There is no cure for dementia, and no treatments exist to halt or reverse the course of the disease. Treatments are aimed at improving cognitive and functional outcomes.
Our objective was to review the basis of pharmacological treatments for dementia and to summarize the benefits and risks of dementia treatments.
We performed a systematic literature search of MEDLINE through November 2014, for English-language trials and observational studies on treatment of dementia and mild cognitive impairment. Additional references were identified by searching bibliographies of relevant publications. Whenever possible, pooled data from meta-analyses or systematic reviews were obtained. Studies were included for review if they were randomized trials or observational studies on dementia or mild cognitive impairment that evaluated efficacy outcomes or adverse outcomes associated with treatment. Studies were excluded if they evaluated non-FDA approved treatments, or if they evaluated treatment in disorders other than dementia and mild cognitive impairment.
The literature search found 540 potentially relevant studies, of which 257 were included in the systematic review. In pooled trial data, cholinesterase inhibitors (ChEIs) produce small improvements in cognitive, functional, and global benefits in patients with mild to moderate Alzheimer’s and Lewy body dementia, but the clinical significance of these effects are unclear. There is no significant benefit seen for vascular dementia. The efficacy of ChEI treatment appears to wane over time, with minimal benefit seen after 1 year. There is no evidence for benefit for those with advanced disease or those aged over 85 years. Adverse effects are significantly increased with ChEIs, in a dose-dependent manner. A two- to fivefold increased risk for gastrointestinal, neurological, and cardiovascular side effects is related to cholinergic stimulation, the most serious being weight loss, debility, and syncope. Those aged over 85 years have double the risk of adverse events compared with younger patients. Memantine monotherapy may provide some cognitive benefit for patients with moderate to severe Alzheimer’s and vascular dementia, but the benefit is small and may wane over the course of several months. Memantine exhibits no significant benefit in mild dementia or Lewy body dementia or as an add-on treatment with ChEIs. Memantine has a relatively favorable side-effect profile, at least under controlled trial conditions.
ChEIs produce small, short-lived improvements in cognitive function in mild to moderate dementia, which may not translate into clinically meaningful effects. Marginal benefits are seen with severe disease, long-term treatment, and advanced age. Cholinergic side effects, including weight loss, debility, and syncope, are clinically significant and could be especially detrimental in the frail elderly population, in which the risks of treatment outweigh the benefits. Memantine monotherapy may have minimal benefits in moderate to severe dementia, balanced by minimal adverse effects.
This is a preview of subscription content, access via your institution.
Buy single article
Instant access to the full article PDF.
Tax calculation will be finalised during checkout.
Qaseem A, Snow V, Cross JT Jr, et al. Current pharmacologic treatment of dementia: a clinical practice guideline from the American College of Physicians and the American Academy of Family Physicians. Ann Intern Med. 2008;148(5):370–8.
Evans JG, Wilcock G, Birks J. Evidence-based pharmacotherapy of Alzheimer’s disease. Int J Neuropsychopharmacol. 2004;7(3):351–69.
American Psychiatric Association. Diagnostic and statistical manual of mental disorders: DSM-IV-TR. 4th ed. Washington, DC; 2000.
Prince M, Bryce R, Albanese E, Wimo A, Ribeiro W, Ferri CP. The global prevalence of dementia: a systematic review and metaanalysis. Alzheimers Dement. 2013;9(1):63–75.e2.
Bachman DL, Wolf PA, Linn RT, et al. Incidence of dementia and probable Alzheimer’s disease in a general population: the Framingham Study. Neurology. 1993;43(3 Pt 1):515–9.
Wimo A, Jonsson L, Bond J, Prince M, Winblad B, Alzheimer Disease I. The worldwide economic impact of dementia 2010. Alzheimers Dement. 2013;9(1):1–11.e3.
Russ TC, Morling JR. Cholinesterase inhibitors for mild cognitive impairment. Cochrane Database Syst Rev. 2012;9:CD009132.
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;25(8):997–1019.
Cummings JL. Challenges to demonstrating disease-modifying effects in Alzheimer’s disease clinical trials. Alzheimers Dement. 2006;2(4):263–71.
Drugs for cognitive loss and dementia. Treat Guidel Med Lett. 2013;11(134):95–100.
Santaguida PS, Raina P, Booker L, et al. Pharmacological treatment of dementia. Evid Rep Technol Assess (Summ). 2004;97:1–16.
Birks J. Cholinesterase inhibitors for Alzheimer’s disease. Cochrane Database Syst Rev. 2006;(1):CD005593.
Bullain SS, Corrada MM. Dementia in the oldest old. Continuum (Minneap Minn). 2013;19(2 Dementia):457–69.
Gill SS, Bronskill SE, Mamdani M, et al. Representation of patients with dementia in clinical trials of donepezil. Can J Clin Pharmacol. 2004;11(2):e274–85.
Schneider LS, Olin JT, Lyness SA, Chui HC. Eligibility of Alzheimer’s disease clinic patients for clinical trials. J Am Geriatr Soc. 1997;45(8):923–8.
Asahina Y, Sugano H, Sugiyama E, Uyama Y. Representation of older patients in clinical trials for drug approval in Japan. J Nutr Health Aging. 2014;18(5):520–3.
Killin LO, Russ TC, Starr JM, Abrahams S, Della Sala S. The effect of funding sources on donepezil randomised controlled trial outcome: a meta-analysis. BMJ Open. 2014;4(4):e004083.
Gilstad JR, Finucane TE. Results, rhetoric, and randomized trials: the case of donepezil. J Am Geriatr Soc. 2008;56(8):1556–62.
Rockwood K, MacKnight C. Assessing the clinical importance of statistically significant improvement in anti-dementia drug trials. Neuroepidemiology. 2001;20(2):51–6.
Lanctot KL, Herrmann N, Yau KK, et al. Efficacy and safety of cholinesterase inhibitors in Alzheimer’s disease: a meta-analysis. CMAJ. 2003;169(6):557–64.
Chui HC, Mack W, Jackson JE, et al. Clinical criteria for the diagnosis of vascular dementia: a multicenter study of comparability and interrater reliability. Arch Neurol. 2000;57(2):191–6.
Qiu C, Kivipelto M, von Strauss E. Epidemiology of Alzheimer’s disease: occurrence, determinants, and strategies toward intervention. Dialogues Clin Neurosci. 2009;11(2):111–28.
Hebert R, Brayne C. Epidemiology of vascular dementia. Neuroepidemiology. 1995;14(5):240–57.
Rocca WA, Kokmen E. Frequency and distribution of vascular dementia. Alzheimer Dis Assoc Disord. 1999;13(Suppl 3):S9–14.
Knopman DS, Parisi JE, Boeve BF, et al. Vascular dementia in a population-based autopsy study. Arch Neurol. 2003;60(4):569–75.
Skoog I, Nilsson L, Palmertz B, Andreasson LA, Svanborg A. A population-based study of dementia in 85-year-olds. N Engl J Med. 1993;328(3):153–8.
Lobo A, Launer LJ, Fratiglioni L, et al. Prevalence of dementia and major subtypes in Europe: a collaborative study of population-based cohorts. Neurologic Diseases in the Elderly Research Group. Neurology. 2000;54(11 Suppl 5):S4–9.
Fitzpatrick AL, Kuller LH, Ives DG, et al. Incidence and prevalence of dementia in the Cardiovascular Health Study. J Am Geriatr Soc. 2004;52(2):195–204.
Schneider JA, Arvanitakis Z, Bang W, Bennett DA. Mixed brain pathologies account for most dementia cases in community-dwelling older persons. Neurology. 2007;69(24):2197–204.
Wang HF, Yu JT, Tang SW, et al. Efficacy and safety of cholinesterase inhibitors and memantine in cognitive impairment in Parkinson’s disease, Parkinson’s disease dementia, and dementia with Lewy bodies: systematic review with meta-analysis and trial sequential analysis. J Neurol Neurosurg Psychiatry. 2015;86(2):135–43. doi:10.1136/jnnp-2014-307659.
Aarsland D, Zaccai J, Brayne C. A systematic review of prevalence studies of dementia in Parkinson’s disease. Mov Disord. 2005;20(10):1255–63.
Mayeux R, Stern Y, Rosenstein R, et al. An estimate of the prevalence of dementia in idiopathic Parkinson’s disease. Arch Neurol. 1988;45(3):260–2.
Shergil S, Mullan E, D’ath P, Katona C. What is the clinical prevalence of Lewy body dementia? Int J Geriatr Psychiatry. 1994;9:907–12.
Vann Jones SA, O’Brien JT. The prevalence and incidence of dementia with Lewy bodies: a systematic review of population and clinical studies. Psychol Med. 2014;44(4):673–83.
Chertkow H, Massoud F, Nasreddine Z, et al. Diagnosis and treatment of dementia: 3. Mild cognitive impairment and cognitive impairment without dementia. CMAJ. 2008;178(10):1273–85.
Sheehan B. Assessment scales in dementia. Ther Adv Neurol Disord. 2012;5(6):349–58.
Folstein MF, Folstein SE, McHugh PR. “Mini-mental state”. A practical method for grading the cognitive state of patients for the clinician. J Psychiatr Res. 1975;12(3):189–98.
Crutch S. The mini mental state examination (MMSE). Fact sheet. 2013. http://www.alzheimers.org.uk/site/scripts/download_info.php?downloadID=1116. Accessed 12 Apr 2015.
Tombaugh TN, Hubley AM, McDowell I, Kristjansson B. Mini-mental state examination (MMSE) and the modified MMSE (3MS): a psychometric comparison and normative data. Psychol Assess. 1996;8(1):48–59.
Kahle-Wrobleski K, Corrada MM, Li B, Kawas CH. Sensitivity and specificity of the mini-mental state examination for identifying dementia in the oldest-old: the 90+ study. J Am Geriatr Soc. 2007;55(2):284–9.
Galea M, Woodward M. Mini-mental state examination (MMSE). Aust J Physiother. 2005;51(3):198.
Lourenco RA, Veras RP. Mini-mental state examination: psychometric characteristics in elderly outpatients. Rev Saude Publica. 2006;40(4):712–9.
Rosen WG, Mohs RC, Davis KL. A new rating scale for Alzheimer’s disease. Am J Psychiatry. 1984;141(11):1356–64.
Doraiswamy PM, Kaiser L, Bieber F, Garman RL. The Alzheimer’s Disease Assessment Scale: evaluation of psychometric properties and patterns of cognitive decline in multicenter clinical trials of mild to moderate Alzheimer’s disease. Alzheimer Dis Assoc Disord. 2001;15(4):174–83.
Skinner J, Carvalho JO, Potter GG, et al. The Alzheimer’s disease assessment scale-cognitive-plus (ADAS-Cog-Plus): an expansion of the ADAS-Cog to improve responsiveness in MCI. Brain Imaging Behav. 2012;6(4):489–501.
Khan A, Yavorsky C, DiClemente G, et al. Reliability of the Alzheimer’s disease assessment scale (ADAS-Cog) in longitudinal studies. Curr Alzheimer Res. 2013;10(9):952–63.
Weyer G, Erzigkeit H, Kanowski S, Ihl R, Hadler D. Alzheimer’s Disease Assessment Scale: reliability and validity in a multicenter clinical trial. Int Psychogeriatr. 1997;9(2):123–38.
Mohs RC, Knopman D, Petersen RC, et al. Development of cognitive instruments for use in clinical trials of antidementia drugs: additions to the Alzheimer’s Disease Assessment Scale that broaden its scope. The Alzheimer’s Disease Cooperative Study. Alzheimer Dis Assoc Disord. 1997;11(Suppl 2):S13–21.
Panisset M, Roudier M, Saxton J, Boller F. Severe impairment battery. A neuropsychological test for severely demented patients. Arch Neurol. 1994;51(1):41–5.
Lawton MP, Brody EM. Assessment of older people: self-maintaining and instrumental activities of daily living. Gerontologist. 1969;9(3):179–86.
Robert P, Ferris S, Gauthier S, Ihl R, Winblad B, Tennigkeit F. Review of Alzheimer’s disease scales: is there a need for a new multi-domain scale for therapy evaluation in medical practice? Alzheimers Res Ther. 2010;2(4):24.
Cummings JL, Mega M, Gray K, Rosenberg-Thompson S, Carusi DA, Gornbein J. The neuropsychiatric inventory: comprehensive assessment of psychopathology in dementia. Neurology. 1994;44(12):2308–14.
Reisberg B. Global measures: utility in defining and measuring treatment response in dementia. Int Psychogeriatr. 2007;19(3):421–56.
Kim DH, Brown RT, Ding EL, Kiel DP, Berry SD. Dementia medications and risk of falls, syncope, and related adverse events: meta-analysis of randomized controlled trials. J Am Geriatr Soc. 2011;59(6):1019–31.
Hebert LE, Scherr PA, Bienias JL, Bennett DA, Evans DA. Alzheimer disease in the US population: prevalence estimates using the 2000 census. Arch Neurol. 2003;60(8):1119–22.
National Institute for Health and Care Excellence. Donepezil, galantamine, rivastigmine and memantine for the treatment of Alzheimer’s disease. NICE technology appraisal guidance 217. NICE; London; 2011.
Anthony JC, LeResche L, Niaz U, von Korff MR, Folstein MF. Limits of the ‘Mini-Mental State’ as a screening test for dementia and delirium among hospital patients. Psychol Med. 1982;12(2):397–408.
O’Bryant SE, Humphreys JD, Smith GE, et al. Detecting dementia with the mini-mental state examination in highly educated individuals. Arch Neurol. 2008;65(7):963–7.
Schmitt FA, Wichems CH. A systematic review of assessment and treatment of moderate to severe Alzheimer’s disease. Prim Care Companion J Clin Psychiatry. 2006;8(3):158–9.
Benson AD, Slavin MJ, Tran TT, Petrella JR, Doraiswamy PM. Screening for early Alzheimer’s disease: is there still a role for the mini-mental state examination? Prim Care Companion J Clin Psychiatry. 2005;7(2):62–9.
Petersen RC. Mild cognitive impairment as a diagnostic entity. J Intern Med. 2004;256(3):183–94.
Pozueta A, Rodriguez-Rodriguez E, Vazquez-Higuera JL, et al. Detection of early Alzheimer’s disease in MCI patients by the combination of MMSE and an episodic memory test. BMC Neurol. 2011;11:78.
Voisin T, Vellas B. Diagnosis and treatment of patients with severe Alzheimer’s disease. Drugs Aging. 2009;26(2):135–44.
Reisberg B, Jamil IA, Khan S, et al. Staging dementia. In: Abou-Saleh MT, Katona CLE, Kumar A, editors. Principles and practice of geriatric psychiatry. 3rd ed. Chichester, Hoboken: Wiley; 2011. p. 162–169.
Frolich L. The cholinergic pathology in Alzheimer’s disease: discrepancies between clinical experience and pathophysiological findings. J Neural Transm. 2002;109(7–8):1003–13.
Francis PT, Perry EK. Cholinergic and other neurotransmitter mechanisms in Parkinson’s disease, Parkinson’s disease dementia, and dementia with Lewy bodies. Mov Disord. 2007;22(Suppl 17):S351–7.
Grantham C, Geerts H. The rationale behind cholinergic drug treatment for dementia related to cerebrovascular disease. J Neurol Sci. 2002;203–204:131–6.
Molinuevo JL, Llado A, Rami L. Memantine: targeting glutamate excitotoxicity in Alzheimer’s disease and other dementias. Am J Alzheimers Dis Other Demen. 2005;20(2):77–85.
Ahmed I, Bose SK, Pavese N, et al. Glutamate NMDA receptor dysregulation in Parkinson’s disease with dyskinesias. Brain. 2011;134(Pt 4):979–86.
Sabbagh MN, Hake AM, Ahmed S, Farlow MR. The use of memantine in dementia with Lewy bodies. J Alzheimers Dis. 2005;7(4):285–9.
Mobius HJ. Pharmacologic rationale for memantine in chronic cerebral hypoperfusion, especially vascular dementia. Alzheimer Dis Assoc Disord. 1999;13(Suppl 3):S172–8.
Blennow K, de Leon MJ, Zetterberg H. Alzheimer’s disease. Lancet. 2006;368(9533):387–403.
Nyakas C, Granic I, Halmy LG, Banerjee P, Luiten PG. The basal forebrain cholinergic system in aging and dementia. Rescuing cholinergic neurons from neurotoxic amyloid-beta42 with memantine. Behav Brain Res. 2011;221(2):594–603.
Danysz W, Parsons CG. Alzheimer’s disease, beta-amyloid, glutamate, NMDA receptors and memantine–searching for the connections. Br J Pharmacol. 2012;167(2):324–52.
Iemolo F, Duro G, Rizzo C, Castiglia L, Hachinski V, Caruso C. Pathophysiology of vascular dementia. Immun Ageing. 2009;6:13.
Ni JW, Matsumoto K, Li HB, Murakami Y, Watanabe H. Neuronal damage and decrease of central acetylcholine level following permanent occlusion of bilateral common carotid arteries in rat. Brain Res. 1995;673(2):290–6.
Tsuboi Y, Uchikado H, Dickson DW. Neuropathology of Parkinson’s disease dementia and dementia with Lewy bodies with reference to striatal pathology. Parkinsonism Relat Disord. 2007;13(Suppl 3):S221–4.
Bohnen NI, Albin RL. The cholinergic system and Parkinson disease. Behav Brain Res. 2011;221(2):564–73.
Grothe MJ, Schuster C, Bauer F, Heinsen H, Prudlo J, Teipel SJ. Atrophy of the cholinergic basal forebrain in dementia with Lewy bodies and Alzheimer’s disease dementia. J Neurol. 2014;261(10):1939–48.
Dalfo E, Albasanz JL, Martin M, Ferrer I. Abnormal metabotropic glutamate receptor expression and signaling in the cerebral cortex in diffuse Lewy body disease is associated with irregular alpha-synuclein/phospholipase C (PLCbeta1) interactions. Brain Pathol. 2004;14(4):388–98.
Starr MS. Glutamate/dopamine D1/D2 balance in the basal ganglia and its relevance to Parkinson’s disease. Synapse. 1995;19(4):264–93.
Petersen RC, Thomas RG, Grundman M, et al. Vitamin E and donepezil for the treatment of mild cognitive impairment. N Engl J Med. 2005;352(23):2379–88.
Lu PH, Edland SD, Teng E, et al. Donepezil delays progression to AD in MCI subjects with depressive symptoms. Neurology. 2009;72(24):2115–21.
Winblad B, Gauthier S, Scinto L, et al. Safety and efficacy of galantamine in subjects with mild cognitive impairment. Neurology. 2008;70(22):2024–35.
Tricco AC, Soobiah C, Berliner S, et al. Efficacy and safety of cognitive enhancers for patients with mild cognitive impairment: a systematic review and meta-analysis. CMAJ. 2013;185(16):1393–401.
Cooper C, Li R, Lyketsos C, Livingston G. Treatment for mild cognitive impairment: systematic review. Br J Psychiatry. 2013;203(3):255–64.
Doody RS, Ferris S, Salloway S, et al. Safety and tolerability of donepezil in mild cognitive impairment: open-label extension study. Am J Alzheimers Dis Other Demen. 2010;25(2):155–9.
Feldman HH, Ferris S, Winblad B, et al. Effect of rivastigmine on delay to diagnosis of Alzheimer’s disease from mild cognitive impairment: the InDDEx study. Lancet Neurol. 2007;6(6):501–12.
Russ TC. Cholinesterase inhibitors should not be prescribed for mild cognitive impairment. Evid Based Med. 2014;19(3):101.
Gauthier S, Touchon J. Mild cognitive impairment is not a clinical entity and should not be treated. Arch Neurol. 2005;62(7):1164–6 (discussion 1167).
Trinh NH, Hoblyn J, Mohanty S, Yaffe K. Efficacy of cholinesterase inhibitors in the treatment of neuropsychiatric symptoms and functional impairment in Alzheimer disease: a meta-analysis. JAMA. 2003;289(2):210–6.
Takeda A, Loveman E, Clegg A, et al. A systematic review of the clinical effectiveness of donepezil, rivastigmine and galantamine on cognition, quality of life and adverse events in Alzheimer’s disease. Int J Geriatr Psychiatry. 2006;21(1):17–28.
Raina P, Santaguida P, Ismaila A, et al. Effectiveness of cholinesterase inhibitors and memantine for treating dementia: evidence review for a clinical practice guideline. Ann Intern Med. 2008;148(5):379–97.
Kavirajan H, Schneider LS. Efficacy and adverse effects of cholinesterase inhibitors and memantine in vascular dementia: a meta-analysis of randomised controlled trials. Lancet Neurol. 2007;6(9):782–92.
McShane R, Areosa Sastre A, Minakaran N. Memantine for dementia. Cochrane Database Syst Rev. 2006;(2):CD003154.
Hansen RA, Gartlehner G, Webb AP, Morgan LC, Moore CG, Jonas DE. Efficacy and safety of donepezil, galantamine, and rivastigmine for the treatment of Alzheimer’s disease: a systematic review and meta-analysis. Clin Interv Aging. 2008;3(2):211–25.
Ellis JM. Cholinesterase inhibitors in the treatment of dementia. J Am Osteopath Assoc. 2005;105(3):145–58.
Hogan DB, Goldlist B, Naglie G, Patterson C. Comparison studies of cholinesterase inhibitors for Alzheimer’s disease. Lancet Neurol. 2004;3(10):622–6.
Nordberg A, Svensson AL. Cholinesterase inhibitors in the treatment of Alzheimer’s disease: a comparison of tolerability and pharmacology. Drug Saf. 1998;19(6):465–80.
Courtney C, Farrell D, Gray R, et al. Long-term donepezil treatment in 565 patients with Alzheimer’s disease (AD2000): randomised double-blind trial. Lancet. 2004;363(9427):2105–15.
Schneider LS, Sano M. Current Alzheimer’s disease clinical trials: methods and placebo outcomes. Alzheimers Dement. 2009;5(5):388–97.
Lee PE, Fischer HD, Rochon PA, et al. Published randomized controlled trials of drug therapy for dementia often lack complete data on harm. J Clin Epidemiol. 2008;61(11):1152–60.
Rolinski M, Fox C, Maidment I, McShane R. Cholinesterase inhibitors for dementia with Lewy bodies, Parkinson’s disease dementia and cognitive impairment in Parkinson’s disease. Cochrane Database Syst Rev. 2012;(3):CD006504.
Schneider LS. Assessing outcomes in Alzheimer disease. Alzheimer Dis Assoc Disord. 2001;15(Suppl 1):S8–18.
Winblad B, Kilander L, Eriksson S, et al. Donepezil in patients with severe Alzheimer’s disease: double-blind, parallel-group, placebo-controlled study. Lancet. 2006;367(9516):1057–65.
Black SE, Doody R, Li H, et al. Donepezil preserves cognition and global function in patients with severe Alzheimer disease. Neurology. 2007;69(5):459–69.
Homma A, Imai Y, Tago H, et al. Donepezil treatment of patients with severe Alzheimer’s disease in a Japanese population: results from a 24-week, double-blind, placebo-controlled, randomized trial. Dement Geriatr Cogn Disord. 2008;25(5):399–407.
Burns A, Bernabei R, Bullock R, et al. Safety and efficacy of galantamine (Reminyl) in severe Alzheimer’s disease (the SERAD study): a randomised, placebo-controlled, double-blind trial. Lancet Neurol. 2009;8(1):39–47.
Feldman H, Gauthier S, Hecker J, et al. Efficacy and safety of donepezil in patients with more severe Alzheimer’s disease: a subgroup analysis from a randomized, placebo-controlled trial. Int J Geriatr Psychiatry. 2005;20(6):559–69.
Ballard C, Margallo-Lana M, Juszczak E, et al. Quetiapine and rivastigmine and cognitive decline in Alzheimer’s disease: randomised double blind placebo controlled trial. BMJ. 2005;330(7496):874.
Cummings J, Jones R, Wilkinson D, et al. Effect of donepezil on cognition in severe Alzheimer’s disease: a pooled data analysis. J Alzheimers Dis. 2010;21(3):843–51.
Froelich L, Andreasen N, Tsolaki M, et al. Long-term treatment of patients with Alzheimer’s disease in primary and secondary care: results from an international survey. Curr Med Res Opin. 2009;25(12):3059–68.
Winblad B, Engedal K, Soininen H, et al. A 1-year, randomized, placebo-controlled study of donepezil in patients with mild to moderate AD. Neurology. 2001;57(3):489–95.
Mohs RC, Doody RS, Morris JC, et al. A 1-year, placebo-controlled preservation of function survival study of donepezil in AD patients. Neurology. 2001;57(3):481–8.
Hager K, Baseman AS, Nye JS, et al. Effects of galantamine in a 2-year, randomized, placebo-controlled study in Alzheimer’s disease. Neuropsychiatr Dis Treat. 2014;10:391–401.
Birks J, McGuinness B, Craig D. Rivastigmine for vascular cognitive impairment. Cochrane Database Syst Rev. 2013;5:CD004744.
Pagano G, Rengo G, Pasqualetti G, et al. Cholinesterase inhibitors for Parkinson’s disease: a systematic review and meta-analysis. J Neurol Neurosurg Psychiatry. 2014.
Tariot PN, Cummings JL, Katz IR, et al. A randomized, double-blind, placebo-controlled study of the efficacy and safety of donepezil in patients with Alzheimer’s disease in the nursing home setting. J Am Geriatr Soc. 2001;49(12):1590–9.
Thompson S, Lanctot KL, Herrmann N. The benefits and risks associated with cholinesterase inhibitor therapy in Alzheimer’s disease. Expert Opin Drug Saf. 2004;3(5):425–40.
Inglis F. The tolerability and safety of cholinesterase inhibitors in the treatment of dementia. Int J Clin Pract Suppl. 2002;127:45–63.
Wilkinson DG, Francis PT, Schwam E, Payne-Parrish J. Cholinesterase inhibitors used in the treatment of Alzheimer’s disease: the relationship between pharmacological effects and clinical efficacy. Drugs Aging. 2004;21(7):453–78.
Gauthier S. Cholinergic adverse effects of cholinesterase inhibitors in Alzheimer’s disease: epidemiology and management. Drugs Aging. 2001;18(11):853–62.
Corey-Bloom J, Anand R, Veach J. A randomized trial evaluating the efficacy and safety of ENA 713 (rivastigmine tartrate), a new acetylcholinesterase inhibitor, in patients with mild-to-moderately severe Alzheimer’s disease. Int J Geriatr Psychopharmacol. 1998;1:55–65.
Rosler M, Anand R, Cicin-Sain A, et al. Efficacy and safety of rivastigmine in patients with Alzheimer’s disease: international randomised controlled trial. BMJ. 1999;318(7184):633–8.
Tariot PN, Solomon PR, Morris JC, Kershaw P, Lilienfeld S, Ding C. A, 5-month, randomized, placebo-controlled trial of galantamine in AD. The Galantamine USA-10 Study Group. Neurology. 2000;54(12):2269–76.
White H, Pieper C, Schmader K. The association of weight change in Alzheimer’s disease with severity of disease and mortality: a longitudinal analysis. J Am Geriatr Soc. 1998;46(10):1223–7.
Keller HH, Ostbye T, Goy R. Nutritional risk predicts quality of life in elderly community-living Canadians. J Gerontol A Biol Sci Med Sci. 2004;59(1):68–74.
Crogan NL, Pasvogel A. The influence of protein-calorie malnutrition on quality of life in nursing homes. J Gerontol A Biol Sci Med Sci. 2003;58(2):159–64.
Payette H, Coulombe C, Boutier V, Gray-Donald K. Nutrition risk factors for institutionalization in a free-living functionally dependent elderly population. J Clin Epidemiol. 2000;53(6):579–87.
Sullivan DH, Morley JE, Johnson LE, et al. The GAIN (Geriatric Anorexia Nutrition) registry: the impact of appetite and weight on mortality in a long-term care population. J Nutr Health Aging. 2002;6(4):275–81.
Stewart JT, Gorelik AR. Involuntary weight loss associated with cholinesterase inhibitors in dementia. J Am Geriatr Soc. 2006;54(6):1013–4.
Gallini A, Sommet A, Salandini AM, Veyssiere P, Montastruc JL, Montastruc JL. Weight-loss associated with anti-dementia drugs in a patient with Parkinson’s disease. Mov Disord. 2007;22(13):1980–1.
Dunn NR, Pearce GL, Shakir SA. Adverse effects associated with the use of donepezil in general practice in England. J Psychopharmacol. 2000;14(4):406–8.
Hernandez RK, Farwell W, Cantor MD, Lawler EV. Cholinesterase inhibitors and incidence of bradycardia in patients with dementia in the veterans affairs New England healthcare system. J Am Geriatr Soc. 2009;57(11):1997–2003.
Park-Wyllie LY, Mamdani MM, Li P, Gill SS, Laupacis A, Juurlink DN. Cholinesterase inhibitors and hospitalization for bradycardia: a population-based study. PLoS Med. 2009;6(9):e1000157.
Gill SS, Anderson GM, Fischer HD, et al. Syncope and its consequences in patients with dementia receiving cholinesterase inhibitors: a population-based cohort study. Arch Intern Med. 2009;169(9):867–73.
Pariente A, Sanctussy DJ, Miremont-Salame G, et al. Factors associated with serious adverse reactions to cholinesterase inhibitors: a study of spontaneous reporting. CNS Drugs. 2010;24(1):55–63.
Brignole M. Distinguishing syncopal from non-syncopal causes of fall in older people. Age Ageing. 2006;35(Suppl 2):ii46–50.
McIntosh S, Da Costa D, Kenny RA. Outcome of an integrated approach to the investigation of dizziness, falls and syncope in elderly patients referred to a ‘syncope’ clinic. Age Ageing. 1993;22(1):53–8.
Shaw FE, Kenny RA. The overlap between syncope and falls in the elderly. Postgrad Med J. 1997;73(864):635–9.
French DD, Campbell R, Spehar A, Cunningham F, Bulat T, Luther SL. Drugs and falls in community-dwelling older people: a national veterans study. Clin Ther. 2006;28(4):619–30.
Tamimi I, Ojea T, Sanchez-Siles JM, et al. Acetylcholinesterase inhibitors and the risk of hip fracture in Alzheimer’s disease patients: a case-control study. J Bone Miner Res. 2012;27(7):1518–27.
Chung KA, Lobb BM, Nutt JG, Horak FB. Effects of a central cholinesterase inhibitor on reducing falls in Parkinson disease. Neurology. 2010;75(14):1263–9.
Kallin K, Gustafson Y, Sandman PO, Karlsson S. Drugs and falls in older people in geriatric care settings. Aging Clin Exp Res. 2004;16(4):270–6.
Tavassoli N, Sommet A, Lapeyre-Mestre M, Bagheri H, Montrastruc JL. Drug interactions with cholinesterase inhibitors: an analysis of the French pharmacovigilance database and a comparison of two national drug formularies (Vidal, British National Formulary). Drug Saf. 2007;30(11):1063–71.
Bentue-Ferrer D, Tribut O, Polard E, Allain H. Clinically significant drug interactions with cholinesterase inhibitors: a guide for neurologists. CNS Drugs. 2003;17(13):947–63.
Seritan AL. Prevent drug-drug interactions with cholinesterase inhibitors: avoid adverse events when prescribing medications for patients with dementia. Curr Psychiatry. 2008;7(2):57–67.
Carnahan RM, Lund BC, Perry PJ, Chrischilles EA. The concurrent use of anticholinergics and cholinesterase inhibitors: rare event or common practice? J Am Geriatr Soc. 2004;52(12):2082–7.
Roe CM, Anderson MJ, Spivack B. Use of anticholinergic medications by older adults with dementia. J Am Geriatr Soc. 2002;50(5):836–42.
Paulison B, Leos CL. Potential cardiotoxic reaction involving rivastigmine and beta-blockers: a case report and review of the literature. Cardiovasc Toxicol. 2010;10(4):306–10.
Agency EM. Ebixa. European Public Assessment Report.2004. www.emea.eu.int/humandocs/Humans/EPAR/ebixa/ebixa.htm. Accessed 12 Apr 2015.
FDA approves memantine drug for treating AD. Am J Alzheimers Dis Other Demen. 2003;18(6):329–30.
Schneider LS, Dagerman KS, Higgins JP, McShane R. Lack of evidence for the efficacy of memantine in mild Alzheimer disease. Arch Neurol. 2011;68(8):991–8.
Wilcock G, Mobius HJ, Stoffler A, Group MMM. A double-blind, placebo-controlled multicentre study of memantine in mild to moderate vascular dementia (MMM500). Int Clin Psychopharmacol. 2002;17(6):297–305.
Orgogozo JM, Rigaud AS, Stoffler A, Mobius HJ, Forette F. Efficacy and safety of memantine in patients with mild to moderate vascular dementia: a randomized, placebo-controlled trial (MMM 300). Stroke. 2002;33(7):1834–9.
Emre M, Tsolaki M, Bonuccelli U, et al. Memantine for patients with Parkinson’s disease dementia or dementia with Lewy bodies: a randomised, double-blind, placebo-controlled trial. Lancet Neurol. 2010;9(10):969–77.
Leroi I, Overshott R, Byrne EJ, Daniel E, Burns A. Randomized controlled trial of memantine in dementia associated with Parkinson’s disease. Mov Disord. 2009;24(8):1217–21.
Aarsland D, Ballard C, Walker Z, et al. Memantine in patients with Parkinson’s disease dementia or dementia with Lewy bodies: a double-blind, placebo-controlled, multicentre trial. Lancet Neurol. 2009;8(7):613–8.
Jones RW. A review comparing the safety and tolerability of memantine with the acetylcholinesterase inhibitors. Int J Geriatr Psychiatry. 2010;25(6):547–53.
Mimica N, Presecki P. Side effects of approved antidementives. Psychiatr Danub. 2009;21(1):108–13.
Stahl SM. Essential psychopharmacology: the prescriber’s guide. Cambridge: Cambridge University Press; 2005.
Lindsay J. Patterns of caring for people with dementia in Canada. The Canadian study of health and aging. Can J Aging. 1994;13:470–87.
Molino I, Colucci L, Fasanaro AM, Traini E, Amenta F. Efficacy of memantine, donepezil, or their association in moderate-severe Alzheimer’s disease: a review of clinical trials. ScientificWorldJournal. 2013;2013:925702.
Shega JW, Ellner L, Lau DT, Maxwell TL. Cholinesterase inhibitor and N-methyl-d-aspartic acid receptor antagonist use in older adults with end-stage dementia: a survey of hospice medical directors. J Palliat Med. 2009;12(9):779–83.
Compliance with ethical standards
No outside funding was used to complete this research. The authors, Jacob Buckley and Shelley Salpeter, have no conflicts of interest that are directly relevant to the content of this study.
About this article
Cite this article
Buckley, J.S., Salpeter, S.R. A Risk-Benefit Assessment of Dementia Medications: Systematic Review of the Evidence. Drugs Aging 32, 453–467 (2015). https://doi.org/10.1007/s40266-015-0266-9
- Mild Cognitive Impairment
- Vascular Dementia
- Cholinesterase Inhibitor