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CC BY 4.0 · Arq Neuropsiquiatr 2023; 81(12): 1152-1162
DOI: 10.1055/s-0043-1777774
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Behavioral or neuropsychiatric symptoms of Alzheimer's disease: from psychopathology to pharmacological management

Sintomas comportamentais ou neuropsiquiátricos da doença de Alzheimer: psicopatologia e abordagem terapêutica
Antonio Lucio Teixeira 
1   University of Texas University of Texas Health Science Center, McGovern Medical School, Department of Psychiatry and Behavioral Sciences, Neuropsychiatry Program, Houston, Texas, United States.
2   Faculdade Santa Casa Belo Horizonte, Belo Horizonte MG, Brazil.
,
Natalia Pessoa Rocha 
3   University of Texas Health Science Center, McGovern Medical School, Department of Neurology, Houston, Texas, United States.
,
Jennifer Gatchel 
4   Massachusetts General Hospital, Department of Psychiatry, Boston, Massachusetts, United States.
5   Baylor College of Medicine, Department of Psychiatry, Houston, Texas, United States.
6   Michael E. Debakey VA Medical Center, Houston, Texas, United States.
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Abstract

Neuropsychiatric or behavioral symptoms of dementia encompass a series of disorders, such as anxiety, depression, apathy, psychosis, and agitation, all commonly present in individuals living with dementia. While they are not required for the diagnosis of Alzheimer's disease (AD), they are ubiquitously present in all stages of the disease, contributing to negative clinical outcomes, including cognitive decline, functional disability, and caregiver burden. Neuropsychiatric symptoms have been conceptualized not only as risk factors but as clinical markers of decline along the AD spectrum. The concept of “mild behavioral impairment”, the behavioral correlate of mild cognitive impairment, has been proposed within this framework. The first steps in the management of behavioral symptoms in AD involve defining the target and investigating potential causes and/or aggravating factors. Once these factors are addressed, non-pharmacological approaches are preferred as first-line interventions. Following the optimization of anticholinesterase treatments, specific pharmacological approaches (e.g., antidepressants, antipsychotics) can be considered weighing potential side effects.

Resumo

Sintomas neuropsiquiátricos ou comportamentais de demência envolvem uma série de condições, como ansiedade, depressão, apatia, psicose e agitação, frequentemente observadas em indivíduos com demência. Embora esses sintomas não sejam necessários para o diagnóstico da doença de Alzheimer, estão presentes em todas as fases ou estágios da doença, contribuindo negativamente para o declínio cognitivo, comprometimento funcional e sobrecarga do cuidador. Os sintomas neuropsiquiátricos têm sido conceituados não apenas como fatores de risco, mas também como marcadores clínicos de progressão da doença de Alzheimer. O construto “comprometimento comportamental leve”, correlato comportamental do comprometimento cognitive leve, tem sido proposto nesse contexto. Os primeiros passos na abordagem dos sintomas comportamentais da doença de Alzheimer envolvem definir os alvos-terapêuticos e investigar potenciais causas ou fatores agravantes. Após intervir nesses fatores, abordagens não farmacológicas constituem a primeira linha de intervenção. Depois da otimização do tratamento anticolinesterásico, terapias farmacológicas específicas (por exemplo, antidepressivos, antipsicóticos) podem ser consideradas, levando-se em conta potencias efeitos colaterais.

Keywords

Alzheimer Disease - Neuropsychiatry - Apathy - Depression - Anxiety - Psychomotor Agitation - Psychotic Disorders - Sleep

Palavras-chave

Doença de Alzheimer - Neuropsiquiatria - Apatia - Depressão - Ansiedade - Agitação Psicomotora - Transtornos Psicóticos - Sono

Authors' Contributions

ALT conceptualized the manuscript; ALT and NPR drafted the first version; JG reviewed it critically and contributed to the final version. All authors have read and approved the final version of the manuscript.




Publication History

Received: 15 September 2023

Accepted: 08 November 2023

Article published online:
29 December 2023

© 2023. The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution 4.0 International License, permitting copying and reproduction so long as the original work is given appropriate credit (https://creativecommons.org/licenses/by/4.0/)

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  • References

  • 1 Scheltens P, De Strooper B, Kivipelto M. et al. Alzheimer's disease. Lancet 2021; 397 (10284): 1577-1590
    CrossrefPubMedSearch in Google Scholar
  • 2 Porsteinsson AP, Isaacson RS, Knox S, Sabbagh MN, Rubino I. Diagnosis of Early Alzheimer's Disease: Clinical Practice in 2021. J Prev Alzheimers Dis 2021; 8 (03) 371-386
    PubMedSearch in Google Scholar
  • 3 Steinberg M, Shao H, Zandi P. et al; Cache County Investigators. Point and 5-year period prevalence of neuropsychiatric symptoms in dementia: the Cache County Study. Int J Geriatr Psychiatry 2008; 23 (02) 170-177
    CrossrefPubMedSearch in Google Scholar
  • 4 Zhao QF, Tan L, Wang HF. et al. The prevalence of neuropsychiatric symptoms in Alzheimer's disease: Systematic review and meta-analysis. J Affect Disord 2016; 190: 264-271
    CrossrefPubMedSearch in Google Scholar
  • 5 Cummings J. The Neuropsychiatric Inventory: Development and Applications. J Geriatr Psychiatry Neurol 2020; 33 (02) 73-84
    CrossrefPubMedSearch in Google Scholar
  • 6 Cummings J. The Role of Neuropsychiatric Symptoms in Research Diagnostic Criteria for Neurodegenerative Diseases. Am J Geriatr Psychiatry 2021; 29 (04) 375-383
    CrossrefPubMedSearch in Google Scholar
  • 7 Cerejeira J, Lagarto L, Mukaetova-Ladinska EB. Behavioral and psychological symptoms of dementia. Front Neurol 2012; 3: 73
    CrossrefPubMedSearch in Google Scholar
  • 8 Benjamin S, MacGillivray L, Schildkrout B, Cohen-Oram A, Lauterbach MD, Levin LL. Six Landmark Case Reports Essential for Neuropsychiatric Literacy. J Neuropsychiatry Clin Neurosci 2018; 30 (04) 279-290
    CrossrefPubMedSearch in Google Scholar
  • 9 Feast A, Moniz-Cook E, Stoner C, Charlesworth G, Orrell M. A systematic review of the relationship between behavioral and psychological symptoms (BPSD) and caregiver well-being. Int Psychogeriatr 2016; 28 (11) 1761-1774
    CrossrefPubMedSearch in Google Scholar
  • 10 Sabates J, Chiu WH, Loi S. et al. The Associations Between Neuropsychiatric Symptoms and Cognition in People with Dementia: A Systematic Review and Meta-Analysis. Neuropsychol Rev 2023
    PubMedSearch in Google Scholar
  • 11 McKhann GM, Knopman DS, Chertkow H. et al. The diagnosis of dementia due to Alzheimer's disease: recommendations from the National Institute on Aging-Alzheimer's Association workgroups on diagnostic guidelines for Alzheimer's disease. Alzheimers Dement 2011; 7 (03) 263-269
    CrossrefPubMedSearch in Google Scholar
  • 12 Geda YE, Roberts RO, Mielke MM. et al. Baseline neuropsychiatric symptoms and the risk of incident mild cognitive impairment: a population-based study. Am J Psychiatry 2014; 171 (05) 572-581
    CrossrefPubMedSearch in Google Scholar
  • 13 Ismail Z, Smith EE, Geda Y. et al; ISTAART Neuropsychiatric Symptoms Professional Interest Area. Neuropsychiatric symptoms as early manifestations of emergent dementia: Provisional diagnostic criteria for mild behavioral impairment. Alzheimers Dement 2016; 12 (02) 195-202
    CrossrefPubMedSearch in Google Scholar
  • 14 Taragano FE, Allegri RF, Lyketsos C. Mild behavioral impairment: A prodromal stage of dementia. Dement Neuropsychol 2008; 2 (04) 256-260
    CrossrefPubMedSearch in Google Scholar
  • 15 Taragano FE, Allegri RF, Krupitzki H. et al. Mild behavioral impairment and risk of dementia: a prospective cohort study of 358 patients. J Clin Psychiatry 2009; 70 (04) 584-592
    CrossrefPubMedSearch in Google Scholar
  • 16 Taragano FE, Allegri RF, Heisecke SL. et al. Risk of Conversion to Dementia in a Mild Behavioral Impairment Group Compared to a Psychiatric Group and to a Mild Cognitive Impairment Group. J Alzheimers Dis 2018; 62 (01) 227-238
    CrossrefPubMedSearch in Google Scholar
  • 17 Ismail Z, Agüera-Ortiz L, Brodaty H. et al; NPS Professional Interest Area of the International Society of to Advance Alzheimer's Research and Treatment (NPS-PIA of ISTAART). The Mild Behavioral Impairment Checklist (MBI-C): A Rating Scale for Neuropsychiatric Symptoms in Pre-Dementia Populations. J Alzheimers Dis 2017; 56 (03) 929-938
    CrossrefPubMedSearch in Google Scholar
  • 18 Sperling RA, Aisen PS, Beckett LA. et al. Toward defining the preclinical stages of Alzheimer's disease: recommendations from the National Institute on Aging-Alzheimer's Association workgroups on diagnostic guidelines for Alzheimer's disease. Alzheimers Dement 2011; 7 (03) 280-292
    CrossrefPubMedSearch in Google Scholar
  • 19 Reisberg B, Monteiro I, Torossian C. et al. The BEHAVE-AD assessment system: a perspective, a commentary on new findings, and a historical review. Dement Geriatr Cogn Disord 2014; 38 (1-2): 89-146
    CrossrefPubMedSearch in Google Scholar
  • 20 Alexopoulos GS, Abrams RC, Young RC, Shamoian CA. Cornell Scale for Depression in Dementia. Biol Psychiatry 1988; 23 (03) 271-284
    CrossrefPubMedSearch in Google Scholar
  • 21 Mathys M. Pharmacologic management of behavioral and psychological symptoms of major neurocognitive disorder. Ment Health Clin 2018; 8 (06) 284-293
    CrossrefPubMedSearch in Google Scholar
  • 22 Kales HC, Gitlin LN, Lyketsos CG. Assessment and management of behavioral and psychological symptoms of dementia. BMJ 2015; 350: h369
    CrossrefPubMedSearch in Google Scholar
  • 23 Canevelli M, Adali N, Voisin T. et al. Behavioral and psychological subsyndromes in Alzheimer's disease using the Neuropsychiatric Inventory. Int J Geriatr Psychiatry 2013; 28 (08) 795-803
    CrossrefPubMedSearch in Google Scholar
  • 24 Kales HC, Lyketsos CG, Miller EM, Ballard C. Management of behavioral and psychological symptoms in people with Alzheimer's disease: an international Delphi consensus. Int Psychogeriatr 2019; 31 (01) 83-90
    CrossrefPubMedSearch in Google Scholar
  • 25 Abraha I, Rimland JM, Trotta FM. et al. Systematic review of systematic reviews of non-pharmacological interventions to treat behavioural disturbances in older patients with dementia. The SENATOR-OnTop series. BMJ Open 2017; 7 (03) e012759
    CrossrefPubMedSearch in Google Scholar
  • 26 Reus VI, Fochtmann LJ, Eyler AE. et al. The American Psychiatric Association Practice Guideline on the Use of Antipsychotics to Treat Agitation or Psychosis in Patients With Dementia. Am J Psychiatry 2016; 173 (05) 543-546
    CrossrefPubMedSearch in Google Scholar
  • 27 Borsje P, Wetzels RB, Lucassen PL, Pot AM, Koopmans RT. The course of neuropsychiatric symptoms in community-dwelling patients with dementia: a systematic review. Int Psychogeriatr 2015; 27 (03) 385-405
    CrossrefPubMedSearch in Google Scholar
  • 28 van der Linde RM, Dening T, Stephan BC, Prina AM, Evans E, Brayne C. Longitudinal course of behavioural and psychological symptoms of dementia: systematic review. Br J Psychiatry 2016; 209 (05) 366-377
    CrossrefPubMedSearch in Google Scholar
  • 29 Tampi RR, Jeste DV. Dementia Is More Than Memory Loss: Neuropsychiatric Symptoms of Dementia and Their Nonpharmacological and Pharmacological Management. Am J Psychiatry 2022; 179 (08) 528-543
    CrossrefPubMedSearch in Google Scholar
  • 30 Caramelli P, Marinho V, Laks J. et al. Treatment of dementia: recommendations of the Scientific Department of Cognitive Neurology and Aging of the Brazilian Academy of Neurology. Dement Neuropsychol 2022; 16 (03, Suppl 1): 88-100
    CrossrefPubMedSearch in Google Scholar
  • 31 Tan ECK, Johnell K, Bell JS. et al. Do Acetylcholinesterase Inhibitors Prevent or Delay Psychotropic Prescribing in People With Dementia? Analyses of the Swedish Dementia Registry. Am J Geriatr Psychiatry 2020; 28 (01) 108-117
    CrossrefPubMedSearch in Google Scholar
  • 32 Xu H, Garcia-Ptacek S, Jönsson L, Wimo A, Nordström P, Eriksdotter M. Long-term Effects of Cholinesterase Inhibitors on Cognitive Decline and Mortality. Neurology 2021; 96 (17) e2220-e2230
    PubMedSearch in Google Scholar
  • 33 Marucci G, Buccioni M, Ben DD, Lambertucci C, Volpini R, Amenta F. Efficacy of acetylcholinesterase inhibitors in Alzheimer's disease. Neuropharmacology 2021; 190: 108352
    CrossrefPubMedSearch in Google Scholar
  • 34 Teixeira AL, Gonzales MM, de Souza LC, Weisenbach SL. Revisiting Apathy in Alzheimer's Disease: From Conceptualization to Therapeutic Approaches. Behav Neurol 2021; 2021: 6319826
    CrossrefPubMedSearch in Google Scholar
  • 35 Salem H, Suchting R, Gonzales MM, Seshadri S, Teixeira AL. Apathy as a Predictor of Conversion from Mild Cognitive Impairment to Alzheimer's Disease: A Texas Alzheimer's Research and Care Consortium (TARCC) Cohort-Based Analysis. J Alzheimers Dis 2023; 92 (01) 129-139
    CrossrefPubMedSearch in Google Scholar
  • 36 Miller DS, Robert P, Ereshefsky L. et al. Diagnostic criteria for apathy in neurocognitive disorders. Alzheimers Dement 2021; 17 (12) 1892-1904
    CrossrefPubMedSearch in Google Scholar
  • 37 Husain M, Roiser JP. Neuroscience of apathy and anhedonia: a transdiagnostic approach. Nat Rev Neurosci 2018; 19 (08) 470-484
    CrossrefPubMedSearch in Google Scholar
  • 38 Sassi KLM, Rocha NP, Colpo GD, John V, Teixeira AL. Amphetamine Use in the Elderly: A Systematic Review of the Literature. Curr Neuropharmacol 2020; 18 (02) 126-135
    CrossrefPubMedSearch in Google Scholar
  • 39 Mintzer J, Lanctôt KL, Scherer RW. et al; ADMET 2 Research Group. Effect of Methylphenidate on Apathy in Patients With Alzheimer Disease: The ADMET 2 Randomized Clinical Trial. JAMA Neurol 2021; 78 (11) 1324-1332
    CrossrefPubMedSearch in Google Scholar
  • 40 Burke AD, Goldfarb D, Bollam P, Khokher S. Diagnosing and Treating Depression in Patients with Alzheimer's Disease. Neurol Ther 2019; 8 (02) 325-350
    CrossrefPubMedSearch in Google Scholar
  • 41 Asmer MS, Kirkham J, Newton H. et al. Meta-Analysis of the Prevalence of Major Depressive Disorder Among Older Adults With Dementia. J Clin Psychiatry 2018; 79 (05) 17r11772
    CrossrefPubMedSearch in Google Scholar
  • 42 Olin JT, Schneider LS, Katz IR. et al. Provisional diagnostic criteria for depression of Alzheimer disease. Am J Geriatr Psychiatry 2002; 10 (02) 125-128
    CrossrefPubMedSearch in Google Scholar
  • 43 Agüera-Ortiz L, García-Ramos R, Grandas Pérez FJ. et al. Depression in Alzheimer's Disease: A Delphi Consensus on Etiology, Risk Factors, and Clinical Management. Front Psychiatry 2021; 12: 638651
    CrossrefPubMedSearch in Google Scholar
  • 44 Mendez MF. The Relationship Between Anxiety and Alzheimer's Disease. J Alzheimers Dis Rep 2021; 5 (01) 171-177
    CrossrefPubMedSearch in Google Scholar
  • 45 Cummings J, Pinto LC, Cruz M. et al. Criteria for Psychosis in Major and Mild Neurocognitive Disorders: International Psychogeriatric Association (IPA) Consensus Clinical and Research Definition. Am J Geriatr Psychiatry 2020; 28 (12) 1256-1269
    CrossrefPubMedSearch in Google Scholar
  • 46 Sano M, Cummings J, Jeste DV, Finkel S, Reichman W. International Psychogeriatric Association (IPA) consensus for defining psychosis in major and mild neurocognitive disorders. Int Psychogeriatr 2022; 34 (03) 203-207
    CrossrefPubMedSearch in Google Scholar
  • 47 Ropacki SA, Jeste DV. Epidemiology of and risk factors for psychosis of Alzheimer's disease: a review of 55 studies published from 1990 to 2003. Am J Psychiatry 2005; 162 (11) 2022-2030
    CrossrefPubMedSearch in Google Scholar
  • 48 Pearce D, Gould RL, Roughley M. et al. Paranoid and misidentification subtypes of psychosis in dementia. Neurosci Biobehav Rev 2022; 134: 104529
    CrossrefPubMedSearch in Google Scholar
  • 49 Nicolato R, Corrêa H, Romano-Silva MA, Teixeira Jr AL. Delusional parasitosis or Ekbom syndrome: a case series. Gen Hosp Psychiatry 2006; 28 (01) 85-87
    CrossrefPubMedSearch in Google Scholar
  • 50 Wang PS, Schneeweiss S, Avorn J. et al. Risk of death in elderly users of conventional vs. atypical antipsychotic medications. N Engl J Med 2005; 353 (22) 2335-2341
    CrossrefPubMedSearch in Google Scholar
  • 51 Yury CA, Fisher JE. Meta-analysis of the effectiveness of atypical antipsychotics for the treatment of behavioural problems in persons with dementia. Psychother Psychosom 2007; 76 (04) 213-218
    CrossrefPubMedSearch in Google Scholar
  • 52 Schneider LS, Tariot PN, Dagerman KS. et al; CATIE-AD Study Group. Effectiveness of atypical antipsychotic drugs in patients with Alzheimer's disease. N Engl J Med 2006; 355 (15) 1525-1538
    CrossrefPubMedSearch in Google Scholar
  • 53 Vigen CL, Mack WJ, Keefe RS. et al. Cognitive effects of atypical antipsychotic medications in patients with Alzheimer's disease: outcomes from CATIE-AD. Am J Psychiatry 2011; 168 (08) 831-839
    CrossrefPubMedSearch in Google Scholar
  • 54 Maher AR, Maglione M, Bagley S. et al. Efficacy and comparative effectiveness of atypical antipsychotic medications for off-label uses in adults: a systematic review and meta-analysis. JAMA 2011; 306 (12) 1359-1369
    CrossrefPubMedSearch in Google Scholar
  • 55 Yunusa I, Alsumali A, Garba AE, Regestein QR, Eguale T. Assessment of Reported Comparative Effectiveness and Safety of Atypical Antipsychotics in the Treatment of Behavioral and Psychological Symptoms of Dementia: A Network Meta-analysis. JAMA Netw Open 2019; 2 (03) e190828
    CrossrefPubMedSearch in Google Scholar
  • 56 Yunusa I, Rashid N, Demos GN, Mahadik BS, Abler VC, Rajagopalan K. Comparative Outcomes of Commonly Used Off-Label Atypical Antipsychotics in the Treatment of Dementia-Related Psychosis: A Network Meta-analysis. Adv Ther 2022; 39 (05) 1993-2008
    CrossrefPubMedSearch in Google Scholar
  • 57 Kirkham J, Sherman C, Velkers C. et al. Antipsychotic Use in Dementia. Can J Psychiatry 2017; 62 (03) 170-181
    CrossrefPubMedSearch in Google Scholar
  • 58 Cummings J, Isaacson S, Mills R. et al. Pimavanserin for patients with Parkinson's disease psychosis: a randomised, placebo-controlled phase 3 trial. Lancet 2014; 383 (9916) 533-540
    CrossrefPubMedSearch in Google Scholar
  • 59 Tariot PN, Cummings JL, Soto-Martin ME. et al. Trial of Pimavanserin in Dementia-Related Psychosis. N Engl J Med 2021; 385 (04) 309-319
    CrossrefPubMedSearch in Google Scholar
  • 60 Moreno GM, Gandhi R, Lessig SL, Wright B, Litvan I, Nahab FB. Mortality in patients with Parkinson disease psychosis receiving pimavanserin and quetiapine. Neurology 2018; 91 (17) 797-799
    CrossrefPubMedSearch in Google Scholar
  • 61 Ismail Z, Creese B, Aarsland D. et al. Psychosis in Alzheimer disease - mechanisms, genetics and therapeutic opportunities. Nat Rev Neurol 2022; 18 (03) 131-144
    CrossrefPubMedSearch in Google Scholar
  • 62 Sano M, Cummings J, Auer S. et al. Agitation in cognitive disorders: Progress in the International Psychogeriatric Association consensus clinical and research definition. Int Psychogeriatr 2023; •••: 1-13
    CrossrefPubMedSearch in Google Scholar
  • 63 Cummings J, Sano M, Auer S. et al. Reduction and prevention of agitation in persons with neurocognitive disorders: an international psychogeriatric association consensus algorithm. Int Psychogeriatr 2023; •••: 1-12
    CrossrefPubMedSearch in Google Scholar
  • 64 Sano M, Zhu CW, Neugroschl J, Grossman HT, Schimming C, Aloysi A. Agitation in Cognitive Disorders: Use of the National Alzheimer's Coordinating Center Uniform Data Set (NACC-UDS) to Evaluate International Psychogeriatric Association Definition. Am J Geriatr Psychiatry 2022; 30 (11) 1198-1208
    CrossrefPubMedSearch in Google Scholar
  • 65 Selbaek G, Engedal K, Benth JŠ, Bergh S. The course of neuropsychiatric symptoms in nursing-home patients with dementia over a 53-month follow-up period. Int Psychogeriatr 2014; 26 (01) 81-91
    CrossrefPubMedSearch in Google Scholar
  • 66 Livingston G, Kelly L, Lewis-Holmes E. et al. Non-pharmacological interventions for agitation in dementia: systematic review of randomised controlled trials. Br J Psychiatry 2014; 205 (06) 436-442
    CrossrefPubMedSearch in Google Scholar
  • 67 Watt JA, Goodarzi Z, Veroniki AA. et al. Comparative Efficacy of Interventions for Aggressive and Agitated Behaviors in Dementia: A Systematic Review and Network Meta-analysis. Ann Intern Med 2019; 171 (09) 633-642
    CrossrefPubMedSearch in Google Scholar
  • 68 Salem H, Nagpal C, Pigott T, Teixeira AL. Revisiting Antipsychotic-induced Akathisia: Current Issues and Prospective Challenges. Curr Neuropharmacol 2017; 15 (05) 789-798
    CrossrefPubMedSearch in Google Scholar
  • 69 Banerjee S, High J, Stirling S. et al. Study of mirtazapine for agitated behaviours in dementia (SYMBAD): a randomised, double-blind, placebo-controlled trial. Lancet 2021; 398 (10310): 1487-1497
    CrossrefPubMedSearch in Google Scholar
  • 70 Porsteinsson AP, Drye LT, Pollock BG. et al; CitAD Research Group. Effect of citalopram on agitation in Alzheimer disease: the CitAD randomized clinical trial. JAMA 2014; 311 (07) 682-691
    CrossrefPubMedSearch in Google Scholar
  • 71 Schneider LS, Frangakis C, Drye LT. et al; CitAD Research Group. Heterogeneity of Treatment Response to Citalopram for Patients With Alzheimer's Disease With Aggression or Agitation: The CitAD Randomized Clinical Trial. Am J Psychiatry 2016; 173 (05) 465-472
    CrossrefPubMedSearch in Google Scholar
  • 72 Administration, F.a.D. FDA Approves First Drug to Treat Agitation Symptoms Associated with Dementia due to Alzheimer's Disease . 2023 05/11/2023 [cited 2023.
    PubMedSearch in Google Scholar
  • 73 Davies SJ, Burhan AM, Kim D. et al. Sequential drug treatment algorithm for agitation and aggression in Alzheimer's and mixed dementia. J Psychopharmacol 2018; 32 (05) 509-523
    CrossrefPubMedSearch in Google Scholar
  • 74 Supasitthumrong T, Bolea-Alamanac BM, Asmer S, Woo VL, Abdool PS, Davies SJC. Gabapentin and pregabalin to treat aggressivity in dementia: a systematic review and illustrative case report. Br J Clin Pharmacol 2019; 85 (04) 690-703
    CrossrefPubMedSearch in Google Scholar
  • 75 Cummings JL, Lyketsos CG, Peskind ER. et al. Effect of Dextromethorphan-Quinidine on Agitation in Patients With Alzheimer Disease Dementia: A Randomized Clinical Trial. JAMA 2015; 314 (12) 1242-1254
    CrossrefPubMedSearch in Google Scholar
  • 76 Herrmann N, Ruthirakuhan M, Gallagher D. et al. Randomized Placebo-Controlled Trial of Nabilone for Agitation in Alzheimer's Disease. Am J Geriatr Psychiatry 2019; 27 (11) 1161-1173
    CrossrefPubMedSearch in Google Scholar
  • 77 Ruthirakuhan M, Lanctôt KL, Vieira D, Herrmann N. Natural and Synthetic Cannabinoids for Agitation and Aggression in Alzheimer's Disease: A Meta-Analysis. J Clin Psychiatry 2019; 80 (02) 18r12617
    CrossrefPubMedSearch in Google Scholar
  • 78 Herrmann N, Wang HJ, Song BX, Bawa KK, Lanctôt KL. Risks and benefits of current and novel drugs to treat agitation in Alzheimer's disease. Expert Opin Drug Saf 2022; 21 (10) 1289-1301
    CrossrefPubMedSearch in Google Scholar
  • 79 Shi L, Chen SJ, Ma MY. et al. Sleep disturbances increase the risk of dementia: A systematic review and meta-analysis. Sleep Med Rev 2018; 40: 4-16
    CrossrefPubMedSearch in Google Scholar
  • 80 Bubu OM, Brannick M, Mortimer J. et al. Sleep, Cognitive impairment, and Alzheimer's disease: A Systematic Review and Meta-Analysis. Sleep 2017;40(01):
  • 81 Casagrande M, Forte G, Favieri F, Corbo I. Sleep Quality and Aging: A Systematic Review on Healthy Older People, Mild Cognitive Impairment and Alzheimer's Disease. Int J Environ Res Public Health 2022; 19 (14) 8457
    CrossrefPubMedSearch in Google Scholar
  • 82 Javed B, Javed A, Kow CS, Hasan SS. Pharmacological and non-pharmacological treatment options for sleep disturbances in Alzheimer's disease. Expert Rev Neurother 2023; 23 (06) 501-514
    CrossrefPubMedSearch in Google Scholar
  • 83 Wade AG, Farmer M, Harari G. et al. Add-on prolonged-release melatonin for cognitive function and sleep in mild to moderate Alzheimer's disease: a 6-month, randomized, placebo-controlled, multicenter trial. Clin Interv Aging 2014; 9: 947-961
    PubMedSearch in Google Scholar
  • 84 Serfaty M, Kennell-Webb S, Warner J, Blizard R, Raven P. Double blind randomised placebo controlled trial of low dose melatonin for sleep disorders in dementia. Int J Geriatr Psychiatry 2002; 17 (12) 1120-1127
    CrossrefPubMedSearch in Google Scholar
  • 85 Gehrman PR, Connor DJ, Martin JL, Shochat T, Corey-Bloom J, Ancoli-Israel S. Melatonin fails to improve sleep or agitation in double-blind randomized placebo-controlled trial of institutionalized patients with Alzheimer disease. Am J Geriatr Psychiatry 2009; 17 (02) 166-169
    CrossrefPubMedSearch in Google Scholar
  • 86 McCleery J, Sharpley AL. Pharmacotherapies for sleep disturbances in dementia. Cochrane Database Syst Rev 2020; 11 (11) CD009178
    CrossrefPubMedSearch in Google Scholar