The DOI matches its Crossref record; 38 of the 40 references it cites were found in a registry or an index; none of the 36 sources its claims cite is checked for support yet.
Alzheimer’s disease drug development pipeline: 2021
Open accessAbstract
Introduction: The number of individuals worldwide with Alzheimer's disease (AD) is growing at a rapid rate. New treatments are urgently needed. We review the current pipeline of drugs in clinical trials for the treatment of AD. Methods: We interrogated ClinicalTrials.gov, the federal registry of clinical trials to identify drugs in trials. Results: There are 126 agents in 152 trials assessing new therapies for AD: 28 treatments in Phase 3 trials, 74 in Phase 2, and 24 in Phase 1. The majority of drugs in trials (82.5%) target the underlying biology of AD with the intent of disease modification; 10.3% are putative cognitive enhancing agents; and 7.1% are drugs being developed to reduce neuropsychiatric symptoms. Discussion: This pipeline analysis shows that target biological processes are more diversified, biomarkers are more regularly used, and repurposed agents are being explored to determine their utility for the treatment of AD.
Overview
AI snapshot
Written from the paper’s full text.
TL;DR
This annual pipeline review identified 126 agents in 152 ongoing Alzheimer’s disease clinical trials as of January 5, 2021, with most agents intended as disease-modifying therapies. The pipeline showed continued target diversification, frequent biomarker use in later-phase disease-modifying trials, and substantial participant burden.
Key findings
- There were 126 agents in 152 trials: 28 agents in 41 Phase 3 trials, 74 agents in 87 Phase 2 trials, and 24 agents in 24 Phase 1 trials.
- Disease-modifying therapies made up 104 agents (82.5%); 13 (10.3%) were cognitive enhancers and 9 (7.1%) targeted neuropsychiatric/behavioral symptoms.
- Repurposed agents numbered 50, or 39.6% of candidate agents; they were more likely to have academic medical center/NIH sponsors (59%) than industry sponsors (16%).
- Currently active trials required 38,826 participants, contributing 2,540,014 participant-weeks; biopharma sponsored 49% of all trials, academic centers/NIH 29%, public–private partnerships 14%, and others 7%.
Methods
- The authors interrogated ClinicalTrials.gov as of January 5, 2021, including Phase 1, 2, and 3 trials listed as recruiting, active but not recruiting, enrolling by invitation, or not yet recruiting.
- They excluded completed, terminated, suspended, unknown, or withdrawn trials, non-pharmacologic therapeutic approaches, and biomarker trials; stem cell therapies were included.
- Agents were classified by mechanism using the Common Alzheimer’s Disease Research Ontology (CADRO), and trials were categorized as disease-modifying, cognitive-enhancing, or neuropsychiatric-symptom treatments based on trial features and stated intent.
Limitations
- The paper states that ClinicalTrials.gov includes the majority of AD agents in trials, making the review “comprehensive but not exhaustive”; Phase 1 trials conducted outside the United States may be under-represented.
- The authors state that not all trial descriptions on ClinicalTrials.gov note whether biomarkers are included, and they recognize that definitions of “disease-modifying” versus “symptomatic” are arbitrary.
- Evident from the design: this is a registry-based descriptive analysis without efficacy outcomes, and it excludes completed, terminated, suspended, unknown, or withdrawn trials, so it does not assess whether agents work.
Model-written summary. Check it against the paper before relying on it.
Integrity signals
Registry
Cites
Statistics
Figures
Verification
Claims the paper makes
119 Own result · 29 Not checked yet · 17 Own interpretation · 16 No basis given · 4 Own method
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
“Of the DMTs 16 (15.4%) have amyloid and 11 (10.6%) have tau as the primary target or as one of several potential effects.”
§ Alzheimer's disease drug development pipeline: 2021 > RESULTS > Overview
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.
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
“There were five Phase 3 prevention trials enrolling cognitively normal participants known to be at risk for AD (preclinical AD).”
§ Alzheimer's disease drug development pipeline: 2021 > RESULTS > Phase 3
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.
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
“There are 10 repurposed agents in Phase 3 trials.”
§ Alzheimer's disease drug development pipeline: 2021 > RESULTS > Phase 3
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.
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
“13 (10.3%) agents in trials target cognitive enhancement”
- Also stated in: § Results · hedged
“10.3% are putative cognitive enhancing agents”
§ Alzheimer's disease drug development pipeline: 2021 > RESULTS > Overview
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.
- Also stated in: § Results · hedged
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
“There were 126 agents in 152 trials of treatments for AD (as of the index date of January 5, 2021).”
- Also stated in: § Results · plain
“There are 126 agents in 152 trials assessing new therapies for AD”
§ Alzheimer's disease drug development pipeline: 2021 > RESULTS > Overview
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.
- Also stated in: § Results · plain
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
“All four of the biological therapies and one of the small molecules—four monoclonal antibodies and one receptor for advanced glycation end products (RAGE) antagonist—have amyloid as the primary or one of several targets (29.4% of DMTs).”
§ Alzheimer's disease drug development pipeline: 2021 > RESULTS > Phase 3
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.
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
“9 (7.1%) are intended to treat neuropsychiatric and behavioral symptoms”
- Also stated in: § Results · plain
“7.1% are drugs being developed to reduce neuropsychiatric symptoms”
§ Alzheimer's disease drug development pipeline: 2021 > RESULTS > Overview
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.
- Also stated in: § Results · plain
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
“74 agents are in 87 Phase 2 trials”
- Also stated in: § Results · plain
“74 in Phase 2”
§ Alzheimer's disease drug development pipeline: 2021 > RESULTS > Overview
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.
- Also stated in: § Results · plain
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
“In Phase 3 there are 28 agents in 41 trials”
§ Alzheimer's disease drug development pipeline: 2021 > RESULTS > Phase 3
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.
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
“DMTs are the most common agents being studied (104; 82.5% of the total number of agents in trial)”
- Also stated in: § Results · plain
“The majority of drugs in trials (82.5%) target the underlying biology of AD with the intent of disease modification”
§ Alzheimer's disease drug development pipeline: 2021 > RESULTS > Overview
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.
- Also stated in: § Results · plain
- It may state two separate claims as one. 44
- The quote only partly states this claim. 1
- Probably not a substantial claim. 16
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
“There is one Phase 3 trial enrolling both preclinical patients and patients with MCI to mild AD dementia (DIAN‐TU trial); 13 trials in patients with prodromal AD/MCI or prodromal/mild AD dementia; 11 trials of patients with mild to moderate AD; and 11 trials of patients with mild‐to‐severe AD (most of the neuropsychiatric agents).”
§ Alzheimer's disease drug development pipeline: 2021 > RESULTS > Phase 3
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 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
“The mean treatment exposure period was 154 weeks for prevention trials, 87 weeks for prodromal AD or prodromal AD/mild AD dementia trials, and 31 weeks for mild‐to‐moderate AD dementia trials.”
§ Alzheimer's disease drug development pipeline: 2021 > RESULTS > Phase 3
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 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
“Two of these trials are assessing monoclonal antibodies (solanezumab, gantenerumab), there is one vaccine trial (CAD106), and two trials of small molecules (icosapent ethyl and a combination of losartan, amlodipine, and atorvastatin).”
§ Alzheimer's disease drug development pipeline: 2021 > RESULTS > Phase 3
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 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
“Phase 3 trials included a mean of 619 participants per trial and a total of 25,373 participants were needed for enrollment.”
§ Alzheimer's disease drug development pipeline: 2021 > RESULTS > Phase 3
plainn = 25,373- 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 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
“Other CADRO mechanisms represented among Phase 3 DMT therapies include tau (one agent; 5.9% of Phase 3 DMTs), inflammation/infection (two agents; 11.8%), oxidative stress (two agents; 11.8%), metabolism and bioenergetics (two agents; 11.8%), vascular factors (one agent; 5.9%), synaptic plasticity/neuroprotection (three agents; 17.6%), and gut–brain axis (one agent; 5.9%).”
§ Alzheimer's disease drug development pipeline: 2021 > RESULTS > Phase 3
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 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
“Across all phases, DMTs comprise 31 (29.8%) biological therapies and 73 (70.2%) small‐molecule drugs.”
§ Alzheimer's disease drug development pipeline: 2021 > RESULTS > Overview
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 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
“There are 50 repurposed agents in the pipeline—39.6% of the candidate agents.”
§ Alzheimer's disease drug development pipeline: 2021 > RESULTS > Overview
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 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
“There are 11 (39.3%) symptomatic agents in Phase 3: six (21.4%) cognitive enhancers and five (17.9%) targeting behavioral symptoms.”
§ Alzheimer's disease drug development pipeline: 2021 > RESULTS > Phase 3
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 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
“Among the 17 DMTs there are four biological therapies and 13 oral agents/small molecule therapies.”
§ Alzheimer's disease drug development pipeline: 2021 > RESULTS > Phase 3
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.
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
“Since the 2020 review, seven Phase 3 trials have been completed or terminated and there are five new agents in this phase.”
§ Alzheimer's disease drug development pipeline: 2021 > RESULTS > Phase 3
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 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
“Considering DMTs only, there are 17 in Phase 3, 64 in Phase 2, 23 in Phase 1.”
§ Alzheimer's disease drug development pipeline: 2021 > RESULTS > Overview
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 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
“Two Phase 2 trials are prevention trials involving participants with preclinical AD (assessing crenezumab and levetiracetam)”
§ Alzheimer's disease drug development pipeline: 2021 > RESULTS > Phase 2
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.
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
“Across all trials, biopharmaceutical companies sponsor 49% of trials and collaborate in another 14% of trials sponsored by public–private partnerships.”
§ Alzheimer's disease drug development pipeline: 2021 > METHODS > HIGHLIGHTS
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 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
“Of Phase 2 candidate treatments, there are 64 potential DMTs, six cognitive enhancing agents, and four drugs targeting behavioral symptoms.”
§ Alzheimer's disease drug development pipeline: 2021 > RESULTS > Phase 2
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.
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
“Since the 2020 review, 16 trials have been completed or terminated and there are 22 new agents in the Phase 2 pipeline.”
§ Alzheimer's disease drug development pipeline: 2021 > RESULTS > Phase 2
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 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
“Among DMTs in Phase 2 there are 21 biologics and 43 small molecules.”
§ Alzheimer's disease drug development pipeline: 2021 > RESULTS > Phase 2
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 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
“Using the CADRO approach, four of the small molecules and seven of the biologics in Phase 2 have amyloid reduction as one of the mechanisms (17.2% of DMTs).”
§ Alzheimer's disease drug development pipeline: 2021 > RESULTS > Phase 2
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 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
“Other CADRO mechanisms represented among Phase 2 DMT therapies include tau (nine agents; 14.1% of Phase 2 DMTs), inflammation/infection/immunity (12 agents; 18.8%), transmitter systems and receptors (two agents; 3.1%), oxidative stress (one agent; 1.6%), cell death (2 agents; 3.1%), proteostasis (four agents; 6.3%), metabolism and bioenergetics (four agents; 6.3%), vascular factors (three agents;”
§ Alzheimer's disease drug development pipeline: 2021 > RESULTS > Phase 2
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. The quote only partly states this claim.
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
“Trial participants make an enormous contribution to clinical trials (calculated to be ≈2.5 million participant‐weeks for currently ongoing trials)”
§ Alzheimer's disease drug development pipeline: 2021 > METHODS > RESEARCH IN CONTEXT
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.
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
“Repurposed agents are more likely to have academic medical centers/NIH sponsors (59%) and less likely to have industry sponsors (16%; Table 5).”
§ Alzheimer's disease drug development pipeline: 2021 > RESULTS > Trial sponsors
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.
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
“Across all phases, 54% of trials are conducted in North America only, 25% are conducted only outside North America, and 21% are conducted with both North American and non–North American sites.”
§ Alzheimer's disease drug development pipeline: 2021 > RESULTS > Global distribution of trials
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 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
“Of these, 25,373 are in Phase 3 trials; 12,414 in Phase 2 trials; and 1039 in Phase 1 trials.”
§ Alzheimer's disease drug development pipeline: 2021 > RESULTS > Trial participants
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 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
“There are 28 agents in Phase 3, 74 in Phase 2, and 24 in Phase 1.”
§ Alzheimer's disease drug development pipeline: 2021 > DISCUSSION
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 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
“There are five prevention trials in Phase 3 and two prevention trials in Phase 2; the number of prevention trials in Phase 3 has remained constant over the past 6 years, while the number of Phase 2 prevention trials has varied (0 to 4).”
§ Alzheimer's disease drug development pipeline: 2021 > DISCUSSION
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 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
“Phase 2 has both more agents in trials and a greater diversity of targets than other phases; this may reflect a more diversified approach to treatment targets in Phase 2 or a reduction of targets in Phase 3 because of the lack of success in Phase 2 outcomes.”
§ Alzheimer's disease drug development pipeline: 2021 > DISCUSSION
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.
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
“The 126 agents in the pipeline compares to 121 in the pipeline in 2020; 13 with one less agent in Phase 3, nine additional agents in Phase 2, and three less agents in Phase 1.”
§ Alzheimer's disease drug development pipeline: 2021 > DISCUSSION
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 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
“Although sponsors plan for slow recruitment, 66.7% of Phase 3 trials and 78.6% of Phase 2 trials took longer to complete than originally anticipated as recorded on ClinicalTrials.gov.”
§ Alzheimer's disease drug development pipeline: 2021 > DISCUSSION
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.
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
“There are 13 cognitive enhancers and nine drugs targeting neuropsychiatric symptoms in the pipeline.”
§ Alzheimer's disease drug development pipeline: 2021 > DISCUSSION
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.
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
“Since the 2020 pipeline, 7 trials in Phase 3, 18 trials in Phase 2, and 9 trials in Phase 1 have been either completed, terminated, suspended, or the status is unknown.”
§ Alzheimer's disease drug development pipeline: 2021 > DISCUSSION
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 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
“Repurposed agents are more common in trials in Phase 2 and more likely to be in trials sponsored by NIH/academic medical centers (Table 5).”
§ Alzheimer's disease drug development pipeline: 2021 > DISCUSSION
plaincorrelational- 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.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“Phase 1 trials are often conducted outside of the United States, may not be registered on ClinicalTrials.gov, and may be under‐represented in our analysis.”
§ Alzheimer's disease drug development pipeline: 2021 > METHODS
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
“AD has preclinical, prodromal, and dementia phases”
§ Alzheimer's disease drug development pipeline: 2021 > METHODS > HIGHLIGHTS
What the sources say
- Not checked yetcites [20] Dubois B, Feldman HH, Jacova C, et al. Advancing research diagnostic criteria for Alzheimer's disease: the IWG‐2 criteria. Lancet Neurol. 2014; 13: 614‐ 629. 24849862 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 reporting of results of clinical trials is required, but trial sponsors are less adherent to this expectation.”
§ Alzheimer's disease drug development pipeline: 2021 > METHODS
What the sources say
- Not checked yetcites [17] DeVito NJ, Bacon S, Goldacre B. Compliance with legal requirement to report clinical trial results on clinicaltrials.gov: a cohort study. Lancet. 2020; 395: 361‐ 369. 31958402 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.
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
“There are 126 agents in clinical trials in 2021; the total number of treatments in trials is similar in 2021 and 2020.”
§ Alzheimer's disease drug development pipeline: 2021 > METHODS > RESEARCH IN CONTEXT
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.
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
“The United States has more clinical trials than any other country”
§ Alzheimer's disease drug development pipeline: 2021 > METHODS
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: fails — The paper may give no reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it. The paper may give no reason why it holds.
None of the sources cited for this claim have been checked yet.
In the paper
“Studies of ClinicalTrials.gov suggest that compliance with the common rule is high.”
§ Alzheimer's disease drug development pipeline: 2021 > METHODS
What the sources say
- Not checked yetcites [15] Lassman SM, Shopshear OM, Jazic I, Ulrich J, Francer J. Clinical trial transparency: a reassessment of industry compliance with clinical trial registration and reporting requirements in the United States. BMJ Open. 2017; 7: e015110. PMC5623439 28942418
- Not checked yetcites [16] Phillips AT, Desai NR, Krumholz HM, Zou CX, Miller JE, Ross JS. Association of the FDA Amendment Act with trial registration, publication, and outcome reporting. Trials. 2017; 18: 333. 28720112 PMC5516301
hedged- 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 Common Alzheimer's Disease Research Ontology (CADRO) provides a means of classifying targets for drug development relevant to AD.”
§ Alzheimer's disease drug development pipeline: 2021 > INTRODUCTION
What the sources say
- Not checked yetcites [5] International Alzheimer's and Related Dementia Research Portfolio; Accessed January 4, 2021; https://iadrp.nia.nih.gov/about/cadro
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.
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
“this review is therefore comprehensive but not exhaustive”
§ Alzheimer's disease drug development pipeline: 2021 > METHODS
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.
Probably not a substantial claim. It may state two separate claims as one.
- Rests on an assumption: Phase 1 trials are often conducted outside of the United States, may not be registered on ClinicalTrials.gov, and may be under-represented in this analysis.
- Rests on an assumption: ClinicalTrials.gov includes the majority of agents currently in clinical trials for Alzheimer's disease.
In the paper
“In 2020, the FDA approved 53 new drugs across all therapeutic categories.”
§ Alzheimer's disease drug development pipeline: 2021 > DISCUSSION
What the sources say
- Not checked yetcites [21] Food and Drug Administration. Advancing Health Through Innovation: New Drug Therapy Approvals 2020. US Food and Drug Administration. Silver Spring, MD. 2020.
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.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“This sum does not include time devoted to screening prior to randomization or the number of participant‐weeks consumed in screen fails of individuals who do not progress to randomization.”
§ Alzheimer's disease drug development pipeline: 2021 > RESULTS > Trial participants
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.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“Some Phase 1 trials conducted outside the United States may not be registered on ClinicalTrials.gov and may have gone undetected in this review.”
§ Alzheimer's disease drug development pipeline: 2021 > RESULTS > Global distribution of trials
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: fails — The paper may give no reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it. The paper may give no 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
“Thirty‐six percent of the CNS approvals were for DMTs, suggesting that DMT‐related targets, biomarkers, and trial designs are progressing.”
§ Alzheimer's disease drug development pipeline: 2021 > DISCUSSION
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.
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
“Phase 2 has both more agents in trials and a greater diversity of targets than other phases; this may reflect a more diversified approach to treatment targets in Phase 2 or a reduction of targets in Phase 3 because of the lack of success in Phase 2 outcomes.”
§ Alzheimer's disease drug development pipeline: 2021 > DISCUSSION
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. It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“Stem cell interventions may promote nerve cell regeneration, adding a dimension to therapeutic response beyond the slowing of cognitive decline targeted by DMTs in current trials. 36 , 37”
§ Alzheimer's disease drug development pipeline: 2021 > DISCUSSION
What the sources say
- Not checked yetcites [36] Vasic V, Barth K, Schmidt MHH. Neurodegeneration and neuro‐regeneration‐Alzheimer's disease and stem cell therapy. Int J Mol Sci. 2019: 20. PMC6747457 31480448
- Not checked yetcites [37] Han F, Bi J, Qiao L, Arancio O. Stem cell therapy for Alzheimer's disease. Adv Exp Med Biol. 2020; 1266: 39‐ 55. 33105494
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.
In the paper
“Cell senescence occurs throughout the lifespan but plays a larger role with aging and is postulated to contribute to many diseases of aging including vascular disease, arthritis, and neurodegeneration. 38”
§ Alzheimer's disease drug development pipeline: 2021 > DISCUSSION
What the sources say
- Not checked yetcites [38] Childs BG, Gluscevic M, Baker DJ, et al. Senescent cells: an emerging target for diseases of ageing. Nat Rev Drug Discov. 2017; 16: 718‐ 735. 28729727 PMC5942225 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. It may state two separate claims as one.
In the paper
“This reflects the increased focus of biopharmaceutical companies on late‐stage development and outsourcing larger portions of the early‐stage drug development enterprise. 31”
§ Alzheimer's disease drug development pipeline: 2021 > DISCUSSION
What the sources say
- Not checked yetcites [31] Dierks RML, Bruyere O, Reginster JY. Critical analysis of valuation and strategical orientation of merger and acquisition deals in the pharmaceutical industry. Expert Rev Pharmacoecon Outcomes Res. 2018; 18: 147‐ 160. 29243501
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 COVID‐19 pandemic further exacerbated recruitment struggles with many clinics suspending research at least temporarily, delaying visits during this time, and experiencing attrition due to SARS‐CoV‐2 infections in patients and family members or an unwillingness to attend medical facilities. 33”
§ Alzheimer's disease drug development pipeline: 2021 > DISCUSSION
What the sources say
- Not checked yetcites [33] Ousset PJ, Vellas B. Viewpoint: impact of the Covid‐19 outbreak on the clinical and research activities of memory clinics: an Alzheimer's disease center facing the Covid‐19 crisis. J Prev Alzheimer's Dis. 2020; 7: 197‐ 198. 32463074 PMC7147199
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.
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
“There are at least an equivalent number of weeks contributed by research partners, doubling the total participant‐partner weeks to 5,080,028 weeks.”
§ Alzheimer's disease drug development pipeline: 2021 > DISCUSSION
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.
- Rests on an assumption: Research partners contribute at least an equivalent number of weeks as trial participants.
None of the sources cited for this claim have been checked yet.
In the paper
“Three senolytics in current AD trials are metformin, rapamycin, and dasatinib plus quercetin; these therapies have shown benefit in non‐clinical models of aging and AD. 39 , 40 , 41”
§ Alzheimer's disease drug development pipeline: 2021 > DISCUSSION
What the sources say
- Not checked yetcites [39] Zhu Y, Tchkonia T, Pirtskhalava T, et al. The Achilles' heel of senescent cells: from transcriptome to senolytic drugs. Aging Cell. 2015; 14: 644‐ 658. 25754370 PMC4531078 source
- Not checked yetcites [40] Farr SA, Roesler E, Niehoff ML, Roby DA, McKee A, Morley JE. Metformin improves learning and memory in the SAMP8 mouse model of Alzheimer's disease. J Alzheimers Dis. 2019; 68: 1699‐ 1710. 30958364
- Not checked yetcites [41] Partridge L, Fuentealba M, Kennedy BK. The quest to slow ageing through drug discovery. Nat Rev Drug Discov. 2020; 19: 513‐ 532. 32467649 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.
None of the sources cited for this claim have been checked yet.
In the paper
“Biomarkers play an increasing role in drug development and use the amyloid (A), tau (T), neurodegeneration (N)—A/T/N—biomarker framework. 22 , 23”
§ Alzheimer's disease drug development pipeline: 2021 > DISCUSSION
What the sources say
- Not checked yetcites [22] Cummings J. The role of biomarkers in Alzheimer's disease drug development. Adv Exp Med Biol. 2019; 1118: 29‐ 61. 30747416 PMC6750734
- Not checked yetcites [23] Jack CR Jr, Bennett DA, Blennow K, et al. NIA‐AA research framework: toward a biological definition of Alzheimer's disease. Alzheimer's Dement. 2018; 14: 535‐ 562. 29653606 PMC5958625 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
“Many questions remain unresolved concerning the relationship of cellular senescence and neurodegeneration/AD; 43 trials of senolytics will provide key insights into the value of these agents as treatments for AD and late‐life cognitive decline.”
§ Alzheimer's disease drug development pipeline: 2021 > DISCUSSION
What the sources say
- Not checked yetcites [43] Saez‐Atienzar S, Masliah E. Cellular senescence and Alzheimer disease: the egg and the chicken scenario. Nat Rev Neurosci. 2020; 21: 433‐ 444. 32601397 PMC12548380 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.
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
“Global trials allow diversified participant exposures and improved understanding of effects of ethnicity, standard of care, body size, nutrition, and educational level on trial outcomes.”
§ Alzheimer's disease drug development pipeline: 2021 > DISCUSSION
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: fails — The paper may give no reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it. The paper may give no 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
“These observations identify a gap in the trial system that requires remedy to accelerate trials and drug development.”
§ Alzheimer's disease drug development pipeline: 2021 > DISCUSSION
plain- Asserted: passes — The authors put it forward as true.
- Checkable: fails — It may be too vague to check 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 be too vague to check against evidence.
The paper relies on this without support.
Phase 1 trials are often conducted outside of the United States, may not be registered on ClinicalTrials.gov, and may be under-represented in this analysis.
“Phase 1 trials are often conducted outside of the United States, may not be registered on ClinicalTrials.gov, and may be under‐represented in our analysis.”
The paper relies on this without support.
ClinicalTrials.gov includes the majority of agents currently in clinical trials for Alzheimer's disease.
“ClinicalTrials.gov includes the majority of agents currently in clinical trials for AD”
The paper relies on this without support.
Information on completed, terminated, suspended, unknown, or withdrawn trials and reasons for their current status are often not publicly revealed.
“We did not include trials listed as completed, terminated, suspended, unknown, or withdrawn as information on these trials and reasons for their current status are often not publicly revealed.”
The paper relies on this without support.
The features of trials (clinical outcomes, trial duration, use of biomarkers, number of participants) can determine whether a trial was attempting to demonstrate disease modification or symptomatic benefit.
“We used the features of the trials (e.g., clinical outcomes, trial duration, use of biomarkers, number of participants) to determine whether a trial was attempting to demonstrate disease medication or symptomatic benefit.”
The paper relies on this without support.
The available literature can identify a dominant mechanism of action for agents with multiple mechanisms of action.
“Some agents have more than one mechanism of action and, in these cases, we noted both mechanisms and depended on the available literature to identify a dominant mechanism.”
The paper relies on this without support.
The trials registered on ClinicalTrials.gov as of January 5, 2021 are representative of the AD drug development pipeline.
“Table 6 shows the biomarkers used as entry criteria or as outcome measures in current Phase 2 and Phase 3 AD clinical trials of DMTs as described on ClinicalTrials.gov; not all trial descriptions on the website note if biomarkers are included in the trial.”
The paper relies on this without support.
Research partners contribute at least an equivalent number of weeks as trial participants.
“There are at least an equivalent number of weeks contributed by research partners, doubling the total participant‐partner weeks to 5,080,028 weeks.”
The paper relies on this without support.
ClinicalTrials.gov is a US trial registry and most trials conducted by sponsors anywhere in the world are registered on ClinicalTrials.gov.
“This is, in part, a reflection of the fact that ClinicalTrials.gov is a US trial registry (although note that most trials conducted by sponsors anywhere in the world are registered on ClinicalTrials.gov).”
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
“The most recent list of studies was provided by the 2024 AD drug development pipeline, which includes 164 trials (of which 127 are exploring possible treatments or medicines).”
From Recent Advances in Therapeutics for the Treatment of Alzheimer’s Disease (2024) · cites this paper as [182]
In the citing paper
“Of these trials, 41% look into disease-modifying small molecule medications, 34% look into biological agents that change disease, and the remaining trials focus on treatments that improve cognitive function or address neuropsychiatric symptoms linked to ADs [68,70,71,182,183,184].”
From Recent Advances in Therapeutics for the Treatment of Alzheimer’s Disease (2024) · cites this paper as [182]
In the citing paper
“Another molecule in Phase 3 is Azeliragon (NTC03980730), an inhibitor of RAGE that can be administered orally [163].”
From Role of Oxidative Damage in Alzheimer’s Disease and Neurodegeneration: From Pathogenic Mechanisms to Biomarker Discovery (2021) · cites this paper as [163]
In the citing paper
“Ginkgo Biloba (NCT03090516) extracts are supposed to improve mitochondrial function and brain blood flow, acting as a cognitive enhancer [163].”
From Role of Oxidative Damage in Alzheimer’s Disease and Neurodegeneration: From Pathogenic Mechanisms to Biomarker Discovery (2021) · cites this paper as [163]
In the citing paper
“Of the 18 agents in phase 3 classified as disease-modifying treatments, three have OS as mechanism of action, two have metabolism/bioenergetic, two have antioxidant properties, and among the three agents acting on synaptic plasticity/neuroprotection, Azeliragon is also meant to ameliorate OS (Table 2).”
From Role of Oxidative Damage in Alzheimer’s Disease and Neurodegeneration: From Pathogenic Mechanisms to Biomarker Discovery (2021) · cites this paper as [163]
In the citing paper
“Looking at the clinical trials that have reached phase 3, beside the very recently approved Aducanumab, there is a progressive interest in the non-amyloid targets [163].”
From Role of Oxidative Damage in Alzheimer’s Disease and Neurodegeneration: From Pathogenic Mechanisms to Biomarker Discovery (2021) · cites this paper as [163]
In the citing paper
“Glucose metabolism amelioration in CNS is supposed to improve the cognitive decline of aMCI patients or prevent the cognitive decline in obese people [163,167].”
From Role of Oxidative Damage in Alzheimer’s Disease and Neurodegeneration: From Pathogenic Mechanisms to Biomarker Discovery (2021) · cites this paper as [163]
In the citing paper
“Indeed, some of the treatments are designed to modify the biology of the disease acting on synaptic dysfunction, mitochondrial dysfunction, microglial modulation, and reducing OS [163].”
From Role of Oxidative Damage in Alzheimer’s Disease and Neurodegeneration: From Pathogenic Mechanisms to Biomarker Discovery (2021) · cites this paper as [163]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
Each contradiction between two passages listed here was confirmed by an independent check.
Rated major: it would touch a result — a value a result rests on, reported and recomputed p-values on opposite sides of the significance level, two passages that conflict with no sign which is right, or a cited work retracted before this paper was published.
In the paper
“Five of the approved agents are DMTs involving neurodegeneration—2 for neuromyelitis optica, 1 for multiple sclerosis, 1 for Duchenne muscular dystrophy, and 1 for spinal muscular atrophy. Treatments for neuroblastoma, neurofibromatosis, migraine, on/off in Parkinson's disease, and an agent for sedation comprised the other CNS approvals. There were no new therapies for AD. Thirty‐six percent of the CNS approvals were for DMTs”
§ Alzheimer's disease drug development pipeline: 2021 > DISCUSSION
Reported 36 · recomputed 45.454545
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
§ Alzheimer's disease drug development pipeline: 2021 > RESULTS > Biomarkers
“| Tau PET | 4 (7%) | 3 (14%) |”
§ Alzheimer's disease drug development pipeline: 2021 > RESULTS > Biomarkers
“Three (13%) of the Phase 3 DMT trials include tau PET imaging as an outcome and nine (12%) of Phase 2 DMT trials include tau PET imaging as an outcome.”
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
§ Alzheimer's disease drug development pipeline: 2021 > RESULTS > Global distribution of trials
“Thirty‐seven percent of Phase 3 trials involve North American only and 71% included North America and non–North American countries.”
§ Alzheimer's disease drug development pipeline: 2021 > RESULTS > Global distribution of trials
“| Both | 14 (34%) | 17 (20%) | 1 (4%) |”
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
“| Academic medical centers/NIH | 8 (20%) | 27 (31%) | 9 (38%) | 49 (29%) | 33 (59%) |”
§ Alzheimer's disease drug development pipeline: 2021 > RESULTS > Trial sponsors
Reported 49 · recomputed 44
Citations
Cites
NIA‐AA Research Framework: Toward a biological definition of Alzheimer's disease
Jack, C. R., Bennett, D. A., Blennow, K., Carrillo, M. C., Dunn, B., Haeberlein, S. B., Holtzman, D. M., Jagust, W., Jessen, F., Karlawish, J., et al. (2018) · Alzheimer's & Dementia · doi:10.1016/j.jalz.2018.02.018 · Cited by 10,537
Scheltens, P., De Strooper, B., Kivipelto, M., Holstege, H., Chételat, G., Teunissen, C. E., Cummings, J., & van der Flier, W. M. (2021) · The Lancet · doi:10.1016/s0140-6736(20)32205-4 · Cited by 5,465
Self-citationAdvancing research diagnostic criteria for Alzheimer's disease: the IWG-2 criteria
Dubois, B., Feldman, H. H., Jacova, C., Hampel, H., Molinuevo, J. L., Blennow, K., DeKosky, S. T., Gauthier, S., Selkoe, D., Bateman, R., et al. (2014) · The Lancet Neurology · doi:10.1016/s1474-4422(14)70090-0 · Cited by 3,321
Self-citationThe Achilles' heel of senescent cells: from transcriptome to senolytic drugs
Zhu, Y., Tchkonia, T., Pirtskhalava, T., Gower, A. C., Ding, H., Giorgadze, N., Palmer, A. K., Ikeno, Y., Hubbard, G. B., Lenburg, M., et al. (2015) · Aging Cell · doi:10.1111/acel.12344 · Cited by 2,584
2020 Alzheimer's disease facts and figures
(2020) · Alzheimer's & Dementia · doi:10.1002/alz.12068 · Cited by 2,353
Palmqvist, S., Janelidze, S., Quiroz, Y. T., Zetterberg, H., Lopera, F., Stomrud, E., Su, Y., Chen, Y., Serrano, G. E., Leuzy, A., et al. (2020) · JAMA · doi:10.1001/jama.2020.12134 · Cited by 1,603
Senescent cells: an emerging target for diseases of ageing
Childs, B. G., Gluscevic, M., Baker, D. J., Laberge, R.-M., Marquess, D., Dananberg, J., & van Deursen, J. M. (2017) · Nature Reviews Drug Discovery · doi:10.1038/nrd.2017.116 · Cited by 1,284
High-precision plasma β-amyloid 42/40 predicts current and future brain amyloidosis
Schindler, S. E., Bollinger, J. G., Ovod, V., Mawuenyega, K. G., Li, Y., Gordon, B. A., Holtzman, D. M., Morris, J. C., Benzinger, T. L. S., Xiong, C., et al. (2019) · Neurology · doi:10.1212/wnl.0000000000008081 · Cited by 885
Alzheimer's disease drug development pipeline: 2019
Cummings, J., Lee, G., Ritter, A., Sabbagh, M., & Zhong, K. (2019) · Alzheimer's & Dementia: Translational Research & Clinical Interventions · doi:10.1016/j.trci.2019.05.008 · Cited by 762
Self-citationMattsson, N., Cullen, N. C., Andreasson, U., Zetterberg, H., & Blennow, K. (2019) · JAMA Neurology · doi:10.1001/jamaneurol.2019.0765 · Cited by 726
Research works printed but not linked: 4
- Food and Drug Administration, 2018, U.S. Department of Health and Human Services, Food and Drug Administration
- International Alzheimer's and Related Dementia Research Portfolio
- Food and Drug Administration, 2020, Advancing Health Through Innovation: New Drug Therapy Approvals 2020
- IQVIA, 2019, The Changing Landscape of Research and Development
Cited by
Sorted by citations
Revised criteria for diagnosis and staging of Alzheimer's disease: Alzheimer's Association Workgroup
Jack, C. R., Andrews, J. S., Beach, T. G., Buracchio, T., Dunn, B., Graf, A., Hansson, O., Ho, C., Jagust, W., McDade, E., et al. (2024) · Alzheimer's & Dementia · doi:10.1002/alz.13859 · Cited by 2,803
“182 Despite the importance of these mechanisms, there is a dearth of available I biomarkers.”
2022 Alzheimer's disease facts and figures
Anonymous (2022) · Alzheimer s & Dementia · doi:10.1002/alz.12638 · Cited by 2,469
Global estimates on the number of persons across the Alzheimer's disease continuum
Gustavsson, A., Norton, N., Fast, T., Frölich, L., Georges, J., Holzapfel, D., Kirabali, T., Krolak‐Salmon, P., Rossini, P. M., Ferretti, M. T., et al. (2023) · Alzheimer's & Dementia · doi:10.1002/alz.12694 · Cited by 895
Alzheimer’s disease drug development pipeline: 2022
Cummings, J., Lee, G., Nahed, P., Kambar, M. E. Z. N., Zhong, K., Fonseca, J., & Taghva, K. (2022) · Alzheimer's & Dementia: Translational Research & Clinical Interventions · doi:10.1002/trc2.12295 · Cited by 665
Alzheimer’s disease drug development pipeline: 2023
Cummings, J., Zhou, Y., Lee, G., Zhong, K., Fonseca, J., & Cheng, F. (2023) · Alzheimer's & Dementia: Translational Research & Clinical Interventions · doi:10.1002/trc2.12385 · Cited by 477
Self-citation
Metadata
- Authors
- Cummings, J., Lee, G., Zhong, K., Fonseca, J., & Taghva, K.
- Affiliations
- University of Nevada, Las Vegas (US)
- Biogen (United States) (US)
- Howard R. Hughes College of Engineering Department of Computer Science University of Nevada, Las Vegas (UNLV) Las Vegas Nevada USA
- Corresponding author
- Cummings, Jeffrey
- Venue
- Alzheimer's & Dementia: Translational Research & Clinical Interventions
- Publisher
- Wiley
- Published
- 2021-01
- Volume
- 7
- Issue
- 1
- Pages
- e12179-e12179
- ISSN
- 2352-8737 (ISSN-L)
- PMC
- PMC8145448
- OpenAlex
- W3164214667
- Semantic Scholar
- bbab7a44a3b914a574816f1b4885797eb472650c
- Cited by
- 539
- References
- 40
- Citations by year
- 2026: 48 · 2025: 95 · 2024: 81 · 2023: 102 · 2022: 156 · 2021: 54
- FWCI
- 61.81
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Alzheimer s & Dementia Translational Research & Clinical Interventions (publishedVersion, cc-by-nc-nd)
- PubMed Central (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- Digital Scholarship - UNLV (University of Nevada Reno) (submittedVersion, cc-by-nc-nd)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- National Institute on Aging (P20AG068053)
- National Institute of General Medical Sciences (P20GM109025)
- 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, drug development pipeline, clinical trials, disease-modifying therapy, cognitive enhancement, neuropsychiatric symptoms, drug repurposing, biomarkers, ClinicalTrials.gov
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
A language model drew the claims from the paper on 2026-10-10, under version 3 of the claim definition (model deepseek-v4.1-flash, prompt extract-v3).
A second model labelled each claim on 2026-10-10 (model jev-1.13-20260917, definition revision gold-guideline-v0.2).
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
