{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,29]],"date-time":"2026-10-29T00:06:44Z","timestamp":1793232404923,"version":"4.5.0"},"reference-count":50,"publisher":"SAGE Publications","issue":"2","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JAD"],"published-print":{"date-parts":[[2022,3,22]]},"abstract":"<jats:p>Background: There is high prevalence of neuropsychiatric symptoms (NPS) among dementia patients. NPS are correlated with dementia progression, functional decline, early institutionalization, and death. There is scarce evidence on the progression of NPS in the latest stages of dementia. Objective: To describe the prevalence of NPS in mild-moderate to severe dementia and to reveal the progression of each NPS over time. Methods: We studied 317 patients (77.3% female, average age: 81.5 years) with a DSM-IV-TR diagnosis of dementia. This is a cross-sectional, and a prospective longitudinal study with 78-month follow-up. We assessed cognitive status (Mini-Mental State Examination and Severe Mini-Mental State Examination), dementia severity (Global Deterioration Scale and Clinical Dementia Rating), and psychopathological measures (Neuropsychiatric Inventory, APADEM-Nursing Home, Apathy Inventory, Cornell Scale for Depression in Dementia, and Cohen-Mansfield Agitation Inventory). Results: Overall prevalence of NPS was 94.6%, being apathy the most prevalent (66.7%) and the one whose severity increased the most with progression of dementia. Agitation\/aggression, irritability, and sleeping and eating disorders also increased over time. Delusions and depressive symptoms decreased in severity with disease progression. In severe dementia, female displayed more depressive symptoms and eating disorders, while male displayed more agitation\/aggression and sleep disturbances. Conclusion: NPS in dementia follow a heterogeneous course. Apathy is the most prevalent NPS and the one that worsens most significantly over time. The course of some NPS differs between sexes. Further research is required to understand the evolution of NPS at advanced stages of dementia.<\/jats:p>","DOI":"10.3233\/jad-215133","type":"journal-article","created":{"date-parts":[[2022,2,8]],"date-time":"2022-02-08T12:04:42Z","timestamp":1644321882000},"page":"861-875","source":"Crossref","is-referenced-by-count":20,"title":["Clinical Trajectories of Neuropsychiatric Symptoms in Mild-Moderate to Advanced Dementia"],"prefix":"10.1177","volume":"86","author":[{"given":"Isabel M.","family":"Castillo-Garc\u00eda","sequence":"first","affiliation":[{"name":"Servicio de Psiquiatr\u00eda, Instituto de Investigaci\u00f3n i+12, Hospital Universitario 12 deOctubre, Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jorge","family":"L\u00f3pez-\u00c1lvarez","sequence":"additional","affiliation":[{"name":"Servicio de Psiquiatr\u00eda, Instituto de Investigaci\u00f3n i+12, Hospital Universitario 12 deOctubre, Madrid, Spain"},{"name":"Alzheimer\u2019s Centre Reina Sofia-CIEN Foundation, Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ricardo","family":"Osorio","sequence":"additional","affiliation":[{"name":"Alzheimer\u2019s Centre Reina Sofia-CIEN Foundation, Madrid, Spain"},{"name":"Department of Psychiatry NYU Grossman School of Medicine, New York, NY, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Javier","family":"Olazar\u00e1n","sequence":"additional","affiliation":[{"name":"Alzheimer\u2019s Centre Reina Sofia-CIEN Foundation, Madrid, Spain"},{"name":"Servicio de Neurolog\u00eda, HGU Gregorio Mara\u00f1\u00f3n, Madrid, Spain"},{"name":"Memory Disorders Clinic, HM Hospitals, Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria I.","family":"Ramos Garc\u00eda","sequence":"additional","affiliation":[{"name":"Alzheimer\u2019s Centre Reina Sofia-CIEN Foundation, Madrid, Spain"},{"name":"Instituto de Psiquiatr\u00eda y Salud Mental, Hospital Cl\u00ednico Universitario San Carlos, Instituto de Investigaci\u00f3n Sanitaria San Carlos (IdISC), Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luis","family":"Ag\u00fcera-Ortiz","sequence":"additional","affiliation":[{"name":"Servicio de Psiquiatr\u00eda, Instituto de Investigaci\u00f3n i+12, Hospital Universitario 12 deOctubre, Madrid, Spain"},{"name":"Alzheimer\u2019s Centre Reina Sofia-CIEN Foundation, Madrid, Spain"},{"name":"Centro deInvestigaci\u00f3n Biom\u00e9dica en Red de Salud Mental (CIBERSAM), Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"179","reference":[{"key":"10.3233\/JAD-215133_ref2","doi-asserted-by":"crossref","first-page":"1026","DOI":"10.1097\/JGP.0b013e3181d6b68d","article-title":"Neuropsychiatric symptoms and syndromes in a large cohort of newly diagnosed, untreated patients with Alzheimer disease","volume":"18","author":"Spalletta","year":"2010","journal-title":"Am J Geriatr Psychiatry"},{"key":"10.3233\/JAD-215133_ref3","doi-asserted-by":"crossref","first-page":"1443","DOI":"10.2147\/NDT.S47133","article-title":"Behavioral symptoms related to cognitive impairment","volume":"9","author":"Dillon","year":"2013","journal-title":"Neuropsychiatr Dis Treat"},{"key":"10.3233\/JAD-215133_ref4","doi-asserted-by":"crossref","first-page":"1043","DOI":"10.1002\/gps.448","article-title":"Neuropsychiatric disturbance in Alzheimer\u2019s disease clusters into three groups: The Cache County study","volume":"16","author":"Lyketsos","year":"2001","journal-title":"Int J Geriatr Psychiatry"},{"key":"10.3233\/JAD-215133_ref5","doi-asserted-by":"crossref","first-page":"523","DOI":"10.1002\/gps.1316","article-title":"The course of neuropsychiatric symptoms in dementia. Part I: Findings from the two year longitudinal Maasbed study","volume":"20","author":"Aalten","year":"2005","journal-title":"Int J Geriatr Psychiatry"},{"key":"10.3233\/JAD-215133_ref6","doi-asserted-by":"crossref","first-page":"204","DOI":"10.1016\/j.jalz.2012.01.003","article-title":"Predictors of progression to severe Alzheimer\u2019s disease in an incidence simple","volume":"9","author":"Rabins","year":"2013","journal-title":"Alzheimers Dement"},{"key":"10.3233\/JAD-215133_ref7","doi-asserted-by":"crossref","first-page":"460","DOI":"10.1176\/appi.ajp.2014.14040480","article-title":"Neuropsychiatric symptoms as predictors of progression to severe Alzheimer\u2019s dementia and death: The Cache County Dementia Progression Study","volume":"172","author":"Peters","year":"2015","journal-title":"Am J Geriatr Psychiatry"},{"key":"10.3233\/JAD-215133_ref8","doi-asserted-by":"crossref","first-page":"445","DOI":"10.1007\/s11136-010-9594-8","article-title":"Cross-cultural adaptation and psychometric validation of a Spanish version of the quality of life in late-stage dementia scale","volume":"19","author":"Garre-Olmo","year":"2010","journal-title":"Qual Life Res"},{"key":"10.3233\/JAD-215133_ref9","doi-asserted-by":"crossref","first-page":"532","DOI":"10.1016\/j.jalz.2011.05.2410","article-title":"Neuropsychiatric symptoms in Alzheimer\u2019s disease","volume":"7","author":"Lyketsos","year":"2011","journal-title":"Alzheimers Dement"},{"key":"10.3233\/JAD-215133_ref10","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1016\/j.mam.2015.05.005","article-title":"Neuropsychiatric symptoms in Alzheimer\u2019s disease: What might be associated brain circuits?","volume":"43","author":"Rosenberg","year":"2015","journal-title":"Mol Aspects Med"},{"key":"10.3233\/JAD-215133_ref11","doi-asserted-by":"crossref","first-page":"43","DOI":"10.1192\/bjp.2019.195","article-title":"The individual course of neuropsychiatric symptoms in people with Alzheimer\u2019s and Lewy body dementia: 12-year longitudinal cohort study","volume":"216","author":"Vik-Mo","year":"2020","journal-title":"Br J Psychiatry"},{"key":"10.3233\/JAD-215133_ref12","doi-asserted-by":"crossref","first-page":"439","DOI":"10.1080\/13607863.2018.1531379","article-title":"The course of neuropsychiatric symptoms in institutionalized patients with young onset dementia","volume":"24","author":"Bauhuis","year":"2020","journal-title":"Aging Ment Health"},{"key":"10.3233\/JAD-215133_ref13","doi-asserted-by":"crossref","first-page":"2257","DOI":"10.1111\/jgs.16709","article-title":"Neuropsychiatric symptoms and functional decline in Alzheimer\u2019s disease and Lewy body dementia","volume":"68","author":"Borda","year":"2020","journal-title":"J Am Geriatr Soc"},{"key":"10.3233\/JAD-215133_ref14","doi-asserted-by":"crossref","first-page":"153","DOI":"10.1002\/gps.3980","article-title":"Vascular risk factors and neuropsychiatric symptoms in Alzheimer\u2019s disease: The Cache County Study","volume":"29","author":"Steinberg","year":"2014","journal-title":"Int J Geriatr Psychiatry"},{"key":"10.3233\/JAD-215133_ref15","doi-asserted-by":"crossref","first-page":"2112","DOI":"10.1016\/S0140-6736(05)67889-0","article-title":"Global prevalence of dementia: A Delphi consensus study","volume":"17","author":"Ferri","year":"2005","journal-title":"Lancet"},{"key":"10.3233\/JAD-215133_ref16","doi-asserted-by":"crossref","first-page":"211","DOI":"10.3233\/JAD-2011-110875","article-title":"Promoting research in advanced dementia: Early clinical results of the Alzheimer Center Reina Sof\u00eda Foundation","volume":"28","author":"Olazar\u00e1n","year":"2002","journal-title":"J Alzheimers Dis"},{"key":"10.3233\/JAD-215133_ref17","doi-asserted-by":"crossref","first-page":"939","DOI":"10.1212\/WNL.34.7.939","article-title":"Clinical diagnosis of Alzheimer\u2019s disease: Report of the NINCDS-ADRDA Work Group under the auspices of Department of Health and Human Services Task Force on Alzheimer\u2018s Disease","volume":"34","author":"McKhann","year":"1984","journal-title":"Neurology"},{"key":"10.3233\/JAD-215133_ref18","doi-asserted-by":"crossref","first-page":"1863","DOI":"10.1212\/01.wnl.0000187889.17253.b1","article-title":"Diagnosis and management of dementia with Lewy bodies: Third report of the DLB consortium","volume":"65","author":"McKeith","year":"2005","journal-title":"Neurology"},{"key":"10.3233\/JAD-215133_ref19","doi-asserted-by":"crossref","first-page":"1546","DOI":"10.1212\/WNL.51.6.1546","article-title":"Frontotemporal lobar degeneration: A consensus on clinical diagnostic criteria","volume":"51","author":"Neary","year":"1998","journal-title":"Neurology"},{"key":"10.3233\/JAD-215133_ref20","doi-asserted-by":"crossref","first-page":"1136","DOI":"10.1176\/ajp.139.9.1136","article-title":"The global deterioration scale for assessment of primary degenerative dementia","volume":"139","author":"Reisberg","year":"1982","journal-title":"Am J Psychiatry"},{"key":"10.3233\/JAD-215133_ref21","first-page":"189","article-title":"The \u201cMini-Examen Cognoscitiuo\u201d: A simple and practicaltest to detect intellectual dysfunctions in psychiatric patient","volume":"3","author":"Lobo","year":"1979","journal-title":"Actas Luso Esp Neurol Psiquiatr Cienc Afines"},{"key":"10.3233\/JAD-215133_ref22","first-page":"363","article-title":"Versiones en espa\u00f1ol del MinimentalState Examination (MMSE). Cuestiones para su uso en la pr\u00e1ctica cl\u00ednica","volume":"6","author":"Llamas-Velasco","year":"2015","journal-title":"Rev Neurol"},{"key":"10.3233\/JAD-215133_ref23","doi-asserted-by":"crossref","first-page":"168","DOI":"10.1097\/00002093-200007000-00008","article-title":"The Severe Mini-Mental State Examination: A new neuropsychologic instrument for the bedside assessment of severely impaired patients with Alzheimer disease","volume":"14","author":"Harrell","year":"2000","journal-title":"Alzheimer Dis Assoc Disord"},{"key":"10.3233\/JAD-215133_ref24","doi-asserted-by":"crossref","first-page":"2308","DOI":"10.1212\/WNL.44.12.2308","article-title":"The Neuropsychiatric Inventory: Comprehensive assessment of psychopathology in dementia","volume":"44","author":"Cummings","year":"1999","journal-title":"Neurology"},{"key":"10.3233\/JAD-215133_ref25","first-page":"15","article-title":"The Neuropsychiatric Inventory. Psychometric properties of its adaptation into Spanish","volume":"29","author":"Vilalta-Franch","year":"1999","journal-title":"Rev Neurol"},{"key":"10.3233\/JAD-215133_ref26","doi-asserted-by":"crossref","first-page":"271","DOI":"10.1016\/0006-3223(88)90038-8","article-title":"Cornell scale for depression in dementia","volume":"23","author":"Alexopoulos","year":"1988","journal-title":"Biol Psychiatry"},{"key":"10.3233\/JAD-215133_ref27","doi-asserted-by":"crossref","first-page":"149","DOI":"10.1016\/j.jagp.2013.01.079","article-title":"A novel rating scale for the measurement of apathy in institutionalizedpersons with dementia: The APADEM-NH","volume":"23","author":"Ag\u00fcera-Ortiz","year":"2015","journal-title":"Am J Geriatr Psychiatry"},{"key":"10.3233\/JAD-215133_ref28","doi-asserted-by":"crossref","first-page":"1099","DOI":"10.1002\/gps.755","article-title":"The apathy inventory: Assessment of apathy and awareness in alzheimer\u2019s disease, parkinson\u2019s disease and mild cognitive impairment","volume":"17","author":"Robert","year":"2002","journal-title":"Int J Geriatr Psychiatry"},{"key":"10.3233\/JAD-215133_ref29","doi-asserted-by":"crossref","first-page":"77","DOI":"10.1093\/geronj\/44.3.M77","article-title":"A description of agitation in a nursing home","volume":"44","author":"Cohen-Mansfield","year":"1989","journal-title":"J Gerontol"},{"key":"10.3233\/JAD-215133_ref30","first-page":"5","article-title":"Prevalencia de conductas agitadas en ancianos","volume":"11","author":"Cervilla","year":"1995","journal-title":"Anal Psiquiatr"},{"key":"10.3233\/JAD-215133_ref31","doi-asserted-by":"crossref","first-page":"1331","DOI":"10.1111\/j.1532-5415.1997.tb02932.x","article-title":"Noncognitive disturbances in Alzheimer\u2019s disease: Frequency, longitudinal course, and relationship to cognitive symptoms","volume":"45","author":"Marin","year":"1997","journal-title":"J Am Geriatr Soc"},{"key":"10.3233\/JAD-215133_ref32","doi-asserted-by":"crossref","first-page":"1475","DOI":"10.1001\/jama.288.12.1475","article-title":"Prevalence of neuropsychiatricsymptoms in dementia and mild cognitive impairment: Results from the Cardiovascular Health Study","volume":"288","author":"Lyketsos","year":"2002","journal-title":"JAMA"},{"key":"10.3233\/JAD-215133_ref33","doi-asserted-by":"crossref","first-page":"346","DOI":"10.1176\/jnp.15.3.346","article-title":"Psychiatric symptoms vary with the severity of dementia in probable Alzheimer\u2019s disease","volume":"15","author":"Lopez","year":"2003","journal-title":"J Neuropsychiatry Clin Neurosci"},{"key":"10.3233\/JAD-215133_ref34","first-page":"976","article-title":"Persistence of and changes in neuropsychiatric symptoms in Alzheimer disease over 6 months: The LASER-AD study","volume":"13","author":"Ryu","year":"2005","journal-title":"Am J Geriatr Psychiatry"},{"key":"10.3233\/JAD-215133_ref35","doi-asserted-by":"crossref","first-page":"170","DOI":"10.1002\/gps.1858","article-title":"Point and 5-year period prevalence of neuropsychiatric symptoms in dementia: The Cache County Study","volume":"23","author":"Steinberg","year":"2008","journal-title":"Int J Geriatr Psychiatry"},{"key":"10.3233\/JAD-215133_ref36","doi-asserted-by":"crossref","first-page":"212","DOI":"10.1192\/bjp.bp.108.049619","article-title":"Prevalence, correlates and course ofbehavioral and psychological symptoms of dementia in the population","volume":"194","author":"Savva","year":"2009","journal-title":"Br J Psychiatry"},{"key":"10.3233\/JAD-215133_ref37","doi-asserted-by":"crossref","first-page":"1231","DOI":"10.1097\/JGP.0b013e3181f60fa1","article-title":"Course of neuropsychiatric symptoms in residents with dementia in nursing homes over 2-year period","volume":"18","author":"Wetzels","year":"2010","journal-title":"Am J Geriatr Psychiatry"},{"key":"10.3233\/JAD-215133_ref38","doi-asserted-by":"crossref","first-page":"319","DOI":"10.1159\/000342824","article-title":"Prevalence of neuropsychiatric symptoms in young-onset compared to late-onset Alzheimer\u2019s disease \u2013Part 1: Findings of the two-year longitudinal NeedYD-Study","volume":"34","author":"Van Vliet","year":"2012","journal-title":"Dement Geriatr Cogn Disord"},{"key":"10.3233\/JAD-215133_ref39","doi-asserted-by":"crossref","first-page":"81","DOI":"10.1017\/S1041610213001609","article-title":"The course of neuropsychiatric symptoms in nursing-home patients with dementia over a 53-month follow-up period","volume":"26","author":"Selbaek","year":"2014","journal-title":"Int Psychogeriatr"},{"key":"10.3233\/JAD-215133_ref40","doi-asserted-by":"crossref","first-page":"380","DOI":"10.1016\/j.jamda.2014.12.018","article-title":"The course of neuropsychiatric symptoms in dementia: A 3-year longitudinal study","volume":"16","author":"Brodaty","year":"2015","journal-title":"J Am Med Dir Assoc"},{"key":"10.3233\/JAD-215133_ref41","doi-asserted-by":"crossref","first-page":"366","DOI":"10.1192\/bjp.bp.114.148403","article-title":"Longitudinal course of behavioral and 348 psychological symptoms of dementia: Systematic review","volume":"209","author":"Van der Linde","year":"2016","journal-title":"Br J Psychiatry"},{"key":"10.3233\/JAD-215133_ref42","doi-asserted-by":"crossref","first-page":"535","DOI":"10.3233\/JAD-2012-120913","article-title":"Apathy syndrome in Alzheimer\u2019s disease epidemiology: Prevalence, incidence, persistence, and risk and mortality factors","volume":"33","author":"Vilalta-Franch","year":"2013","journal-title":"J Alzheimers Dis"},{"key":"10.3233\/JAD-215133_ref43","doi-asserted-by":"crossref","first-page":"73","DOI":"10.3389\/fneur.2012.00073","article-title":"Behavioral and psychological symptoms of dementia","volume":"3","author":"Cerejeira","year":"2012","journal-title":"Front Neurol"},{"key":"10.3233\/JAD-215133_ref44","doi-asserted-by":"crossref","first-page":"532","DOI":"10.1097\/JGP.0b013e3181faec23","article-title":"Progression of cognitive, functional, and neuropsychiatric symptom domains in a population cohort with Alzheimer dementia: The Cache County Dementia Progression study","volume":"19","author":"Tschanz","year":"2011","journal-title":"Am J Geriatr Psychiatry"},{"key":"10.3233\/JAD-215133_ref45","doi-asserted-by":"crossref","first-page":"1361","DOI":"10.1002\/gps.4933","article-title":"Course of neuropsychiatric symptoms in dementia: 5-year longitudinal study","volume":"33","author":"Vik-Mo","year":"2018","journal-title":"Int J Geriatr Psychiatry"},{"key":"10.3233\/JAD-215133_ref46","doi-asserted-by":"crossref","first-page":"8","DOI":"10.1136\/jnnp.2005.069575","article-title":"A prospective longitudinal study of apathy in Alzheimer\u2019s disease","volume":"77","author":"Starkstein","year":"2006","journal-title":"J Neurol Neurosurg Psychiatry"},{"key":"10.3233\/JAD-215133_ref47","doi-asserted-by":"crossref","first-page":"130","DOI":"10.1016\/j.jagp.2013.03.014","article-title":". Depressed mood, and agitation\/aggression","volume":"23","author":"Zahodne","year":"2015","journal-title":"Am J Geriatr Psychiatry"},{"issue":"5S","key":"10.3233\/JAD-215133_ref48","doi-asserted-by":"crossref","first-page":"S95","DOI":"10.1016\/j.jalz.2012.10.005","article-title":"Frontolimbic atrophy is associated with agitation and aggression in mild cognitive impairment and Alzheimer\u2019s disease","volume":"9","author":"Trzepacz","year":"2013","journal-title":"Alzheimers Dement"},{"key":"10.3233\/JAD-215133_ref49","doi-asserted-by":"crossref","first-page":"1519","DOI":"10.3233\/JAD-160780","article-title":"Risk factors and pathological substrates associated with agitation\/aggression in Alzheimer\u2019s disease: A preliminary study using NACC data","volume":"55","author":"Sennik","year":"2016","journal-title":"J Alzheimers Dis"},{"key":"10.3233\/JAD-215133_ref50","doi-asserted-by":"crossref","first-page":"1585","DOI":"10.1212\/WNL.46.6.1585","article-title":"Low body weight in Alzheimer\u2019s disease is associated with mesial temporal cortex atrophy","volume":"46","author":"Grundman","year":"1996","journal-title":"Neurology"},{"key":"10.3233\/JAD-215133_ref51","doi-asserted-by":"crossref","first-page":"65","DOI":"10.1111\/psyg.12069","article-title":"Sleep disturbances and dementia","volume":"15","author":"Cipriani","year":"2015","journal-title":"Psychogeriatrics"}],"container-title":["Journal of Alzheimer's Disease"],"original-title":[],"link":[{"URL":"https:\/\/content.iospress.com\/download?id=10.3233\/JAD-215133","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,4,28]],"date-time":"2026-04-28T10:05:13Z","timestamp":1777370713000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.sagepub.com\/doi\/full\/10.3233\/JAD-215133"}},"subtitle":[],"editor":[{"given":"Janine","family":"Diehl-Schmid","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2022,3,22]]},"references-count":50,"journal-issue":{"issue":"2"},"URL":"https:\/\/doi.org\/10.3233\/jad-215133","relation":{},"ISSN":["1387-2877","1875-8908"],"issn-type":[{"value":"1387-2877","type":"print"},{"value":"1875-8908","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,3,22]]}}}