Behavioral and psychological symptoms of dementia

J Cerejeira, L Lagarto, E B Mukaetova-Ladinska, J Cerejeira, L Lagarto, E B Mukaetova-Ladinska

Abstract

Behavioral and psychological symptoms of dementia (BPSD), also known as neuropsychiatric symptoms, represent a heterogeneous group of non-cognitive symptoms and behaviors occurring in subjects with dementia. BPSD constitute a major component of the dementia syndrome irrespective of its subtype. They are as clinically relevant as cognitive symptoms as they strongly correlate with the degree of functional and cognitive impairment. BPSD include agitation, aberrant motor behavior, anxiety, elation, irritability, depression, apathy, disinhibition, delusions, hallucinations, and sleep or appetite changes. It is estimated that BPSD affect up to 90% of all dementia subjects over the course of their illness, and is independently associated with poor outcomes, including distress among patients and caregivers, long-term hospitalization, misuse of medication, and increased health care costs. Although these symptoms can be present individually it is more common that various psychopathological features co-occur simultaneously in the same patient. Thus, categorization of BPSD in clusters taking into account their natural course, prognosis, and treatment response may be useful in the clinical practice. The pathogenesis of BPSD has not been clearly delineated but it is probably the result of a complex interplay of psychological, social, and biological factors. Recent studies have emphasized the role of neurochemical, neuropathological, and genetic factors underlying the clinical manifestations of BPSD. A high degree of clinical expertise is crucial to appropriately recognize and manage the neuropsychiatric symptoms in a patient with dementia. Combination of non-pharmacological and careful use of pharmacological interventions is the recommended therapeutic for managing BPSD. Given the modest efficacy of current strategies, there is an urgent need to identify novel pharmacological targets and develop new non-pharmacological approaches to improve the adverse outcomes associated with BPSD.

Keywords: Alzheimer’s disease; behavioral and psychological symptoms; dementia; neuropsychiatric symptoms.

References

    1. Aalten P., de Vugt M. E., Jaspers N., Jolles J., Verhey F. R. (2005a). The course of neuropsychiatric symptoms in dementia. Part I: findings from the two-year longitudinal Maasbed study. Int. J. Geriatr. Psychiatry 20, 523–53010.1002/gps.1317
    1. Aalten P., de Vugt M. E., Jaspers N., Jolles J., Verhey F. R. (2005b). The course of neuropsychiatric symptoms in dementia. Part II: relationships among behavioural sub-syndromes and the influence of clinical variables. Int. J. Geriatr. Psychiatry 20, 531–53610.1002/gps.1317
    1. Aalten P., de Vugt M. E., Lousberg R., Korten E., Jaspers N., Senden B., Jolles J., Verhey F. R. (2003). Behavioral problems in dementia: a factor analysis of the neuropsychiatric inventory. Dement. Geriatr. Cogn. Disord. 15, 99–10510.1159/000067972
    1. Aalten P., Verhey F. R., Boziki M., Brugnolo A., Bullock R., Byrne E. J., Camus V., Caputo M., Collins D., De Deyn P. P., Elina K., Frisoni G., Holmes C., Hurt C., Marriott A., Mecocci P., Nobili F., Ousset P. J., Reynish E., Salmon E., Tsolaki M., Vellas B., Robert P. H. (2008). Consistency of neuropsychiatric syndromes across dementias: results from the European Alzheimer Disease Consortium. Part II. Dement. Geriatr. Cogn. Disord. 25, 1–810.1159/000111082
    1. Aalten P., Verhey Caputo M., Collins D., De Deyn P. P., Elina K., Frisoni G., Girtler N., Holmes C., Hurt C., Marriott A., Mecocci P., Nobili F., Ousset P. J., Reynish E., Salmon E., Tsolaki M., Vellas B., Robert P. H. (2007). Neuropsychiatric syndromes in dementia. Results from the European Alzheimer Disease Consortium: part I. Dement. Geriatr. Cogn. Disord. 24, 457–46310.1159/000110738
    1. Aharon-Peretz J., Kliot D., Tomer R. (2000). Behavioral differences between white matter lacunar dementia and Alzheimer’s disease: a comparison on the neuropsychiatric inventory. Dement. Geriatr. Cogn. Disord. 11, 294–29810.1159/000017252
    1. Alexopoulos G. S. (2005). Depression in the elderly. Lancet 365, 1961–197010.1016/S0140-6736(05)66665-2
    1. American Psychiatric Association (1994). Diagnostic and Statistical Manual of Mental Disorders, 4th Edn. Washington, DC: American Psychiatric Association
    1. Angelucci F., Bernardini S., Gravina P., Bellincampi L., Trequattrini A., Di Iulio F., Vanni D., Federici G., Caltagirone C., Bossù P., Spalletta G. (2009). Delusion symptoms and response to antipsychotic treatment are associated with the 5-HT2A receptor polymorphism (102T/C) in Alzheimer’s disease: a 3-year follow-up longitudinal study. J. Alzheimers Dis. 17, 203–211
    1. Apostolova L. G., Akopyan G. G., Partiali N., Steiner C. A., Dutton R. A., Hayashi K. M., Dinov I. D., Toga A. W., Cummings J. L., Thompson P. M. (2007). Structural correlates of apathy in Alzheimer’s disease. Dement. Geriatr. Cogn. Disord. 24, 91–9710.1159/000103914
    1. Azermai M., Petrovic M., Elseviers M. M., Bourgeois J., Van Bortel L. M., Vander Stichele R. H. (2011). Systematic appraisal of dementia guidelines for the management of behavioural and psychological symptoms. Ageing Res. Rev. 11, 78–8610.1016/j.arr.2011.07.002
    1. Ballard C., Brown R., Fossey J., Douglas S., Bradley P., Hancock J., James I. A., Juszczak E., Bentham P., Burns A., Lindesay J., Jacoby R., O’Brien J., Bullock R., Johnson T., Holmes C., Howard R. (2009). Brief psychosocial therapy for the treatment of agitation in Alzheimer disease (the CALM-AD trial). Am. J. Geriatr. Psychiatry 17, 726–73310.1097/JGP.0b013e3181b0f8c0
    1. Ballard C., Day S., Sharp S., Wing G., Sorensen S. (2008). Neuropsychiatric symptoms in dementia: importance and treatment considerations. Int. Rev. Psychiatry 20, 396–40410.1080/09540260802099968
    1. Ballard C., Neill D., O’Brien J., McKeith I. G., Ince P., Perry R. (2000a). Anxiety, depression and psychosis in vascular dementia: prevalence and associations. J. Affect. Disord. 59, 97–10610.1016/S0165-0327(99)00057-9
    1. Ballard C., Piggott M., Johnson M., Cairns N., Perry R., McKeith I., Jaros E., O’Brien J., Holmes C., Perry E. (2000b). Delusions associated with elevated muscarinic binding in dementia with Lewy bodies. Ann. Neurol. 48, 868–87610.1002/1531-8249(200012)48:6<868::AID-ANA7>;2-S
    1. Ballard C., O’Brien J., Gray A., Cormack F., Ayre G., Rowan E., Thompson P., Bucks R., McKeith I., Walker M., Tovee M. (2001). Attention and fluctuating attention in patients with dementia with Lewy bodies and Alzheimer disease. Arch. Neurol. 58, 977–98210.1001/archneur.58.6.977
    1. Ballard C. G., Jacoby R., Del Ser T., Khan M. N., Munoz D. G., Holmes C., Nagy Z., Perry E. K., Joachim C., Jaros E., O’Brien J. T., Perry R. H., McKeith I. G. (2004). Neuropathological substrates of psychiatric symptoms in prospectively studied patients with autopsy-confirmed dementia with Lewy bodies. Am. J. Psychiatry 161, 843–84910.1176/appi.ajp.161.5.843
    1. Bathgate D., Snowden J. S., Varma A., Blackshaw A., Neary D. (2001). Behaviour in frontotemporal dementia, Alzheimer’s disease and vascular dementia. Acta Neurol. Scand. 103, 367–37810.1034/j.1600-0404.2001.2000236.x
    1. Beeri M. S., Werner P., Davidson M., Noy S. (2002). The cost of behavioral and psychological symptoms of dementia (BPSD) in community dwelling Alzheimer’s disease patients. Int. J. Geriatr. Psychiatry 17, 403–40810.1002/gps.490
    1. Benoit M., Dygai I., Migneco O., Robert P. H., Bertogliati C., Darcourt J., Benoliel J., Aubin-Brunet V., Pringuey D. (1999). Behavioral and psychological symptoms inAlzheimer’s disease. Dement. Geriatr. Cogn. Disord. 10, 511–51710.1159/000017198
    1. Bergh S., Engedal K., Røen I., Selbæk G. (2011). The course of neuropsychiatric symptoms in patients with dementia in Norwegian nursing homes. Int. Psychogeriatr. 23, 1231–123910.1017/S1041610211001177
    1. Berlow Y. A., Wells W. M., Ellison J. M., Sung Y. H., Renshaw P. F., Harper D. G. (2010). Neuropsychiatric correlates of white matter hyperintensities in Alzheimer’s disease. Int. J. Geriatr. Psychiatry 25, 780–78810.1002/gps.2418
    1. Borroni B., Grassi M., Agosti C., Costanzi C., Archetti S., Franzoni S., Caltagirone C., Di Luca M., Caimi L., Padovani A. (2006). Genetic correlates of behavioral endophenotypes in Alzheimer disease: role of COMT, 5-HTTLPR and APOE polymorphisms. Neurobiol. Aging 27, 1595–160310.1016/j.neurobiolaging.2005.09.029
    1. Bozeat S., Gregory C. A., Ralph M. A., Hodges J. R. (2000). Which neuropsychiatric and behavioural features distinguish frontal and temporal variants of frontotemporal dementia from Alzheimer’s disease? J. Neurol. Neurosurg. Psychiatr. 69, 178–18610.1136/jnnp.69.2.178
    1. Briesacher B. A., Limcangco M. R., Simoni-Wastila L., Doshi J. A., Levens S. R., Shea D. G., Stuart B. (2005). The quality of antipsychotic drug prescribing in nursing homes. Arch. Intern. Med. 165, 1280–128510.1001/archinte.165.11.1280
    1. Bruen P. D., McGeown W. J., Shanks M. F., Venneri A. (2008). Neuroanatomical correlates of neuropsychiatric symptoms in Alzheimer’s disease. Brain 131(Pt 9), 2455–246310.1093/brain/awn151
    1. Campbell P., Wright J., Oyebode J., Job D., Crome P., Bentham P., Jones L., Lendon C. (2008). Determinants of burden in those who care for someone with dementia. Int. J. Geriatr. Psychiatry 23, 1078–108510.1002/gps.2071
    1. Caraci F., Copani A., Nicoletti F., Drago F. (2010). Depression and Alzheimer’s disease: neurobiological links and common pharmacological targets. Eur. J. Pharmacol. 626, 64–7110.1016/j.ejphar.2009.10.022
    1. Casanova M. F., Starkstein S. E., Jellinger K. A. (2011). Clinicopathological correlates of behavioral and psychological symptoms of dementia. Acta Neuropathol. 122, 117–13510.1007/s00401-011-0821-3
    1. Chan D. C., Kasper J. D., Black B. S., Rabins P. V. (2003). Presence of behavioral and psychological symptoms predicts nursing home placement in community-dwelling elders with cognitive impairment in univariate but not multivariate analysis. J. Gerontol. A Biol. Sci. Med. Sci. 58, 548–55410.1093/gerona/58.6.M548
    1. Chan W. C., Lam L. C., Tam C. W., Lui V. W., Leung G. T., Lee A., Chan S. S., Fung A. W., Chiu H. F., Chan W. M. (2011). Neuropsychiatric symptoms are associated with increased risks of progression to dementia: a 2-year prospective study of 321 Chinese older persons with mild cognitive impairment. Age Ageing 40, 30–3510.1093/ageing/afq151
    1. Chen J. C., Borson S., Scanlan J. M. (2000). Stage-specific prevalence of behavioral symptoms in Alzheimer’s disease in a multi-ethnic community sample. Am. J. Geriatr. Psychiatry 8, 123–13310.1176/appi.ajgp.8.2.123
    1. Cheng T. W., Chen T. F., Yip P. K., Hua M. S., Yang C. C., Chiu M. J. (2009). Comparison of behavioral and psychological symptoms of Alzheimer’s disease among institution residents and memory clinic outpatients. Int. Psychogeriatr. 21, 1134–114110.1017/S1041610209990767
    1. Chiu M. J., Chen T. F., Yip P. K., Hua M. S., Tang L. Y. (2006). Behavioral and psychologic symptoms in different types of dementia. J. Formos. Med. Assoc. 105, 556–56210.1016/S0929-6646(09)60134-0
    1. Choi A. N., Lee M. S., Cheong K. J., Lee J. S. (2009). Effects of group music intervention on behavioral and psychological symptoms in patients with dementia: a pilot-controlled trial. Int. J. Neurosci. 119, 471–48110.1080/00207450802328136
    1. Chow T. W., Liu C. K., Fuh J. L., Leung V. P., Tai C. T., Chen L. W., Wang S. J., Chiu H. F., Lam L. C., Chen Q. L., Cummings J. L. (2002). Neuropsychiatric symptoms of Alzheimer’s disease differ in Chinese and American patients. Int. J. Geriatr. Psychiatry 17, 22–2810.1002/gps.509
    1. Cohen-Mansfield J. (1999). Measurement of inappropriate behavior associated with dementia. J. Gerontol. Nurs. 25, 42–51
    1. Cohen-Mansfield J., Marx M. S., Dakheel-Ali M., Regier N. G., Thein K., Freedman L. (2010). Can agitated behavior of nursing home residents with dementia be prevented with the use of standardized stimuli? J. Am. Geriatr. Soc. 58, 1459–146410.1111/j.1532-5415.2010.03172.x
    1. Craig A. H., Cummings J. L., Fairbanks L., Itti L., Miller B., Li J., Mena I. (1996). Cerebral blood flow correlates of apathy in Alzheimer disease. Arch. Neurol. 53, 1116–112010.1001/archneur.1996.00550110056012
    1. Craig D., Mirakhur A., Hart D. J., McIlroy S. P., Passmore A. P. (2005). A cross-sectional study of neuropsychiatric symptoms in 435 patients with Alzheimer’s disease. Am. J. Geriatr. Psychiatry 13, 460–46810.1176/appi.ajgp.13.6.460
    1. Cummings J. L. (1997). The neuropsychiatric inventory: assessing psychopathology in dementia patients. Neurology 48(5 Suppl. 6), S10–S16
    1. Cummings J. L. (2004). Treatment of Alzheimer’s disease: current and future therapeutic approaches. Rev. Neurol. Dis. 1, 60–69
    1. de Vugt M. E., Stevens F., Aalten P., Lousberg R., Jaspers N., Winkens I., Jolles J., Verhey F. R. (2003). Behavioural disturbances in dementia patients and quality of the marital relationship. Int. J. Geriatr. Psychiatry 18, 149–15410.1002/gps.807
    1. de Vugt M. E., Stevens F., Aalten P., Lousberg R., Jaspers N., Winkens I., Jolles J., Verhey F. R. (2004). Do caregiver management strategies influence patient behaviour in dementia? Int. J. Geriatr. Psychiatry 19, 85–9210.1002/gps.1044
    1. Dechamps A., Jutand M. A., Onifade C., Richard-Harston S., Bourdel-Marchasson I. (2008). Co-occurrence of neuropsychiatric syndromes in demented and psychotic institutionalized elderly. Int. J. Geriatr. Psychiatry 23, 1182–119010.1002/gps.2052
    1. Devanand D. P., Brockington C. D., Moody B. J., Brown R. P., Mayeux R., Endicott J., Sackeim H. A. (1992). Behavioral syndromes in Alzheimer’s disease. Int. Psychogeriatr. 4(Suppl. 2), 161–184
    1. Di Iulio F., Palmer K., Blundo C., Casini A. R., Gianni W., Caltagirone C., Spalletta G. (2010). Occurrence of neuropsychiatric symptoms and psychiatric disorders in mild Alzheimer’s disease and mild cognitive impairment subtypes. Int. Psychogeriatr. 22, 629–64010.1017/S1041610210000281
    1. Di Maria E., Bonvicini C., Bonomini C., Alberici A., Zanetti O., Gennarelli M. (2009). Genetic variation in the G720/G30 gene locus (DAOA) influences the occurrence of psychotic symptoms in patients with Alzheimer’s disease. J. Alzheimers Dis. 18, 953–960
    1. Egger K., Schocke M., Weiss E., Auffinger S., Esterhammer R., Goebel Walch T., Mechtcheriakov S., Marksteiner J. (2008). Pattern of brain atrophy in elderly patients with depression revealed by voxel-based morphometry. Psychiatry Res. 164, 237–24410.1016/j.pscychresns.2007.12.018
    1. Emanuel J. E., Lopez O. L., Houck P. R., Becker J. T., Weamer E. A., Demichele-Sweet M. A., Kuller L., Sweet R. A. (2011). Trajectory of cognitive decline as a predictor of psychosis in early Alzheimer disease in the cardiovascular health study. Am. J. Geriatr. Psychiatry 19, 160–16810.1097/JGP.0b013e3181e446c8
    1. Farber N. B., Rubin E. H., Newcomer J. W., Kinscherf D. A., Miller J. P., Morris J., Olney J. W., McKeel D. W., Jr. (2000). Increased neocortical neurofibrillary tangle density in subjects with Alzheimer disease and psychosis. Arch. Gen. Psychiatry 57, 1165–117310.1001/archpsyc.57.12.1165
    1. Feldman H., Gauthier S., Hecker J., Vellas B., Xu Y., Ieni J. R., Schwam E. M., Donepezil MSAD Study Investigators Group (2005). Donepezil MSAD Study Investigators Group. Efficacy and safety of donepezil in patients with more severe Alzheimer’s disease: a subgroup analysis from a randomized, placebo-controlled trial. Int. J. Geriatr. Psychiatry 20, 559–56910.1002/gps.1325
    1. Fernández Martínez M., Castro J., Molano A., Zarranz J. J., Rodrigo R. M., Ortega R. (2008a). Prevalence of neuropsychiatric symptoms in Alzheimer’s disease and vascular dementia. Curr. Alzheimer Res. 5, 61–6910.2174/156720508783884585
    1. Fernández Martínez M., Castro Flores J., Pérez de las Heras S., Mandaluniz Lekumberri A., Gordejuela Menocal M., Zarranz Imirizaldu J. J. (2008b). Prevalence of neuropsychiatric symptoms in elderly patients with dementia in Mungialde County (Basque Country, Spain). Dement. Geriatr. Cogn. Disord. 25, 103–10810.1159/000112215
    1. Fernandez-Martinez M., Molano A., Castro J., Zarranz J. J. (2010). Prevalence of neuropsychiatric symptoms in mild cognitive impairment and Alzheimer’s disease, and its relationship with cognitive impairment. Curr. Alzheimer Res. 7, 517–52610.2174/156720510792231748
    1. Finkel S. I., Costa e Silva J., Cohen G., Miller S., Sartorius N. (1996). Behavioral and psychological signs and symptoms of dementia: a consensus statement on current knowledge and implications for research and treatment. Int. Psychogeriatr. 8(Suppl. 3), 497–500
    1. Förstl H., Burns A., Levy R., Cairns N. (1994). Neuropathological correlates of psychotic phenomena in confirmed Alzheimer’s disease. Br. J. Psychiatry 165, 53–5910.1192/bjp.165.1.53
    1. Frisoni G. B., Rozzini L., Gozzetti A., Binetti G., Zanetti O., Bianchetti A., Trabucchi M., Cummings J. L. (1999). Behavioral syndromes in Alzheimer’s disease: description and correlates. Dement. Geriatr. Cogn. Disord. 10, 130–13810.1159/000017113
    1. Fuh J. L., Liu C. K., Mega M. S., Wang S. J., Cummings J. L. (2001). Behavioral disorders and caregivers’ reaction in Taiwanese patients with Alzheimer’s disease. Int. Psychogeriatr. 13, 121–12810.1017/S1041610201007517
    1. Fuh J. L., Wang S. J., Cummings J. L. (2005). Neuropsychiatric profiles in patients with Alzheimer’s disease and vascular dementia. J. Neurol. Neurosurg. Psychiatr. 76, 1337–134110.1136/jnnp.2004.056408
    1. Gabryelewicz T., Styczynska M., Luczywek E., Barczak A., Pfeffer A., Androsiuk W., Chodakowska-Zebrowska M., Wasiak B., Peplonska B., Barcikowska M. (2007). The rate of conversion of mild cognitive impairment to dementia: predictive role of depression. Int. J. Geriatr. Psychiatry 22, 563–56710.1002/gps.1716
    1. García-Alberca J. M., Lara Muñoz J. P., Berthier Torres M. (2010). Neuropsychiatric and behavioral symptomatology in Alzheimer disease. Actas Esp. Psiquiatr. 38, 212–222
    1. Garre-Olmo J., Genís Batlle D., del Mar Fernández M., Marquez Daniel F., de Eugenio Huélamo R., Casadevall T., Turbau Recio J., Turon Estrada A., López-Pousa S., Registry of Dementia of Girona Study Group (ReDeGi Study Group) (2010a). Incidence and subtypes of early-onset dementia in a geographically defined general population. Neurology 75, 1249–125510.1212/WNL.0b013e3181f5d4c4
    1. Garre-Olmo J., López-Pousa S., Vilalta-Franch J., de Gracia Blanco M., Vilarrasa A. B. (2010b). Grouping and trajectories of the neuropsychiatric symptoms in patients with Alzheimer’s disease, part I: symptom clusters. J. Alzheimers Dis. 22, 1157–1167
    1. Garre-Olmo J., López-Pousa S., Vilalta-Franch J., de Gracia Blanco M., Vilarrasa A. B. (2010c). Grouping and trajectories of neuropsychiatric symptoms in patients with Alzheimer’s disease. Part II: two-year patient trajectories. J. Alzheimers Dis. 22, 1169–1180
    1. Gauthier S., Cummings J., Ballard C., Brodaty H., Grossberg G., Robert P., Lyketsos C. (2010). Management of behavioral problems in Alzheimer’s disease. Int. Psychogeriatr. 22, 346–37210.1017/S1041610210000888
    1. Geda Y. E., Smith G. E., Knopman D. S., Boeve B. F., Tangalos E. G., Ivnik R. J., Mrazek D. A., Edland S. D., Petersen R. C. (2004). De novo genesis of neuropsychiatric symptoms in mild cognitive impairment (MCI). Int. Psychogeriatr. 16, 51–6010.1017/S1041610204000067
    1. Harding A. J., Broe G. A., Halliday G. M. (2002). Visual hallucinations in Lewy body disease. Relate to Lewy bodies in the temporal lobe. Brain 125(Pt 2), 391–40310.1093/brain/awf033
    1. Harwood D. G., Ownby R. L., Barker W. W., Duara R. (1998). The behavioral pathology in Alzheimer’s disease scale (BEHAVE-AD): factor structure among community-dwelling Alzheimer’s disease patients. Int. J. Geriatr. Psychiatry 13, 793–80010.1002/(SICI)1099-1166(1998110)13:11<793::AID-GPS875>;2-Q
    1. Henry G., Williamson D., Tampi R. R. (2011). Efficacy and tolerability of antidepressants in the treatment of behavioral and psychological symptoms of dementia, a literature review of evidence. Am. J. Alzheimers Dis. Other Demen. 26, 169–18310.1177/1533317511402051
    1. Herrmann N., Black S. E., Chow T., Cappell J., Tang-Wai D. F., Lanctôt K. L. (2011). Serotonergic function and treatment of behavioral and psychological symptoms of frontotemporal dementia. Am. J. Geriatr. Psychiatry. [Epub ahead of print].10.1097/JGP.0b013e31823033f3
    1. Herrmann N., Lanctôt K. L., Sambrook R., Lesnikova N., Hébert R., McCracken P., Robillard A., Nguyen E. (2006). The contribution of neuropsychiatric symptoms to the cost of dementia care. Int. J. Geriatr. Psychiatry 21, 972–97610.1002/gps.1594
    1. Hirono N., Kitagaki H., Kazui H., Hashimoto M., Mori E. (2000). Impact of white matter changes on clinical manifestation of Alzheimer’s disease: a quantitative study. Stroke 31, 2182–218810.1161/01.STR.31.9.2182
    1. Hirono N., Mori E., Ishii K., Ikejiri Y., Imamura T., Shimomura T., Hashimoto M., Yamashita H., Sasaki M. (1998). Frontal lobe hypometabolism and depression in Alzheimer’s disease. Neurology 50, 380–383
    1. Hollingworth P., Hamshere M. L., Moskvina V., Dowzell K., Moore P. J., Foy C., Archer N., Lynch A., Lovestone S., Brayne C., Rubinsztein D. C., Lawlor B., Gill M., Owen M. J., Williams J. (2006). Four components describe behavioral symptoms in 1,120 individuals with late-onset Alzheimer’s disease. J. Am. Geriatr. Soc. 54, 1348–135410.1111/j.1532-5415.2006.00854.x
    1. Holmes C., Wilkinson D., Dean C., Vethanayagam S., Olivieri S., Langley A., Pandita-Gunawardena N. D., Hogg F., Clare C., Damms J. (2004). The efficacy of donepezil in the treatment of neuropsychiatric symptoms in Alzheimer disease. Neurology 63, 214–219
    1. Holroyd S., Shepherd M. L., Downs J. H., III. (2000). Occipital atrophy is associated with visual hallucinations in Alzheimer’s disease. J. Neuropsychiatry Clin. Neurosci. 12, 25–2810.1176/appi.neuropsych.12.4.517
    1. Hope T., Keene J., Fairburn C., McShane R., Jacoby R. (1997). Behaviour changes in dementia. 2: are there behavioural syndromes? Int. J. Geriatr. Psychiatry 12, 1074–107810.1002/(SICI)1099-1166(199711)12:11<1074::AID-GPS696>;2-B
    1. Howard R., McShane R., Lindesay J., Ritchie C., Baldwin A., Barber R., Burns A., Dening T., Findlay D., Holmes C., Hughes A., Jacoby R., Jones R., Jones R., McKeith I., Macharouthu A., O’Brien J., Passmore P., Sheehan B., Juszczak E., Katona C., Hills R., Knapp M., Ballard C., Brown R., Banerjee S., Onions C., Griffin M., Adams J., Gray R., Johnson T., Bentham P., Phillips P. (2012). Donepezil and memantine for moderate-to-severe Alzheimer’s disease. N. Engl. J. Med. 366, 893–90310.1056/NEJMoa1106668
    1. Hsieh C. J., Chang C. C., Lin C. C. (2009). Neuropsychiatric profiles of patients with Alzheimer’s disease and vascular dementia in Taiwan. Int. J. Geriatr. Psychiatry 24, 570–57710.1002/gps.2156
    1. Huang S. S., Lee M. C., Liao Y. C., Wang W. F., Lai T. J. (2011). Caregiver burden associated with behavioral and psychological symptoms of dementia (BPSD) in Taiwanese elderly. Arch. Gerontol. Geriatr. [Epub ahead of print]10.1016/j.archger.2011.04.009
    1. Ikeda M., Brown J., Holland A. J., Fukuhara R., Hodges J. R. (2002). Changes in appetite, food preference, and eating habits in frontotemporal dementia and Alzheimer’s disease. J. Neurol. Neurosurg. Psychiatr. 73, 371–37610.1136/jnnp.73.2.204
    1. Ikeda M., Fukuhara R., Shigenobu K., Hokoishi K., Maki N., Nebu A., Komori K., Tanabe H. (2004). Dementia associated mental and behavioural disturbances in elderly people in the community: findings from the first Nakayama study. J. Neurol. Neurosurg. Psychiatr. 75, 146–148
    1. Ismail Z., Nguyen M. Q., Fischer C. E., Schweizer T. A., Mulsant B. H., Mamo D. (2011). Neurobiology of delusions in Alzheimer’s disease. Curr. Psychiatry Rep. 13, 211–21810.1007/s11920-011-0195-1
    1. Iwata B. A., Volmer T. R., Zarcone J. R. (1993). “The experimental (functional) analysis of behavioral disorders: methodology, application, and limitations,” in Perspectives on the Use of Nonaversive and Aversive Interventions for Persons with Developmental Disabilities, eds Repp A. C., Singh N. N. (Sycamore, IL: Sycamore Press; ), 301–330
    1. Jeste D. V., Meeks T. W., Kim D. S., Zubenko G. S. (2006). Research agenda for DSM-V: diagnostic categories and criteria for neuropsychiatric syndromes in dementia. J. Geriatr. Psychiatry. Neurol. 19, 160–17110.1177/0891988706291087
    1. Kales H. C., Kim H. M., Zivin K., Valenstein M., Seyfried L. S., Chian C., Cunningham F., Schneider L. S., Blow F. C. (2012). Risk of mortality among individual antipsychotics in patients with dementia. Am. J. Psychiatry 169, 71–79
    1. Kang H. S., Ahn I. S., Kim J. H., Kim D. K. (2010). Neuropsychiatric symptoms in korean patient with Alzheimer’s disease: exploratory factor analysis and confirmatory factor analysis of the neuropsychiatric inventory. Dement. Geriatr. Cogn. Disord. 29, 82–8710.1159/000264629
    1. Karlawish J. H., Zbrozek A., Kinosian B., Gregory A., Ferguson A., Low D. V., Glick H. A. (2008). Caregivers’ assessments of preference-based quality of life in Alzheimer’s disease. Alzheimers Dement. 4, 203–21110.1016/j.jalz.2008.05.576
    1. Karttunen K., Karppi P., Hiltunen A., Vanhanen M., Välimäki T., Martikaine Valtonen H., Sivenius J., Soininen H., Hartikainen S., Suhonen J., Pirttilä T., ALSOVA study group (2011). Neuropsychiatric symptoms and quality of life in patients with very mild and mild Alzheimer’s disease. Int. J. Geriatr. Psychiatry 26, 473–48210.1002/gps.2550
    1. Katona C., Livingston G., Cooper C., Ames D., Brodaty H., Chiu E. (2007). International Psychogeriatric Association consensus statement on defining and measuring treatment benefits in dementia. Int. Psychogeriatr. 19, 345–35410.1017/S1041610207005145
    1. Kim J. M., Lyons D., Shin I. S., Yoon J. S. (2003). Differences in the behavioral and psychological symptoms between Alzheimer’s disease and vascular dementia: are the different pharmacologic treatment strategies justifiable? Hum. Psychopharmacol. 18, 215–22010.1002/hup.466
    1. Kong E. H., Evans L. K., Guevara J. P. (2009). Nonpharmacological intervention for agitation in dementia: a systematic review and meta-analysis. Aging Ment. Health 13, 512–52010.1080/13607860902774394
    1. Konovalov S., Muralee S., Tampi R. R. (2008). Anticonvulsants for the treatment of behavioral and psychological symptoms of dementia: a literature review. Int. Psychogeriatr. 20, 293–30810.1017/S1041610207006540
    1. Korczyn A. D., Halperin I. (2009). Depression and dementia. J. Neurol. Sci. 283, 139–14210.1016/j.jns.2009.02.346
    1. Kotrla K. J., Chacko R. C., Harper R. G., Jhingran S., Doody R. (1995). SPECT findings on psychosis in Alzheimer’s disease. Am. J. Psychiatry 152, 1470–1475
    1. Kunik M. E., Snow A. L., Davila J. A., McNeese T., Steele A. B., Balasubramanyam V., Doody R., Schulz P. E., Kalavar J. S., Walder A., Morgan R. O. (2010). Consequences of aggressive behavior in patients with dementia. J. Neuropsychiatry Clin. Neurosci. 22, 40–4710.1176/appi.neuropsych.22.1.40
    1. Lai C. K., Yeung J. H., Mok V., Chi I. (2009). Special care units for dementia individuals with behavioural problems. Cochrane Database Syst. Rev. 4, CD006470.
    1. Lanari A., Amenta F., Silvestrelli G., Tomassoni D., Parnetti L. (2006). Neurotransmitter deficits in behavioural and psychological symptoms of Alzheimer’s disease. Mech. Ageing Dev. 127, 158–16510.1016/j.mad.2005.09.016
    1. Lanctôt K. L., Herrmann N., Nadkarni N. K., Leibovitch F. S., Caldwell C. B., Black S. E. (2004). Medial temporal hypoperfusion and aggression in Alzheimer disease. Arch. Neurol. 61, 1731–173710.1001/archneur.61.11.1731
    1. Lanctôt K. L., Herrmann N., Rothenburg L., Eryavec G. (2007a). Behavioral correlates of GABAergic disruption in Alzheimer’s disease. Int. Psychogeriatr. 19, 151–15810.1017/S1041610206003899
    1. Lanctôt K. L., Moosa S., Herrmann N., Leibovitch F. S., Rothenburg L., Cotter A., Black S. E. (2007b). A SPECT study of apathy in Alzheimer’s disease. Dement. Geriatr. Cogn. Disord. 24, 65–7210.1159/000103633
    1. Lee G. J., Lu P. H., Hua X., Lee S., Wu S., Nguyen K., Teng E., Leow A. D., Jack C. R., Jr., Toga A. W., Weiner M. W., Bartzokis G., Thompson P. M., Alzheimer’s Disease Neuroimaging Initiative (2012). Depressive symptoms in mild cognitive impairment predict greater atrophy in Alzheimer’s disease-related regions. Biol. Psychiatry 71, 814–82110.1016/j.biopsych.2011.12.024
    1. Levy M. L., Miller B. L., Cummings J. L., Fairbanks L. A., Craig A. (1996). Alzheimer disease and frontotemporal dementias. Behavioral distinctions. Arch. Neurol. 53, 687–69010.1001/archneur.1996.00550070129021
    1. Livingston G., Johnston K., Katona C., Paton J., Lyketsos C. G., Old Age Task Force of the World Federation of Biological Psychiatry (2005). Systematic review of psychological approaches to the management of neuropsychiatric symptoms of dementia. Am. J. Psychiatry 162, 1996–202110.1176/appi.ajp.162.11.1996
    1. Logsdon R. G., Teri L., Weiner M. F., Gibbons L. E., Raskind M., Peskind E., Grundman M., Koss E., Thomas R. G., Thal L. J. (1999). Assessment of agitation in Alzheimer’s disease: the agitated behavior in dementia scale. Alzheimer’s Disease Cooperative Study. J. Am. Geriatr. Soc. 47, 1354–1358
    1. Lonergan E., Luxenberg J. (2009). Valproate preparations for agitation in dementia. Cochrane Database Syst. Rev. 3, CD003945.
    1. Lopez O. L., Becker J. T., Sweet R. A., Klunk W., Kaufer D. I., Saxton J., Grundman M., Koss E., Thomas R. G., Thal L. J. (2003). Psychiatric symptoms vary with the severity of dementia in probable Alzheimer’s disease. J. Neuropsychiatry Clin. Neurosci. 15, 346–535210.1176/appi.neuropsych.15.3.346
    1. Lövheim H., Sandman P. O., Karlsson S., Gustafson Y. (2008). Behavioral and psychological symptoms of dementia in relation to level of cognitive impairment. Int. Psychogeriatr. 20, 777–78910.1017/S1041610208006777
    1. Lövheim H., Sandman P. O., Karlsson S., Gustafson Y. (2009). Sex differences in the prevalence of behavioral and psychological symptoms of dementia. Int. Psychogeriatr. 21, 469–47510.1017/S1041610209990329
    1. Lyketsos C. G., Lopez O., Jones B., Fitzpatrick A. L., Breitner J., DeKosky S. (2002). Prevalence of neuropsychiatric symptoms in dementia and mild cognitive impairment: results from the cardiovascular health study. JAMA 288, 1475–148310.1001/jama.288.12.1475
    1. Lyketsos C. G., Sheppard J. M., Steinberg M., Tschanz J. A., Norton M. C., Steffens D. C., Breitner J. C. (2001). Neuropsychiatric disturbance in Alzheimer’s disease clusters into three groups: the Cache County study. Int. J. Geriatr. Psychiatry 16, 1043–105310.1002/gps.440
    1. Lyketsos C. G., Steinberg M., Tschanz J. T., Norton M. C., Steffens D. C., Breitner J. C. (2000). Mental and behavioral disturbances in dementia: findings from the Cache County Study on Memory in Aging. Am. J. Psychiatry 157, 708–71410.1176/appi.ajp.157.3.475
    1. Marshall G. A., Monserratt L., Harwood D., Mandelkern M., Cummings J. L., Sultzer D. L. (2007). Positron emission tomography metabolic correlates of apathy in Alzheimer disease. Arch. Neurol. 64, 1015–102010.1001/archneur.64.7.1015
    1. Massimo L., Powers C., Moore P., Vesely L., Avants B., Gee J., Libon D. J., Grossman M. (2009). Neuroanatomy of apathy and disinhibition in frontotemporal lobar degeneration. Dement. Geriatr. Cogn. Disord. 27, 96–10410.1159/000194658
    1. Matsui T., Nakaaki S., Murata Y., Sato J., Shinagawa Y., Tatsumi H., Furukawa T. A. (2006). Determinants of the quality of life in Alzheimer’s disease patients as assessed by the Japanese version of the Quality of Life-Alzheimer’s disease scale. Dement. Geriatr. Cogn. Disord. 21, 182–19110.1159/000090744
    1. Matthews K. L., Chen C. P., Esiri M. M., Keene J., Minger S. L., Francis P. T. (2002). Noradrenergic changes, aggressive behavior, and cognition in patients with dementia. Biol. Psychiatry 51, 407–41610.1016/S0006-3223(01)01235-5
    1. McKeith I. G., Dickson D. W., Lowe J., Emre M., O’Brien J. T., Feldman H., Cummings J., Duda J. E., Lippa C., Perry E. K., Aarsland D., Arai H., Ballard C. G., Boeve B., Burn D. J., Costa D., Del Ser T., Dubois B., Galasko D., Gauthier S., Goetz C. G., Gomez-Tortosa E., Halliday G., Hansen L. A., Hardy J., Iwatsubo T., Kalaria R. N., Kaufer D., Kenny R. A., Korczyn A., Kosaka K., Lee V. M., Lees A., Litvan I., Londos E., Lopez O. L., Minoshima S., Mizuno Y., Molina J. A., Mukaetova-Ladinska E. B., Pasquier F., Perry R. H., Schulz J. B., Trojanowski J. Q., Yamada M., Consortium on DLB (2005). Diagnosis and management of dementia with Lewy bodies: third report of the DLB Consortium. Neurology 65, 1992.10.1212/01.wnl.0000187889.17253.b1
    1. Mirakhur A., Craig D., Hart D. J., McLlroy S. P., Passmore A. P. (2004). Behavioural and psychological syndromes in Alzheimer’s disease. Int. J. Geriatr. Psychiatry 19, 1035–103910.1002/gps.1203
    1. Mitchell R. A., Herrmann N., Lanctôt K. L. (2011). The role of dopamine in symptoms and treatment of apathy in Alzheimer’s disease. CNS Neurosci. Ther. 17, 411–42710.1111/j.1755-5949.2010.00161.x
    1. Miyamoto Y., Tachimori H., Ito H. (2010). Formal caregiver burden in dementia: impact of behavioral and psychological symptoms of dementia and activities of daily living. Geriatr. Nurs. 31, 246–25310.1016/j.gerinurse.2010.01.002
    1. Modrego P. J., Ferrández J. (2004). Depression in patients with mild cognitive impairment increases the risk of developing dementia of Alzheimer type: a prospective cohort study. Arch. Neurol. 61, 1290–129310.1001/archneur.61.8.1290
    1. Monastero R., Mangialasche F., Camarda C., Ercolani S., Camarda R. (2009). A systematic review of neuropsychiatric symptoms in mild cognitive impairment. J. Alzheimers Dis. 18, 11–30
    1. Mossello E., Ridolfi A., Mello A. M., Lorenzini G., Mugnai F., Piccini C., Barone D., Peruzzi A., Masotti G., Marchionni N. (2011). Animal-assisted activity and emotional status of patients with Alzheimer’s disease in day care. Int. Psychogeriatr. 1, 1–7
    1. Mukaetova-Ladinska E. B., Harrington C. R., Xuereb J., Roth M., Wischik C. M. (1995). Biochemical, neuropathological, and clinical correlations of neurofibrillary degeneration in Alzheimer’s disease,” in Treating Alzheimer’s and Other Dementias, eds Bergener M., Finkel S. I. (New York: Springer; ), 57–80
    1. Mulin E., Leone E., Dujardin K., Delliaux M., Leentjen Dessi B., Tible O., Agüera-Ortiz L., Osorio R. S., Yessavage J., Dachevsky D., Verhey F. R., Cruz Jentoft A. J., Blanc O., Llorca P. M., Robert P. H. (2011). Diagnostic criteria for apathy in clinical practice. Int. J. Geriatr. Psychiatry 26, 158–16510.1002/gps.2508
    1. Neary D., Snowden J., Mann D. (2005). Frontotemporal dementia. Lancet Neurol. 4, 771–78010.1016/S1474-4422(05)70223-4
    1. Nyatsanza S., Shetty T., Gregory C., Lough S., Dawson K., Hodges J. R. (2003). A study of stereotypic behaviours in Alzheimer’s disease and frontal and temporal variant frontotemporal dementia. J. Neurol. Neurosurg. Psychiatr. 74, 1398–140210.1136/jnnp.74.10.1398
    1. O’Neil M. E., Freeman M., Christensen V., Telerant R., Addleman A., Kansagara D. (2011). A Systematic Evidence Review of Non-pharmacological Interventions for Behavioral Symptoms of Dementia. Washington, DC: Department of Veterans Affairs
    1. Ostling S., Gustafson D., Waern M. (2009). Psychotic and behavioural symptoms in a population-based sample of the very elderly subjects. Acta Psychiatr. Scand. 120, 147–15210.1111/j.1600-0447.2009.01371.x
    1. Palmer K., Di Iulio F., Varsi A. E., Gianni W., Sancesario G., Caltagirone C., Spalletta G. (2010). Neuropsychiatric predictors of progression from amnestic-mild cognitive impairment to Alzheimer’s disease: the role of depression and apathy. J. Alzheimers Dis. 20, 175–183
    1. Pinto T., Lanctôt K. L., Herrmann N. (2011). Revisiting the cholinergic hypothesis of behavioral and psychological symptoms in dementia of the Alzheimer’s type. Ageing Res. Rev. 10, 404–412
    1. Poulin S. P., Dautoff R., Morris J. C., Barrett L. F., Dickerson B. C. (2011). Amygdala atrophy is prominent in early Alzheimer’s disease and relates to symptom severity. Psychiatry Res. 194, 7–1310.1016/j.pscychresns.2011.06.014
    1. Prado-Jean A., Couratier P., Druet-Cabanac M., Nubukpo P., Bernard-Bourzeix L., Thomas P., Dechamps N., Videaud H., Dantoine T., Clément J. P. (2010). Specific psychologicaland behavioral symptoms of depression in patients with dementia. Int. J. Geriatr. Psychiatry 25, 1065–107210.1002/gps.2468
    1. Prick A. E., de Lange J., Scherder E., Pot A. M. (2011). Home-based exercise and support programme for people with dementia and their caregivers: study protocol of a randomised controlled trial. BMC Public Health 11, 894.10.1186/1471-2458-11-894
    1. Proitsi P., Lupton M. K., Reeves S. J., Hamilton G., Archer N., Martin B. M., Iyegbe C., Hollingworth P., Lawlor B., Gill M., Brayne C., Rubinsztein D. C., Owen M. J., Williams J., Lovestone S., Powell J. F. (2012). Association of serotonin and dopamine gene pathways with behavioral subphenotypes in dementia. Neurobiol. Aging 33, 791–80310.1016/j.neurobiolaging.2010.06.011
    1. Rapp M. A., Schnaider-Beeri M., Grossman H. T., Sano M., Perl D. P., Purohit D. P., Gorman J. M., Haroutunian V. (2006). Increased hippocampal plaques and tangles in patients with Alzheimer disease with a lifetime history of major depression. Arch. Gen. Psychiatry 63, 161–16710.1001/archpsyc.63.2.161
    1. Rapp M. A., Schnaider-Beeri M., Purohit D. P., Perl D. P., Haroutunian V., Sano M. (2008). Increased neurofibrillary tangles in patients with Alzheimer disease with comorbid depression. Am. J. Geriatr. Psychiatry 16, 168–17410.1097/JGP.0b013e31816029ec
    1. Reisberg B., Borenstein J., Salob S. P., Ferris S. H., Franssen E., Georgotas A. (1987). Behavioral symptoms in Alzheimer’s disease: phenomenology and treatment. J. Clin. Psychiatry 48(Suppl.), 9–15
    1. Robert P. H., Onyike C. U., Leentjens A. F. G., Dujardin K., Aalten P., Starkstein S., Verhey F. R., Yessavage J., Clement J. P., Drapier D., Bayle F., Benoit M., Boyer P., Lorca P. M., Thibaut F., Gauthier S., Grossberg G., Vellas B., Byrne J. (2009). Proposed diagnostic criteria for apathy in Alzheimer’s disease and other neuropsychiatric disorders. Eur. Psychiatry 24, 98–10410.1016/j.eurpsy.2008.09.001
    1. Rocca P., Leotta D., Liffredo C., Mingrone C., Sigaudo M., Capellero B., Rocca G., Simoncini M., Pirfo E., Bogetto F. (2010). Neuropsychiatric symptoms underlying caregiver stress and insight in Alzheimer’s disease. Dement. Geriatr. Cogn. Disord. 30, 57–6310.1159/000315513
    1. Rockwell E., Choure J., Galasko D., Olichney J., Jeste D. V. (2000). Psychopathology at initial diagnosis in dementia with Lewy bodies versus Alzheimer disease: comparison of matched groups with autopsy-confirmed diagnoses. Int. J. Geriatr. Psychiatry 15, 819–82310.1002/1099-1166(200009)15:9<819::AID-GPS206>;2-1
    1. Rodda J., Morgan S., Walker Z. (2009). Are cholinesterase inhibitors effective in the management of the behavioral and psychological symptoms of dementia in Alzheimer’s disease? A systematic review of randomized, placebo-controlled trials of donepezil, rivastigmine and galantamine. Int. Psychogeriatr. 21, 813–82410.1017/S1041610209990354
    1. Rongve A., Boeve B. F., Aarsland D. (2010). Frequency and correlates of caregiver-reported sleep disturbances in a sample of persons with early dementia. J. Am. Geriatr. Soc. 58, 480–48610.1111/j.1532-5415.2010.02733.x
    1. Rosen H. J., Allison S. C., Schauer G. F., Gorno-Tempini M. L., Weiner M. W., Miller B. L. (2005). Neuroanatomical correlates of behavioural disorders in dementia. Brain 128(Pt 11), 2612–262510.1093/brain/awh628
    1. Rosenberg P. B., Mielke M. M., Appleby B., Oh E., Leoutsakos J. M., Lyketsos C. G. (2011). Neuropsychiatric symptoms in MCI subtypes: the importance of executive dysfunction. Int. J. Geriatr. Psychiatry 26, 364–37210.1002/gps.2535
    1. Rozzini L., Vicini Chilovi B., Conti M., Delrio I., Borroni B., Trabucchi M., Padovani A. (2008). Neuropsychiatric symptoms in amnestic and nonamnestic mild cognitive impairment. Dement. Geriatr. Cogn. Disord. 25, 32–3610.1159/000111133
    1. Russ T. C., Batty G. D., Starr J. M. (2011). Cognitive and behavioural predictors of survival in Alzheimer disease: results from a sample of treated patients in a tertiary-referral memory clinic. Int. J. Geriatr. Psychiatry10.1002/gps.2795
    1. Ryu S. H., Ha J. H., Park D. H., Yu J., Livingston G. (2011). Persistence of neuropsychiatric symptoms over six months in mild cognitive impairment in community-dwelling Korean elderly. Int. Psychogeriatr. 23, 214–22010.1017/S1041610210001766
    1. Salzman C., Jeste D. V., Meyer R. E., Cohen-Mansfield J., Cummings J., Grossberg G. T., Jarvik L., Kraemer H. C., Lebowitz B. D., Maslow K., Pollock B. G., Raskind M., Schultz S. K., Wang P., Zito J. M., Zubenko G. S. (2008). Elderly patients with dementia-related symptoms of severe agitation and aggression: consensus statement on treatment options, clinical trials methodology, and policy. J. Clin. Psychiatry 69, 889–89810.4088/JCP.v69n0602
    1. Savva G. M., Zaccai J., Matthews F. E., Davidson J. E., McKeith I., Brayne C., Medical Research Council Cognitive Function and Ageing Study (2009). Prevalence, correlates and course of behavioural and psychological symptoms of dementia in the population. Br. J. Psychiatry 194, 212–21910.1192/bjp.bp.108.049619
    1. Scarmeas N., Brandt J., Albert M., Hadjigeorgiou G., Papadimitriou A., Dubois B., Sarazin M., Devanand D., Honig L., Marder K., Bell K., Wegesin D., Blacker D., Stern Y. (2005). Delusions and hallucinations are associated with worse outcome in Alzheimer disease. Arch. Neurol. 62, 1601–160810.1001/archneur.62.10.1601
    1. Schreinzer D., Ballaban T., Brannath W., Lang T., Hilger E., Fasching P., Fischer P. (2005). Components of behavioral pathology in dementia. Int. J. Geriatr. Psychiatry 20, 137–14510.1002/gps.1263
    1. Seitz D. P., Adunuri N., Gill S. S., Gruneir A., Herrmann N., Rochon P. (2011). Antidepressants for agitation and psychosis in dementia. Cochrane Database Syst. Rev. 2, CD008191.
    1. Selbaek G., Kirkevold Ø., Engedal K. (2008). The course of psychiatric and behavioral symptoms and the use of psychotropic medication in patients with dementia in Norwegian nursing homes – a 12-month follow-up study. Am. J. Geriatr. Psychiatry 16, 528–53610.1097/JGP.0b013e318167ae76
    1. Selbæk G., Engedal K. (2012). Stability of the factor structure of the neuropsychiatric inventory in a 31-month follow-up study of a large sample of nursing-home patients with dementia. Int. Psychogeriatr. 24, 62–7310.1017/S104161021100086X
    1. Serra L., Perri R., Cercignani M., Spanò B., Fadda L., Marra C., Carlesimo G. A., Caltagirone C., Bozzali M. (2010a). Are the behavioral symptoms of Alzheimer’s disease directly associated with neurodegeneration? J. Alzheimers Dis. 21, 627–639
    1. Serra L., Perri R., Fadda L., Padovani A., Lorusso S., Pettenati C., Caltagirone C., Carlesimo G. A. (2010b). Relationship between cognitive impairment and behavioural disturbances in Alzheimer’s disease patients. Behav. Neurol. 23, 123–130
    1. Sink K. M., Covinsky K. E., Barnes D. E., Newcomer R. J., Yaffe K. (2006). Caregiver characteristics are associated with neuropsychiatric symptoms of dementia. J. Am. Geriatr. Soc. 54, 796–80310.1111/j.1532-5415.2006.00697.x
    1. Snow A. L., Kunik M. E., Molinari V. A., Orengo C. A., Doody R., Graham D. P., Norris M. P. (2005). Accuracy of self-reported depression in persons with dementia. J. Am. Geriatr. Soc. 53, 389–39610.1111/j.1532-5415.2005.53154.x
    1. Spalletta G., Musicco M., Padovani A., Rozzini L., Perri R., Fadda L., Canonico V., Trequattrini A., Pettenati C., Caltagirone C., Palmer K. (2010). Neuropsychiatric symptoms and syndromes in a large cohort of newly diagnosed, untreated patients with Alzheimer disease. Am. J. Geriatr. Psychiatry 18, 1026–103510.1097/JGP.0b013e3181d6b68d
    1. Srikanth S., Nagaraja A. V., Ratnavalli E. (2005). Neuropsychiatric symptoms in dementia-frequency, relationship to dementia severity and comparison in Alzheimer’s disease, vascular dementia and frontotemporal dementia. J. Neurol. Sci. 236, 43–4810.1016/j.jns.2005.04.014
    1. Staekenborg S. S., Su T., van Straaten E. C., Lane R., Scheltens P., Barkhof F., van der Flier W. M. (2010). Behavioural and psychological symptoms in vascular dementia; differences between small- and large-vessel disease. J. Neurol. Neurosurg. Psychiatr. 81, 547–55110.1136/jnnp.2009.187500
    1. Staff R. T., Venneri A., Gemmell H. G., Shanks M. F., Pestell S. J., Murray A. D. (2000). HMPAO SPECT imaging of Alzheimer’s disease patients with similar content-specific autobiographic delusion: comparison using statistical parametric mapping. J. Nucl. Med. 41, 1451–1455
    1. Staffen W., Bergmann J., Schönauer U., Zauner H., Kronbichler M., Golaszewski S., van der Flier W. M. (2009). Cerebral perfusion (HMPAO-SPECT) in patients with depression with cognitive impairment versus those with mild cognitive impairment and dementia of Alzheimer’s type: a semiquantitative and automated evaluation. Eur. J. Nucl. Med. Mol. Imaging 36, 801–81010.1007/s00259-008-1028-2
    1. Starkstein S. E., Mizrahi R., Capizzano A. A., Acion L., Brockman S., Power B. D. (2009). Neuroimaging correlates of apathy and depression in Alzheimer’s disease. J. Neuropsychiatry Clin. Neurosci. 21, 259–26510.1176/appi.neuropsych.21.3.259
    1. Starr J. M., Lonie J. (2007). Relationship between behavioural and psychological symptoms of dementia and cognition in Alzheimer’s disease. Dement. Geriatr. Cogn. Disord. 24, 343–34710.1159/000108632
    1. Stavitsky K., Brickman A. M., Scarmeas N., Torgan R. L., Tang M. X., Albert M., Brandt J., Blacker D., Stern Y. (2006). The progression of cognition, psychiatric symptoms, and functional abilities in dementia with Lewy bodies and Alzheimer disease. Arch. Neurol. 63, 1450–145610.1001/archneur.63.10.1450
    1. Steinberg M., Tschanz J. T., Corcoran C., Steffens D. C., Norton M. C., Lyketsos C. G., Breitner J. C. (2004). The persistence of neuropsychiatric symptoms in dementia: the Cache County Study. Int. J. Geriatr. Psychiatry 19, 19–2610.1002/gps.1025
    1. Sultzer D. L., Brown C. V., Mandelkern M. A., Mahler M. E., Mendez M. F., Chen S. T., Cummings J. L. (2003). Delusional thoughts and regional frontal/temporal cortex metabolism in Alzheimer’s disease. Am. J. Psychiatry 160, 341–34910.1176/appi.ajp.160.2.341
    1. Sultzer D. L., Mahler M. E., Mandelkern M. A., Cummings J. L., Van Gorp W. G., Hinkin C. H., Berisford M. A. (1995). The relationship between psychiatric symptoms and regional cortical metabolism in Alzheimer’s disease. J. Neuropsychiatry Clin. Neurosci. 7, 476–484
    1. Sweet R. A., Hamilton R. L., Butters M. A., Mulsant B. H., Pollock B. G., Lewis D. A., Lopez O. L., DeKosky S. T., Reynolds C. F., III. (2004). Neuropathologic correlates of late-onset major depression. Neuropsychopharmacology 29, 2242–225010.1038/sj.npp.1300554
    1. Sweet R. A., Hamilton R. L., Lopez O. L., Klunk W. E., Wisniewski S. R., Kaufer D. I., Healy M. T., DeKosky S. T. (2000). Psychotic symptoms in Alzheimer’s disease are not associated with more severe neuropathologic features. Int. Psychogeriatr. 12, 547–55810.1017/S1041610200006657
    1. Sweet R. A., Panchalingam K., Pettegrew J. W., McClure R. J., Hamilton R. L., Lopez O. L., Kaufer D. I., DeKosky S. T., Klunk W. E. (2002). Psychosis in Alzheimer disease: postmortem magnetic resonance spectroscopy evidence of excess neuronal and membrane phospholipid pathology. Neurobiol. Aging 23, 547–55310.1016/S0197-4580(02)00009-X
    1. Tariot P. N., Mack J. L., Patterson M. B., Edland S. D., Weiner M. F., Fillenbaum G., Blazina L., Teri L., Rubin E., Mortimer J.A., Stern Y., the Behavioral Pathology Committee of the Consortium to Establish a Registry for Alzheimer’s Disease (1995). The Behavior Rating Scale for dementia of the consortium to establish a registry for Alzheimer’s disease. Am. J. Psychiatry 152, 1349–1357
    1. Tatsumi H., Nakaaki S., Torii K., Shinagawa Y., Watanabe N., Murata Y., Sato J., Mimura M., Furukawa T. A. (2009). Neuropsychiatric symptoms predict change in quality of life of Alzheimer disease patients: a two-year follow-up study. Psychiatry Clin. Neurosci. 63, 374–38410.1111/j.1440-1819.2009.01955.x
    1. Teaktong T., Piggott M. A., Mckeith I. G., Perry R. H., Ballard C. G., Perry E. K. (2005). Muscarinic M2 and M4 receptors in anterior cingulate cortex: relation to neuropsychiatric symptoms in dementia with Lewy bodies. Behav. Brain Res. 161, 299–30510.1016/j.bbr.2005.02.019
    1. Tekin S., Mega M. S., Masterman D. M., Chow T., Garakian J., Vinters H. V., Cummings J. L. (2001). Orbitofrontal and anterior cingulate cortex neurofibrillary tangle burden is associated with agitation in Alzheimer disease. Ann. Neurol. 49, 355–36110.1002/ana.72
    1. Thompson C., Brodaty H., Trollor J., Sachdev P. (2010). Behavioral and psychological symptoms associated with dementia subtype and severity. Int. Psychogeriatr. 22, 300–30510.1017/S1041610209991220
    1. Toyota Y., Ikeda M., Shinagawa S., Matsumoto T., Matsumoto N., Hokoishi K., Fukuhara R., Ishikawa T., Mori T., Adachi H., Komori K., Tanabe H. (2007). Comparison of behavioral and psychological symptoms in early-onset and late-onset Alzheimer’s disease. Int. J. Geriatr. Psychiatry 22, 896–90110.1002/gps.1760
    1. Tsai C. F., Wang S. J., Zheng L., Fuh J. L. (2010). Category verbal fluency predicted changes in behavioral and psychological symptoms of dementia in patients with Alzheimer’s disease. Psychiatry Clin. Neurosci. 64, 408–41410.1111/j.1440-1819.2010.02107.x
    1. Tsang S. W., Francis P. T., Esiri M. M., Wong P. T., Chen C. P., Lai M. K. (2008). Loss of [3H]4-DAMP binding to muscarinic receptors in the orbitofrontal cortex of Alzheimer’s disease patients with psychosis. Psychopharmacology (Berl.) 198, 251–25910.1007/s00213-008-1124-9
    1. Tschanz J. T., Corcoran C. D., Schwartz S., Treiber K., Green R. C., Norton M. C., Mielke M. M., Piercy K., Steinberg M., Rabins P. V., Leoutsakos J. M., Welsh-Bohmer K. A., Breitner J. C., Lyketsos C. G. (2011). Progression of cognitive, functional, and neuropsychiatric symptom domains in a population cohort with Alzheimer dementia: the Cache County Dementia Progression study. Am. J. Geriatr. Psychiatry 19, 532–54210.1097/JGP.0b013e3181faec23
    1. Tsopelas C., Stewart R., Savva G. M., Brayne C., Ince P., Thomas A., Matthews F. E., Medical Research Council Cognitive Function and Ageing Study (2011). Neuropathological correlates of late-life depression in older people. Br. J. Psychiatry 198, 109–11410.1192/bjp.bp.110.078816
    1. Tsuang D., Larson E. B., Bolen E., Thompson M. L., Peskind E., Bowen J., McCormick W., Teri L., Kukull W., Vavrek D., Montine T., Leverenz J. B. (2009). Visual hallucinations in dementia: a prospective community-based study with autopsy. Am. J. Geriatr. Psychiatry 17, 317–32310.1097/JGP.0b013e3181953b9a
    1. Tun S. M., Murman D. L., Long H. L., Colenda C. C., von Eye A. (2007). Predictive validity of neuropsychiatric subgroups on nursing home placement and survival in patients with Alzheimer disease. Am. J. Geriatr. Psychiatry 15, 314–32710.1097/01.JGP.0000239263.52621.97
    1. Tunnard C., Whitehead D., Hurt C., Wahlund L. O., Mecocci P., Tsolaki M., Vellas B., Spenger C., Kloszewska I., Soininen H., Lovestone S., Simmons A., AddNeuroMed Consortium (2011). Apathy and cortical atrophy in Alzheimer’s disease. Int. J. Geriatr. Psychiatry 26, 741–74810.1002/gps.2603
    1. Verkaik R., Nuyen J., Schellevis F., Francke A. (2007). The relationship between severity of Alzheimer’s disease and prevalence of comorbid depressive symptoms and depression: a systematic review. Int. J. Geriatr. Psychiatry 22, 1063–108610.1002/gps.1809
    1. Vogel A., Waldorff F. B., Waldemar G. (2010). Impaired awareness of deficits and neuropsychiatric symptoms in early Alzheimer’s disease: the Danish Alzheimer Intervention Study (DAISY). J. Neuropsychiatry Clin. Neurosci. 22, 93–9910.1176/appi.neuropsych.22.1.93
    1. Wancata J., Benda N., Meise U., Windhaber J. (2003). Non-cognitive symptoms of dementia in nursing homes: frequency, course and consequences. Soc. Psychiatry Psychiatr. Epidemiol. 38, 637–64310.1007/s00127-003-0683-7
    1. Weamer E. A., Emanuel J. E., Varon D., Miyahara S., Wilkosz P. A., Lopez O. L., Dekosky S. T., Sweet R. A. (2009). The relationship of excess cognitive impairment in MCI and early Alzheimer’s disease to the subsequent emergence of psychosis. Int. Psychogeriatr. 21, 78–8510.1017/S1041610208007734
    1. Weitzel T., Robinson S., Mercer S., Berry T., Barnes M., Vollmer C., Foster T., Friedrich L., Allen L., Holmes J., Kirkbride G. (2011). Pilot testing an educational intervention to improve communication with patients with dementia. J. Nurses Staff. Dev. 27, 220–22610.1097/NND.0b013e31822e0738
    1. Wetzels R. B., Zuidema S. U., de Jonghe J. F., Verhey F. R., Koopmans R. T. (2010). Course of neuropsychiatric symptoms in residents with dementia in nursing homes over 2-year period. Am. J. Geriatr. Psychiatry 18, 1054–106510.1097/JGP.0b013e3181f60fa1
    1. Wilson R. S., Schneider J. A., Bienias J. L., Arnold S. E., Evans D. A., Bennett D. A. (2003). Depressive symptoms, clinical AD, and cortical plaques and tangles in older persons. Neurology 61, 1102–1107
    1. Yesavage J. A., Friedman L., Ancoli-Israel S., Bliwise D., Singer C., Vitiello M. V., Monjan A. A., Lebowitz B. (2003). Development of diagnostic criteria for defining sleep disturbance in Alzheimer’s disease. J. Geriatr. Psychiatry. Neurol. 16, 131–13910.1177/0891988703255684
    1. Youn J. C., Lee D. Y., Jhoo J. H., Kim K. W., Choo I. H., Woo J. I. (2011). Prevalence of neuropsychiatric syndromes in Alzheimer’s disease (AD). Arch. Gerontol. Geriatr. 52, 258–26310.1016/j.archger.2010.04.015
    1. Zubenko G. S., Moossy J., Martinez A. J., Rao G., Claassen D., Rosen J., Kopp U. (1991). Neuropathologic and neurochemical correlates of psychosis in primary dementia. Arch. Neurol. 48, 619–62410.1001/archneur.1991.00530180075020
    1. Zuidema S. U., de Jonghe J. F., Verhey F. R., Koopmans R. T. (2007). Neuropsychiatric symptoms in nursing home patients: factor structure invariance of the Dutch nursing home version of the neuropsychiatric inventory in different stages of dementia. Dement. Geriatr. Cogn. Disord. 24, 169–17610.1159/000105603
    1. Zuidema S. U., de Jonghe J. F., Verhey F. R., Koopmans R. T. (2010). Environmental correlates of neuropsychiatric symptoms in nursing home patients with dementia. Int. J. Geriatr. Psychiatry 25, 14–22

Source: PubMed

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