CoChat
Sign Up
Cited by 36Cholinesterase and Neurodegenerative DiseasesDementia and Cognitive Impairment ResearchAlzheimer's disease research and treatments

Predictors of response to acetylcholinesterase inhibitors in dementia: A systematic review

Open access
Pozzi, Federico Emanuele, Conti, Elisa, Appollonio, Ildebrando, Ferrarese, Carlo, Tremolizzo, Lucio·2022·Frontiers in Neuroscience
DOI 10.3389/fnins.2022.998224PMC PMC9530658
Open this paper in CoChat — free account

Abstract

Background: The mainstay of therapy for many neurodegenerative dementias still relies on acetylcholinesterase inhibitors (AChEI); however, there is debate on various aspects of such treatment. A huge body of literature exists on possible predictors of response, but a comprehensive review is lacking. Therefore, our aim is to perform a systematic review of the predictors of response to AChEI in neurodegenerative dementias, providing a categorization and interpretation of the results. Methods: We conducted a systematic review of the literature up to December 31 st, 2021, searching five different databases and registers, including studies on rivastigmine, donepezil, and galantamine, with clearly defined criteria for the diagnosis of dementia and the response to AChEI therapy. Records were identified through the string:predict*AND respon*AND (acetylcholinesterase inhibitors OR donepezil OR rivastigmine OR galantamine). The results were presented narratively. Results: We identified 1,994 records in five different databases; after exclusion of duplicates, title and abstract screening, and full-text retrieval, 122 studies were finally included. Discussion: The studies show high heterogeneity in duration, response definition, drug dosage, and diagnostic criteria. Response to AChEI seems associated with correlates of cholinergic deficit (hallucinations, fluctuating cognition, substantia innominate atrophy) and preserved cholinergic neurons (faster alpha on REM sleep EEG, increased anterior frontal and parietal lobe perfusion after donepezil); white matter hyperintensities in the cholinergic pathways have shown inconsistent results. The K-variant of butyrylcholinesterase may correlate with better response in late stages of disease, while the role of polymorphisms in other genes involved in the cholinergic system is controversial. Factors related to drug availability may influence response; in particular, low serum albumin (for donepezil), CYP2D6 variants associated with reduced enzymatic activity and higher drug doses are the most consistent predictors, while AChEI concentration influence on clinical outcomes is debatable. Other predictors of response include faster disease progression, lower serum cholesterol, preserved medial temporal lobes, apathy, absence of concomitant diseases, and absence of antipsychotics. Short-term response may predict subsequent cognitive response, while higher education might correlate with short-term good response (months), and long-term poor response (years). Age, gender, baseline cognitive and functional levels, and APOE relationship with treatment outcome is controversial.

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Integrity signals

Registry

Crossref · 10.3389/fnins.2022.998224

Cites

9 of 9 references verified0 citation errors · 0 not checkable

Statistics

Claims the paper makes

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

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?

  • Cholinergic dysfunction should be viewed as part of a networked pathology where neurotransmitter, metabolic, inflammatory, and proteostatic processes converge.

    “These bidirectional relationships suggest that cholinergic dysfunction should be viewed not in isolation, but as part of a networked pathology where neurotransmitter, metabolic, inflammatory, and proteostatic processes converge [100].”

    From Toward a Unified Framework in Molecular Neurobiology of Alzheimer’s Disease: Revisiting the Pathophysiological Hypotheses (2026) · cites this paper as [100]

    The Introduction (‘The cholinergic pathways’; page not available) describes cholinergic dysfunction as a common target of interacting factors, including amyloid pathology, tau phosphorylation, and neuroinflammation. The Introduction (‘The cholinergic synapse’; page not available) also discusses cholinergic links to inflammatory pathways. The copy does not establish metabolic pathology as one of the converging processes; its mention of glycolysis concerns acetylcholine synthesis. (LLM, conf=0.83)

    Experimental — accuracy not yet measured

  • Loss of cholinergic tone may worsen synaptic plasticity deficits, neurovascular dysregulation, and glial capacity to regulate cortical networks.

    “Conversely, loss of cholinergic tone may itself worsen synaptic plasticity deficits, neurovascular dysregulation, and the capacity of glial cells to regulate cortical networks.”

    From Toward a Unified Framework in Molecular Neurobiology of Alzheimer’s Disease: Revisiting the Pathophysiological Hypotheses (2026) · cites this paper as [100]

    The Introduction (‘The cholinergic synapse’; page unavailable) links cholinergic receptors to hippocampal long-term potentiation, supporting the synaptic-plasticity part. The Discussion (‘Other predictors’; page unavailable) says cholinergic stimulation increases frontal perfusion in Alzheimer’s disease, but does not establish that loss of cholinergic tone causes neurovascular dysregulation. The passages do not link that loss to impaired glial regulation of cortical networks. (LLM, conf=0.82)

    Experimental — accuracy not yet measured

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

The self-check needs the paper’s full text.

Cites

Flagged first, then by citations

Research works printed but not linked: 148

  1. Adler G. Bektas M. Ko-Inoshishi Y. Tracik F. (2009). Prediction of treatment response to rivastigmine in Parkinson's disease dementia. Alzheimers Dement. 5: 252. 10.1016/j.jalz.2009.04.266 · DOI
  2. Albani D. Martinelli Boneschi F. Biella G. Giacalone G. Lupoli S. Clerici F.. (2012). Replication study to confirm the role of CYP2D6 polymorphism rs1080985 on donepezil efficacy in Alzheimer's disease patients. J. Alzheimers Dis. 30, 745– 749. 10.3233/JAD-2012-112123 22465999 · DOI
  3. Angiulli F. Conti E. Zoia C. P. Da Re F. Appollonio I. Ferrarese C.. (2021). Blood-based biomarkers of neuroinflammation in Alzheimer's disease: a central role for periphery? Diagnostics (Basel) 11: 1525. 10.3390/diagnostics11091525 34573867 PMC8464786 · DOI
  4. Armstrong M. J. Mullins C. D. Gronseth G. S. Gagliardi A. R. (2018). Impact of patient involvement on clinical practice guideline development: a parallel group study. Implement. Sci. 13: 55. 10.1186/s13012-018-0745-6 29661195 PMC5902835 · DOI
  5. Baakman A. C. Gavan C. Doeselaar L. Kam M. Broekhuizen K. Bajenaru O.. (2022). Acute response to cholinergic challenge predicts long-term response to galantamine treatment in patients with Alzheimer's disease. Br. J. Clin. Pharmacol. 88, 2814– 2829. 10.1111/bcp.15206 34964149 PMC9306507 · DOI
  6. Babiloni C. Cassetta E. Forno D. Percio D. Ferreri F. Ferri R.. (2006). Donepezil effects on sources of cortical rhythms in mild Alzheimer' s disease: responders vs. non-responders. Neuroimage 31, 1650– 1665. 10.1016/j.neuroimage.2006.02.015 16600641 · DOI
  7. Ballinger E. Ananth M. Talmage D. A. Role L. W. (2017). Basal forebrain cholinergic circuits and signaling in cognition and cognitive decline. Neuron 91, 1199– 1218. 10.1016/j.neuron.2016.09.006 27657448 PMC5036520 · DOI
  8. Barbash S. Garfinkel B. P. Maoz R. Simchovitz A. Nadorp B. Guffanti A.. (2017). Alzheimer's brains show inter-related changes in RNA and lipid metabolism. Neurobiol. Dis. 106, 1– 13. 10.1016/j.nbd.2017.06.008 28630030 PMC5560656 · DOI
  9. Bartus R. T. Dean R. L. Beer B. Lippa A. S. (1982). The cholinergic hypothesis of geriatric memory dysfunction. Science 217, 408– 414. 10.1126/science.7046051 7046051 · DOI · Paper page
  10. Birks J. Harvey R. (2018). Donepezil for dementia due to Alzheimer's disease (Review). Cochrane Database Syst. Rev. 2108:CD001190. 10.1002/14651858.CD001190.pub3 12917900 · DOI · Paper page
  11. Boccardi V. Baroni M. Smirne N. Clodomiro A. Ercolani S. Longo A.. (2017). Short-term response is not predictive of long-term response to acetylcholinesterase inhibitors in old age subjects with Alzheimer's disease: a “real world” study. J. Alzheimers Dis. 56, 239– 248. 10.3233/JAD-160904 27911323 · DOI
  12. Borroni B. Pettenati C. Bordonali T. Akkawi N. Di Luca M. Padovani A.. (2003). Serum cholesterol levels modulate long-term efficacy of cholinesterase inhibitors in Alzheimer disease. Neurosci. Lett. 343, 213– 215. 10.1016/S0304-3940(03)00336-7 12770699 · DOI
  13. Borroni V. Barrantes F. J. (2021). Homomeric and heteromeric α7 nicotinic acetylcholine receptors in health and some central nervous system diseases. Membranes (Basel) 11: 664. 10.3390/membranes11090664 34564481 PMC8465519 · DOI
  14. Braga I. L. S. Silva P. N. Furuya T. K. Santos L. C. Pires B. C. Mazzotti D. R.. (2015). Effect of APOE and CHRNA7 genotypes on the cognitive response to cholinesterase inhibitor treatment at different stages of Alzheimer's disease. Am. J. Alzheimers Dis. Other Demen. 30, 139– 144. 10.1177/1533317514539540 24951635 PMC10852661 · DOI
  15. Brown D. Chisholm J. A. Owens J. Pimlott S. Patterson J. Wyper D.. (2003). Acetylcholine muscarinic receptors and response to anti-cholinesterase therapy in patients with Alzheimer's disease. Eur. J. Nucl. Med. Mol. Imaging 30, 296– 300. 10.1007/s00259-002-1028-6 12552349 · DOI
  16. Burns A. Yeates A. Akintade L. del Valle M. Zhang R. Y. Schwam E. M.. (2008). Defining treatment response to donepezil in Alzheimer's disease. Drugs Aging 25, 707– 714. 10.2165/00002512-200825080-00007 18665662 · DOI
  17. Calabria M. Geroldi C. Lussignoli G. Sabbatini F. Zanetti O. (2009). Efficacy of acetyl-cholinesterase-inhibitor (ACHEI) treatment in Alzheimer's disease: a 21-month follow-up “real world” study. Arch. Gerontol. Geriatr. 49, e6– e11. 10.1016/j.archger.2008.07.006 18768226 · DOI
  18. Chang Y. S. Wu Y. H. Wang C. J. Tang S. H. Chen H. L. (2018). Higher levels of thyroxine may predict a favorable response to donepezil treatment in patients with Alzheimer disease: a prospective, case-control study. BMC Neurosci. 19: 36. 10.1186/s12868-018-0436-x 29929471 PMC6013955 · DOI
  19. Chen T. H. Chou M. C. Lai C. L. Wu S. J. Hsu C. L. Yang Y. H.. (2017). Factors affecting therapeutic response to Rivastigmine in Alzheimer's disease patients in Taiwan. Kaohsiung J. Med. Sci. 33, 277– 283. 10.1016/j.kjms.2017.04.006 28601231 PMC11916238 · DOI
  20. Cheng Y. C. Huang Y. C. Liu H. C. (2018). Effect of apolipoprotein E white-matter change cognitive response to acetylcholinesterase inhibitors in patients with Alzheimer's disease: a systematic review and meta-analysis. Dement. Geriatr. Cogn. Disord. 45, 335– 352. 10.1159/000490175 30041236 · DOI
  21. Cheng Y. W. Chen T. F. Cheng T. W. Lai Y. M. Hua M. S. Chen Y. F.. (2015). Hippocampal atrophy but not white-matter changes predicts the long-term cognitive response to cholinesterase inhibitors in Alzheimer's disease. Alzheimers Res. Ther. 7: 72. 10.1186/s13195-015-0155-9 26592961 PMC4655489 · DOI
  22. Chianella C. Gragnaniello D. Maisano Delser P. Visentini M. F. Sette E. Tola M. R.. (2011). BCHE and CYP2D6 genetic variation in Alzheimer's disease patients treated with cholinesterase inhibitors. Eur. J. Clin. Pharmacol. 67, 1147– 1157. 10.1007/s00228-011-1064-x 21630031 · DOI
  23. Cho H. Huang L. Lee Y. Chan L. Hong C. (2018). Suboptimal baseline serum vitamin B12 is associated with cognitive decline in people with Alzheimer's disease undergoing cholinesterase inhibitor treatment. Front. Neurol. 9: 325. 10.3389/fneur.2018.00325 29867734 PMC5954104 · DOI
  24. Choi S. H. Kim S. Y. Na H. R. Kim B. K. Yang D. W. Kwon J. C.. (2008). Effect of ApoE genotype on response to donepezil in patients with Alzheimer's disease. Dement. Geriatr. Cogn. Disord. 25, 445– 450. 10.1159/000124752 18401173 · DOI
  25. Chou P. S. Huang L. C. Hour T. C. Yen C. W. Yang Y. H. (2021). Impact of the CYP2D6 single nucleotide polymorphism on the concentration of and therapeutic response to donepezil in mild-to-moderate Alzheimer's disease. J. Formos. Med. Assoc. 121(1 Pt 2), 409– 415. 10.1016/j.jfma.2021.05.026 34120801 · DOI
  26. Clarelli F. Mascia E. Santangelo R. Mazzeo S. Giacalone G. Galimberti D.. (2016). CHRNA7 gene and response to cholinesterase inhibitors in an italian cohort of Alzheimer's disease patients. J. Alzheimers Dis. 52, 1203– 1208. 10.3233/JAD-160074 27104904 · DOI
  27. Connelly P. J. Adams F. Tayar Z. I. Khan F. (2019). Peripheral vascular responses to acetylcholine as a predictive tool for response to cholinesterase inhibitors in Alzheimer's disease. BMC Neurol. 19: 88. 10.1186/s12883-019-1316-4 31053120 PMC6500049 · DOI
  28. Connelly P. J. Prentice N. P. (2005). Current smoking and response to cholinesterase inhibitor therapy in Alzheimer's disease. Dement. Geriatr. Cogn. Disord. 19, 11– 14. 10.1159/000080964 15383739 · DOI
  29. Connelly P. J. Prentice N. P. Fowler K. G. (2005a). Hypertension, white matter change and response to cholinesterase inhibitors in Alzheimer's disease. Int. J. Geriatr. Psychiatry 20, 623– 628. 10.1002/gps.1331 16021654 · DOI
  30. Connelly P. J. Prentice N. P. Fowler K. G. (2005b). Predicting the outcome of cholinesterase inhibitor treatment in Alzheimer's disease. J. Neurol. Neurosurg. Psychiatry 76, 320– 324. 10.1136/jnnp.2004.043539 15716519 PMC1739548 · DOI
  31. Conti E. Tremolizzo L. Santarone M. E. Tironi M. Radice I. Zoia C. P.. (2016). Donepezil modulates the endogenous immune response: implications for Alzheimer's disease. Hum. Psychopharmacol. Clin. Exp. 31, 296– 303. 10.1002/hup.2538 27297668 · DOI
  32. Crary J. F. Trojanowski J. Q. Schneider J. A. Abisambra J. F. Abner E. L. Alafuzoff I.. (2014). Primary age-related tauopathy (PART): a common pathology associated with human aging. Acta Neuropathol. 128, 755– 766. 10.1007/s00401-014-1349-0 25348064 PMC4257842 · DOI · Paper page
  33. Csernansky J. G. Wang L. Miller J. P. Galvin J. E. Morris J. C. (2005). Neuroanatomical predictors of response to donepezil therapy in patients with dementia. Arch. Neurol. 62, 1718– 1722. 10.1001/archneur.62.11.1718 16286546 · DOI
  34. De Beaumont L. Pelleieux S. Lamarre-Théroux L. Dea D. Poirier J. (2016). Butyrylcholinesterase K and apolipoprotein E-ϵ4 reduce the age of onset of alzheimer's disease, accelerate cognitive decline, and modulate donepezil response in mild cognitively impaired subjects. J. Alzheimers Dis. 54, 913– 922. 10.3233/JAD-160373 27567841 · DOI
  35. Devanand D. P. Lentz C. Chunga R. E. Ciarleglio A. Scodes J. M. Andrews H.. (2017). Change in odor identification impairment is associated with improvement with cholinesterase inhibitor treatment in mild cognitive impairment. J. Alzheimers Dis. 60, 1525– 1531. 10.3233/JAD-170497 29081417 · DOI
  36. Di Lazzaro V. Oliviero A. Pilato F. Saturno E. Dileone M. Marra C.. (2005). Neurophysiological predictors of long term response to AChE inhibitors in AD patients. J. Neurol. Neurosurg. Psychiatry 76, 1064– 1069. 10.1136/jnnp.2004.051334 16024879 PMC1739760 · DOI
  37. Dos Santos Moraes W. A. Poyares D. R. Guilleminault C. Ramos L. R. Ferreira Bertolucci P. H. Tufik S.. (2006). The effect of donepezil on sleep and REM sleep EEG in patients with Alzheimer disease: a double-blind placebo-controlled study. Sleep 29, 199– 205. 10.1093/sleep/29.2.199 16494088 · DOI
  38. Droogsma E. Van Asselt D. Diekhuis M. Veeger N. Van Der Hooft C. Deyn D.. (2015). Initial cognitive response to cholinesterase inhibitors and subsequent long-term course in patients with mild Alzheimer's disease. Int. Psychogeriatr. 27, 1323– 1333. 10.1017/S1041610215000289 25779465 · DOI
  39. Dunn B. Stein P. Cavazzoni P. (2021). Approval of aducanumab for Alzheimer disease — the FDA's perspective. JAMA Intern. Med. 181, 1276– 1278. 10.1001/jamainternmed.2021.4607 34254984 · DOI · Paper page
  40. Farlow M. R. Sadowsky C. H. Velting D. M. Meng X. Islam M. Z. (2015). Evaluating response to high-dose 13.3 mg/24 h rivastigmine patch in patients with severe Alzheimer's disease. CNS Neurosci. Ther. 21, 513– 519. 10.1111/cns.12385 25675992 PMC6495641 · DOI
  41. Fiala M. Zhang L. Gan X. Sherry B. Taub D. Graves M. C.. (1998). Amyloid-β induces chemokine secretion and monocyte migration across a human blood-brain barrier model. Mol. Med. 4, 480– 489. 10.1007/BF03401753 9713826 PMC2230332 · DOI
  42. Frankfort S. V. Appels B. A. de Boer A. Tulner L. R. van Campen J. P. C. M. Koks C. H. W.. (2007). Identification of responders and reactive domains to rivastigmine in Alzheimer's disease. Pharmacoepidemiol. Drug Saf. 16, 545– 551. 10.1002/pds.1345 17109476 · DOI
  43. Fritz H. christian J. Ray N Dyrba, M. Sorg C. Teipel S. Grothe M. J. (2018). The corticotopic organization of the human basal forebrain as revealed by regionally selective functional connectivity profiles. Hum. Brain Mapp. 40, 868– 878. 10.1002/hbm.24417 30311315 PMC6865372 · DOI
  44. Fukui T. Taguchi S. (2005). Do vascular lesions and related risk factors influence responsiveness to donepezil chloride in patients with Alzheimer's disease? Dement. Geriatr. Cogn. Disord. 20, 15– 24. 10.1159/000085069 15832031 · DOI
  45. Gallacher J. de Reydet de Vulpillieres F. Amzal B. Angehrn Z. Bexelius C. Bintener C.. (2019). Challenges for optimizing real-world evidence in Alzheimer's disease: the ROADMAP project. J. Alzheimers Dis. 67, 495– 501. 10.3233/JAD-180370 30584137 PMC6398537 · DOI
  46. Gallucci M. Spagnolo P. Aricò M. Grossi E. (2016). Predictors of response to cholinesterase inhibitors treatment of Alzheimer's disease: date mining from the TREDEM registry. J. Alzheimers Dis. 50, 969– 979. 10.3233/JAD-150747 26836164 · DOI
  47. Gaugler J. E. Kane R. L. Johnston J. A. Sarsour K. (2013). Sensitivity and specificity of diagnostic accuracy in Alzheimer' s disease: a synthesis of existing evidence. Am. J. Alzheimers Dis. Other Demen. 28, 337– 347. 10.1177/1533317513488910 23687179 PMC10852625 · DOI
  48. Gault J. Robinson M. Berger R. Drebing C. Logel J. Hopkins J.. (1998). Genomic organization and partial duplication of the human α7 neuronal nicotinic acetylcholine receptor gene (CHRNA7). Genomics 52, 173– 185. 10.1006/geno.1998.5363 9782083 · DOI
  49. Graff-Radford J. Boeve B. F. Pedraza O. Ferman T. J. Przybelski S. Lesnick T. G.. (2012). Imaging and acetylcholinesterase inhibitor response in dementia with Lewy bodies. Brain 135(Pt 8), 2470– 2477. 10.1093/brain/aws173 22810436 PMC3407425 · DOI
  50. Hampel H. Mesulam M. M. Cuello A. C. Farlow M. R. Giacobini E. Grossberg G. T.. (2018). The cholinergic system in the pathophysiology and treatment of Alzheimer's disease. Brain 141, 1917– 1933. 10.1093/brain/awy132 29850777 PMC6022632 · DOI · Paper page
  51. Hampel H. Mesulam M. M. Cuello A. C. Khachaturian A. S. Vergallo A. Farlow M. R.. (2019). Revisiting the cholinergic hypothesis in Alzheimer's disease: emerging evidence from translational and clinical research. J. Prev. Alzheimers Dis. 6, 2– 15. 10.14283/jpad.2018.43 30569080 · DOI
  52. Hanyu H. Shimizu T. Tanaka Y. Takasaki M. Koizumi K. Abe K.. (2003). Regional cerebral blood flow patterns and response to donepezil treatment in patients with Alzheimer's disease. Dement. Geriatr. Cogn. Disord. 15, 177– 182. 10.1159/000068785 12626849 · DOI
  53. Hanyu H. Tanaka Y. Sakurai H. Takasaki M. Abe K. (2002). Atrophy of the substantia innominata on magnetic resonance imaging and response to donepezil treatment in Alzheimer's disease. Neurosci. Lett. 319, 33– 36. 10.1016/S0304-3940(01)02507-1 11814647 · DOI
  54. Harold D. Macgregor S. Patterson C. E. Hollingworth P. Moore P. Owen M. J.. (2006). A single nucleotide polymorphism in CHAT influences response to acetylcholinesterase inhibitors in Alzheimer's disease. Pharmacogenet. Genomics 16, 75– 77. 10.1097/01.fpc.0000189799.88596.04 16424819 · DOI
  55. Ho B. L. Kao Y. H. Chou M. C. Yang Y. H. (2016). Cerebral white matter changes on therapeutic response to rivastigmine in Alzheimer's disease. J. Alzheimers Dis. 54, 351– 357. 10.3233/JAD-160364 27567838 · DOI
  56. Hongo J. Nakaaki S. Shinagawa Y. Murata Y. Sato J. Tatsumi H.. (2008). SPECT-identified neuroanatomical predictor of the cognitive effects of donepezil treatment in patients with Alzheimer's disease. Dement. Geriatr. Cogn. Disord. 26, 556– 566. 10.1159/000181148 19066429 · DOI
  57. Horikoshi S. Kunii Y. Matsumoto J. Gotoh D. Miura I. Yabe H.. (2020). Does Treatment response with antidementia drugs after 6 months in Alzheimer's disease predict long-term treatment outcome? J. Clin. Psychopharmacol. 40, 195– 197. 10.1097/JCP.0000000000001176 32134856 · DOI
  58. Jacobo-albavera L. Dom M. Medina-leyte D. J. (2021). The role of the ATP-binding cassette A1 (ABCA1) in human disease. Int. J. Mol. Sci. 22: 1593. 10.3390/ijms22041593 33562440 PMC7915494 · DOI
  59. Jessen F. Traeber F. Freymann K. Maier W. Schild H. H. Block W.. (2006). Treatment monitoring and response prediction with proton MR spectroscopy in AD. Neurology 67, 528– 530. 10.1212/01.wnl.0000228218.68451.31 16894124 · DOI
  60. Kanetaka H. Hanyu H. Hirao K. Shimizu S. Sato T. Akai T.. (2008). Prediction of response to donepezil in Alzheimer's disease: combined MRI analysis of the substantia innominata and SPECT measurement of cerebral perfusion. Nucl. Med. Commun. 29, 568– 573. 10.1097/MNM.0b013e3282f5e5f4 18458605 · DOI
  61. Kapaki E. Paraskevas G. P. Mantzou E. Papapostolou A. Alevizaki M. Vassilopoulos D.. (2006). Thyroid function in patients with Alzheimer disease: implications on response to anticholinesterase treatment. Alzheimer Dis. Assoc. Disord. 20, 242– 247. 10.1097/01.wad.0000213856.89613.59 17132968 · DOI
  62. Kasuya M. Meguro K. Okamura N. Funaki Y. Ishikawa H. Tanaka N.. (2012). Greater responsiveness to donepezil in Alzheimer patients with higher levels of acetylcholinesterase based on attention task scores and a donepezil PET study. Alzheimers Dis. Assoc. Disord. 26, 113– 118. 10.1097/WAD.0b013e3182222bc0 21666432 · DOI
  63. Klimkowicz-Mrowiec A. Marona M. Spisak K. Jagiella J. Wolkow P. Szczudlik A.. (2011). Paraoxonase 1 gene polymorphisms do not influence the response to treatment in Alzheimer's disease. Dement. Geriatr. Cogn. Disord. 32, 26– 31. 10.1159/000330343 21829028 · DOI
  64. Lemstra A. W. Kuiper R. B. Schmand B. Van Gool W. A. (2007). Identification of responders to rivastigmine: a prospective cohort study. Dement. Geriatr. Cogn. Disord. 25, 60– 66. 10.1159/000111549 18033962 · DOI
  65. Li Y. Hai S. Zhou Y. Br D. (2015). Cholinesterase inhibitors for rarer dementias associated with neurological conditions (Review). Cochrane Database Syst. Rev. 3:CD009444. 10.1002/14651858.CD009444.pub3 25734590 PMC10644993 · DOI · Paper page
  66. Lin Y. T. Chou M. C. Wu S. J. Yang Y. H. (2019). Galantamine plasma concentration and cognitive response in Alzheimer's disease. PeerJ. 7: e6887. 10.7717/peerj.6887 31106076 PMC6500725 · DOI
  67. Liu M. Zhang Y. Huo Y. R. Liu S. Liu S. Wang J.. (2014). Influence of the rs1080985 single nucleotide polymorphism of the CYP2D6 gene and APOE polymorphism on the response to donepezil treatment in patients with Alzheimer' s disease in China. Dement. Geriatr. Cogn. Dis. Extra 4, 450– 456. 10.1159/000367596 25538729 PMC4264516 · DOI
  68. Lu J. Fu J. Zhong Y. Chen P. Yang Q. Zhao Y.. (2016). The roles of apolipoprotein E3 and CYP2D6 (rs1065852) gene polymorphisms in the predictability of responses to individualized therapy with donepezil in Han Chinese patients with Alzheimer's disease. Neurosci. Lett. 614, 43– 48. 10.1016/j.neulet.2015.12.062 26768225 · DOI
  69. Lu J. Fu J. Zhong Y. Yang Q. Huang J. Li J.. (2018). Association between ABCA1 gene polymorphisms and the therapeutic response to donepezil therapy in Han Chinese patients with Alzheimer's disease. Brain Res. Bull. 140, 1– 4. 10.1016/j.brainresbull.2018.03.014 29605487 · DOI
  70. Lu J. Wan L. L. Yu Q. Zhong Y. Guo C. (2015). CYP2D6 gene and plasma concentration of S-donepezil as biomarkers to predict and evaluate clinical outcome of donepezil in Chinese Alzheimer's disease patients. Neurodegener. Dis. 15: 944. 10.1016/j.jphs.2015.10.010 26603528 · DOI
  71. Ma S. L. Tang N. L. S. Wat K. H. Y. Tang J. H. Y. Lau K. H. Law C. B.. (2019). Effect of CYP2D6 and CYP3A4 genotypes on the efficacy of cholinesterase inhibitors in Southern Chinese patients with Alzheimer's disease. Am. J. Alzheimers. Dis. Other Demen. 34, 302– 307. 10.1177/1533317519848237 31064198 PMC10852420 · DOI
  72. MacGowan S. H. Wilcock G. K. Scott M. (1998). Effect of gender and apolipoprotein E genotype on response to anticholinesterase therapy in Alzheimer's disease. Int. J. Geriatr. Psychiatry 13, 625– 630. 10.1002/(sici)1099-1166(199809)13:9<625::aid-gps835>3.0.co;2-2 9777427 · DOI
  73. Magliulo L. Dahl M. L. Lombardi G. Fallarini S. Villa L. M. Biolcati A.. (2011). Do CYP3A and ABCB1 genotypes influence the plasma concentration and clinical outcome of donepezil treatment? Eur. J. Clin. Pharmacol. 67, 47– 54. 10.1007/s00228-010-0883-5 20931330 · DOI
  74. Mahase E. (2021). Aducanumab: European agency rejects Alzheimer's drug over efficacy and safety concerns. BMJ 375: n3127. 10.1136/bmj.n3127 34930757 · DOI
  75. Margalit I. Cohen E. Goldberg E. Krause I. (2018). Vitamin B12 deficiency and the role of gender: a cross-sectional study of a large cohort. Ann. Nutr. Metab. 72, 265– 271. 10.1159/000488326 29597190 · DOI
  76. Maroli A. Di Lascio S. Drufuca L. Cardani S. Setten E. Locati M.. (2019). Effect of donepezil on the expression and responsiveness to LPS of CHRNA7 and CHRFAM7A in macrophages: a possible link to the cholinergic anti-inflammatory pathway. J. Neuroimmunol. 332, 155– 166. 10.1016/j.jneuroim.2019.04.012 31048268 · DOI
  77. Martinelli-Boneschi F. Giacalone G. Magnani G. Biella G. Coppi E. Santangelo R.. (2013). Pharmacogenomics in Alzheimer's disease: a genome-wide association study of response to cholinesterase inhibitors. Neurobiol. Aging 34, 1711.e7–1711.e13. 10.1016/j.neurobiolaging.2012.12.008 23374588 · DOI
  78. McKeith I. G. Wesnes K. A. Perry E. Ferrara R. (2004). Hallucinations predict attentional improvements with rivastigmine in dementia with lewy bodies. Dement. Geriatr. Cogn. Disord. 18, 94– 100. 10.1159/000077816 15087584 · DOI
  79. Meador K. J. Loring D. W. Adams R. J. Patel B. R. Davis H. C. (1987). Central cholinergic systems and the P3 evoked potential. Int. J. Neurosci. 33, 199– 205. 10.3109/00207458708987404 3596949 · DOI
  80. Mecocci P. Grossi E. Buscema M. Intraligi M. Savarè R. Rinaldi P.. (2002). Use of artificial networks in clinical trials: a pilot study to predict responsiveness to donepezil in Alzheimer's disease. J. Am. Geriatr. Soc. 50, 1857– 1860. 10.1046/j.1532-5415.2002.50516.x 12410907 · DOI
  81. Mega M. S. Dinov I. D. Lee L. O'Connor S. M. Masterman D. M. Wilen B.. (2000). Orbital and dorsolateral frontal perfusion defect associated with behavioral response to cholinesterase inhibitor therapy in Alzheimer's disease. J. Neuropsychiatry Clin. Neurosci. 12, 209– 218. 10.1176/jnp.12.2.209 11001599 · DOI
  82. Mega M. S. Masterman D. M. O'Connor S. M. Barclay T. R. Cummings J. L. (1999). The spectrum of behavioral responses to cholinesterase inhibitor therapy in Alzheimer disease. Arch. Neurol. 56, 1388– 1393. 10.1001/archneur.56.11.1388 10555660 · DOI
  83. Meng D. Li X. Bauer M. Taylor J. P. Auer D. P. (2018). Altered nucleus basalis connectivity predicts treatment response in mild cognitive impairment. Radiology 289, 775– 785. 10.1148/radiol.2018180092 30204076 PMC6283326 · DOI
  84. Miettinen P. S. Jauhiainen A. M. Tarkka I. M. Pihlajamäki M. Gröhn H. Niskanen E.. (2015). Long-term response to cholinesterase inhibitor treatment is related to functional MRI response in Alzheimer's disease. Dement. Geriatr. Cogn. Disord. 40, 243– 255. 10.1159/000435948 26305064 · DOI
  85. Miranda L. F. J. R. Gomes K. B. Silveira J. N. Pianetti G. A. Byrro R. M. D. Peles P. R. H.. (2015). Predictive factors of clinical response to cholinesterase inhibitors in mild and moderate Alzheimer's disease and mixed dementia: a one-year naturalistic study. J. Alzheimers Dis. 45, 609– 620. 10.3233/JAD-142148 25589728 · DOI
  86. Miranda L. F. J. R. Gomes K. B. Tito P. A. L. Silveira J. N. Pianetti G. A. Byrro R. M. D.. (2017). Clinical response to donepezil in mild and moderate dementia: relationship to drug plasma concentration and CYP2D6 and APOE genetic polymorphisms. J. Alzheimers Dis. 55, 539– 549. 10.3233/JAD-160164 27716659 · DOI
  87. Modrego P. J. Monleon I. Sarasa M. (2008). The clinical significance of plasmatic amyloid Aβ-40 peptide levels in Alzheimer's disease patients treated with galantamine. Am. J. Alzheimers Dis. Other Demen. 23, 286– 290. 10.1177/1533317507313675 18591211 PMC10846209 · DOI
  88. Modrego P. J. Rios C. Pérez Trullen J. M. García-Gómara M. J. Errea J. M. (2009). Carotid intima-media thickness as a predictor of response to cholinesterase inhibitors in Alzheimer's disease: an open-label trial. CNS Drugs 23, 253– 260. 10.2165/00023210-200923030-00006 19320533 · DOI
  89. Mohr F. Krejci E. Zimmermann M. Klein J. (2015). Dysfunctional presynaptic M2 receptors in the presence of chronically high acetylcholine levels: data from the PRiMA knockout mouse. PLoS ONE 10: e0141136. 10.1371/journal.pone.0141136 26506622 PMC4624712 · DOI
  90. Molinuevo J. L. Frölich L. Grossberg G. T. Galvin J. E. Cummings J. L. Krahnke T.. (2015). Responder analysis of a randomized comparison of the 13.3 mg/24 h and 9.5 mg/24 h rivastigmine patch. Alzheimers Res. Ther. 7: 9. 10.1186/s13195-014-0088-8 25755685 PMC4353453 · DOI
  91. Mori E. Ikeda M. Nakagawa M. Miyagishi H. Kosaka K. (2016). Pretreatment cognitive profile likely to benefit from donepezil treatment in dementia with lewy bodies: pooled analyses of two randomized controlled trials. Dement. Geriatr. Cogn. Disord. 42, 58– 68. 10.1159/000447586 27537084 · DOI
  92. Mossello E. Tonon E. Caleri V. Tilli S. Cantini C. Cavallini M.. (2004). Effectiveness and safety of cholinesterase inhibitors in elderly subjects with Alzheimer's disease: a “real world” study. Arch. Gerontol. Geriatr. Suppl. 9, 297– 307. 10.1016/j.archger.2004.04.040 15207427 · DOI
  93. Motter J. N. Liu X. Qian M. Cohen H. R. Devanand D. P. (2021). Odor identification impairment and cholinesterase inhibitor treatment in Alzheimer's disease. Alzheimers Dement. 13: e12158. 10.1002/dad2.12158 33816753 PMC8010480 · DOI
  94. Nelson P. T. Dickson D. W. Trojanowski J. Q. Jack C. R. Boyle P. A. Arfanakis K.. (2019). Limbic-predominant age-related TDP-43 encephalopathy (LATE): consensus working group report. Brain 142, 1503– 1527. 10.1093/brain/awz099 31039256 PMC6536849 · DOI · Paper page
  95. Ohnishi T. Sakiyama Y. Okuri Y. Kimura Y. Sugiyama N. Saito T.. (2014). The prediction of response to galantamine treatment in patients with mild to moderate Alzheimer's disease. Curr. Alzheimer Res. 11, 110– 118. 10.2174/15672050113106660167 24156269 PMC3979115 · DOI
  96. Onofrj M. Thomas A. Iacono D. Luciano A. L. Iorio A. D. (2003). The effects of a cholinesterase inhibitor are prominent in patients with fluctuating cognition: a part 3 study of the main mechanism of cholinesterase inhibitors in dementia. Clin. Neuropharmacol. 26, 239– 251. 10.1097/00002826-200309000-00008 14520164 · DOI
  97. Ortner M. Stange M. Schneider H. Schröder C. Buerger K. Müller C.. (2020). Therapeutic drug monitoring of rivastigmine and donepezil under consideration of CYP2D6 genotype-dependent metabolism of donepezil. Drug Des. Dev. Ther. 14, 3251– 3262. 10.2147/DDDT.S247259 32848364 PMC7431170 · DOI
  98. Ouchi Y. Meguro K. Akanuma K. Kato Y. Yamaguchi S. (2015). Normal hearing ability but impaired auditory selective attention associated with prediction of response to donepezil in patients with Alzheimer's disease. Behav. Neurol. 2015: 540348. 10.1155/2015/540348 26161001 PMC4487900 · DOI
  99. Pakrasi S. Mukaetova-Ladinska E. B. McKeith I. G. O'Brien J. T. (2003). Clinical predictors of response to acetyl cholinesterase inhibitors: experience from routine clinical use in Newcastle. Int. J. Geriatr. Psychiatry 18, 879– 886. 10.1002/gps.928 14533120 · DOI
  100. Palmqvist S. Minthon L. Wattmo C. Londos E. Hansson O. A. (2010). A Quick Test of cognitive speed is sensitive in detecting early treatment response in Alzheimer disease. Alzheimers. Res. Ther. 2: 29. 10.1186/alzrt53 20950460 PMC2983438 · DOI
  101. Paroni G. Seripa D. Fontana A. D'Onofrio G. Gravina C. Urbano M.. (2014). FOXO1 locus and acetylcholinesterase inhibitors in elderly patients with Alzheimer's disease. Clin. Interv. Aging. 9, 1783– 1791. 10.2147/CIA.S64758 25364236 PMC4211854 · DOI
  102. Patterson C. E. Todd S. A. Passmore A. P. (2011). Effect of apolipoprotein e and butyrylcholinesterase genotypes on cognitive response to cholinesterase inhibitor treatment at different stages of Alzheimer's disease. Pharmacogenomics J. 11, 444– 450. 10.1038/tpj.2010.61 20644562 · DOI
  103. Pelton G. H. Soleimani L. Roose S. P. Tabert M. H. Devanand D. P. (2016). Olfactory deficits predict cognitive improvement on donepezil in patients with depression and cognitive impairment. Alzheimer Dis. Assoc. Disord. 30, 67– 69. 10.1097/WAD.0000000000000107 26398910 PMC4764438 · DOI
  104. Perera G. Khondoker M. Broadbent M. Breen G. Stewart R. (2014). Factors associated with response to acetylcholinesterase inhibition in dementia: a cohort study from a secondary mental health care case register in london. PLoS ONE 9: e109484. 10.1371/journal.pone.0109484 25411838 PMC4239015 · DOI
  105. Pilotto A. Franceschi M. D'Onofrio G. Bizzarro A. Mangialasche F. Cascavilla L.. (2009). Effect of a cyp2d6 polymorphism on the efficacy of donepezil in patients with Alzheimer disease. Neurology 73, 761– 767. 10.1212/WNL.0b013e3181b6bbe3 19738170 PMC2739607 · DOI
  106. Pola R. Flex A. Ciaburri M. Rovella E. Valiani A. Reali G.. (2005). Responsiveness to cholinesterase inhibitors in Alzheimer's disease: a possible role for the 192 Q/R polymorphism of the PON-1 gene. Neurosci. Lett. 382, 338– 341. 10.1016/j.neulet.2005.03.027 15925115 · DOI
  107. Raschetti R. Maggini M. Sorrentino G. C. Martini N. Caffari B. Vanacore N. A.. (2005). cohort study of effectiveness of acetylcholinesterase inhibitors in Alzheimer's disease. Eur. J. Clin. Pharmacol. 61, 361– 368. 10.1007/s00228-005-0946-1 15912389 · DOI
  108. Rigaud A. S. Traykov L. Latour F. Couderc R. Moulin F. Forette F.. (2002). Presence or absence of at least one epsilon 4 allele and gender are not predictive for the response to donepezil treatment in Alzheimer's disease. Pharmacogenetics 12, 415– 420. 10.1097/00008571-200207000-00009 12142731 · DOI
  109. Rocha-dias P. F. Simao-silva D. P. Suellen S. Piovezan M. R. Souza R. K. M. Darreh-shori T.. (2020). Influence of a genetic variant of CHAT gene over the profile of plasma soluble ChAT in Alzheimer disease. Genet. Mol. Biol. 43: e20190404. 10.1590/1678-4685-gmb-2019-0404 33306773 PMC7783728 · DOI
  110. Rota E. Ferrero P. Ursone R. Migliaretti G. (2007). Short term response is predictive of long term response to acetylcholinesterase inhibitors in Alzheimer's disease: a starting point to explore Bayesian approximation in clinical practice. Bioinformation 2, 43– 49. 10.6026/97320630002039 18188418 PMC2174418 · DOI
  111. Rozzini L. Chilovi V. Bertoletti E. Ghianda D. Conti M. Trabucchi M.. (2008). Serum albumin level interferes with the effect of Donepezil in Alzheimer's disease. Aging Clin. Exp. Res. 20, 509– 512. 10.1007/BF03324877 19179833 · DOI
  112. Salib Tony Sheridan Mark Allington E. (2001). Ventricular measurements in computed tomography of responders and non-responders to donepezil in the treatment of Alzheimer's disease. Int. J. Psychiatry Clin. Pract. 5, 189– 194. 10.1080/136515001317021653 24926752 · DOI
  113. Sayer R. Law E. Connelly P. J. Breen K. C. (2004). Association of a salivary acetylcholinesterase with Alzheimer's disease and response to cholinesterase inhibitors. Clin. Biochem. 37, 98– 104. 10.1016/j.clinbiochem.2003.10.007 14725939 · DOI
  114. Scacchi R. Gambina G. Broggio E. Corbo R. M. (2014). Sex and ESR1 genotype may influence the response to treatment with donepezil and rivastigmine in patients with Alzheimer's disease. Int. J. Geriatr. Psychiatry. 29, 610– 615. 10.1002/gps.4043 24150894 · DOI · Paper page
  115. Scacchi R. Gambina G. Moretto G. Corbo R. M. (2009). Variability of AChE, BChE, and ChAT genes in the late-onset form of Alzheimer's disease and relationships with response to treatment with donepezil and rivastigmine. Am. J. Med. Genet. B Neuropsychiatr. Genet. 150, 502– 507. 10.1002/ajmg.b.30846 18780301 · DOI
  116. Selden N. R. Gitelman D. R. Salamon-murayama N. Parrish T. B. Mesulam M. (1998). Trajectories of cholinergic pathways within the cerebral hemispheres of the human brain. Brain 121(Pt 12), 2249– 2257. 10.1093/brain/121.12.2249 9874478 · DOI · Paper page
  117. Seripa D. Bizzarro A. Pilotto A. D'Onofrio G. Vecchione G. Gallo A. P.. (2011). Role of cytochrome P4502D6 functional polymorphisms in the efficacy of donepezil in patients with Alzheimer's disease. Pharmacogenet. Genomics 21, 225– 230. 10.1097/FPC.0b013e32833f984c 20859244 · DOI
  118. Siek G. C. Katz L. S. Fishman E. B. Korosi T. S. Marquis J. K. (1990). Molecular forms of acetylcholinesterase in subcortical areas of normal and Alzheimer disease brain. Biol. Psychiatry 27, 573– 580. 10.1016/0006-3223(90)90524-6 2322617 · DOI
  119. Sobow T. Flirski M. Liberski P. Kloszewska I. (2007). Plasma Abeta levels as predictors of response to rivastigmine treatment in Alzheimer's disease. Acta Neurobiol. Exp. (Wars). 67, 131– 139. 17691220
  120. Sokolow S. Li X. Chen L. Taylor K. D. Rotter J. I. Rissman R. A.. (2017). Deleterious Effect of butyrylcholinesterase K-variant in donepezil treatment of mild cognitive impairment. J. Alzheimers Dis. 56, 229– 237. 10.3233/JAD-160562 27911294 PMC5534361 · DOI
  121. Sumirtanurdin R. Thalib A. Y. Cantona K. Abdulah R. (2019). Effect of genetic polymorphisms on Alzheimer's disease treatment outcomes: an update. Clin. Interv. Aging. 14, 631– 642. 10.2147/CIA.S200109 30992661 PMC6445219 · DOI
  122. Tanaka M. Namiki C. Thuy D. H. D. Yoshida H. Kawasaki K. Hashikawa K.. (2004). Prediction of psychiatric response to donepezil in patients with mild to moderate Alzheimer's disease. J. Neurol. Sci. 225, 135– 141. 10.1016/j.jns.2004.07.009 15465097 · DOI
  123. Tanaka Y. Hanyu H. Sakurai H. Takasaki M. Abe K. (2003). Atrophy of the substantia innominata on magnetic resonance imaging predicts response to donepezil treatment in Alzheimer's disease patients. Dement. Geriatr. Cogn. Disord. 16, 119– 125. 10.1159/000070998 12826736 · DOI
  124. Tei E. Yamamoto H. Watanabe T. Miyazaki A. Nakadate T. Kato N.. (2008). Use of serum insulin-like growth factor-I levels to predict psychiatric non-response to donepezil in patients with Alzheimer's disease. Growth Horm. IGF Res. 18, 47– 54. 10.1016/j.ghir.2007.07.006 17714966 · DOI
  125. Teipel S. J. Cavedo E. Grothe M. J. Lista S. Galluzzi S. Colliot O.. (2016). Predictors of cognitive decline and treatment response in a clinical trial on suspected prodromal Alzheimer's disease. Neuropharmacology 108, 128– 135. 10.1016/j.neuropharm.2016.02.005 26876309 · DOI
  126. Tepmongkol S. Hemrungrojn S. Dupont P. Tunvirachaisakul C. Aniwattanapong D. Likitjareon Y.. (2019). Early prediction of donepezil cognitive response in Alzheimer's disease by brain perfusion single photon emission tomography. Brain Imaging Behav. 13, 1665– 1673. 10.1007/s11682-019-00182-9 31432319 · DOI
  127. Touchon J. Bergman H. Bullock R. Rapatz G. Nagel J. Lane R.. (2006). Response to rivastigmine or donepezil in Alzheimer's patients with symptoms suggestive of concomitant Lewy body pathology. Curr. Med. Res. Opin. 22, 49– 59. 10.1185/030079906X80279 16393430 · DOI
  128. Tsai P. H. Chang S. C. Liu F. C. Tsao J. Wang Y. H. Lo M. T. A.. (2015). Novel application of multiscale entropy in electroencephalography to predict the efficacy of acetylcholinesterase inhibitor in Alzheimer's disease. Comput. Math. Methods Med. 2015: 953868. 10.1155/2015/953868 26120358 PMC4450304 · DOI
  129. Ullrich C. Pirchl M. Humpel C. (2010). Hypercholesterolemia in rats impairs the cholinergic system and leads to memory deficits. Mol. Cell. Neurosci. 45, 408– 417. 10.1016/j.mcn.2010.08.001 20696249 PMC2977849 · DOI
  130. Um Y. H. Kim T. W. Jeong J. H. Seo H. J. Han J. H. Hong S. C.. (2017). Prediction of treatment response to donepezil using automated hippocampal subfields volumes segmentation in patients with mild Alzheimer's disease. Psychiatry Investig. 14, 698– 702. 10.4306/pi.2017.14.5.698 29042898 PMC5639141 · DOI
  131. Vaknine S. Soreq H. (2020). Central and peripheral anti-inflammatory effects of acetylcholinesterase inhibitors. Neuropharmacology 168: 108020. 10.1016/j.neuropharm.2020.108020 32143069 · DOI
  132. Villiger Y. Szanto I. Jaconi S. Blanchet C. Buisson B. Krause K. H.. (2002). Expression of an α7 duplicate nicotinic acetylcholine receptor-related protein in human leukocytes. J. Neuroimmunol. 126, 86– 98. 10.1016/S0165-5728(02)00057-7 12020960 · DOI
  133. Visser P. J. Scheltens P. Pelgrim E. Verhey F. R. J. (2005). Medial temporal lobe atrophy and APOE genotype do not predict cognitive improvement upon treatment with rivastigmine in Alzheimer's disease patients. Dement. Geriatr. Cogn. Disord. 19, 126– 133. 10.1159/000082883 15627759 · DOI
  134. Wallin A. K. Hansson O. Blennow K. Londos E. Minthon L. (2009). Can CSF biomarkers or pre-treatment progression rate predict response to cholinesterase inhibitor treatment in Alzheimer's disease? Int. J. Geriatr. Psychiatry 24, 638– 647. 10.1002/gps.2195 19123199 · DOI
  135. Wattmo C. Londos E. Minthon L. (2018). Short-term response to cholinesterase inhibitors in Alzheimer's disease delays time to nursing home placement. Curr. Alzheimer Res. 15, 905– 916. 10.2174/1567205015666180507105326 29732972 PMC6174634 · DOI
  136. Wattmo C. Wallin Å. K. (2017). Early- versus late-onset Alzheimer's disease in clinical practice: cognitive and global outcomes over 3 years. Alzheimers Res. Ther. 9, 70. 10.1186/s13195-017-0294-2 28859660 PMC5580278 · DOI
  137. Wattmo C. Wallin A. K. Londos E. Minthon L. (2011). Predictors of long-term cognitive outcome in Alzheimer's disease. Alzheimers Res. Ther. 3: 23. 10.1186/alzrt85 21774798 PMC3226278 · DOI
  138. Wattmo C. Wallin A. K. Minthon L. (2012). Functional response to cholinesterase inhibitor therapy in a naturalistic Alzheimer's disease cohort. BMC Neurol. 12: 134. 10.1186/1471-2377-12-134 23126532 PMC3534216 · DOI
  139. Weng P. H. Chen J. H. Chen T. F. Sun Y. Wen L. L. Yip P. K.. (2013). CHRNA7 polymorphisms and response to cholinesterase inhibitors in Alzheimer's disease. PLoS ONE 8: e84059. 10.1371/journal.pone.0084059 24391883 PMC3877150 · DOI
  140. Wu M. N. Kao Y. H. Chou P. S. Lin T. C. Kao L. L. Yang Y. H.. (2018). Location of white matter changes and response to donepezil in patients with Alzheimer's disease: a retrospective and observational study. Geriatr. Gerontol. Int. 18, 123– 129. 10.1111/ggi.13153 28853195 · DOI
  141. Xiao T. Jiao B. Zhang W. Tang B. Shen L. (2016). Effect of the CYP2D6 and APOE polymorphisms on the efficacy of donepezil in patients with Alzheimer's disease: a systematic review and meta-analysis. CNS Drugs 30, 899– 907. 10.1007/s40263-016-0356-1 27282366 · DOI
  142. Yamagata B. Watanabe T. Tomioka H. Kobayashi H. Nakano Y. Mimura M.. (2010). Preliminary use of insulin-like growth factor-I as a biomarker for sorting high-dose donepezil responders among Japanese patients with Alzheimer's disease. Regul. Pept. 163, 137– 142. 10.1016/j.regpep.2010.04.010 20451565 · DOI
  143. Yang Y. H. Chen C. H. Chou M. C. Li C. H. Liu C. K. Chen S. H.. (2013). Concentration of donepezil to the cognitive response in alzheimer disease. J. Clin. Psychopharmacol. 33, 351– 355. 10.1097/JCP.0b013e31828b5087 23609381 · DOI
  144. Yaowaluk T. Senanarong V. Limwongse C. Boonprasert R. Kijsanayotin P. (2019). Influence of CYP2D6, CYP3A5, ABCB1, APOE polymorphisms and nongenetic factors on donepezil treatment in patients with Alzheimer's disease and vascular dementia. Pharmgenomics Pers. Med. 12, 209– 224. 10.2147/PGPM.S211259 31564952 PMC6732559 · DOI
  145. Yoon H. Myung W. Lim S. W. Kang H. S. Kim S. Won H. H.. (2015). Association of the choline acetyltransferase gene with responsiveness to acetylcholinesterase inhibitors in Alzheimer's disease. Pharmacopsychiatry 48, 111– 117. 10.1055/s-0035-1545300 25730470 · DOI
  146. Yoshida T. Ha-Kawa S. Yoshimura M. Nobuhara K. Kinoshita T. Sawada S.. (2007). Effectiveness of treatment with donepezil hydrochloride and changes in regional cerebral blood flow in patients with Alzheimer's disease. Ann. Nucl. Med. 21, 257– 265. 10.1007/s12149-007-0022-2 17634843 · DOI
  147. Zhong Y. Zheng X. Miao Y. Wan L. Yan H. Wang B.. (2013). Effect of CYP2D6*10 and APOE polymorphisms on the efficacy of donepezil in patients with Alzheimer's disease. Am. J. Med. Sci. 345, 222– 226. 10.1097/MAJ.0b013e318255a8f9 22986607 · DOI
  148. Zhu C. W. Livote E. E. Scarmeas N. Albert M. Brandt J. Blacker D.. (2013). Long-term associations between cholinesterase inhibitors and memantine use and health outcomes among patients with Alzheimer' s disease. Alzheimers Dement. 9, 733– 740. 10.1016/j.jalz.2012.09.015 23332671 PMC3633652 · DOI

Cited by

Sorted by citations

Authors
Pozzi, F. E., Conti, E., Appollonio, I., Ferrarese, C., & Tremolizzo, L.
Affiliations
  • Azienda Ospedaliera San Gerardo (IT)
  • University of Milano-Bicocca (IT)
Corresponding author
Pozzi, Federico Emanuele
ORCID
Venue
Frontiers in Neuroscience
Publisher
Frontiers Media SA
Published
2022-09-20
Volume
16
Pages
998224-998224
ISSN
1662-453X (ISSN-L)
DOI
10.3389/fnins.2022.998224
PMC
PMC9530658
OpenAlex
W4297907278
Cited by
36
References
9
Citations by year
2026: 11 · 2025: 9 · 2024: 8 · 2023: 8
FWCI
0.90
Type
journal article
Language
en
Open access
Licence
Locations
  • Frontiers in Neuroscience (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • BOA (University of Milano-Bicocca) (submittedVersion, cc-by)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Topics
  • Health Sciences › Medicine › Pharmacology › Cholinesterase and Neurodegenerative Diseases
  • Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
  • Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
Keywords
acetylcholinesterase inhibitors, dementia, predictors of treatment response, cholinergic deficit, hallucinations, fluctuating cognition, donepezil, white matter hyperintensities, CYP2D6 polymorphism, serum albumin, apolipoprotein E, disease progression, serum cholesterol, apathy, antipsychotic drugs, educational attainment

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.

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