Current Neurology and Neuroscience Reports

, Volume 5, Issue 5, pp 345–354

Psychiatric and behavioral symptoms in Alzheimer’s disease and other dementias: Etiology and management

  • Dag Aarsland
  • Sally Sharp
  • Clive Ballard


Psychiatric and behavioral symptoms are common in all types of dementia and have important consequences for patients, caregivers, and society. This paper reviews recent studies of the etiology and management of these symptoms. Genetic and neurochemical studies indicate that cholinergic, serotonergic, and dopaminergic systems may influence the risk of psychiatric symptoms in patients with dementia. There is still no consensus regarding the management of such symptoms. Controlled studies of psychosocial interventions, usually performed in the nursing home setting, report encouraging results. Atypical antipsychotics may be effective in some cases but have a high risk of adverse events. There is emerging evidence that cholinesterase inhibitors may reduce and prevent such symptoms. More studies are needed to clarify the role of cholinergic and other psychotropic agents as well as nonpharmacologic interventions for psychiatric and behavioral symptoms in patients with dementia.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References and Recommended Reading

  1. 1.
    Benoit M, Robert PH, Staccini P, et al.: One-year Longitudinal Evaluation of Neuropsychiatric Symptoms in Alzheimer’s Disease. The REAL.FR study. J Nutr Health Aging 2005, 9:95–99. This is among the largest prospective studies of the psychiatric symptoms in dementia.PubMedGoogle Scholar
  2. 2.
    Gilley DW, Bienias JL, Wilson RS, et al.: Influence of behavioral symptoms on rates of institutionalization for persons with Alzheimer’s disease. Psychol Med 2004, 34:1129–1135.PubMedCrossRefGoogle Scholar
  3. 3.
    Lyketsos CG, Steinberg M, Tschanz JT, et al.: Mental and behavioral disturbances in dementia: findings from the Cache County Study on Memory in Aging. Am J Psychiatry 2000, 157:708–714.PubMedCrossRefGoogle Scholar
  4. 4.
    Mirakhur A, Craig D, Hart DJ, et al.: Behavioral and psychological syndromes in Alzheimer’s disease. Int J Geriatr Psychiatry 2004, 19:1035–1039.PubMedCrossRefGoogle Scholar
  5. 5.
    Aarsland D, Ballard C, Larsen JP, McKeith I: A comparative study of psychiatric symptoms in dementia with Lewy bodies and Parkinson’s disease with and without dementia. Int J Geriatr Psychiatry 2001, 16:528–536.PubMedCrossRefGoogle Scholar
  6. 6.
    Cummings J: The Neuropsychiatry of Alzheimer’s Disease and Related Dementias. London: Martin Dunitz Ltd; 2003.Google Scholar
  7. 7.
    Holmes C, Smith H, Ganderton R, et al.: Psychosis and aggression in Alzheimer’s disease: the effect of dopamine receptor gene variation. J Neurol Neurosurg Psychiatry Dec 2001, 71:777–779.CrossRefGoogle Scholar
  8. 8.
    Sweet RA, Nimgaonkar VL, Devlin B, Jeste DV: Psychotic symptoms in Alzheimer disease: evidence for a distinct phenotype. Mol Psychiatry 2003, 8:383–392.PubMedCrossRefGoogle Scholar
  9. 9.
    Sweet RA, Hamilton RL, Healy MT, et al.: Alterations of striatal dopamine receptor binding in Alzheimer disease are associated with Lewy body pathology and antemortem psychosis. Arch Neurol 2001, 58:466–472.PubMedCrossRefGoogle Scholar
  10. 10.
    Craig D, Hart DJ, Carson R, et al.: Psychotic symptoms in Alzheimer’s disease are not influenced by polymorphic variation at the dopamine receptor DRD3 gene. Neurosci Lett 2004, 368:33–36.PubMedCrossRefGoogle Scholar
  11. 11.
    Sukonick DL, Pollock BG, Sweet RA, et al.: The 5-HTTPR*S/*L polymorphism and aggressive behavior in Alzheimer disease. Arch Neurol 2001, 58:1425–1428.PubMedCrossRefGoogle Scholar
  12. 12.
    Assal F, Alarcon M, Solomon EC, et al.: Association of the serotonin transporter and receptor gene polymorphisms in neuropsychiatric symptoms in Alzheimer disease. Arch Neurol 2004, 61:1249–1253.PubMedCrossRefGoogle Scholar
  13. 13.
    Rocchi A, Micheli D, Ceravolo R, et al.: Serotoninergic polymorphisms (5-HTTLPR and 5-HT2A): association studies with psychosis in Alzheimer disease. Genet Test 2003, 7:309–314.PubMedCrossRefGoogle Scholar
  14. 14.
    Engelborghs S, Holmes C, McCulley M, De Deyn PP: 5-HT2A receptor polymorphism may modulate antipsychotic treatment response in Alzheimer’s disease. Int J Geriatr Psychiatry 2004, 19:1108–1109. This is an interesting pilot study suggesting that genetic polymorphisms are associated with the response to antipsychotics in patients with AD.PubMedCrossRefGoogle Scholar
  15. 15.
    Craig D, Hart DJ, McCool K, et al.: The interleukin 1beta gene promoter polymorphism (-511) acts as a risk factor for psychosis in Alzheimer’s dementia. Ann Neurol 2004, 56:121–124. This is one of several interesting studies from this group of the genetics of psychiatric symptoms in a large and well-defined cohort of patients with AD.PubMedCrossRefGoogle Scholar
  16. 16.
    Craig D, Hart DJ, Carson R, et al.: Allelic variation at the A218C tryptophan hydroxylase polymorphism influences agitation and aggression in Alzheimer’s disease. Neurosci Lett 2004, 363:199–202.PubMedCrossRefGoogle Scholar
  17. 17.
    Craig D, Hart DJ, McCool K, et al.: Apolipoprotein E e4 allele influences aggressive behaviour in Alzheimer’s disease. J Neurol Neurosurg Psychiatry 2004, 75:1327–1330.PubMedCrossRefGoogle Scholar
  18. 18.
    Craig D, Hart DJ, McIlroy SP, Passmore AP: Association analysis of apolipoprotein E genotype and risk of depressive symptoms in Alzheimer’s disease. Dement Geriatr Cogn Disord 2005, 19:154–157.PubMedCrossRefGoogle Scholar
  19. 19.
    Holmes C, Arranz M, Collier D, et al.: Depression in Alzheimer’s disease: the effect of serotonin receptor gene variation. Am J Med Genet B Neuropsychiatr Genet 2003, 119:40–43.PubMedCrossRefGoogle Scholar
  20. 20.
    Ballard CG, Jacoby R, Del Ser T, et al.: Neuropathological substrates of psychiatric symptoms in prospectively studied patients with autopsy-confirmed dementia with Lewy bodies. Am J Psychiatry May 2004, 161:843–849. This is among the largest studies exploring the morphologic correlates of psychiatric symptoms in AD and DLB.CrossRefGoogle Scholar
  21. 21.
    Matthews KL, Chen CP, Esiri MM, et al.: Noradrenergic changes, aggressive behavior, and cognition in patients with dementia. Biol Psychiatry 2002, 51:407–416.PubMedCrossRefGoogle Scholar
  22. 22.
    Peskind ER, Wingerson D, Murray S, et al.: Effects of Alzheimer’s disease and normal aging on cerebrospinal fluid norepinephrine responses to yohimbine and clonidine. Arch Gen Psychiatry 1995, 52:774–782.PubMedGoogle Scholar
  23. 23.
    Herrmann N, Lanctot KL, Eryavec G, Khan LR: Noradrenergic activity is associated with response to pindolol in aggressive Alzheimer’s disease patients. J Psychopharmacol 2004, 18:215–220.PubMedCrossRefGoogle Scholar
  24. 24.
    Sharp SI, Ballard CG, Francis PT: Association between alpha-1 Adrenoreceptor binding and behavioral symptoms in dementia. Paper presented at Annual Meeting of the British Pharmacological Society, Newcastle, December 14–16, 2004.Google Scholar
  25. 25.
    Lai MK, Tsang SW, Francis PT, et al.: Reduced serotonin 5-HT1A receptor binding in the temporal cortex correlates with aggressive behavior in Alzheimer disease. Brain Res 2003, 974:82–87.PubMedCrossRefGoogle Scholar
  26. 26.
    Lai MK, Tsang SW, Francis PT, et al.: [3H]GR113808 binding to serotonin 5-HT(4) receptors in the postmortem neocortex of Alzheimer disease: a clinicopathological study. J Neural Transm 2003, 110:779–788.PubMedGoogle Scholar
  27. 27.
    Lanctot KL, Herrmann N, Mazzotta P, et al.: GABAergic function in Alzheimer’s disease: evidence for dysfunction and potential as a therapeutic target for the treatment of behavioral and psychological symptoms of dementia. Can J Psychiatry 2004, 49:439–453.PubMedGoogle Scholar
  28. 28.
    Minger SL, Esiri MM, McDonald B, et al.: Cholinergic deficits contribute to behavioral disturbance in patients with dementia. Neurology 2000, 55:1460–1467.PubMedGoogle Scholar
  29. 29.
    Ballard C, Piggott M, Johnson M, et al.: Delusions associated with elevated muscarinic binding in dementia with Lewy bodies. Ann Neurol 2000, 48:868–876.PubMedCrossRefGoogle Scholar
  30. 30.
    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, 289:210–216.PubMedCrossRefGoogle Scholar
  31. 31.
    McKeith I, Del Ser T, Spano P, et al.: Efficacy of rivastigmine in dementia with Lewy bodies: a randomized, double-blind, placebo-controlled international study. Lancet 2000, 356:2031–2036.PubMedCrossRefGoogle Scholar
  32. 32.
    Cohen-Mansfield J, Mintzer JE: Time for change: the role of nonpharmacological interventions in treating behavior problems in nursing home residents with dementia. Alzheimer Dis Assoc Disord 2005, 19:37–40.PubMedCrossRefGoogle Scholar
  33. 33.
    Brodaty H, Draper BM, Millar J, et al.: Randomized controlled trial of different models of care for nursing home residents with dementia complicated by depression or psychosis. J Clin Psychiatry 2003, 64:63–72.PubMedCrossRefGoogle Scholar
  34. 34.
    Teri L, Logsdon RG, Peskind E, et al.: Treatment of agitation in AD: a randomized, placebo-controlled clinical trial. Neurology 2000, 55:1271–1278.PubMedGoogle Scholar
  35. 35.
    Teri L, Logsdon RG, Uomoto J, McCurry SM: Behavioral treatment of depression in dementia patients: a controlled clinical trial. J Gerontol Br Psychol Sci Soc Sci 1997, 52:P159-P166.Google Scholar
  36. 36.
    Teri L, Gibbons LE, McCurry SM, et al.: Exercise plus behavioral management in patients with Alzheimer disease: a randomized controlled trial. JAMA 2003, 290:2015–2022.PubMedCrossRefGoogle Scholar
  37. 37.
    Tibaldi V, Aimonino N, Ponzetto M, et al.: A randomized controlled trial of a home hospital intervention for frail elderly demented patients: behavioral disturbances and caregiver’s stress. Arch Gerontol Geriatr Suppl 2004, 431–436.Google Scholar
  38. 38.
    van Weert JC, van Dulmen AM, Spreeuwenberg PM, et al.:Behavioral and mood effects of snoezelen integrated into 24-hour dementia care. J Am Geriatr Soc 2005, 53:24–33. This is a well-designed trial showing that intervention focusing on caregivers can improve psychiatric symptoms and well-being of nursing home patients with dementia.PubMedCrossRefGoogle Scholar
  39. 39.
    Kovach CR, Taneli Y, Dohearty P, et al.: Effect of the BACE intervention on agitation of people with dementia. Gerontologist 2004, 44:797–806.PubMedGoogle Scholar
  40. 40.
    Nobili A, Riva E, Tettamanti M, et al.: The effect of a structured intervention on caregivers of patients with dementia and problem behaviors: a randomized controlled pilot study. Alzheimer Dis Assoc Disord 2004, 18:75–82.PubMedCrossRefGoogle Scholar
  41. 41.
    Cummings JL, Mega M, Gray K, et al.: The Neuropsychiatric Inventory: comprehensive assessment of psychopathology in dementia. Neurology 1994, 44:2308–2314.PubMedGoogle Scholar
  42. 42.
    Sink KM, Holden KF, Yaffe K: Pharmacological treatment of neuropsychiatric symptoms of dementia. JAMA 2005, 293:596–608. This is a comprehensive, critical, and updated review of the pharmacologic treatments of psychiatric symptoms in patients with dementia, also providing useful guidelines for treatment.PubMedCrossRefGoogle Scholar
  43. 43.
    Martin-Cook K, Hynan LS, Rice-Koch K, et al.: Responsiveness of the quality of life in late-stage dementia scale to psychotropic drug treatment in late-stage dementia. Dement Geriatr Cogn Disord 2005, 19:82–85.PubMedCrossRefGoogle Scholar
  44. 44.
    Frank L, Kleinman L, Ciesla G, et al.: The effect of risperidone on nursing burden associated with caring for patients with dementia. J Am Geriatr Soc 2004, 52:1449–1455.PubMedCrossRefGoogle Scholar
  45. 45.
    Zhong KT, Minkwitz MC, Devine NC, Mintzer J: Quetiapine for the treatment of agitation in elderly institutionalized patients with dementia: a randomized, double-blind trial. Paper presented at meeting of American Association of Geriatric Psychiatry, San Diego, CA, 2005.Google Scholar
  46. 46.
    McShane R, Keene J, Gedling K, et al.: Do neuroloeptic drugs hasten cognitive decline in dementia? Prosepctive study with follow-up. BMJ 1997, 314:266–270.PubMedGoogle Scholar
  47. 47.
    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, 330:874. This is the first study comparing a cholinesterase inhibitor and an atypical antipsychotic agent for severely demented nursing home patients with behavioral disturbances.PubMedCrossRefGoogle Scholar
  48. 48.
    Perry EK, Kilford L, Lees AJ, et al.: Increased Alzheimer pathology in Parkinson’s disease related to antimuscarinic drugs. Ann Neurol 2003, 54:235–238.PubMedCrossRefGoogle Scholar
  49. 49.
    Aarsland D, Perry R, Larsen JP, et al.: Neuroleptic sensitivity in Parkinson’s disease and parkinsonian dementias. J Clin Psychiatry 2005, In press.Google Scholar
  50. 50.
    Smith DA, Beier MT: Association between risperidone treatment and cerebrovascular adverse events: examining the evidence and postulating hypotheses for an underlying mechanism. J Am Med Dir Assoc 2004, 5:129–132.PubMedCrossRefGoogle Scholar
  51. 51.
    Gill SS, Rochon PA, Herrmann N, et al.: Atypical antipsychotic drugs and risk of ischaemic stroke: population based retrospective cohort study. BMJ 2005, 330:445.PubMedCrossRefGoogle Scholar
  52. 52.
    Moretti R, Torre P, Antonello RM, et al.: Olanzapine as a possible treatment of behavioral symptoms in vascular dementia: risks of cerebrovascular events. A controlled, open-label study. J Neurol 2005, In press.Google Scholar
  53. 53.
    Herrmann N, Lanctot KL: Do atypical antipsychotics cause stroke? CNS Drugs 2005, 19:91–103.PubMedCrossRefGoogle Scholar
  54. 54.
    Herrmann N, Mamdani M, Lanctot KL: Atypical antipsychotics and risk of cerebrovascular accidents. Am J Psychiatry 2004, 161:1113–1115.PubMedCrossRefGoogle Scholar
  55. 55.
    Nasrallah HA, White T, Nasrallah AT: Lower mortality in geriatric patients receiving risperidone and olanzapine versus haloperidol: preliminary analysis of retrospective data. Am J Geriatr Psychiatry 2004, 12:437–439.PubMedCrossRefGoogle Scholar
  56. 56.
    Ruths S, Straand J, Nygaard HA, et al.: Effect of antipsychotic withdrawal on behavior and sleep/wake activity in nursing home residents with dementia: a randomized, placebocontrolled, double-blinded study. The Bergen District Nursing Home Study. J Am Geriatr Soc 2004, 52:1737–1743.PubMedCrossRefGoogle Scholar
  57. 57.
    Lyketsos CG, DelCampo L, Steinberg M, et al.: Treating depression in Alzheimer disease: efficacy and safety of sertraline therapy, and the benefits of depression reduction: the DIADS. Arch Gen Psychiatry 2003, 60:737–746. This is one of the best designed trials of a serotonin reuptake inhibitor for AD patients with depression.PubMedCrossRefGoogle Scholar
  58. 58.
    Pollock BG, Mulsant BH, Rosen J, et al.: Comparison of citalopram, perphenazine, and placebo for the acute treatment of psychosis and behavioral disturbances in hospitalized, demented patients. Am J Psychiatry 2002, 159:460–465.PubMedCrossRefGoogle Scholar
  59. 59.
    Lonergan ET, Cameron M, Luxenberg J: Valproic acid for agitation in dementia. Cochrane Database Syst Rev 2004, 2:CD003945.PubMedGoogle Scholar
  60. 60.
    Herrmann N, Lanctot KL, Eryavec G, et al.: Growth hormone response to clonidine predicts aggression in Alzheimer’s disease. Psychoneuroendocrinology 2004, 29:1192–1197.PubMedCrossRefGoogle Scholar
  61. 61.
    Peskind ER, Tsuang DW, Bonner LT, et al.: Propranolol for disruptive behaviors in nursing home residents with probable or possible Alzheimer disease: a placebocontrolled study. Alzheimer Dis Assoc Disord 2005, 19:23–28. This is among the first placebo-controlled studies of a noradrenergic agent for psychiatric symptoms in dementia, and includes a 6-month open-label extension.PubMedCrossRefGoogle Scholar
  62. 62.
    Gauthier S, Wirth Y, Mobius HJ: Effects of memantine on behavioral symptoms in Alzheimer’s disease patients: an analysis of the Neuropsychiatric Inventory (NPI) data of two randomised, controlled studies. Int J Geriatr Psychiatry 2005, 20:459–464.PubMedCrossRefGoogle Scholar
  63. 63.
    Tariot PN, Cummings JL, Katz IR, et al.: A randomized, doubleblind, 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, 49:1590–1599.PubMedCrossRefGoogle Scholar
  64. 64.
    Holmes C, Wilkinson D, Dean C, et al.: The efficacy of donepezil in the treatment of neuropsychiatric symptoms in Alzheimer disease. Neurology 2004, 63:214–219. This is one of the first placebo-controlled studies of a cholinesterase inhibitor for patients with AD selected for the presence of psychiatric symptoms.PubMedGoogle Scholar
  65. 65.
    Cummings JL, Schneider L, Tariot PN, et al.: Reduction of behavioral disturbances and caregiver distress by galantamine in patients with Alzheimer’s disease. Am J Psychiatry 2004, 161:532–538.PubMedCrossRefGoogle Scholar
  66. 66.
    Finkel SI: Effects of rivastigmine on behavioral and psychological symptoms of dementia in Alzheimer’s disease. Clin Ther 2004, 26:980–990.PubMedCrossRefGoogle Scholar
  67. 67.
    Suh DC, Arcona S, Thomas SK, et al.: Risk of antipsychotic drug use in patients with Alzheimer’s disease treated with rivastigmine. Drugs Aging 2004, 21:395–403.PubMedCrossRefGoogle Scholar
  68. 68.
    McKeith IG, Wesnes KA, Perry E, Ferrara R: Hallucinations predict attentional improvements with rivastigmine in dementia with Lewy bodies. Dement Geriatr Cogn Disord 2004, 18:94–100.PubMedCrossRefGoogle Scholar
  69. 69.
    Emre M, Aarsland D, Albanese A, et al.: Rivastigmine in Parkinson’s disease patients with dementia: a randomized, double-blind, placebo-controlled study. N Engl J Med 2004, 351:2509–2518. This is the first large-scale study of patients with dementia associated with Parkinson’s disease showing that the cholinesterase inhibitor rivastigmine could improve psychiatric symptoms in addition to cognition and activities of daily living.PubMedCrossRefGoogle Scholar
  70. 70.
    Deakin JB, Rahman S, Nestor PJ, et al.: Paroxetine does not improve symptoms and impairs cognition in frontotemporal dementia: a double-blind randomized controlled trial. Psychopharmacology (Berl) 2004, 172:400–408.CrossRefGoogle Scholar
  71. 71.
    Lebert F, Stekke W, Hasenbroekx C, Pasquier F: Frontotemporal dementia: a randomised, controlled trial with trazodone. Dement Geriatr Cogn Disord 2004, 17:355–359. This is the first placebo-controlled trial of a psychotropic drug for patients with FTD, indicating that a serotonergic drug can improve psychiatric symptoms.PubMedCrossRefGoogle Scholar
  72. 72.
    Moretti R, Torre P, Antonello RM, et al.: Rivastigmine in frontotemporal dementia: an open-label study. Drugs Aging 2004, 21:931–937. This open-label study is the first systematic indication that cholinesterase inhibitors might improve behavior in patients with FTD.PubMedCrossRefGoogle Scholar
  73. 73.
    Ballard CG, O’Brien JT, Reichelt K, Perry EK: Aromatherapy as a safe and effective treatment for the management of agitation in severe dementia: the results of a double-blind, placebocontrolled trial with Melissa. J Clin Psychiatry 2002, 63:553–558.PubMedGoogle Scholar
  74. 74.
    Snow LA, Hovanec L, Brandt J: A controlled trial of aromatherapy for agitation in nursing home patients with dementia. J Altern Complement Med 2004, 10:431–437.PubMedCrossRefGoogle Scholar
  75. 75.
    Woods DL, Craven RF, Whitney J: The effect of therapeutic touch on behavioral symptoms of persons with dementia. Altern Ther Health Med 2005, 11:66–74.PubMedGoogle Scholar
  76. 76.
    Skjerve A, Holsten F, Aarsland D, et al.: Improvement in behavioral symptoms and advance of activity acrophase after short-term bright light treatment in severe dementia. Psychiatry Clin Neurosci 2004, 58:343–347.PubMedCrossRefGoogle Scholar
  77. 77.
    Forbes D, Morgan DG, Bangma J, et al.: Light therapy for managing sleep, behaviour, and mood disturbances in dementia. Cochrane Database Syst Rev 2004, 2:CD003946.PubMedGoogle Scholar
  78. 78.
    McCulley MC, Day IN, Holmes C: Association between interleukin 1-beta promoter (-511) polymorphism and depressive symptoms in Alzheimer’s disease. Am J Med Genet B Neuropsychiatr Genet 2004, 124:50–53.PubMedCrossRefGoogle Scholar
  79. 79.
    De Deyn PP, Carrasco MM, Deberdt W, et al.: Olanzapine versus placebo in the treatment of psychosis with or without associated behavioral disturbances in patients with Alzheimer’s disease. Int J Geriatr Psychiatry 2004, 19:115–126.PubMedCrossRefGoogle Scholar

Copyright information

© Current Science Inc 2005

Authors and Affiliations

  • Dag Aarsland
    • 1
  • Sally Sharp
  • Clive Ballard
  1. 1.Centre for Clinical Neuroscience ResearchStavanger University HospitalStavangerNorway

Personalised recommendations