{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T15:06:13Z","timestamp":1790694373308,"version":"4.1.0"},"reference-count":104,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2021,8,17]],"date-time":"2021-08-17T00:00:00Z","timestamp":1629158400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Psychiatry"],"abstract":"<jats:p><jats:bold>Background:<\/jats:bold> The interaction between neuropsychiatric symptoms, mild cognitive impairment (MCI), and dementia is complex and remains to be elucidated. An additive or multiplicative effect of neuropsychiatric symptoms such as apathy or depression on cognitive decline has been suggested. Unraveling these interactions may allow the development of better prevention and treatment strategies. In the absence of available treatments for neurodegeneration, a timely and adequate identification of neuropsychiatric symptom changes in cognitive decline is highly relevant and can help identify treatment targets.<\/jats:p><jats:p><jats:bold>Methods:<\/jats:bold> An existing memory clinic-based research database of 476 individuals with MCI and 978 individuals with dementia due to Alzheimer's disease (AD) was reanalyzed. Neuropsychiatric symptoms were assessed in a prospective fashion using a battery of neuropsychiatric assessment scales: Middelheim Frontality Score, Behavioral Pathology in Alzheimer's Disease Rating Scale (Behave-AD), Cohen-Mansfield Agitation Inventory, Cornell Scale for Depression in Dementia (CSDD), and Geriatric Depression Scale (30 items). We subtyped subjects suffering from dementia as mild, moderate, or severe according to their Mini-Mental State Examination (MMSE) score and compared neuropsychiatric scores across these groups. A group of 126 subjects suffering from AD with a significant cerebrovascular component was examined separately as well. We compared the prevalence, nature, and severity of neuropsychiatric symptoms between subgroups of patients with MCI and dementia due to AD in a cross-sectional analysis.<\/jats:p><jats:p><jats:bold>Results:<\/jats:bold> Affective and sleep-related symptoms are common in MCI and remain constant in prevalence and severity across dementia groups. Depressive symptoms as assessed by the CSDD further increase in severe dementia. Most other neuropsychiatric symptoms (such as agitation and activity disturbances) progress in parallel with severity of cognitive decline. There are no significant differences in neuropsychiatric symptoms when comparing \u201cpure\u201d AD to AD with a significant vascular component.<\/jats:p><jats:p><jats:bold>Conclusion:<\/jats:bold> Neuropsychiatric symptoms such as frontal lobe symptoms, psychosis, agitation, aggression, and activity disturbances increase as dementia progresses. Affective symptoms such as anxiety and depressive symptoms, however, are more frequent in MCI than mild dementia but otherwise remain stable throughout the cognitive spectrum, except for an increase in CSDD score in severe dementia. There is no difference in neuropsychiatric symptoms when comparing mixed dementia (defined here as AD + significant cerebrovascular disease) to pure AD.<\/jats:p>","DOI":"10.3389\/fpsyt.2021.707580","type":"journal-article","created":{"date-parts":[[2021,8,17]],"date-time":"2021-08-17T05:41:28Z","timestamp":1629178888000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":47,"title":["Neuropsychiatric Symptoms in Mild Cognitive Impairment and Dementia Due to AD: Relation With Disease Stage and Cognitive Deficits"],"prefix":"10.3389","volume":"12","author":[{"given":"Wietse A.","family":"Wiels","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mandy M. J.","family":"Wittens","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dieter","family":"Zeeuws","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chris","family":"Baeken","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sebastiaan","family":"Engelborghs","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2021,8,17]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"532","DOI":"10.1016\/j.jalz.2011.05.2410","article-title":"Neuropsychiatric symptoms in Alzheimer's disease","volume":"7","author":"Lyketsos","year":"2011","journal-title":"Alzheimers Dement."},{"key":"B2","doi-asserted-by":"publisher","first-page":"51","DOI":"10.1159\/000358234","article-title":"Caregiver burden in Alzheimer's disease: differential associations in adult-child and spousal caregivers in the GERAS observational study","volume":"4","author":"Reed","year":"2014","journal-title":"Dement Geriatr Cogn Disord Extra"},{"key":"B3","doi-asserted-by":"publisher","first-page":"105","DOI":"10.3233\/JAD-2009-1016","article-title":"Does cognitive impairment influence burden in caregivers of patients with Alzheimer's disease?","volume":"17","author":"Germain","year":"2009","journal-title":"J Alzheimers Dis"},{"key":"B4","doi-asserted-by":"publisher","first-page":"263","DOI":"10.1016\/j.psychres.2011.11.018","article-title":"The role of persistent and incident major depression on rate of cognitive deterioration in newly diagnosed Alzheimer's disease patients","volume":"198","author":"Spalletta","year":"2012","journal-title":"Psychiatry Res."},{"key":"B5","doi-asserted-by":"publisher","first-page":"627","DOI":"10.3233\/JAD-150391","article-title":"Longitudinal neuropsychiatric predictors of death in Alzheimer's disease","volume":"48","author":"Spalletta","year":"2015","journal-title":"J Alzheimers Dis."},{"key":"B6","doi-asserted-by":"publisher","first-page":"175","DOI":"10.3233\/JAD-2010-1352","article-title":"Neuropsychiatric predictors of progression from amnestic-mild cognitive impairment to Alzheimer's disease: the role of depression and apathy","volume":"20","author":"Palmer","year":"2010","journal-title":"J Alzheimers Dis."},{"key":"B7","doi-asserted-by":"publisher","first-page":"293","DOI":"10.1192\/bjp.bp.114.148130","article-title":"Psychological treatments for depression and anxiety in dementia and mild cognitive impairment: systematic review and meta-analysis","volume":"207","author":"Orgeta","year":"2015","journal-title":"Br J Psychiatry."},{"key":"B8","doi-asserted-by":"publisher","first-page":"577","DOI":"10.1111\/j.1532-5415.2011.03355.x","article-title":"A systematic review and meta-analysis of placebo-controlled antidepressant studies in people with depression and dementia","volume":"59","author":"Nelson","year":"2011","journal-title":"J Am Geriatr Soc."},{"key":"B9","doi-asserted-by":"publisher","first-page":"492","DOI":"10.1038\/nrn1926","article-title":"Neuroleptic drugs in dementia: benefits and harm","volume":"7","author":"Ballard","year":"2006","journal-title":"Nat Rev Neurosci."},{"key":"B10","doi-asserted-by":"publisher","first-page":"160","DOI":"10.1038\/s41398-020-0839-1","article-title":"Depression\u2014an underrecognized target for prevention of dementia in Alzheimer's disease","volume":"10","author":"Dafsari","year":"2020","journal-title":"Transl Psychiatry"},{"key":"B11","doi-asserted-by":"publisher","first-page":"e0194735","DOI":"10.1371\/journal.pone.0194735","article-title":"Predicting dementia from primary care records: a systematic review and meta-analysis","volume":"13","author":"Ford","year":"2018","journal-title":"PLoS ONE."},{"key":"B12","doi-asserted-by":"publisher","first-page":"2673","DOI":"10.1016\/S0140-6736(17)31363-6","article-title":"Dementia prevention, intervention, and care","volume":"390","author":"Livingston","year":"2017","journal-title":"Lancet."},{"key":"B13","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1159\/000111082","article-title":"Consistency of neuropsychiatric syndromes across dementias: results from the European Alzheimer Disease Consortium","volume":"25","author":"Aalten","year":"2008","journal-title":"Part II Dement Geriatr Cogn Disord."},{"key":"B14","doi-asserted-by":"publisher","first-page":"212","DOI":"10.1192\/bjp.bp.108.049619","article-title":"Prevalence, correlates and course of behavioural and psychological symptoms of dementia in the population","volume":"194","author":"Savva","year":"2009","journal-title":"Br J Psychiatry"},{"key":"B15","doi-asserted-by":"publisher","first-page":"264","DOI":"10.1016\/j.jad.2015.09.069","article-title":"The prevalence of neuropsychiatric symptoms in Alzheimer's disease: systematic review and meta-analysis","volume":"190","author":"Zhao","year":"2016","journal-title":"J Affect Disord."},{"key":"B16","doi-asserted-by":"publisher","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":"B17","doi-asserted-by":"publisher","first-page":"278","DOI":"10.1017\/S2045796016001098","article-title":"Behavioural and psychological symptoms in general hospital patients with dementia, distress for nursing staff and complications in care: results of the General Hospital Study","volume":"27","author":"Hessler","year":"2018","journal-title":"Epidemiol Psychiatr Sci."},{"key":"B18","doi-asserted-by":"publisher","first-page":"669","DOI":"10.3233\/JAD-180641","article-title":"Neuropsychiatric inventory in community-dwelling older adults with mild cognitive impairment and dementia","volume":"68","author":"Nunes","year":"2019","journal-title":"J Alzheimers Dis."},{"key":"B19","doi-asserted-by":"publisher","first-page":"1102","DOI":"10.1212\/WNL.0000000000003089","article-title":"Late-onset depressive symptoms increase the risk of dementia in small vessel disease","volume":"87","author":"van Uden","year":"2016","journal-title":"Neurology."},{"key":"B20","doi-asserted-by":"publisher","first-page":"273","DOI":"10.1001\/archpsyc.63.3.273","article-title":"Depressive symptoms, vascular disease, and mild cognitive impairment: findings from the Cardiovascular Health Study","volume":"63","author":"Barnes","year":"2006","journal-title":"Arch Gen Psychiatry."},{"key":"B21","doi-asserted-by":"publisher","first-page":"785","DOI":"10.1001\/archpsyc.59.9.785","article-title":"Ischemic basis for deep white matter hyperintensities in major depression: a neuropathological study","volume":"59","author":"Thomas","year":"2002","journal-title":"Arch Gen Psychiatry."},{"key":"B22","doi-asserted-by":"publisher","first-page":"4","DOI":"10.1037\/per0000268","article-title":"Personality and Alzheimer's disease: an integrative review","volume":"10","author":"Terracciano","year":"2019","journal-title":"Personal Disord."},{"key":"B23","doi-asserted-by":"publisher","first-page":"456","DOI":"10.23736\/S0026-4806.21.07571-6","article-title":"Later life depression as risk factor for developing dementia: epidemiological evidence, predictive models, preventive strategies and future trends","volume":"112","author":"Piras","year":"2021","journal-title":"Minerva Med."},{"key":"B24","doi-asserted-by":"publisher","first-page":"1409","DOI":"10.1017\/S1041610216000405","article-title":"Associations between depression, sleep disturbance, and apolipoprotein E in the development of Alzheimer's disease: dementia","volume":"28","author":"Burke","year":"2016","journal-title":"Int Psychogeriatr."},{"key":"B25","doi-asserted-by":"publisher","first-page":"34","DOI":"10.3389\/fphar.2020.00034","article-title":"Depressive symptoms in the elderly-an early symptom of dementia? A systematic review","volume":"11","author":"Wiels","year":"2020","journal-title":"Front Pharmacol."},{"key":"B26","doi-asserted-by":"publisher","first-page":"134","DOI":"10.1007\/s12603-011-0147-9","article-title":"Course of neuropsychiatric symptoms during a 4-year follow up in the REAL-FR cohort","volume":"16","author":"Gonfrier","year":"2012","journal-title":"J Nutr Health Aging."},{"key":"B27","doi-asserted-by":"publisher","first-page":"143","DOI":"10.3233\/JAD-2012-111916","article-title":"Trajectories of behavioral disturbance in dementia","volume":"31","author":"Chow","year":"2012","journal-title":"J Alzheimers Dis."},{"key":"B28","doi-asserted-by":"publisher","first-page":"1078","DOI":"10.1111\/j.1532-5415.1996.tb02942.x","article-title":"The evolution of psychiatric symptoms in Alzheimer's disease: a natural history study","volume":"44","author":"Jost","year":"1996","journal-title":"J Am Geriatr Soc."},{"key":"B29","doi-asserted-by":"publisher","first-page":"543","DOI":"10.1016\/S0006-3223(02)01468-3","article-title":"Comorbidity of late life depression: an opportunity for research on mechanisms and treatment","volume":"52","author":"Alexopoulos","year":"2002","journal-title":"Biol Psychiatry."},{"key":"B30","doi-asserted-by":"publisher","first-page":"188","DOI":"10.1038\/s41398-019-0514-6","article-title":"Mechanisms and treatment of late-life depression","volume":"9","author":"Alexopoulos","year":"2019","journal-title":"Transl Psychiatry."},{"key":"B31","doi-asserted-by":"publisher","first-page":"947","DOI":"10.1002\/gps.3909","article-title":"Prevalence and associated behavioral symptoms of depression in mild cognitive impairment and dementia due to Alzheimer's disease","volume":"28","author":"Van der Mussele","year":"2013","journal-title":"Int J Geriatr Psychiatry."},{"key":"B32","doi-asserted-by":"publisher","first-page":"265","DOI":"10.1002\/gps.3820","article-title":"Behavioral symptoms in mild cognitive impairment as compared with Alzheimer's disease and healthy older adults","volume":"28","author":"Van der Mussele","year":"2013","journal-title":"Int J Geriatr Psychiatry."},{"key":"B33","doi-asserted-by":"publisher","first-page":"1028","DOI":"10.1002\/gps.1395","article-title":"Neuropsychiatric symptoms of dementia: cross-sectional analysis from a prospective, longitudinal Belgian study","volume":"20","author":"Engelborghs","year":"2005","journal-title":"Int J Geriatr Psychiatry."},{"key":"B34","doi-asserted-by":"publisher","first-page":"189","DOI":"10.1016\/0022-3956(75)90026-6","article-title":"\u201cMini-mental state\u201d. A practical method for grading the cognitive state of patients for the clinician","volume":"12","author":"Folstein","year":"1975","journal-title":"J Psychiatr Res"},{"key":"B35","doi-asserted-by":"publisher","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":"B36","doi-asserted-by":"publisher","first-page":"240","DOI":"10.1111\/j.1365-2796.2004.01380.x","article-title":"Mild cognitive impairment \u2013 beyond controversies, towards a consensus: report of the International Working Group on Mild Cognitive Impairment","volume":"256","author":"Winblad","year":"2004","journal-title":"J Internal Med."},{"key":"B37","doi-asserted-by":"publisher","first-page":"126","DOI":"10.1212\/WNL.0000000000004826","article-title":"Practice guideline update summary: mild cognitive impairment: report of the guideline development, dissemination, and implementation subcommittee of the American Academy of Neurology","volume":"90","author":"Petersen","year":"2018","journal-title":"Neurology."},{"key":"B38","doi-asserted-by":"publisher","first-page":"939","DOI":"10.1212\/WNL.34.7.939","article-title":"Clinical diagnosis of Alzheimer's disease: report of the NINCDS-ADRDA Work Group under the auspices of Department of Health and Human Services Task Force on Alzheimer's Disease","volume":"34","author":"McKhann","year":"1984","journal-title":"Neurology."},{"key":"B39","unstructured":"866Washington, DCAmerican Psychiatric AssociationDiagnostic and Statistical Manual of Mental Disorders: DSM-IV1994"},{"key":"B40","doi-asserted-by":"publisher","first-page":"250","DOI":"10.1212\/WNL.43.2.250","article-title":"Vascular dementia: diagnostic criteria for research studies. Report of the NINDS-AIREN International Workshop","volume":"43","author":"Rom\u00e1n","year":"1993","journal-title":"Neurology."},{"key":"B41","doi-asserted-by":"publisher","first-page":"383","DOI":"10.3233\/JAD-151097","article-title":"A decade of cerebrospinal fluid biomarkers for Alzheimer's disease in Belgium","volume":"54","author":"Somers","year":"2016","journal-title":"J Alzheimers Dis."},{"key":"B42","doi-asserted-by":"publisher","first-page":"70","DOI":"10.1002\/gps.1249","article-title":"The Middelheim Frontality Score: a behavioural assessment scale that discriminates frontotemporal dementia from Alzheimer's disease","volume":"20","author":"De Deyn","year":"2005","journal-title":"Int J Geriatr Psychiatry."},{"key":"B43","doi-asserted-by":"publisher","first-page":"M77","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":"B44","doi-asserted-by":"publisher","first-page":"9","DOI":"10.1037\/t13385-000","article-title":"Behavioral symptoms in Alzheimer's disease: phenomenology and treatment","volume":"48","author":"Reisberg","year":"1987","journal-title":"J Clin Psychiatry."},{"key":"B45","doi-asserted-by":"publisher","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":"B46","doi-asserted-by":"publisher","first-page":"37","DOI":"10.1016\/0022-3956(82)90033-4","article-title":"Development and validation of a geriatric depression screening scale: a preliminary report","volume":"17","author":"Yesavage","year":"","journal-title":"J Psychiatr Res."},{"key":"B47","doi-asserted-by":"publisher","first-page":"360","DOI":"10.1080\/08039480600937066","article-title":"The geriatric depression scale and the cornell scale for depression in dementia. A validity study","volume":"60","author":"K\u00f8rner","year":"2006","journal-title":"Nord J Psychiatry."},{"key":"B48","doi-asserted-by":"publisher","first-page":"556","DOI":"10.1002\/gps.2154","article-title":"Is the geriatric depression scale a reliable screening tool for depressive symptoms in elderly patients with cognitive impairment?","volume":"24","author":"Debruyne","year":"2009","journal-title":"Int J Geriatr Psychiatry."},{"key":"B49","doi-asserted-by":"publisher","first-page":"139","DOI":"10.1097\/01.JGP.0000192478.82189.a8","article-title":"Mapping scores onto stages: mini-mental state examination and clinical dementia rating","volume":"14","author":"Perneczky","year":"2006","journal-title":"Am J Geriatr Psychiatry."},{"key":"B50","doi-asserted-by":"publisher","first-page":"7475","DOI":"10.3390\/ijerph17207475","article-title":"Association of late life depression, (non-) modifiable risk and protective factors with dementia and alzheimer's disease: literature review on current evidences, preventive interventions and possible future trends in prevention and treatment of dementia","volume":"17","author":"Kuo","year":"2020","journal-title":"Int J Environ Res Public Health."},{"key":"B51","doi-asserted-by":"publisher","first-page":"434","DOI":"10.1186\/s12888-020-02820-9","article-title":"Sex differences in dementia: on the potentially mediating effects of educational attainment and experiences of psychological distress","volume":"20","author":"Hasselgren","year":"2020","journal-title":"BMC Psychiatry."},{"key":"B52","doi-asserted-by":"publisher","first-page":"1157","DOI":"10.3233\/JAD-2010-101212","article-title":"Grouping and trajectories of the neuropsychiatric symptoms in patients with Alzheimer's disease, part I: symptom clusters","volume":"22","author":"Garre-Olmo","year":"2010","journal-title":"J Alzheimers Dis."},{"key":"B53","doi-asserted-by":"publisher","first-page":"70","DOI":"10.1016\/j.jagp.2015.06.001","article-title":"Trajectories of neuropsychiatric symptoms and cognitive decline in mild cognitive impairment","volume":"24","author":"David","year":"2016","journal-title":"Am J Geriatr Psychiatry"},{"key":"B54","doi-asserted-by":"publisher","first-page":"389","DOI":"10.1017\/cjn.2015.266","article-title":"Trajectories of behavioural disturbances across dementia types","volume":"42","author":"Linds","year":"2015","journal-title":"Can J Neurol Sci."},{"key":"B55","doi-asserted-by":"publisher","first-page":"147","DOI":"10.1016\/j.maturitas.2014.05.026","article-title":"Late-life depression in the primary care setting: challenges, collaborative care, and prevention","volume":"79","author":"Hall","year":"2014","journal-title":"Maturitas."},{"key":"B56","doi-asserted-by":"publisher","first-page":"184","DOI":"10.1016\/j.maturitas.2014.05.009","article-title":"Depression and dementia: cause, consequence or coincidence?","volume":"79","author":"Bennett","year":"2014","journal-title":"Maturitas."},{"key":"B57","doi-asserted-by":"publisher","first-page":"1369","DOI":"10.1002\/gps.5125","article-title":"A survey on the prevalence of apathy in elderly people referred to specialized memory centers","volume":"34","author":"Manera","year":"2019","journal-title":"Int J Geriatr Psychiatry."},{"key":"B58","doi-asserted-by":"publisher","first-page":"179","DOI":"10.1016\/j.jad.2014.05.008","article-title":"Neuroanatomical correlates of apathy in late-life depression and antidepressant treatment response","volume":"166","author":"Yuen","year":"2014","journal-title":"J Affect Disord."},{"key":"B59","unstructured":"Side effects of antipsychotics in the elderly439\n            MasandPS\n          J Clin Psychiatry.612000"},{"key":"B60","doi-asserted-by":"publisher","first-page":"943","DOI":"10.1002\/gps.4083","article-title":"Melancholia in later life: late and early onset differences in presentation, course, and dementia risk","volume":"29","author":"Sachs-Ericsson","year":"2014","journal-title":"Int J Geriatr Psychiatry."},{"key":"B61","doi-asserted-by":"publisher","first-page":"23","DOI":"10.1016\/S1098-3597(01)90059-6","article-title":"Assessing psychiatric illness in geriatric patients","volume":"3","author":"Tune","year":"2001","journal-title":"Clin Cornerstone."},{"key":"B62","doi-asserted-by":"publisher","first-page":"405","DOI":"10.1111\/j.1532-5415.2007.01600.x","article-title":"Reaction to a dementia diagnosis in individuals with Alzheimer's disease and mild cognitive impairment","volume":"56","author":"Carpenter","year":"2008","journal-title":"J Am Geriatr Soc."},{"key":"B63","doi-asserted-by":"publisher","first-page":"26","DOI":"10.3109\/08039488.2011.593100","article-title":"Validation of the Icelandic version of the neuropsychiatric inventory with caregiver distress (NPI-D)","volume":"66","author":"Davidsdottir","year":"2012","journal-title":"Nord J Psychiatry."},{"key":"B64","doi-asserted-by":"publisher","first-page":"793","DOI":"10.1002\/(SICI)1099-1166(1998110)13:11<793::AID-GPS875>3.0.CO;2-Q","article-title":"The behavioral pathology in Alzheimer's disease scale (BEHAVE-AD): factor structure among community-dwelling Alzheimer's disease patients","volume":"13","author":"Harwood","year":"1998","journal-title":"Int J Geriatr Psychiatry."},{"key":"B65","doi-asserted-by":"publisher","first-page":"9","DOI":"10.3389\/fnagi.2020.00009","article-title":"Depression, anxiety, and apathy in mild cognitive impairment: current perspectives","volume":"12","author":"Ma","year":"2020","journal-title":"Front Aging Neurosci."},{"key":"B66","doi-asserted-by":"publisher","first-page":"563","DOI":"10.1016\/j.cger.2018.06.005","article-title":"Mild cognitive impairment in geriatrics","volume":"34","author":"Tangalos","year":"2018","journal-title":"Clin Geriatr Med."},{"key":"B67","doi-asserted-by":"publisher","first-page":"185","DOI":"10.1017\/S1041610217001880","article-title":"Affective and emotional dysregulation as pre-dementia risk markers: exploring the mild behavioral impairment symptoms of depression, anxiety, irritability, and euphoria","volume":"30","author":"Ismail","year":"2018","journal-title":"Int Psychogeriatr."},{"key":"B68","doi-asserted-by":"publisher","first-page":"29","DOI":"10.1093\/arclin\/acaa057","article-title":"Dementia worry and neuropsychological performance in healthy older adults","volume":"36","author":"Caughie","year":"2021","journal-title":"Arch Clin Neuropsychol."},{"key":"B69","doi-asserted-by":"publisher","first-page":"39","DOI":"10.1007\/s10433-018-0462-7","article-title":"Dementia worry in middle-aged and older adults in Germany: sociodemographic, health-related and psychological correlates","volume":"16","author":"Bowen","year":"2018","journal-title":"Eur J Ageing."},{"key":"B70","doi-asserted-by":"publisher","first-page":"227","DOI":"10.3233\/JAD-170632","article-title":"Risk of conversion to dementia in a mild behavioral impairment group compared to a psychiatric group and to a mild cognitive impairment group","volume":"62","author":"Taragano","year":"2018","journal-title":"J Alzheimers Dis."},{"key":"B71","doi-asserted-by":"publisher","first-page":"300","DOI":"10.1002\/gps.2106","article-title":"Anxiety symptoms in mild cognitive impairment","volume":"24","author":"Rozzini","year":"2009","journal-title":"Int J Geriatr Psychiatry."},{"key":"B72","doi-asserted-by":"publisher","first-page":"346","DOI":"10.1176\/jnp.15.3.346","article-title":"Psychiatric symptoms vary with the severity of dementia in probable Alzheimer's disease","volume":"15","author":"Lopez","year":"2003","journal-title":"J Neuropsychiatry Clin Neurosci."},{"key":"B73","doi-asserted-by":"publisher","first-page":"103","DOI":"10.1017\/S1041610217001879","article-title":"Frequency and subgroups of neuropsychiatric symptoms in mild cognitive impairment and different stages of dementia in Alzheimer's disease","volume":"30","author":"Siafarikas","year":"2018","journal-title":"Int Psychogeriatr."},{"key":"B74","doi-asserted-by":"publisher","first-page":"82","DOI":"10.1016\/j.archger.2018.10.011","article-title":"Associations of potentially inappropriate medication use with four year survival of an inception cohort of nursing home residents","volume":"80","author":"Paque","year":"2019","journal-title":"Arch Gerontol Geriatr."},{"key":"B75","doi-asserted-by":"publisher","first-page":"640","DOI":"10.1002\/gps.5282","article-title":"New use of psychotropic medication after hospitalization among people with dementia","volume":"35","author":"M\u00f6llers","year":"2020","journal-title":"Int J Geriatr Psychiatry."},{"key":"B76","doi-asserted-by":"publisher","first-page":"CD003944","DOI":"10.1002\/14651858.CD003944.pub2","article-title":"Antidepressants for treating depression in dementia","volume":"8","author":"Dudas","year":"2018","journal-title":"Cochrane Database Syst Rev."},{"key":"B77","doi-asserted-by":"publisher","first-page":"32","DOI":"10.1002\/gps.4566","article-title":"What is the therapeutic value of antidepressants in dementia? A narrative review","volume":"32","author":"Farina","year":"2017","journal-title":"Int J Geriatr Psychiatry."},{"key":"B78","doi-asserted-by":"publisher","first-page":"19m13205","DOI":"10.4088\/JCP.19m13205","article-title":"To be continued? Long-term treatment effects of antidepressant drug classes and individual antidepressants on the risk of developing dementia: a German Case-Control Study","volume":"81","author":"Bartels","year":"2020","journal-title":"J Clin Psychiatry."},{"key":"B79","doi-asserted-by":"publisher","first-page":"279","DOI":"10.1016\/j.jamda.2018.12.004","article-title":"Depression and antidepressants as potential risk factors in dementia: a systematic review and meta-analysis of 18 longitudinal studies","volume":"20","author":"Chan","year":"2019","journal-title":"J Am Med Dir Assoc."},{"key":"B80","doi-asserted-by":"publisher","first-page":"15","DOI":"10.1080\/17512433.2020.1697676","article-title":"STOPP\/START criteria for potentially inappropriate medications\/potential prescribing omissions in older people: origin and progress","volume":"13","author":"O'Mahony","year":"2020","journal-title":"Expert Rev Clin Pharmacol"},{"key":"B81","doi-asserted-by":"publisher","first-page":"213","DOI":"10.1093\/ageing\/afu145","article-title":"STOPP\/START criteria for potentially inappropriate prescribing in older people: version 2","volume":"44","author":"O'Mahony","year":"2015","journal-title":"Age Ageing."},{"key":"B82","doi-asserted-by":"publisher","first-page":"1415","DOI":"10.1017\/S1041610213000859","article-title":"Association between behavioral and psychological symptoms and psychotropic drug use among old people with cognitive impairment living in geriatric care settings","volume":"25","author":"Gustafsson","year":"2013","journal-title":"Int Psychogeriatr."},{"key":"B83","doi-asserted-by":"publisher","first-page":"375","DOI":"10.1002\/gps.1477","article-title":"Progression of cerebral white matter lesions is not associated with development of depressive symptoms in elderly subjects at risk of cardiovascular disease: the PROSPER study","volume":"21","author":"Versluis","year":"2006","journal-title":"Int J Geriatr Psychiatry"},{"key":"B84","doi-asserted-by":"publisher","first-page":"729","DOI":"10.1001\/jamapsychiatry.2017.0984","article-title":"Association of microvascular dysfunction with late-life depression: a systematic review and meta-analysis","volume":"74","author":"van Agtmaal","year":"2017","journal-title":"JAMA Psychiatry."},{"key":"B85","doi-asserted-by":"publisher","first-page":"157","DOI":"10.1192\/bjp.180.2.157","article-title":"Vascular basis of late-onset depressive disorder","volume":"180","author":"Baldwin","year":"2002","journal-title":"Br J Psychiatry."},{"key":"B86","doi-asserted-by":"publisher","first-page":"45","DOI":"10.1007\/7854_2016_28","article-title":"Inflammation-associated co-morbidity between depression and cardiovascular disease","volume":"31","author":"Halaris","year":"2017","journal-title":"Curr Top Behav Neurosci."},{"key":"B87","doi-asserted-by":"publisher","first-page":"617","DOI":"10.1111\/jnc.14271","article-title":"White matter degeneration in vascular and other ageing-related dementias","volume":"144","author":"Hase","year":"2018","journal-title":"J Neurochem."},{"key":"B88","doi-asserted-by":"publisher","first-page":"E1","DOI":"10.1503\/jpn.180136","article-title":"Impact of white matter hyperintensity location on depressive symptoms in memory-clinic patients: a lesion\u2013symptom mapping study","volume":"44","author":"Leeuwis","year":"2019","journal-title":"J Psychiatry Neurosci"},{"key":"B89","doi-asserted-by":"publisher","first-page":"66","DOI":"10.1136\/jnnp.67.1.66","article-title":"White matter lesions on magnetic resonance imaging in dementia with Lewy bodies, Alzheimer's disease, vascular dementia, and normal aging","volume":"67","author":"Barber","year":"1999","journal-title":"J Neurol Neurosurg Psychiatry."},{"key":"B90","doi-asserted-by":"publisher","first-page":"127","DOI":"10.1159\/000455127","article-title":"Neuropsychiatric symptoms in Alzheimer disease, vascular dementia, and mixed dementia","volume":"17","author":"Anor","year":"2017","journal-title":"Neurodegener Dis."},{"key":"B91","doi-asserted-by":"publisher","first-page":"326","DOI":"10.1097\/WAD.0b013e31820d89b6","article-title":"Neuropsychiatric profiles in dementia","volume":"25","author":"Johnson","year":"2011","journal-title":"Alzheimer Dis Assoc Disord."},{"key":"B92","doi-asserted-by":"publisher","first-page":"274","DOI":"10.14283\/jpad.2020.37","article-title":"A framework for developing pharmacotherapy for agitation in Alzheimer's disease: recommendations of the ISCTM* Working Group","volume":"7","author":"O'Gorman","year":"2020","journal-title":"J Prev Alzheimers Dis."},{"key":"B93","doi-asserted-by":"publisher","first-page":"325","DOI":"10.3233\/JAD-2012-112003","article-title":"Apathy and depression in mild Alzheimer's disease: a cross-sectional study using diagnostic criteria","volume":"31","author":"Benoit","year":"2012","journal-title":"J Alzheimers Dis."},{"key":"B94","doi-asserted-by":"publisher","first-page":"314","DOI":"10.1176\/jnp.10.3.314","article-title":"Apathy is not depression","volume":"10","author":"Levy","year":"1998","journal-title":"J Neuropsychiatry Clin Neurosci."},{"key":"B95","doi-asserted-by":"publisher","first-page":"e3280","DOI":"10.1212\/WNL.0000000000010951","article-title":"Apathy and risk of probable incident dementia among community-dwelling older adults","volume":"95","author":"Bock","year":"2020","journal-title":"Neurology."},{"key":"B96","doi-asserted-by":"publisher","first-page":"1012","DOI":"10.1001\/jamapsychiatry.2018.1877","article-title":"Association of apathy with risk of incident dementia: a systematic review and meta-analysis","volume":"75","author":"van Dalen","year":"2018","journal-title":"JAMA Psychiatry."},{"key":"B97","doi-asserted-by":"publisher","first-page":"204","DOI":"10.1159\/000338239","article-title":"Symptoms of apathy are associated with progression from mild cognitive impairment to Alzheimer's disease in non-depressed subjects","volume":"33","author":"Richard","year":"2012","journal-title":"Dement Geriatr Cogn Disord"},{"key":"B98","doi-asserted-by":"publisher","first-page":"873","DOI":"10.1016\/j.jagp.2019.02.003","article-title":"The roles of apathy and depression in predicting Alzheimer disease: a longitudinal analysis in older adults with mild cognitive impairment","volume":"27","author":"Ruthirakuhan","year":"2019","journal-title":"Am J Geriatr Psychiatry."},{"key":"B99","doi-asserted-by":"publisher","first-page":"186","DOI":"10.1016\/j.jagp.2012.10.024","article-title":"Quality of life in community-dwelling older persons with apathy","volume":"22","author":"Groeneweg-Koolhoven","year":"2014","journal-title":"Am J Geriatr Psychiatry."},{"key":"B100","doi-asserted-by":"publisher","first-page":"751","DOI":"10.1007\/s11136-018-2041-y","article-title":"Apathy and health-related quality of life in nursing home residents","volume":"28","author":"Nijsten","year":"2019","journal-title":"Qual Life Res."},{"key":"B101","doi-asserted-by":"publisher","first-page":"628","DOI":"10.1016\/S2215-0366(16)00097-3","article-title":"10-year trajectories of depressive symptoms and risk of dementia: a population-based study","volume":"3","author":"Mirza","year":"2016","journal-title":"Lancet Psychiatry."},{"key":"B102","doi-asserted-by":"publisher","first-page":"525","DOI":"10.1001\/jamapsychiatry.2016.0004","article-title":"Trajectories of depressive symptoms in older adults and risk of dementia","volume":"73","author":"Kaup","year":"2016","journal-title":"JAMA Psychiatry."},{"key":"B103","doi-asserted-by":"publisher","first-page":"393","DOI":"10.1007\/s11065-018-9396-2","article-title":"Prevalence of depression, anxiety and PTSD in people with dementia: a systematic review and meta-analysis","volume":"28","author":"Kuring","year":"2018","journal-title":"Neuropsychol Rev."},{"key":"B104","doi-asserted-by":"publisher","first-page":"1475","DOI":"10.1001\/jama.288.12.1475","article-title":"Prevalence of neuropsychiatric symptoms in dementia and mild cognitive impairment: results from the cardiovascular health study","volume":"288","author":"Lyketsos","year":"2002","journal-title":"JAMA."}],"container-title":["Frontiers in Psychiatry"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fpsyt.2021.707580\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,8,17]],"date-time":"2021-08-17T05:41:32Z","timestamp":1629178892000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fpsyt.2021.707580\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,8,17]]},"references-count":104,"alternative-id":["10.3389\/fpsyt.2021.707580"],"URL":"https:\/\/doi.org\/10.3389\/fpsyt.2021.707580","relation":{},"ISSN":["1664-0640"],"issn-type":[{"value":"1664-0640","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,8,17]]},"article-number":"707580"}}