the all-important approaches to counter or mitigate them might hopefully lead to novel and effective treatments of human AD [51].”
BackgroundTherapeutic potential of quinazoline derivatives for Alzheimer's disease: A comprehensive review
Haghighijoo, Z., Zamani, L., Moosavi, F., & Emami, S. (2021) · European Journal of Medicinal Chemistry · doi:10.1016/j.ejmech.2021.113949 · Cited by 77
Is Alzheimer's disease an infectious neurological disease? A review of the literature
Uwishema, O., Mahmoud, A., Sun, J., Correia, I. F. S., Bejjani, N., Alwan, M., Aderinto, N., Adekunbi, O. A., & Dost, B. (2022) · Brain and Behavior · doi:10.1002/brb3.2728 · Cited by 71
“Approximately 50 million people across the globe suffer from the most common manifestation of the disease—dementia—and this figure is expected to double every 5 years, with an estimated 152 million cases by the year 2050 (Livingston et al., 2020; Yiannopoulou & Papageorgiou, 2020).”
BackgroundAssociation of peripheral blood DNA methylation level with Alzheimer’s disease progression
Li, Q. S., Vasanthakumar, A., Davis, J. W., Idler, K. B., Nho, K. T., Waring, J. F., Saykin, A. J., & Initiative, A. D. N. (2021) · Clinical Epigenetics · doi:10.1186/s13148-021-01179-2 · Cited by 66
“Although no curative treatments currently exist for AD, several disease-modifying therapies that aim to slow disease progression, especially during early stage, are under investigation [4, 5].”
BackgroundAlCl3 induced learning and memory deficit in zebrafish
Kaur, K., Narang, R. K., & Singh, S. (2022) · NeuroToxicology · doi:10.1016/j.neuro.2022.07.004 · Cited by 71
Drug Delivery Systems as a Strategy to Improve the Efficacy of FDA-Approved Alzheimer’s Drugs
Nunes, D., Loureiro, J. A., & Pereira, M. C. (2022) · Pharmaceutics · doi:10.3390/pharmaceutics14112296 · Cited by 68
“There are only symptomatic treatments, with drugs used to maintain the patient’s quality of life, improve their cognitive functions and decrease disease progression [21].”
BackgroundInfluentialMansour, H. M., Fawzy, H. M., El-Khatib, A. S., & Khattab, M. M. (2021) · Neuroscience · doi:10.1016/j.neuroscience.2021.06.013 · Cited by 69
Current and evolving treatment strategies for the Alzheimer disease continuum
Marasco, R. (2020) · The American Journal of Managed Care · doi:10.37765/ajmc.2020.88481 · Cited by 67
Sendi, M. S. E., Zendehrouh, E., Miller, R. L., Fu, Z., Du, Y., Liu, J., Mormino, E. C., Salat, D. H., & Calhoun, V. D. (2021) · Frontiers in Neural Circuits · doi:10.3389/fncir.2020.593263 · Cited by 63
“To date, there is no way to cure AD, but some medications can decelerate its progress (Yiannopoulou and Papageorgiou, 2020).”
BackgroundKról-Grzymała, A., Sienkiewicz‐Szłapka, E., Fiedorowicz, E., Rozmus, D., Cieślińska, A., & Grzybowski, A. E. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms231710123 · Cited by 74
A review of the mechanisms underlying selected comorbidities in Alzheimer’s disease
Maciejewska, K., Czarnecka, K., & Szymański, P. (2021) · Pharmacological Reports · doi:10.1007/s43440-021-00293-5 · Cited by 64
Wu, H., Song, Y., Yang, X., Chen, S., Ge, H., Yan, Z., Qi, W., Yuan, Q., Liang, X., Lin, X., et al. (2023) · CNS Neuroscience & Therapeutics · doi:10.1111/cns.14092 · Cited by 63
Elfiky, A. M., Mahmoud, A. A., Elreedy, H. A., et al. (2021) · Life Sciences · doi:10.1016/j.lfs.2021.119964 · Cited by 62
He, S., Xu, Z., & Han, X. (2025) · Molecular Neurodegeneration · doi:10.1186/s13024-025-00803-6 · Cited by 62
“The present strategy for management of AD is largely composed of behavioral/lifestyle adjustment, and pharmacological intervention [334].”
Advances on Therapeutic Strategies for Alzheimer’s Disease: From Medicinal Plant to Nanotechnology
Hassan, N. A., Alshamari, A. K., Hassan, A. A., Elharrif, M. G., Alhajri, A. M., Sattam, M., & Khattab, R. R. (2022) · Molecules · doi:10.3390/molecules27154839 · Cited by 68
Alhawarri, M. B., Al-Thiabat, M. G., Dubey, A., Tufail, A., Fouad, D., Alrimawi, B. H., & Dayoob, M. (2024) · RSC Advances · doi:10.1039/d4ra01070a · Cited by 67
Inflammasome Signaling in the Aging Brain and Age-Related Neurodegenerative Diseases
Brahadeeswaran, S., Sivagurunathan, N., & Latchoumycandane, C. (2022) · Molecular Neurobiology · doi:10.1007/s12035-021-02683-5 · Cited by 63
“To date, there is no cure for this devastating disease, but a few therapeutic drugs are available to reduce its symptomatic progression [39].”
BackgroundArioz, B. I., Tüfekçi, K. U., Olcum, M., Durur, D. Y., Akarlar, B. A., Özlü, N., Bağrıyanık, A., Keskinoğlu, P., Yener, G., & Genç, Ş. (2021) · Neuroscience Letters · doi:10.1016/j.neulet.2021.135914 · Cited by 58
Azargoonjahromi, A., & Abutalebian, F. (2024) · Nutrition & Metabolism · doi:10.1186/s12986-024-00792-1 · Cited by 62
“Various substances, including nutrients, are now recognized as effective in early stages of AD, supporting brain function and slowing down AD progression [6, 12, 13, 19, 20].”
BackgroundKim, Y., Lim, J., & Oh, J. (2024) · Biomedicine & Pharmacotherapy · doi:10.1016/j.biopha.2024.117277 · Cited by 67
Lessons Learnt from the Second Generation of Anti-Amyloid Monoclonal Antibodies Clinical Trials
Kwan, A. T. H., Arfaie, S., Therriault, J., Rosa‐Neto, P., & Gauthier, S. G. (2020) · Dementia and Geriatric Cognitive Disorders · doi:10.1159/000511506 · Cited by 59
The Burden of Alzheimer’s Disease Mortality in the United States, 1999-2018
Zhao, X., Li, C., Ding, G., Heng, Y., Li, A., Wang, W., Hou, H., Wen, J., & Zhang, Y. (2021) · Journal of Alzheimer s Disease · doi:10.3233/jad-210225 · Cited by 55
“It is undeniable that age is the most important factor among the constellation of AD-related features [34, 35].”
Baek, H., Sanjay, S., Park, M., & Lee, H. (2023) · Journal of Neuroinflammation · doi:10.1186/s12974-023-02950-3 · Cited by 59
Lerose, V., Ponticelli, M., Benedetto, N., Carlucci, V., Lela, L., Tzvetkov, N. T., & Milella, L. (2024) · Plants · doi:10.3390/plants13060771 · Cited by 66
Armijo, E., Edwards, G. A., Flores, A., Vera, J. R., Shahnawaz, M., Moda, F., González, C., Sanhueza, M., & Soto, C. A. (2021) · Cells · doi:10.3390/cells10071802 · Cited by 57
“The existing therapeutic interventions, such as cholinesterase inhibitors, have only a very modest effect in alleviating the symptoms of AD and do not alter the course of the disease [4,45].”
BackgroundSendi, M. S. E., Zendehrouh, E., Fu, Z., Liu, J., Du, Y., Mormino, E. C., Salat, D. H., Calhoun, V. D., & Miller, R. L. (2021) · Brain Connectivity · doi:10.1089/brain.2020.0847 · Cited by 52
Kamli, M. R., Sharaf, A. A. M., Sabir, J. S. M., & Rather, I. A. (2022) · Plants · doi:10.3390/plants11040514 · Cited by 55
“Among them, the most successful approach used so far is the cholinergic hypothesis [5].”
BackgroundLinks between COVID-19 and Alzheimer’s Disease—What Do We Already Know?
Rudnicka-Drożak, E., Drożak, P., Mizerski, G., Zaborowski, T., Ślusarska, B. J., Nowicki, G., & Drożak, M. (2023) · International Journal of Environmental Research and Public Health · doi:10.3390/ijerph20032146 · Cited by 57
“Thus, ACEI, such as galantamine, rivastigmine, and donepezil, are among the currently implemented effective therapeutic strategies for the treatment of AD [94].”
BackgroundNeprilysin inhibitors and risk of Alzheimer's disease: A future perspective
Ali, N. H., Al-Kuraishy, H. M., Al-Gareeb, A. I., Alnaaim, S. A., Alexiou, A. T., Papadakis, M., Khalifa, A. A., Saad, . M., & Batiha, G. E. (2023) · Journal of Cellular and Molecular Medicine · doi:10.1111/jcmm.17993 · Cited by 56
“4,5 Moreover, different mechanisms are also proposed in AD pathogenesis, including inflammation, oxidative stress, cholinergic dysfunction and impairment of the melatonin pathway.”
BackgroundModeling the neuroimmune system in Alzheimer’s and Parkinson’s diseases
Balestri, W., Sharma, R., da Silva, V. A., Bobotis, B. C., Curle, A. J., Kothakota, V., Kalantarnia, F., Hangad, M. V., Hoorfar, M., Jones, J., et al. (2024) · Journal of Neuroinflammation · doi:10.1186/s12974-024-03024-8 · Cited by 55
Binda, A., Murano, C., & Rivolta, I. (2020) · International Journal of Nanomedicine · doi:10.2147/ijn.s231480 · Cited by 56
Mandal, P. K., Roy, R. G., & Samkaria, A. (2022) · ACS Omega · doi:10.1021/acsomega.2c02760 · Cited by 56
Recent Advances in Therapeutics for the Treatment of Alzheimer’s Disease
Thawabteh, A. M., Ghanem, A. W., AbuMadi, S., Thaher, D., Jaghama, W., Karaman, D., & Karaman, R. (2024) · Molecules · doi:10.3390/molecules29215131 · Cited by 56
“Donepezil, galantamine, and rivastigmine are the cholinesterase inhibitors that are most frequently prescribed [102–106].”
BackgroundKohli, M., Kar, A. K., Bangalore, A., & Prathosh, A. P. (2022) · Brain Informatics · doi:10.1186/s40708-022-00164-6 · Cited by 66
“These assessment scales have been deployed to make diagnoses and treatment road-map for conditions such as Parkinson [43], Alzheimer [44], multiple sclerosis [45], dementia in the elderly [46], ADHD [47], and ASD [48, 49].”
MethodTimsina, J., Ali, M., Do, A. N., Wang, L., Western, D., Sung, Y. J., & Cruchaga, C. (2023) · Neurobiology of Disease · doi:10.1016/j.nbd.2023.106373 · Cited by 48
Kaur, P., Khera, A., Alajangi, H. K., Sharma, A., Jaiswal, P. K., Singh, G., & Barnwal, R. P. (2022) · Molecular Neurobiology · doi:10.1007/s12035-022-03164-z · Cited by 55
Biomarkers in Alzheimer’s disease
Rajendran, K., & Krishnan, U. M. (2024) · Clinica Chimica Acta · doi:10.1016/j.cca.2024.119857 · Cited by 53
Exploring pathological link between antimicrobial and amyloid peptides
Tang, Y., Zhang, Y., Zhang, D., Liu, Y., Nussinov, R., & Zheng, J. (2024) · Chemical Society Reviews · doi:10.1039/d3cs00878a · Cited by 53
Mitochondrial dysfunction in Alzheimer’s disease - a proteomics perspective
Abyadeh, M., Gupta, V., Chitranshi, N., Gupta, V., Wu, Y., Saks, D., Wall, R. V., Fitzhenry, M. J., Basavarajappa, D. K., You, Y., et al. (2021) · Expert Review of Proteomics · doi:10.1080/14789450.2021.1918550 · Cited by 51
Agbavor, F., & Liang, H. (2022) · Brain Sciences · doi:10.3390/brainsci13010028 · Cited by 47
“Thus far, there is no cure available for AD treatment [5].”
BackgroundInsights on the Use of Transgenic Mice Models in Alzheimer’s Disease Research
Pádua, M. S., Guil-Guerrero, J. L., Prates, J. A. M., & Lopes, P. A. (2024) · International Journal of Molecular Sciences · doi:10.3390/ijms25052805 · Cited by 46
Stem cell therapy for Alzheimer’s disease: An overview of experimental models and reality
Qin, C., Wang, K., Zhang, L., & Bai, L. (2022) · Animal Models and Experimental Medicine · doi:10.1002/ame2.12207 · Cited by 49
Fronza, M. G., Alves, D. A. C., Praticò, D., & Savegnago, L. (2023) · Ageing Research Reviews · doi:10.1016/j.arr.2023.102033 · Cited by 47
Noviandy, T. R., Maulana, A., Idroes, G. M., Maulydia, N. B., Patwekar, M. F., Suhendra, R., & Idroes, R. (2023) · Malacca Pharmaceutics · doi:10.60084/mp.v1i2.60 · Cited by 45
Global Diseases Deserve Global Solutions: Alzheimer’s Disease
Twiss, E., McPherson, C., & Weaver, D. F. (2025) · Neurology International · doi:10.3390/neurolint17060092 · Cited by 60
“AD may require multiple pharmaceuticals given the pathogenic complexity of AD; combination therapies targeting multiple receptor-mediated mechanisms may offer effective treatment regimens for the disease [50].”
Hang, Z., Lei, T., Zeng, Z., Cai, S., Bi, W., & Du, H. (2021) · Biomedicine & Pharmacotherapy · doi:10.1016/j.biopha.2021.112343 · Cited by 45
Natural Alkaloids as Multi-Target Compounds towards Factors Implicated in Alzheimer’s Disease
Vrabec, R., Blunden, G., & Cahlíková, L. (2023) · International Journal of Molecular Sciences · doi:10.3390/ijms24054399 · Cited by 50
“development and progression, thus playing an eminent role in the pathogenesis of AD [6].”
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Transplantation of Nasal Olfactory Mucosa Mesenchymal Stem Cells Benefits Alzheimer’s Disease
Hong, C., Chen, M., Duan, R., Wang, X., Pang, Z., Ge, L., Lü, M., Xie, H., & Liu, Z. (2022) · Molecular Neurobiology · doi:10.1007/s12035-022-03044-6 · Cited by 44
“To date, no effective treatment has been available to cure AD by repairing damaged neural network [4, 8].”
BackgroundCannabidiol for the Treatment of Brain Disorders: Therapeutic Potential and Routes of Administration
Yau, G. T. Y., Tai, W., Arnold, J. C., Chan, H., & Kwok, P. C. L. (2023) · Pharmaceutical Research · doi:10.1007/s11095-023-03469-1 · Cited by 48
“Currently available drugs are symptom-modifying but not disease-modifying [80, 81].”
BackgroundLopes, M. K. S., Cassani, R., & Falk, T. H. (2023) · Computational Intelligence and Neuroscience · doi:10.1155/2023/3198066 · Cited by 51
Basal Forebrain Cholinergic Neurons: Linking Down Syndrome and Alzheimer’s Disease
Martinez, J. L., Zammit, M. D., West, N. R., Christian, B. T., & Bhattacharyya, A. (2021) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2021.703876 · Cited by 47
Metadata
- Authors
- Yiannopoulou, K. G., & Papageorgiou, S. G.
- Affiliations
- Henry Dunant Hospital (GR)
- National and Kapodistrian University of Athens (GR)
- Corresponding author
- Yiannopoulou, Konstantina G
- Venue
- Journal of Central Nervous System Disease
- Publisher
- SAGE Publications
- Published
- 2020-01
- Volume
- 12
- Pages
- 117957352090739
- ISSN
- 1179-5735 (ISSN-L)
- PMC
- PMC7050025
- OpenAlex
- W3007853567
- Semantic Scholar
- 35a37a9e5cb7e502b1d43a326dbbe0efe4d86057
- Cited by
- 966
- References
- 96
- Citations by year
- 2026: 122 · 2025: 171 · 2024: 214 · 2023: 204 · 2022: 136 · 2021: 93 · 2020: 26
- FWCI
- 14.69
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- Journal of Central Nervous System Disease (publishedVersion, cc-by-nc)
- Europe PMC (PubMed Central) (publishedVersion, cc-by-nc)
- PubMed Central (publishedVersion, cc-by-nc)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Alzheimer's disease research and treatments
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Health Sciences › Medicine › Pharmacology (medical) › Cholinesterase and Neurodegenerative Diseases
- Keywords
- Alzheimer's disease, disease-modifying therapy, cholinesterase inhibitors, memantine, amyloid plaques, neurofibrillary tangles, neuroprotection, anti-inflammatory therapy, growth factor therapy, stem cell therapy, biomarkers, precision medicine, clinical trial design
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