Skip to main content
×
Home
    • Aa
    • Aa

Management of behavioral problems in Alzheimer's disease

  • Serge Gauthier (a1), Jeffrey Cummings (a2), Clive Ballard (a3), Henry Brodaty (a4), George Grossberg (a5), Philippe Robert (a6) and Constantine Lyketsos (a7)...
Abstract
ABSTRACT

Alzheimer's disease (AD) is a complex progressive brain degenerative disorder that has effects on multiple cerebral systems. In addition to cognitive and functional decline, diverse behavioral changes manifest with increasing severity over time, presenting significant management challenges for caregivers and health care professionals. Almost all patients with AD are affected by neuropsychiatric symptoms at some point during their illness; in some cases, symptoms occur prior to diagnosis of the dementia syndrome. Further, behavioral factors have been identified, which may have their origins in particular neurobiological processes, and respond to particular management strategies. Improved clarification of causes, triggers, and presentation of neuropsychiatric symptoms will guide both research and clinical decision-making. Measurement of neuropsychiatric symptoms in AD is most commonly by means of the Neuropsychiatric Inventory; its utility and future development are discussed, as are the limitations and difficulties encountered when quantifying behavioral responses in clinical trials. Evidence from clinical trials of both non-pharmacological and pharmacological treatments, and from neurobiological studies, provides a range of management options that can be tailored to individual needs. We suggest that non-pharmacological interventions (including psychosocial/psychological counseling, interpersonal management and environmental management) should be attempted first, followed by the least harmful medication for the shortest time possible. Pharmacological treatment options, such as antipsychotics, antidepressants, anticonvulsants, cholinesterase inhibitors and memantine, need careful consideration of the benefits and limitations of each drug class.

Copyright
Corresponding author
Correspondence should be addressed to: Serge Gauthier, Director of the Alzheimer's Disease and Related Disorders Unit at the McGill Center for Studies in Aging, Douglas Mental Health University Institute, Montreal, Canada. Phone: +1 514 766 2010; Fax: +1 514 888 4050. Email: serge.gauthier@mcgill.ca.
References
Hide All
Aalten P. et al. (2007). Neuropsychiatric syndromes in dementia. Results from the European Alzheimer Disease Consortium: Part I. Dementia and Geriatric Cognitive Disorders, 24, 457463.
Alagiakrishnan K. et al. (2005). Sexually inappropriate behaviour in demented elderly people. Postgraduate Medical Journal, 81, 463466.
Alexopoulos G. S., Abrams R. C., Young R. C. and Shamoian C. A. (1988). Cornell scale for depression in dementia. Biological Psychiatry, 23, 271284.
Algase D. L. et al. (1996). Need-driven dementia-compromised behavior: an alternative view of disruptive behavior. American Journal of Alzheimer's Disease and Other Dementias, 11, 1019.
Apostolova L. G. et al. (2007). Structural correlates of apathy in Alzheimer's disease. Dementia and Geriatric Cognitive Disorders, 24, 9197.
Archer N. et al. (2007). Premorbid personality and behavioral and psychological symptoms in probable Alzheimer disease. American Journal of Geriatric Psychiatry, 15, 202213.
Assal F., Alarcón M., Solomon E. C., Masterman D., Geschwind D. H. and Cummings J. L. (2004). Association of the serotonin transporter and receptor gene polymorphisms in neuropsychiatric symptoms in Alzheimer disease. Archives of Neurology, 61, 12491253.
Auchus A. P. and Bissey-Black C. (1997). Pilot study of haloperidol, fluoxetine, and placebo for agitation in Alzheimer's disease. Journal of Neuropsychiatry and Clinical Neuroscience, 9, 591593.
Aupperle P. M., Koumaras B., Chen M., Rabinowicz A. and Mirski D. (2004). Long-term effects of rivastigmine treatment on neuropsychiatric and behavioral disturbances in nursing home residents with moderate to severe Alzheimer's disease: results of a 52-week open-label study. Current Medical Research and Opinion, 20, 16051612.
Baines S., Saxby P. and Ehlert K. (1987). Reality orientation and reminiscence therapy. A controlled cross-over study of elderly confused people. British Journal of Psychiatry, 151, 222231.
Ballard C. and Howard R. (2006). Neuroleptic drugs in dementia: benefits and harm. Nature Reviews Neuroscience, 7, 492500.
Ballard C. G., O'Brien J. T., Reichelt K. and Perry E. K. (2002). Aromatherapy as a safe and effective treatment for the management of agitation in severe dementia: the results of a double-blind, placebo-controlled trial with Melissa. Journal of Clinical Psychiatry, 63, 553558.
Ballard C. G. et al. (2004). A 3-month, randomized, placebo-controlled, neuroleptic discontinuation study in 100 people with dementia: the neuropsychiatric inventory median cutoff is a predictor of clinical outcome. Journal of Clinical Psychiatry, 65, 114119.
Ballard C. et al. (2005). Quetiapine and rivastigmine and cognitive decline in Alzheimer's disease: randomised double blind placebo controlled trial. BMJ, 330, 874.
Ballard C. et al. ; Investigators DART AD. (2008). A randomised, blinded, placebo-controlled trial in dementia patients continuing or stopping neuroleptics (the DART-AD trial). PLoS Medicine, 5, e76.
Ballard C. G. et al. (2009a). Management of agitation and aggression associated with Alzheimer disease. Nature Reviews Neurology, 5, 245255.
Ballard C. et al. ; DART-AD investigators. (2009b). The dementia antipsychotic withdrawal trial (DART-AD): long-term follow-up of a randomised placebo-controlled trial. Lancet Neurology, 8, 151157.
Banerjee S. et al. (2006). Quality of life in dementia: more than just cognition. An analysis of associations with quality of life in dementia. Journal of Neurology, Neurosurgery, and Psychiatry, 77, 146148.
Barak Y., Bodner E., Zemishlani H., Mirecki I. and Aizenberg D. (2001). Donepezil for the treatment of behavioral disturbances in Alzheimer's disease: a 6-month open trial. Archives of Gerontology and Geriatrics, 33, 237241.
Barton S., Findlay D. and Blake R. A. (2005). The management of inappropriate vocalisation in dementia: a hierarchical approach. International Journal of Geriatric Psychiatry, 20, 11801186.
Bergman J., Brettholz I., Shneidman M. and Lerner V. (2003). Donepezil as add-on treatment of psychotic symptoms in patients with dementia of the Alzheimer's type. Clinical Neuropharmacology, 26, 8892.
Bird M., Alexopoulos P. and Adamowicz J. (1995). Success and failure in five case studies: use of cued recall to ameliorate behaviour problems in senile dementia. International Journal of Geriatric Psychiatry, 10, 305311.
Black S. E. et al. (2007). Donepezil preserves cognition and global function in patients with severe Alzheimer disease. Neurology, 69, 459469.
Bridges-Parlet S., Knopman D. and Steffes S. (1997). Withdrawal of neuroleptic medications from institutionalised dementia patients, results of a double-blind baseline-treatment-controlled pilot study. Journal of Geriatric Psychiatry and Neurology, 10, 119126.
Brodaty H. et al. (2001). Psychosis, depression and behavioural disturbances in Sydney nursing home residents: prevalence and predictors. International Journal of Geriatric Psychiatry, 16, 504512.
Brodaty H. et al. (2005). Risperidone for psychosis of Alzheimer's disease and mixed dementia: results of a double-blind, placebo-controlled trial. International Journal of Geriatric Psychiatry, 20, 11531157.
Burgio L., Scilley K., Hardin J. M., Hsu C. and Yancey J. (1996). Environmental “white noise”: an intervention for verbally agitated nursing home residents. Journals of Gerontology. Series B, Psychological Sciences and Social Sciences, 51, P364P373.
Butt Z. A. and Strauss M. E. (2001). Relationship of family and personal history to the occurrence of depression in persons with Alzheimer's disease. American Journal of Geriatric Psychiatry, 9, 249254.
Chen J. C., Borson S. and Scanlan J. M. (2000). Stage-specific prevalence of behavioral symptoms in Alzheimer's disease in a multi-ethnic community sample. American Journal of Geriatric Psychiatry, 8, 123133.
Chenoweth L. et al. (2009). Caring for aged dementia care resident study (CADRES) of person-centred care, dementia-care mapping, and usual care in dementia: a cluster-randomised trial. Lancet Neurology, 8, 317325.
Clark M. E., Lipe A. W. and Bilbrey M. (1998). Use of music to decrease aggressive behaviors in people with dementia. Journal of Gerontological Nursing, 24, 1017.
Cohen C. I., Hyland K. and Kimhy D. (2003). The utility of mandatory depression screening of dementia patients in nursing homes. American Journal of Psychiatry, 160, 20122017.
Cohen-Mansfield J. (1986). Agitated behaviors in the elderly II. Preliminary results in the cognitively deteriorated. Journal of American Geriatrics Society, 34, 722727.
Cohen-Mansfield J. (2000) Theoretical frameworks for behavioural problems in dementia. Alzheimer's Care Quarterly, 1, 821.
Cohen-Mansfield J. (2001). Nonpharmacologic interventions for inappropriate behaviors in dementia: a review, summary, and critique. American Journal of Geriatric Psychiatry, 9, 361381.
Cohen-Mansfield J. et al. (1999). Withdrawal of haloperidol, thioridazine, and lorazepam in the nursing home: a controlled, double-blind study. Archives of Internal Medicine, 159, 17331740.
Cooney C., Mortimer A., Smith A., Newton N. and Wrigley M. (1996). Carbamazepine use in aggressive behaviour associated with senile dementia. International Journal of Geriatric Psychiatry, 11, 901905.
Craig D., Hart D. J., Carson R., McIlroy S. P. and Passmore A. P. (2004). Psychotic symptoms in Alzheimer's disease are not influenced by polymorphic variation at the dopamine receptor DRD3 gene. Neuroscience Letters, 368, 3336.
Craig D., Mirakhur A., Hart D. J., McIlroy S. P. and Passmore A. P. (2005). A cross-sectional study of neuropsychiatric symptoms in 435 patients with Alzheimer's disease. American Journal of Geriatric Psychiatry, 13, 460468.
Cummings J. L. (2003). The Neuropsychiatry of Alzheimer's Disease and Related Dementias. London: Martin Dunitz.
Cummings J. L. and Back C. (1998). The cholinergic hypothesis of neuropsychiatric symptoms in Alzheimer's disease. American Journal of Geriatric Psychiatry, 6 (2 Suppl. 1), S64S78.
Cummings J. L., Mega M. S., Gray K., Rosemberg-Thompson S. and Gornbein T. (1994). The Neuropsychiatric Inventory: comprehensive assessment of psychopathology in dementia. Neurology, 44, 2380–2314.
Cummings J. L., Schneider L., Tariot P. N., Kershaw P. R. and Yuan W. (2004a). Reduction of behavioral disturbances and caregiver distress by galantamine in patients with Alzheimer's disease. American Journal of Psychiatry, 161, 532538.
Cummings J. L., Tractenberg R. E., Gamst A., Teri L., Masterman D. and Thal L. J. (2004b). Regression to the mean: implications for clinical trials of psychotropic agents in dementia. Current Alzheimer Research, 1 (4), 323328.
Cummings J. L., Koumaras B., Chen M. and Mirski D. (2005). Effects of rivastigmine treatment on the neuropsychiatric and behavioral disturbances of nursing home residents with moderate to severe probable Alzheimer's disease: a 26-week, multicenter, open-label study. American Journal of Geriatric Pharmacotherapy, 3, 137148.
Cummings J. L., McRae T. and Zhang R. (2006a). Effects of donepezil on neuropsychiatric symptoms in patients with dementia and severe behavioral disorders. American Journal of Geriatric Psychiatry, 14, 605612.
Cummings J. L., Schneider E., Tariot P. N. and Graham S. M.; Memantine MEM-MD-02 Study Group. (2006b). Behavioral effects of memantine in Alzheimer disease patients receiving donepezil treatment. Neurology, 67, 5763.
Cummings J., Mackell J. and Kaufer D. (2008). Behavioural effects of current Alzheimer's disease treatments: a descriptive review. Alzheimer's and Dementia, 4, 4960.
Day K., Carreon D. and Stump C. (2000). The therapeutic design of environments for people with dementia: a review of the empirical research. Gerontologist, 40, 397416.
de Medeiros K. et al. (2009). The NPI-C: a clinician-rated assessment of neuropsychiatric symptoms in dementia. International Psychogeriatrics, 21 (Suppl. 2), S92S93.
Deschenes C. L. and McCurry S. M. (2009). Current treatments for sleep disturbances in individuals with dementia. Current Psychiatry Reports, 11, 2026.
Deudon A. et al. (2009). Non-pharmacological management of behavioural symptoms in nursing homes. International Journal of Geriatric Psychiatry, In Press: PMID: 19370714.
Devanand D. P. et al. (1992). Behavioral syndromes in Alzheimer's disease. International Psychogeriatrics, 4 (Suppl 2), 161184.
Doyle C., Zapparoni T., O'Connor D. and Runci S. (1997). Efficacy of psychosocial treatments for noisemaking in severe dementia. International Psychogeriatrics, 9, 405422.
Draper B. et al. (2003). Outcome of treatment of vocally disruptive behaviour in nursing home residents. Australasian Journal on Ageing, 22, 8185.
Drevets W. C. and Rubin E. H. (1989). Psychotic symptoms and the longitudinal course of senile dementia of the Alzheimer type. Biological Psychiatry, 25, 3948.
Edberg A. K. and Hallberg I. R. (1996). Effects of clinical supervision on nurse-patient cooperation quality: a controlled study in dementia care. Clinical Nursing Research, 5, 127146, discussion 147–149.
Edberg A. K., Norberg A. and Hallberg I. R. (1999). Mood and general behavior of patients with severe dementia during one year of supervised, individualized planned care and systematic clinical supervision. Comparison with a similar control group. Aging-Clinical & Experimental Research, 11, 395403.
Eisai Limited (2009). Aricept. Summary of Product Characteristics. April 2009.
EMEA (2004). Atypical Antipsychotic Drugs and Stroke, 9 March 2004. European Medicines Agency.
EMEA (2008). CHMP Assessment Report on Conventional Antipsychotics. 20 November 2008. European Medicines Agency.
Emre M., Cummings J. L. and Lane R. M. (2007). Rivastigmine in dementia associated with Parkinson's disease and Alzheimer's disease: similarities and differences. Journal of Alzheimer's Disease, 11, 509519.
Farber N. B. et al. (2000). Increased neocortical neurofibrillary tangle density in subjects with Alzheimer disease and psychosis. Archives of General Psychiatry, 57, 11651173.
FDA. (2005). Deaths with Antipsychotics in Elderly Patients with Behavioral Disturbances. U.S. Food and Drug Administration, FDA Public Health Advisory, Centre for Drug Evaluation and Research, 13 July 2005.
Feldman H. et al. ; MSAD Study Investigators Group (2005). Efficacy and safety of donepezil in patients with more severe Alzheimer's disease: a subgroup analysis from a randomised, placebo-controlled trial. International Journal of Geriatric Psychiatry, 20, 559569.
Filan S. L. and Llewellyn-Jones R. H. (2006). Animal-assisted therapy for dementia: a review of the literature. International Psychogeriatrics, 18, 597611.
Finkel S. I., Mintzer J. E., Dysken M., Krishnan K. R., Burt T. and McRae T. (2004) A randomized, placebo-controlled study of the efficacy and safety of sertraline in the treatment of the behavioral manifestations of Alzheimer's disease in outpatients treated with donepezil. International Journal of Geriatric Psychiatry, 19, 918.
Forbes D., Morgan D. G., Bangma J., Peacock S. and Adamson J. (2004). Light therapy for managing sleep, behaviour, and mood disturbances in dementia. Cochrane Database of Systematic Reviews, Issue 2, Art. No.: CD003946. DOI: 10.1002/14651858.CD003946.pub2.
Francis P. T., Palmer A. M., Snape M. and Wilcock G. K. (1999). The cholinergic hypothesis of Alzheimer's disease: a review of progress. Journal of Neurology, Neurosurgery, and Psychiatry, 66, 137147.
Frisoni G. B. et al. (1999). Behavioral syndromes in Alzheimer's disease: description and correlates. Dementia and Geriatric Cognitive Disorders, 10, 130138.
Gaber S., Ronzoli S., Bruno A. and Biagi A. (2001). Sertraline versus small doses of haloperidol in the treatment of agitated behavior in patients with dementia. Archives of Gerontology and Geriatrics Supplement, 7, 159162.
Garcia-Alloza M., Hirst W. D., Chen C. P., Lasheras B., Francis P. T. and Ramírez M. J. (2004). Differential involvement of 5-HT(1B/1D) and 5-HT6 receptors in cognitive and non-cognitive symptoms in Alzheimer's disease. Neuropsychopharmacology, 29, 410416.
Gaugler J. E., Davey A., Pearlin L. I. and Zarit S. H. (2000). Modeling caregiver adaptation over time: the longitudinal impact of behavior problems. Psychology and Aging, 15, 437450.
Gaugler J. E., Yu F., Krichbaum K., Wyman J. F. (2009). Predictors of nursing home admission for persons with dementia. Medical Care, 47, 191198.
Gauthier S. et al. ; Donepezil MSAD Study Investigators Group. (2002a) Efficacy of donepezil on behavioral symptoms in patients with moderate to severe Alzheimer's disease. International Psychogeriatrics, 14, 389404.
Gauthier S., Feldman H., Hecker J., Vellas B., Emir B. and Subbiah P.; Donepezil MSAD Study Investigators’ Group. (2002b). Functional, cognitive and behavioral effects of donepezil in patients with moderate Alzheimer's disease. Current Medical Research and Opinion, 18, 347354.
Gauthier S., Wirth Y. and Möbius H. J. (2005). Effects of memantine on behavioural symptoms in Alzheimer's disease patients; an analysis of the neuropsychiatric inventory (NPI) data of two randomised, controlled studies. International Journal of Geriatric Psychiatry, 20, 459464.
Gauthier S., Loft H. and Cummings J. (2008). Improvement in behavioral symptoms in patients with moderate to severe Alzheimer's disease by memantine: a pooled data analysis. International Journal of Geriatric Psychiatry, 23, 537545.
Gerdner L. A. (2000). Effects of individualized versus classical “relaxation” music on the frequency of agitation in elderly persons with Alzheimer's disease and related disorders. International Psychogeriatrics, 12, 4965.
Gill S. S. et al. (2005). Atypical antipsychotic drugs and risk of ischaemic stroke: population based retrospective cohort study. BMJ, 330, 445.
Goldwasser A. N., Auerbach S. M. and Harkins S. W. (1987). Cognitive, affective, and behavioral effects of reminiscence group therapy on demented elderly. International Journal of Aging and Human Development, 25, 209222.
Gonyea J. G., O'Connor M. K. and Boyle P. A. (2006). Project CARE: a randomized controlled trial of a behavioral intervention group for Alzheimer's disease caregivers. Gerontologist, 46, 827832.
Grant J. E. and Mohan S. N. (2001). Treatment of agitation and aggression in four demented patients using ECT. Journal of ECT, 17, 205209.
Gsell W., Jungkunz G. and Riederer P. (2004). Functional neurochemistry of Alzheimer's disease. Current Pharmaceutical Design, 10, 265293.
Hall G. R. and Buckwalter K. C. (1987). Progressively lowered stress threshold: a conceptual model for care of adults with Alzheimer's disease. Archives of Psychiatric Nursing, 1, 399406.
Hart D. J. et al. (2003). A retrospective study of the behavioural and psychological symptoms of mid and late phase Alzheimer's disease. International Journal of Geriatric Psychiatry, 18, 10371042.
Herrmann N., Mamdani M. and Lanctôt K. L. (2004). Atypical antipsychotics and risk of cerebrovascular accidents. American Journal of Psychiatry, 161, 11131115.
Herrmann N., Rabheru K., Wang J. and Binder C. (2005). Galantamine treatment of problematic behavior in Alzheimer disease: post-hoc analysis of pooled data from three large trials. American Journal Geriatric Psychiatry, 13, 527534.
Herrmann N., Lanctôt K., Rothenburg L. and Eryave G. (2007a). A placebo-controlled trial of valproate for agitation and aggression in Alzheimer's disease. Dementia and Geriatric Cognitive Disorders, 23, 116119.
Herrmann N., Gauthier S. and Lysy P. G. (2007b). Clinical practice guidelines for severe Alzheimer's disease. Alzheimer's & Dementia, 3, 385397.
Hirono N. et al. (1998). Frontal lobe hypometabolism and depression in Alzheimer's disease. Neurology, 50, 380383.
Hollis J., Grayson D., Forrester L., Brodaty H., Touyz S. and Cumming R. (2007). Antipsychotic medication dispensing and risk of death in veterans and war widows 65 years and older. American Journal of Geriatric Psychiatry, 15, 932941.
Holmes C., Hopkins V., Hensford C., MacLaughlin V., Wilkinson D. and Rosenvinge H. (2002). Lavender oil as a treatment for agitated behaviour in severe dementia: a placebo controlled study. International Journal of Geriatric Psychiatry, 17, 305308.
Holmes C. et al. (2004). The efficacy of donepezil in the treatment of neuropsychiatric symptoms in Alzheimer disease. Neurology, 63, 214219.
Holthoff V. A. et al. (2005). Regional cerebral metabolism in early Alzheimer's disease with clinically significant apathy or depression. Biological Psychiatry, 57, 412421.
Howard R. J. et al. ; CALM-AD Trial Group. (2007). Donepezil for the treatment of agitation in Alzheimer's disease. New England Journal of Medicine, 357 (14), 13821392.
ICH Tripartite Guideline (2000). Choice of Control Group and Related Issues in Clinical Trials. July 2000. International Conference on Harmonisation.
Jeste D. V. et al. (2008). ACNP White Paper: update on use of antipsychotic drugs in elderly persons with dementia. Neuropsychopharmacology, 33, 957970.
Jost B. C. and Grossberg G. T. (1996). The evolution of psychiatric symptoms in Alzheimer's disease: a natural history study. Journal of the American Geriatrics Society, 44, 10781081.
Kales H. C. et al. (2007). Mortality risk in patients with dementia treated with antipsychotics versus other psychiatric medications. American Journal of Psychiatry, 164, 15681576.
Karlsson I. et al. (2000). A randomised, double-blind comparison of the efficacy and safety of citalopram compared to mianserin in elderly, depressed patients with or without mild to moderate dementia. International Journal of Geriatric Psychiatry, 15, 295305.
Katagai H., Yasui-Furukori N., Kikuchi A. and Kaneko S. (2007). Effective electroconvulsive therapy in a 92-year-old dementia patient with psychotic feature. Psychiatry and Clinical Neurosciences, 61, 568570.
Katona C. L., Hunter B. N. and Bray J. (1998). A double-blind comparison of the efficacy and safely of paroxetine and imipramine in the treatment of depression with dementia. International Journal of Geriatric Psychiatry, 13, 100108.
Kaufer D. I. et al. (2000). Validation of the NPI-Q, a brief clinical form of the Neuropsychiatric Inventory. Journal of Neuropsychiatry & Clinical Neurosciences, 12, 233239.
Kelly K. G. and Zisselman M. (2000). Update on electroconvulsive therapy (ECT) in older adults. Journal of the American Geriatrics Society, 48, 560566.
Kotrla K. J., Chacko R. C., Harper R. G. and Doody R. (1995). Clinical variables associated with psychosis in Alzheimer's disease. American Journal of Psychiatry, 152, 13771379.
Lai M. K. P. et al. (2001). Psychosis of Alzheimer's disease is associated with elevated muscarinic M2 binding in the cortex. Neurology, 57, 805811.
Lanctôt K. L., Herrmann N., van Reekum R., Eryavec G. and Naranjo C. A. (2002). Gender, aggression and serotonergic function are associated with response to sertraline for behavioral disturbances in Alzheimer's disease. International Journal of Geriatric Psychiatry, 17, 531541.
Lawlor B. A., Radcliffe J., Molchan S. A., Martinez R. A., Hill J. L. and Sunderland T. (1994). A pilot placebo-controlled study of trazodone and buspirone in Alzheimer's disease. International Journal of Geriatric Psychiatry, 9, 5559.
Leroi I., Voulgari A., Breitner J. C. and Lyketsos C. G. (2003). The epidemiology of psychosis in dementia. American Journal of Geriatric Psychiatry, 11, 8391.
Lesser J. M. and Hughes S. (2006). Psychosis-related disturbances. Psychosis, agitation, and disinhibition in Alzheimer's disease: definitions and treatment options. Geriatrics, 61, 1420.
Lin P. W., Chan W. C., Ng B. F. and Lam L. C. (2007). Efficacy of aromatherapy (Lavandula angustifolia) as an intervention for agitated behaviours in Chinese older persons with dementia: a cross-over randomized trial. International Journal of Geriatric Psychiatry, 22, 405410.
Livingston G., Johnston K., Katona C., Paton J. and Lyketsos C. G. (2005). Systematic review of psychological approaches to the management of neuropsychiatric symptoms of dementia: American Journal of Psychiatry, 162, 19962021.
Lonergan E. and Luxenberg J. (2004). Valproate preparations for agiation in dementia. Cochrane Database of Systematic Reviews, Issue 2. Art No.: CD003945. DOI: 10.1002/14651858.CD003945.pub2.
Lonergan E., Luxenberg J., Colford J. and Birks J. (2002). Haloperidol for agitation in dementia. Cochrane Database of Systematic Reviews, Issue 2. Art. No.: CD002852. DOI: 10.1002/14651858.CD002852.
Lundbeck Limited (2009). Ebixa 10 mg/g oral drops, 20 mg and 10 mg tablets and treatment initiation pack. Summary of Product Characteristics. January 2009.
Lyketsos C. G. (2007). Neuropsychiatric symptoms (behavioral and psychological symptoms of dementia) and the development of dementia treatments. International Psychogeriatrics, 19, 409420.
Lyketsos C. G. and Olin J. (2002) Depression in Alzheimer's disease: overview and treatment. Biological Psychiatry, 52, 243252.
Lyketsos C. G., Tune L. E., Pearlson G. and Steele C. (1996). Major depression in Alzheimer's disease: an interaction between gender and family history. Psychosomatics, 37, 380384.
Lyketsos C. G., Steinberg M., Tschanz J. T., Norton M. C., Steffens D. C. and Breitner J. C. (2000). Mental and behavioral disturbances in dementia: findings from the Cache County Study on Memory in Aging. American Journal of Psychiatry, 157, 708714.
Lyketsos C. G. et al. (2001). Neuropsychiatric disturbance in Alzheimer's disease clusters into three groups: the Cache County study. International Journal of Geriatric Psychiatry, 16, 10431053.
Lyketsos C. G., Lopez O., Jones B., Fitzpatrick A. L., Breitner J. and DeKosky S. (2002). Prevalence of neuropsychiatric symptoms in dementia and mild cognitive impairment: results from the cardiovascular health study. JAMA, 288, 14751483.
Lyketsos C. G. et al. (2003). Treating depression in Alzheimer disease: efficacy and safety of sertraline therapy, and the benefits of depression reduction: the DIADS. Archives of General Psychiatry, 60, 737746.
Lyketsos C. G. et al. ; Task Force of American Association for Geriatric Psychiatry (2006). Position statement of the American Association for Geriatric Psychiatry regarding principles of care for patients with dementia resulting from Alzheimer's disease. American Journal of Geriatric Psychiatry, 14, 561572.
Magai C., Kennedy G., Cohen C. I. and Gomberg D. (2000). A controlled clinical trial of sertraline in the treatment of depression in nursing home patients with late-stage Alzheimer's disease. American Journal of Geriatric Psychiatry, 8, 6674.
Margallo-Lana M. et al. (2001). Prevalence and pharmacological management of behavioural and psychological symptoms amongst dementia sufferers living in care environments. International Journal of Geriatric Psychiatry, 16, 3944.
Marin R. S., Biedrzycki R. C. and Firinciogullari S. (1991). Reliability and validity of the Apathy Evaluation Scale. Psychiatry Research, 38, 143162.
Marshall G. A., Fairbanks L. A., Tekin S., Vinters H. V. and Cummings J. L. (2006). Neuropathologic correlates of apathy in Alzheimer's disease. Dementia and Geriatric Cognitive Disorders, 21, 144147.
Marshall G. A., Monserratt L., Harwood D., Mandelkern M., Cummings J. L. and Sultzer D. L. (2007). Positron emission tomography metabolic correlates of apathy in Alzheimer disease. Archives of Neurology, 64, 10151020.
Martin B. K. et al. (2006). Design of depression in Alzheimer's disease study-2. American Journal of Geriatric Psychiatry, 14, 920930.
Matthews H. P., Korbey J., Wilkinson D. G. and Rowden J. (2000). Donepezil in Alzheimer's disease: eighteen month results from Southampton memory clinic. International Journal of Geriatric Psychiatry, 15, 713720.
Mayer L. S. et al. (2006). Comparison of three rating scales as outcome measures for treatment trials of depression in Alzheimer disease: findings from DIADS. International Journal of Geriatric Psychiatry, 21, 930936.
McKeith I. et al. (2000). Efficacy of rivastigmine in dementia with Lewy bodies: a randomised, double-blind, placebo-controlled international study. Lancet, 356, 20312036.
Mega M. S. et al. (2000). Orbital and dorsolateral frontal perfusion defect associated with behavioral response to cholinesterase inhibitor therapy in Alzheimer's disease. Journal of Neuropsychiatry and Clinical Neuroscience, 12, 209218.
MHRA (2004). Summary of Clinical Trial Data on Cerebrovascular Adverse Events (CVAEs) in Randomized Clinical Trials of Risperidone Conducted in Patients with Dementia. 9 March 2004. Medicines and Healthcare Products Regulatory Agency. Available at: http://www.mhra.gov.uk/home/groups/pl-p/documents/websiteresources/con019490.pdf.
Miesen B. M. L. and Jones G. M. M. (eds.) (1997). Care-giving in Dementia: Research and Applications. Vol. 2. London and New York: Routledge.
Migneco O. et al. (2001). Perfusion brain SPECT and statistical parametric mapping analysis indicate that apathy is a cingulate syndrome: a study in Alzheimer's disease and nondemented patients. NeuroImage, 13, 896902.
Minger S. L. et al. (2000). Cholinergic deficits contribute to behavioral disturbance in patients with dementia. Neurology, 55, 14601467.
Mintzer J. et al. (2006). Risperidone in the treatment of psychosis of Alzheimer disease: results from a prospective clinical trial. American Journal of Geriatric Psychiatry, 14, 280291.
Mintzer J. et al. (2007). Aripiprazole for the treatment of psychoses in institutionalized patients with Alzheimer dementia: a multicenter, randomized, double-blind, placebo-controlled assessment of three fixed doses. American Journal of Geriatric Psychiatry, 15, 918931.
Montgomery S. and Åsberg M. (1979). A new depression scale designed to be sensitive to change. British Journal of Psychiatry, 134, 382389.
Moran M., Walsh C., Lynch A., Coen R., Coakley D. and Lawlor B. (2004). Syndromes of behavioural and psychological symptoms in mild Alzheimer's disease. International Journal of Geriatric Psychiatry, 19, 359364.
Moran M., Lynch C. A., Walsh C., Coen R., Coakley D. and Lawlor B. A. (2005). Sleep disturbance in mild to moderate Alzheimer's disease. Sleep Medicine, 6, 347352.
Müller W. E., Mutschler E. and Riederer P. (1995). Noncompetitive NMDA receptor antagonists with fast open-channel blocking kinetics and strong voltage-dependency as potential therapeutic agents for Alzheimer's dementia. Pharmacopsychiatry, 28, 113124.
Novartis Pharmaceuticals U.K. Limited (2009). Exelon: Summary of Product Characteristics. March, Novartis Pharmaceuticals U.K. Ltd.
Nyth A. L. et al. (1992). A controlled multicenter clinical study of citalopram and placebo in elderly depressed patients with and without concomitant dementia. Acta Psychiatrica Scandinavica, 86, 138145.
Olin J. T., Fox L. S., Pawluczyk S., Taggart N. A. and Schneider L. S. (2001). A pilot randomized trial of carbamazepine for behavioral symptoms in treatment-resistant outpatients with Alzheimer disease. American Journal of Geriatric Psychiatry, 9, 400405.
Olin J. T. et al. (2002). Provisional diagnostic criteria for depression of Alzheimer disease. American Journal of Geriatric Psychiatry, 10, 125128.
Onyike C. U. et al. (2007) Epidemiology of apathy in older adults: the Cache County Study. American Journal of Geriatric Psychiatry, 15, 365375.
Pachana N. A., Byrne G. J., Siddle H., Koloski N., Harley E. and Arnold E. (2007). Development and validation of the geriatric anxiety inventory. International Psychogeriatrics, 19, 103114.
Pearlson G. D., Ross C. A., Lohr W. D., Rovner B. W., Chase G. A. and Folstein M. F. (1990). Association between family history of affective disorder and the depressive syndrome of Alzheimer's disease. American Journal of Psychiatry, 147, 452456.
Perry E. K., Perry R. H., Blessed G. and Tomlinson B. E. (1977). Necropsy evidence of central cholinergic deficits in senile dementia. Lancet, 1, 189.
Petracca G., Tesón A., Chemerinski E., Leiguarda R. and Starkstein S. E. (1996). A double-blind placebo-controlled study of clomipramine in depressed patients with Alzheimer's disease. Journal of Neuropsychiatry and Clinical Neurosciences, 8, 270275.
Pollock B. G. et al. (2002). Comparison of citalopram, perphenazine, and placebo for the acute treatment of psychosis and behavioral disturbances in hospitalized, demented patients. American Journal of Psychiatry, 159, 460465.
Pollock B. G. et al. (2007). A double-blind comparison of citalopram and risperidone for the treatment of behavioral and psychotic symptoms associated with dementia. American Journal of Geriatric Psychiatry, 15, 942952.
Porsteinsson A. P. (2006). Divalproex sodium for the treatment of behavioural problems associated with dementia in the elderly. Drugs and Aging, 23, 877886.
Porsteinsson A. P. et al. (2001). Placebo-controlled study of divalproex sodium for agitation in dementia. American Journal of Geriatric Psychiatry, 9, 5866.
Price T. R. and McAllister T. W. (1989). Safety and efficacy of ECT in depressed patients with dementia: a review of clinical experience. Convulsive Therapy, 5, 6174.
Ramadan F. H., Naughton B. J. and Bassanelli A. G. (2000). Treatment of verbal agitation with a selective serotonin reuptake inhibitor. Journal of Geriatric Psychiatry and Neurology, 13, 5659.
Rao V. and Lyketsos C. G. (2000). The benefits and risks of ECT for patients with primary dementia who also suffer from depression. International Journal of Geriatric Psychiatry, 15, 729735.
Rapp M. et al. (2006). Increased hippocampal plaques and tangles in patients with Alzheimer disease with a lifetime history of major depression. Archives of General Psychiatry, 63, 161167.
Raskind M. A. and Peskind E. R. (1994). Neurobiologic bases of noncognitive behavioural problems in Alzheimer disease. Alzheimer Disease and Associated Disorders, 8 (Suppl. 3), 5460.
Reifler B. V. et al. (1989). Double-blind trial of imipramine in Alzheimer's disease patients with and without depression. American Journal of Psychiatry, 146, 4549.
Reilly J. G., Ayis S. A., Ferrier I. N., Jones S. J. and Thomas S. H. (2000). QTc-interval abnormalities and psychotropic drug therapy in psychiatric patients. Lancet, 355, 10481052.
Reisberg B., Borenstein J., Salob S. P., Ferris S. H. and Franssen E. (1987). Behavioural symptoms in Alzheimer's disease: phenomenology and treatment. Journal of Clinical Psychiatry, 48, 915.
Reisberg B., Doody R., Stöffler A, Schmitt F., Ferris S. and Möbius H. J.; Memantine Study Group (2003). Memantine in moderate-to-severe Alzheimer's disease. New England Journal of Medicine, 348, 13331341.
Reynish E. et al. ; ICTUS Study Group. (2007). The ICTUS Study: a prospective longitudinal observational study of 1,380 AD patients in Europe. Study design and baseline characteristics of the cohort. Neuroepidemiology, 29 (1–2), 2938.
Rinne J. O. et al. (2003). Brain acetylcholinesterase activity in mild cognitive impairment and early Alzheimer's disease. Journal of Neurology, Neurosurgery, and Psychiatry, 74, 113115.
Robert P. H. et al. (2002). The Apathy Inventory: assessment of apathy and awareness in Alzheimer's disease, Parkinson's disease and mild cognitive impairment. International Journal of Geriatric Psychiatry, 17, 10991105.
Robert P. H. et al. (2005). Grouping for behavioral and psychological symptoms in dementia: clinical and biological aspects. Consensus paper of the European Alzheimer Disease Consortium. European Psychiatry, 20, 490496.
Robert P. H. et al. ; PréAL Study Group. (2008a). Importance of lack of interest in patients with mild cognitive impairment. American Journal of Geriatric Psychiatry, 16, 770776.
Robert P. H., Reynish E., Cantet C. and Vellas B. (2008b). Measurement of behavioural symptoms and response to treatment in clinical trials. Journal of Nutrition, Health and Aging, 12, 539.
Rösler M., Retz W., Retz-Junginger P. and Dennler H. J. (1998). Effects of two-year treatment with the cholinesterase inhibitor rivastigmine on behavioural symptoms in Alzheimer's disease. Behavioural Neurology, 11, 211216.
Roth M., Mountjoy C. Q. and Amrein R. (1996). Moclobemide in elderly patients with cognitive decline and depression: an international double-blind, placebo-controlled trial. British Journal of Psychiatry, 168, 149157.
Scarmeas N. et al. (2007). Disruptive behavior as a predictor in Alzheimer disease. Archives of Neurology, 64, 17551871.
Schneider L. S., Pollock V. E. and Lyness S. A. (1990). A meta-analysis of controlled trials of neuroleptic treatment in dementia. Journal of the American Geriatrics Society, 38, 553563.
Schneider L. S., Dagerman K. S. and Insel P. (2005). Risk of death with atypical antipsychotic drug treatment for dementia: meta-analysis of randomized placebo-controlled trials. Journal of the American Medical Association, 294, 19341943.
Schneider L. S., Dagerman K. and Insel P. S. (2006a). Efficacy and adverse effects of atypical antipsychotics for dementia: meta-analysis of randomized, placebo-controlled trials. American Journal of Geriatric Psychiatry, 14, 191210.
Schneider L. S. et al. ; CATIE-AD Study Group (2006b). Effectiveness of atypical antipsychotic drugs in patients with Alzheimer's disease. New England Journal of Medicine, 355, 15251538.
Senanarong V. et al. (2004). Agitation in Alzheimer's disease is a manifestation of frontal lobe dysfunction. Dementia and Geriatric Cognitive Disorders, 17, 1420.
Sernyak M. J., Leslie D. L., Alarcon R. D., Losonczy M. F. and Rosenheck R. (2002). Association of diabetes mellitus with use of atypical neuroleptics in the treatment of schizophrenia. American Journal of Psychiatry, 159, 561566.
Shire Pharmaceuticals Limited (2008). Reminyl tablets. Summary of Product Characteristics. May 2008.
Sival R. C., Haffmans P. M., Jansen P. A., Duursma S. A. and Eikelenboom P. (2002). Sodium valproate in the treatment of aggressive behavior in patients with dementia – a randomized placebo controlled clinical trial. International Journal of Geriatric Psychiatry, 17, 579585.
Spalletta G. et al. (2004). Cognition and behaviour are independent and heterogeneous dimensions in Alzheimer's disease. Journal of Neurology, 251, 688695.
Steinberg M. et al. ; Cache County Investigators. (2008). Point and 5-year period prevalence of neuropsychiatric symptoms in dementia: the Cache County Study. International Journal of Geriatric Psychiatry, 23, 170177.
Stek M. L., van der Wurff F. F. B., Hoogendijk W. J. G. and Beekman A. T. F. (2003). Electroconvulsive therapy for the depressed elderly. Cochrane Database of Systematic Reviews, Issue 2. Art. No.: CD003593. DOI: 10.1002/14651858.CD003593.
Strauss M. E. and Ogrocki P. K. (1996). Confirmation of an association between family history of affective disorder and the depressive syndrome in Alzheimer's disease. American Journal of Psychiatry, 153, 13401342.
Sultzer D. L., Gray K. F., Gunay I., Berisford M. A. and Mahler M. E. (1997). A double-blind comparison of trazodone and haloperidol for treatment of agitation in patients with dementia. American Journal of Geriatric Psychiatry, 5, 6069.
Sutor B. and Rasmussen K. G. (2008). Electroconvulsive therapy for agitation in Alzheimer disease: a case series. Journal of ECT, 24, 239241.
Talassi E., Cipriani G., Bianchetti A., and Trabucchi M. (2007). Personality changes in Alzheimer's disease. Aging and Mental Health, 11, 526531.
Taragano F. E., Lyketsos C. G., Mangone C. A., Allegri R. F. and Comesaña-Diaz E. (1997). A double-blind, randomized, fixed-dose trial of fluoxetine vs. amitriptyline in the treatment of major depression complicating Alzheimer's disease. Psychosomatics, 38, 246252.
Tariot P. N. et al. (1994). Carbamazepine treatment of agitation in nursing home patients with dementia: a preliminary study. Journal of the American Geriatrics Society, 42, 11601166.
Tariot P. N. et al. (1998). Efficacy and tolerability of carbamazepine for agitation and aggression in dementia. American Journal of Psychiatry, 155, 5461.
Tariot P. N., Solomon P. R., Morris J. C., Kershaw P., Lilienfeld S. and Ding C. (2000). A 5-month, randomized, placebo-controlled trial of galantamine in AD. The galantamine USA-10 study group. Neurology, 54, 22692276.
Tariot P. N. et al. (2001a). Safety and tolerability of divalproex sodium for the treatment of signs and symptoms of mania in elderly patients with dementia: results of a double-blind, placebo-controlled trial. Current Therapeutic Research, 62, 5167.
Tariot P. N. et al. (2001b). 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. Journal of the American Geriatrics Society, 49, 15901599.
Tariot P. N., Farlow M. R., Grossberg G. T., Graham S. M., McDonald S. and Gergel I.; Memantine Study Group. (2004). Memantine treatment in patients with moderate to severe Alzheimer disease already receiving donepezil. Journal of the American Medical Association, 291, 317324.
Tariot P. N. et al. ; the Alzheimer's Disease Cooperative Study; Valproate Nursing Home Study Group. (2005). Divalproex sodium in nursing home residents with possible or probable Alzheimer Disease complicated by agitation: a randomized, controlled trial. American Journal of Geriatric Psychiatry, 13, 942949.
Tekin S. et al. (2001). Orbitofrontal and anterior cingulate cortex neurofibrillary tangle burden is associated with agitation in Alzheimer disease. Annals of Neurology, 49, 355361.
Teng E., Lu P. H. and Cummings J. L. (2007). Neuropsychiatric symptoms are associated with progression from mild cognitive impairment to Alzheimer's disease. Dementia and Geriatric Cognitive Disorders, 24, 253259.
Teri L., Logsdon R. G., Uomoto J. and McCurry S. M. (1997). Behavioral treatment of depression in dementia patients: a controlled clinical trial. Journals of Gerontology Series B: Psychological Sciences and Social Sciences, 52, 159166.
Teri L. et al. ; Alzheimer's Disease Cooperative Study (2000). Treatment of agitation in AD: a randomized, placebo-controlled clinical trial. Neurology, 55, 12711278.
Treiber K. A. et al. (2008). Vascular factors and risk for neuropsychiatric symptoms in Alzheimer's disease: the Cache County Study. International Psychogeriatrics, 20, 538553.
Tune L. E., Steele C. and Cooper T. (1991). Neuroleptic drugs in the management of behavioral symptoms of Alzheimer's disease. Psychiatric Clinics of North America, 14, 353373.
van der Flier W. M. et al. (2007). Apolipoprotein E genotype influences presence and severity of delusions and aggressive behavior in Alzheimer disease. Dementia and Geriatric Cognitive Disorders, 23, 4246.
van Dyck C. H., Tariot P. N., Meyers B. and Resnick M. E.; for the Memantine MEM-MD-01 Study Group (2007). A 24-week randomized, controlled trial of memantine in patients with moderate-to-severe Alzheimer disease. Alzheimer Disease and Associated Disorders, 21, 136143.
Vidal J. S. et al. (2008). Evaluation of the impact of memantine treatment initiation on psychotropics use: a study from the French national health care database. Neuroepidemiology, 31, 193200.
Vitiello M. V. and Borson S. (2001). Sleep disturbances in patients with Alzheimer's disease: epidemiology, pathophysiology and treatment. CNS Drugs, 15, 777796.
Wang P. S. et al. (2005). Risk of death in elderly users of conventional vs. atypical antipsychotic medications. New England Journal of Medicine, 353, 23352341.
Welden S. and Yesavage J. A. (1982). Behavioral Improvement with relaxation training in senile dementia. Clinical Gerontologist, 1, 4549.
Whall A. L., Black M. E., Groh C.J., Yankou D. J., Kupferschmid B. J. and Foster N. L. (1997). The effect of natural environments upon agitation and aggression in late stage dementia patients. American Journal of Alzheimer's Disease and Other Dementias, 12, 216220.
Wilcock G. K., Ballard C. G., Cooper J. A. and Loft H. (2008). Memantine for agitation/aggression and psychosis in moderately severe to severe Alzheimer's disease: a pooled analysis of 3 studies. Journal of Clinical Psychiatry, 69, 341348.
Winblad B. et al. ; Severe Alzheimer's Disease Study Group. (2006). Donepezil in patients with severe Alzheimer's disease: double-blind, parallel-group, placebo-controlled study. Lancet, 367, 10571065.
Winblad B., Jones R. W., Wirth Y., Stöffler A. and Möbius H. J. (2007). Memantine in moderate to severe Alzheimer's disease: a meta-analysis of randomised clinical trials. Dementia and Geriatric Cognitive Disorders, 24, 2027.
Wooltorton E. (2004). Olanzapine (Zyprexa): increased incidence of cerebrovascular events in dementia trials. Canadian Medical Association Journal, 170, 1395.
Wu H. Z., Low L. F., Xia o S. and Brodaty H. (2009). A pilot study of differences in behavioral and psychological symptoms of dementia in nursing home residents in Sydney and Shanghai. International Psychogeriatrics, 21, 476484.
Wu Y. H. et al. (2006) Pineal clock gene oscillation is disturbed in Alzheimer's disease, due to functional disconnection from the “master clock”. Federation of American Societies for Experimental Biology Journal, 20, 18741876.
Yaffe K. et al. (2002). Patient and caregiver characteristics and nursing home placement in patients with dementia. JAMA, 287, 20902097.
Yesavage J. A. et al. (1982–1983). Development and validation of a geriatric depression screening scale: a preliminary report. Journal of Psychiatric Research, 17, 3749.
Zarros A. C., Kalopita K. S. and Tsakiris S. T. (2005). Serotoninergic impairment and aggressive behaviour in Alzheimer's disease. Acta Neurobiologiae Experimentalis, 65, 277286.
Zink M., Sartorius A., Lederbogen F. and Henn F. A. (2002). Electroconvulsive therapy in a patient receiving rivastigmine. Journal of ECT, 18, 162164.
Recommend this journal

Email your librarian or administrator to recommend adding this journal to your organisation's collection.

International Psychogeriatrics
  • ISSN: 1041-6102
  • EISSN: 1741-203X
  • URL: /core/journals/international-psychogeriatrics
Please enter your name
Please enter a valid email address
Who would you like to send this to? *
×

Keywords:

Metrics

Altmetric attention score

Full text views

Total number of HTML views: 49
Total number of PDF views: 289 *
Loading metrics...

Abstract views

Total abstract views: 1240 *
Loading metrics...

* Views captured on Cambridge Core between September 2016 - 20th October 2017. This data will be updated every 24 hours.