pharmaceutical agents for treatment of Alzheimer's disease (Alzheimer's agent)
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Adverse effects
- risk of pneumonia highest with memantine (RR=1.6)*[40]
- diarrhea, bradycardia, syncope, urge incontinence with cholinesterase inhibitors
- risk of Major Adverse Cardiovascular/Cerebrovascular Events (MACCE) 96% higher in Alzheimer's disease patients receiving both an antipsychotic & a cholinesterase inhibitor or memantine[57]
- mean time until MACCE 3.9 years vs 6,4 years for patients receiving neither
- relative risk of MACCE with antipsychotic 1.79 with mean time until MACCE 4.2 years
- relative risk of MACCE with cholinesterase inhibitor &/or memantine 1.32 with mean time until MACCE 5.9 years[57]
- also see individual agents
* relative to donepezil
Management
no agent shown to improve clinically relevant outcomes[19]
- cholinesterase inhibitors are option for mild-moderate AD*
- some patients have subjective delay in worsening of cognitive impairment but many do not[51]
- 12 week trial adequate[33]
- modest benefit in cognitive perfomance without improvement in daily function[19]
- may improve apathy more than memory
- may diminish rate of deterioration[14]
- only 1 in 12 patients show any improvement[18]
- 1st line treatment for mild-moderate Alzheimer's disease[19]
- treatment option for moderate Alzheimer's disease only[20]
- minimal benefit; disproportionate adverse effects[43]
- donepezil (Aricept)
- 100% oral bioavailability
- metabolized by cyt P450 2D6 (CYP2D6) & cyt P450 3A4 (CYP3A4)
- 4 metabolites, of which 2 are active
- only cholinesterase inhibitor approved for severe AD[19]
- NEJM Knowledge+ recommends continuing donepezil despite loss of questionable benefit citing[22][50]
- rivastigmine (Exelon)
- bioavailability of 40% - food increases absorption
- metabolized by cholinesterase
- not likely to interact with other drugs
- galantamine (Reminyl, Nivalin)
- oral bioavailability 90% -> food delays absorption, but does not affect bioavailability, available as elixir
- eliminated unchanged or as glucuronide in the urine
- metabolized by cyt P450s CYP2D6 & CYP3A4 (1/3)
- tetrahydroaminoacridine (Tacrine, Cognex)
- absolute oral bioavailability 17% & variable
- food diminishes bioavailability by 30-40%
- metabolized principally by cyt P450 1A2 (CYP1A2)
- significant potential for drug-drug interactions
- 20% develop a reversible increase in transaminases
- absolute oral bioavailability 17% & variable
- Huperzine A (Chinese traditional herb) contains cholinesterase inhibitor(s) {not FDA approved}[2]
- Numovil contains Huperzine A
- clinical trials
- see donepezil & rivastigmine
- meta-analysis of 29 trials (JAMA 2003) shows marginal clinical benefit
- memantine* (Namenda) is an option for severe AD or moderate AD for patients with contraindication to cholinesterase inhibitors
- NMDA receptor antagonist
- FDA approved Oct 2003
- benefit in combination with cholinesterase inhibitor[5][17][42]
- may diminish rate of deterioration[15]
- 1st line treatment for moderate-severe Alzheimer's disease 19]
- no benefit for mild to moderate Alzheimer's disease[19][20][28]
- minimal benefit[43]
- combination of cholinesterase inhibitor plus memantine may have more benefit than cholinesterase inhibitor alone[17][42]
- adding memantine to donepezil no better than donepezil alone[22]
- NICE does not recommend combination of cholinesterase inhibitor plus memantine
- oligomannan approved for use in China
- rotigotine may improve frontal lobe function & activities of daily living in patients with mild-moderate Alzheimer's disease[44]
- anti-Alzheimer monoclonal antibody
- aducanumab (Aduhelm) FDA-approved; removes amyloid plaques
- cognitive benefit controversial
- lecanemab (Leqembi)
- humanized IgG1 monoclonal antibody
- binds with high affinity to amyloid-beta soluble protofibrils
- small cognitive benefit in industry-sponsored phase 3 clinical trial
- donanemab (investigational) targets beta-amyloid
- directed at an epitope present only in established amyloid plaques
- modest improvement in patients with early Alzheimer's disease
- gantenerumab (investigational)
- reduces amyldoid plaques & lowers CSF total tau & phosphorylated tau
- solanezumab (investigational)
- targets the mid-domain of the amyloid-beta monomer
- no benefit in patients with mild-moderate or preclinical Alzheimer's disease[53][54]
- semorinemab (investigational)
- binds N-terminal part of microtubule-associated protein tau (MAP-tau)
- anti-tau antibodies unlikely to significantly slow cognitive impairment[49]
- benefits of anti-Alzheimer monoclonal antibodies vs donepezil discussed[53]
- plasma p-tau217 outperforms plasma p-tau181 & plasma p-tau231 & other plasma biomarkers of Alzheimer's disease in identifying which patients may benefit from an anti-beta-amyloid anti-Alzheimer monoclonal antibody[56]
- aducanumab (Aduhelm) FDA-approved; removes amyloid plaques
- tau aggregation inhibitors (investigational)
- idalopirdine of no benefit added to cholinesterase inhibitor[39]
- Hydergine
- FDA approved
- of questionable value
associated behavioral syndromes
- depression (antidepressant with low anticholinergic effects)
- SSRI (agents of choice)
- citalopram (Celexa), sertraline (Zoloft)
- trazodone
- antidepressant no better than placebo[21][45]
- SSRI (agents of choice)
- anxiety: anxiolytics
- benzodiazepines, especially in combination with antidepressants are associated with faster functional decline[46]
- agitation (see psychosis & agitation in the elderly)
- atypical antipsychotics[8][9][10]
- risperidone (Risperdal)
- olanzapine (Zyprexa)
- quetiapine (Seroquel)
- considered off-label use[19]
- use associated with poorer cognition & function[45]
- Haldol considered off-label use[19]
- benzodiazepines (short acting)
- trazodone may be useful[3]
- atypical antipsychotics[8][9][10]
- apathy: methylphenidate is safe & effective for treatment of apathy[48]
- may improve motivation, cognition,mood, functioning, & caregiver burden in community-dwelling men with Alzheimer's disease[41]
- does not affect patients' function or quality of life[48]
- no drug class associated with improvement in neuropsychiatric symptoms[45]
sleep disturbance
- ref[37] claims a meta-analysis of melatonin for sleep disturbance in patients with dementia found it beneficial (but cites[38] which states the opposite)
- melatonin of no benefit[38]
- trazodone may be of benefit[38]
others (also see early intervention for Alzheimer's disease)
- vitamin E 2000 IU/day with mixed results
- L-deprenyl (Selegiline) 5 mg BID may be of some benefit
- Ginkgo biloba of no benefit[36]
- estrogen NOT useful, may be risk
- statins may diminish rate of deterioration[14]
- centrally-acting ACE inhibitors may diminish rate of deterioration[15][26]
- idalopirdine, a 5HT6 receptor antagonist, failed to slow cognitive decline in patients with Alzheimer's disease[39]
- cholinesterase inhibitors, memantine, & statins inappropriate in patients with advanced dementia[32]
* FDA proposes approval of new drugs for treatment of preclinical Alzheimer's disease based on changes in biomarkers without demonstration of actual clinical benefit[6]
* NICE (UK) recommends cholinesterase inhibitors & memantine no longer be used for treating Alzheimer's disease. These drugs do NOT delay institutionalization & are NOT cost-effective[8]
* NICE (UK) recommends cholinesterase inhibitor as an option for moderately severe AD (MMSE 10-20)[8]
* NICE does NOT recommend memantine except for clinical trials, OK to continue if currently prescribed medication[8]
* benefits of cholinesterase inhibitors in Alzheimer disease patients are relatively small & likely extend to only a subset of AD patients that can't be identified in advance[11]
* treatment of dementia with cholinesterase inhibitors & memantine can result in statistically significant but clinically marginal improvement in measures of cognition & global assessment of dementia[15]
* neither donepezil nor memantine significantly affects outcomes important to caregivers[22]
* continuing donepezil in patients with moderate-severe AD
- may exceed minimum clinically relevant threshold[22]
- reduces nursing home placement within 12 months, but not within 2 or 4 years[35]
* evidence is insufficient to compare the effectiveness of different pharmaceutical agents to treat dementia[15]
* Also see cholinesterase inhibitor clinical trials
More general terms
More specific terms
- anti-Alzheimer monoclonal antibody
- donepezil (Aricept, Aricept ODT, Adlarity)
- donepezil/memantine (Namzaric)
- ergoloid mesylates (Hydergine)
- galantamine (Reminyl, Razadyne, Nivalin)
- homotaurine; 3-Amino-1-propanesulfonic acid; tramiprosate; ALZ-801
- memantine (Auzura, Namenda, Exiba, Akatinol)
- neflamapimod
- oligomannate
- rivastigmine (Exelon)
- simufilam
- sumifilam
- tacrine; tetrahydroaminoacridine (Cognex, THA, Romotal)
- tarenflurbil (Flurizan, R-flurbiprofen)
- tau aggregation inhibitor
Additional terms
- agents for treatment of associated behavioral symptoms of Alzheimer's disease
- Alzheimer's disease (AD)
- cholinesterase inhibitor
- cholinesterase inhibitor clinical trials
- CNS cholinergic system
- early intervention for Alzheimer's disease
- ergoloid mesylates (Hydergine)
- Ginkgo biloba
- Huperzine A (Huperzia serrata, Fordine)
- investigational therapies for treatment of Alzheimer's disease
- L-deprenyl (Selegiline, Eldepryl, Emsam, Zelapar)
- vitamin E
References
- ↑ Prescriber's Letter 8(7):40 2001
- ↑ 2.0 2.1 www.alz.org
- ↑ 3.0 3.1 UCLA Intensive Course in Geriatric Medicine & Board Review, Marina Del Ray, CA, Sept 12-15, 2001
- ↑ Journal Watch 23(4):36, 2003 Trinh N-H et al, JAMA 289:210, 2003
- ↑ 5.0 5.1 Tariot PN JAMA 291:317, 2003 http://jama.ama-assn.org/cgi/content/abstract/291/3/317
- ↑ 6.0 6.1 MedPage Today Staff. February 15, 2018 Sea Change for Alzheimer's Drug Development (FDA) Agency may approve drugs for 'preclinical' disease solely on biomarker effects. https://www.medpagetoday.com/neurology/alzheimersdisease/71185
U.S. Department of Health and Human Services Food and Drug Administration Center for Drug Evaluation and Research (CDER) Center for Biologics Evaluation and Research (CBER) Early Alzheimer's Disease: Developing Drugs for Treatment Guidance for Industry. Draft Guidance. February 2018 https://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/UCM596728.pdf - ↑ Espinosa R. In: Intensive Course in Geriatric Medicine & Board Review, Marina Del Ray, CA, Sept 29-Oct 2, 2004
- ↑ 8.0 8.1 8.2 8.3 8.4 Internal Medicine News, April 15, 2005, pg 12
- ↑ 9.0 9.1 Journal Watch 24(17):133, 2004 Lee PE, Gill SS, Freedman M, Bronskill SE, Hillmer MP, Rochon PA. Atypical antipsychotic drugs in the treatment of behavioural and psychological symptoms of dementia: systematic review. BMJ. 2004 Jul 10;329(7457):75. Epub 2004 Jun 11. Review. <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/15194601 <Internet> http://bmj.bmjjournals.com/cgi/content/full/329/7457/75
- ↑ 10.0 10.1 FDA Public Health Advisory Deaths with Antipsychotics in Elderly Patients with Behavioral Disturbances http://www.fda.gov/cder/drug/advisory/antipsychotics.htm http://www.fda.gov/medwatch/SAFETY/2005/safety05.htm#atypical
- ↑ 11.0 11.1 Kaduszkiewicz H et al Cholinesterase inhibitors for patients with Alzheimer's disease: Systematic review of randomised clinical trials. BMJ 2005 Aug 6; 331:321-7. <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/16081444 <Internet> http://bmj.bmjjournals.com/cgi/content/full/331/7512/321
- ↑ Prescriber's Letter 13(10): 2006 Drug Treatment of Dementia Due to Alzheimer's Disease Detail-Document#: http://prescribersletter.com/(5bhgn1a4ni4cyp2tvybwfh55)/pl/ArticleDD.aspx?li=1&st=1&cs=&s=PRL&pt=3&fpt=25&dd=221005&pb=PRL (subscription needed) http://www.prescribersletter.com
- ↑ Schneider LS Effectiveness of atypical antipsychotic drugs in patients with Alzheimer's disease N Engl J Med 2006, 355:1525 PMID: https://www.ncbi.nlm.nih.gov/pubmed/17035647
Karlawish J Alzheimer's disease - Clinical trials and the logic of clinical purpose. N Engl J Med 2006, 355:1604 PMID: https://www.ncbi.nlm.nih.gov/pubmed/17035654 - ↑ 14.0 14.1 14.2 Ellul J, Archer N, Foy CM, Poppe M, Boothby H, Nicholas H, Brown RG, Lovestone S. The effects of commonly prescribed drugs in patients with Alzheimer's disease on the rate of deterioration. J Neurol Neurosurg Psychiatry. 2007 Mar;78(3):233-9. PMID: https://www.ncbi.nlm.nih.gov/pubmed/17012333
- ↑ 15.0 15.1 15.2 15.3 15.4 Qaseem A et al, Current pharmacologic treatment of dementia: a clinical practice guideline from the American College of Physicians and the American Academy of Family Physicians. Annals of Internal Medicine 2008, 148:370 <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/18316755 <Internet> http://www.annals.org/cgi/content/full/148/5/370 (corresponding NGC guideline withdrawn Jan 2014)
Raina P et al, Effectiveness of cholinesterase inhibitors and memantine for treating dementia: evidence review for a clinical practice guideline. Annals of Internal Medicine 2008, 148:379 <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/18316756 <Internet> http://www.annals.org/cgi/content/full/148/5/379 - ↑ Prescriber's Letter 15(5): 2008 Pharmacotherapy Choices for Patients with Dementia CHART: Drugs to Avoid in Patients with Dementia COMMENTARY: Efficacy of Dementia Drugs and Guidelines for Use GUIDELINES: American College of Physicians and the American Academy of Family Physicians Clinical Practice Guideline on Current Pharmacologic Treatment of Dementia Detail-Document#: http://prescribersletter.com/(5bhgn1a4ni4cyp2tvybwfh55)/pl/ArticleDD.aspx?li=1&st=1&cs=&s=PRL&pt=3&fpt=25&dd=240510&pb=PRL (subscription needed) http://www.prescribersletter.com
- ↑ 17.0 17.1 17.2 Atri A et al, Long-term course and effectiveness of combination therapy in Alzheimer's disease. Alzheimer Dis Assoc Disord. 2008 Jul-Sep;22(3):209-21. PMID: https://www.ncbi.nlm.nih.gov/pubmed/18580597
- ↑ 18.0 18.1 Prescriber's Letter 16(7): 2009 PATIENT HANDOUT: Cholinesterase Inhibitors for Dementia COMMENTARY: Cardiac Effects of Cholinesterase Inhibitors Detail-Document#: http://prescribersletter.com/(5bhgn1a4ni4cyp2tvybwfh55)/pl/ArticleDD.aspx?li=1&st=1&cs=&s=PRL&pt=3&fpt=25&dd=250126&pb=PRL (subscription needed) http://www.prescribersletter.com
- ↑ 19.0 19.1 19.2 19.3 19.4 19.5 19.6 19.7 Medical Knowledge Self Assessment Program (MKSAP) 15, 16, 17, 19. American College of Physicians, Philadelphia 2009, 2012, 2015, 2021
- ↑ 20.0 20.1 20.2 Schneider LS et al. Lack of evidence for the efficacy of memantine in mild Alzheimer disease. Arch Neurol 2011 Apr 11; <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/21482915 <Internet> http://archneur.ama-assn.org/cgi/content/abstract/archneurol.2011.69v1
- ↑ 21.0 21.1 Banerjee S et al Sertraline or mirtazapine for depression in dementia (HTA-SADD): a randomised, multicentre, double-blind, placebo- controlled trial The Lancet, Early Online Publication, 18 July 2011 <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/21764118 <Internet> http://www.thelancet.com/journals/lancet/article/PIIS0140-6736(11)60830-1/abstract
- ↑ 22.0 22.1 22.2 22.3 22.4 Howard R et al Donepezil and Memantine for Moderate-to-Severe Alzheimer's Disease. N Engl J Med 2012; 366:893-903March 8, 2012 <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/22397651 <Internet> http://www.nejm.org/doi/full/10.1056/NEJMoa1106668
Schneider LS. Discontinuing donepezil or starting memantine for Alzheimer's disease. N Engl J Med. 2012 Mar 8;366(10):957-9 PMID: https://www.ncbi.nlm.nih.gov/pubmed/22397659
Burke D. ACP Journal Club. Donepezil or memantine improved cognitive functioning in moderate-to-severe Alzheimer disease (EDJ). Ann Intern Med. 19 June 2012; 156(12):JC6-JC10 PMID: https://www.ncbi.nlm.nih.gov/pubmed/22711111 - ↑ Prescriber's Letter 19(5): 2012 COMMENTARY: Pharmacotherapy and Advancing Alzheimer's Disease Detail-Document#: http://prescribersletter.com/(5bhgn1a4ni4cyp2tvybwfh55)/pl/ArticleDD.aspx?li=1&st=1&cs=&s=PRL&pt=3&fpt=25&dd=280527&pb=PRL (subscription needed) http://www.prescribersletter.com
- ↑ Schneider LS. EDITORIAL. Discontinuing donepezil or starting memantine for Alzheimer's disease. N Engl J Med 2012; 366:957-959 PMID: https://www.ncbi.nlm.nih.gov/pubmed/22397659
- ↑ Burke D. ACP Journal Club. Donepezil or memantine improved cognitive functioning in moderate-to-severe Alzheimer disease (EDJ). Ann Intern Med 19 June 2012; 156(12):JC6-JC10 PMID: https://www.ncbi.nlm.nih.gov/pubmed/22711111
- ↑ 26.0 26.1 Gao Y, O'Caoimh R, Healy L et al Effects of centrally acting ACE inhibitors on the rate of cognitive decline in dementia. BMJ Open 2013;3:e002881 <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/23887090 <Internet> http://bmjopen.bmj.com/content/3/7/e002881
- ↑ Mangialasche F, Solomon A, Winblad B, Mecocci P, Kivipelto M. Alzheimer's disease: clinical trials and drug development. Lancet Neurol. 2010 Jul;9(7):702-16 PMID: https://www.ncbi.nlm.nih.gov/pubmed/20610346
- ↑ 28.0 28.1 28.2 Dysken MW et al Effect of Vitamin E and Memantine on Functional Decline in Alzheimer Disease. The TEAM-AD VA Cooperative Randomized Trial. JAMA. 2014;311(1):33-4 <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/24381967 <Internet> http://jama.jamanetwork.com/article.aspx?articleid=1810379
Evans DA et al Vitamin E, Memantine, and Alzheimer Disease. JAMA. 2014;311(1):29-30 <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/24381966 <Internet> http://jama.jamanetwork.com/article.aspx?articleid=1810360 - ↑ O'Brien JT, Burns A; BAP Dementia Consensus Group. Clinical practice with anti-dementia drugs: a revised (second) consensus statement from the British Association for Psychopharmacology. J Psychopharmacol. 2011 Aug;25(8):997-1019. PMID: https://www.ncbi.nlm.nih.gov/pubmed/21088041
- ↑ Lopez OL, Becker JT, Wahed AS Long-term effects of the concomitant use of memantine with cholinesterase inhibition in Alzheimer disease. J Neurol Neurosurg Psychiatry. 2009 Jun;80(6):600-7. PMID: https://www.ncbi.nlm.nih.gov/pubmed/19204022
- ↑ 31.0 31.1 Farina N, Isaac MG, Clark AR, et al. Vitamin E for Alzheimer's dementia and mild cognitive impairment. Cochrane Database Syst Rev. 2012; 11:CD002854. PMID: https://www.ncbi.nlm.nih.gov/pubmed/23152215
- ↑ 32.0 32.1 Tjia J et al Use of Medications of Questionable Benefit in Advanced Dementia. JAMA Intern Med. Published online September 08, 2014 <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/25201279 <Internet> http://archinte.jamanetwork.com/article.aspx?articleid=1901117
Sachs GA Improving Prescribing Practices Late in Life. A Task for all Clinicians, Not Just Nursing Home Physicians. JAMA Intern Med. Published online September 08, 2014. <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/25200598 <Internet> http://archinte.jamanetwork.com/article.aspx?articleid=1901111 - ↑ 33.0 33.1 AGS Choosing Wisely Workgroup. American Geriatrics Society identifies another five things that healthcare providers and patients should question. J Am Geriatr Soc. 2014;62:950-960. PMID: https://www.ncbi.nlm.nih.gov/pubmed/24575770
- ↑ Delrieu J, Piau A, Caillaud C, Voisin T, Vellas B. Managing cognitive dysfunction through the continuum of Alzheimer's disease: role of pharmacotherapy. CNS Drugs. 2011 Mar;25(3):213-26 PMID: https://www.ncbi.nlm.nih.gov/pubmed/21323393
- ↑ 35.0 35.1 Howard R et al. Nursing home placement in the Donepezil and Memantine in Moderate to Severe Alzheimer's Disease (DOMINO-AD) trial: Secondary and post-hoc analyses. Lancet Neurol 2015 Oct 26 PMID: https://www.ncbi.nlm.nih.gov/pubmed/26515660
- ↑ 36.0 36.1 Vellas B, Coley N, Ousset PJ et al Long-term use of standardised ginkgo biloba extract for the prevention of Alzheimer's disease (GuidAge): a randomised placebo-controlled trial Lancet Neurol. 2012 Oct;11(10):851-9. <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/22959217 <Internet> http://www.thelancet.com/journals/laneur/article/PIIS1474-4422%2812%2970206-5/abstract
- ↑ 37.0 37.1 Geriatric Review Syllabus, 9th edition (GRS9) Medinal-Walpole A, Pacala JT, Porter JF (eds) American Geriatrics Society, 2016
- ↑ 38.0 38.1 38.2 38.3 McCleery J, Cohen DA, Sharpley AL. Pharmacotherapies for sleep disturbances in Alzheimer's disease. Cochrane Database Syst Rev. 2014 Mar 21;(3):CD009178. Review. PMID: https://www.ncbi.nlm.nih.gov/pubmed/24659320
- ↑ 39.0 39.1 39.2 Fiore K NeuroBreak: Alzheimer's Drug Bombs; Elephant Tranquilizer ODs. MEDPAGE TODAY. Sept 27, 2016 http://www.medpagetoday.com/Neurology/GeneralNeurology/60482
Fiore K AAIC 2017 Meeting Coverage. 5HT6 Blocker a Dud in Alzheimer Trials - May shake confidence in similar drugs being developed. https://www.medpagetoday.com/MeetingCoverage/AAIC/66784
Atri A, Frolich L, Ballard C et al Effect of Idalopirdine as Adjunct to Cholinesterase Inhibitors on Change in Cognition in Patients With Alzheimer Disease. Three Randomized Clinical Trials. JAMA. 2018;319(2):130-142 PMID: https://www.ncbi.nlm.nih.gov/pubmed/29318278 https://jamanetwork.com/journals/jama/article-abstract/2668349
Bennett DA Lack of Benefit With Idalopirdine for Alzheimer Disease. Another Therapeutic Failure in a Complex Disease Process. JAMA. 2018;319(2):123-125. Jan 9. PMID: https://www.ncbi.nlm.nih.gov/pubmed/29318261 https://jamanetwork.com/journals/jama/article-abstract/2668332 - ↑ 40.0 40.1 Lampela P, Tolppanen AM, Tanskanen A et al Use of antidementia drugs and risk of pneumonia in older persons with Alzheimer's disease. Ann Med. 2016 Oct 27:1-25. [Epub ahead of print] PMID: https://www.ncbi.nlm.nih.gov/pubmed/27786552
- ↑ 41.0 41.1 Padala PR, Padala KP, Lensing SY et al. Methylphenidate for apathy in community-dwelling older veterans with mild Alzheimer's disease: A double-blind, randomized, placebo-controlled trial. Am J Psychiatry 2017 Sep 15 PMID: https://www.ncbi.nlm.nih.gov/pubmed/28945120
- ↑ 42.0 42.1 42.2 Chen R, Chan PT, Chu H et al. Treatment effects between monotherapy of donepezil versus combination with memantine for Alzheimer disease: A meta- analysis. PLoS One 2017 Aug 21; 12:e0183586. <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/28827830 Free PMC Article <Internet> http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0183586
- ↑ 43.0 43.1 43.2 Therapeutics Letter #108. Therapeutics Initiative Drugs to Avoid. http://www.ti.ubc.ca/2018/01/04/108-drugs-avoid/
- ↑ 44.0 44.1 44.2 Koch G et al Effect of Rotigotine vs Placebo on Cognitive Functions Among Patients With Mild to Moderate Alzheimer Disease. A Randomized Clinical Trial. JAMA Netw Open. 2020;3(7):e2010372 PMID: https://www.ncbi.nlm.nih.gov/pubmed/32667654 Free article https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2768248
- ↑ 45.0 45.1 45.2 45.3 Oh ES, Rosenberg PB, Rattinger GB et al Psychotropic Medication and Cognitive, Functional, and Neuropsychiatric Outcomes in Alzheimer's Disease (AD) J Am Geriatr Soc. 2021 Apr;69(4):955-963 PMID: https://www.ncbi.nlm.nih.gov/pubmed/33382921
- ↑ 46.0 46.1 Borda MG, Jaramillo-Jimenez A, Oesterhus R et al Benzodiazepines and antidepressants: effects on cognitive and functional decline in Alzheimer's disease and Lewy body dementia. Int J Geriatr Psychiatry. 2020 Dec 31. PMID: https://www.ncbi.nlm.nih.gov/pubmed/33382911
- ↑ 47.0 47.1 Miller ER 3rd, Pastor-Barriuso R, Dalal D, Riemersma RA, Appel LJ, Guallar E. Meta-analysis: high-dosage vitamin E supplementation may increase all-cause mortality. Ann Intern Med. 2005 Jan 4;142(1):37-46. PMID: https://www.ncbi.nlm.nih.gov/pubmed/15537682 Free article
- ↑ 48.0 48.1 48.2 Mintzer J,Lanctot KL, Scherer RW et al Effect of Methylphenidate on Apathy in Patients With Alzheimer Disease. The ADMET 2 Randomized Clinical Trial. JAMA Neurol. 2021;78(11):1324-1332. PMID: https://www.ncbi.nlm.nih.gov/pubmed/34570180 PMCID: PMC8477302 (available on 2022-09-27) https://jamanetwork.com/journals/jamaneurology/fullarticle/2784538
Fredericks C Methylphenidate for Apathy in Alzheimer Disease - Why Should We Care? JAMA Neurol. 2021;78(11):1311-1313. PMID: https://www.ncbi.nlm.nih.gov/pubmed/34570178 https://jamanetwork.com/journals/jamaneurology/fullarticle/2784541 - ↑ 49.0 49.1 Zheng X et al Effectiveness and safety of anti-tau drugs for Alzheimer's disease: Systematic review and meta-analysis. J Am Geriatr Soc. 2022 Nov;70(11):3281-3292. ePub 2022 Oct 22 PMID: https://www.ncbi.nlm.nih.gov/pubmed/36208415 Review. https://agsjournals.onlinelibrary.wiley.com/doi/full/10.1111/jgs.18025
- ↑ 50.0 50.1 Arvanitakis Z, Shah RC, Bennett DA. Diagnosis and Management of Dementia: Review JAMA. 2019 Oct 22;322(16):1589-1599 PMID: https://www.ncbi.nlm.nih.gov/pubmed/31638686 PMCID: PMC7462122 Free PMC article https://jamanetwork.com/journals/jama/fullarticle/2753376
- ↑ 51.0 51.1 NEJM Knowledge+ Psychiatry
- ↑ Sims JR, Zimmer JA, Evans CD et al Donanemab in Early Symptomatic Alzheimer Disease. The TRAILBLAZER-ALZ 2 Randomized Clinical Trial. JAMA. Published online July 17, 2023 PMID: https://www.ncbi.nlm.nih.gov/pubmed/37459141 PMCID: PMC10352931 Free PMC article https://jamanetwork.com/journals/jama/fullarticle/2807533
- ↑ 53.0 53.1 53.2 Honig LS, Vellas B, Woodward M et al Trial of Solanezumab for Mild Dementia Due to Alzheimer's Disease. N Engl J Med 2018; 378:321-330. Jan 25, 2018 <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/29365294 <Internet> http://www.nejm.org/doi/full/10.1056/NEJMoa1705971
- ↑ 54.0 54.1 Sperling RA et al. Trial of solanezumab in preclinical Alzheimer's disease. N Engl J Med 2023 Jul 17; PMID: https://www.ncbi.nlm.nih.gov/pubmed/37458272 https://www.nejm.org/doi/10.1056/NEJMoa2305032
- ↑ Molchan S, Fugh-Berman A. Are New Alzheimer Drugs Better Than Older Drugs? JAMA Intern Med. 2023;183(9):902-903. July 31 PMID: https://www.ncbi.nlm.nih.gov/pubmed/37523164 https://jamanetwork.com/journals/jamainternalmedicine/fullarticle/2807943
- ↑ 56.0 56.1 George J Alzheimer's Blood Test Predicts Who Might Benefit Most From Anti-Amyloid Drugs. Novel two-cutoff approach may reduce need for confirmatory PET scans. MedPage Today December 5, 2023 https://www.medpagetoday.com/neurology/alzheimersdisease/107691
Mattsson-Carlgren N, Collij LE, Stomrud E et al Plasma Biomarker Strategy for Selecting Patients With Alzheimer Disease for Antiamyloid Immunotherapies. JAMA Neurol. Published online December 4, 2023. PMID: https://www.ncbi.nlm.nih.gov/pubmed/38048096 https://jamanetwork.com/journals/jamaneurology/article-abstract/2812432 - ↑ 57.0 57.1 57.2 DeMercy HM, Brenner CA. The Relationship Between Antipsychotics, Cognitive Enhancers, and Major Adverse Cardiovascular/Cerebrovascular Events (MACCE) in Older Adults with Behavioral and Psychological Symptoms of Dementia. Drugs Aging. 2024 Aug 9. PMID: https://www.ncbi.nlm.nih.gov/pubmed/39120787 (open access) https://link.springer.com/article/10.1007/s40266-024-01134-9
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