{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T21:53:39Z","timestamp":1790114019351,"version":"4.0.1"},"reference-count":39,"publisher":"SAGE Publications","issue":"2","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JAD"],"published-print":{"date-parts":[[2015,11,27]]},"abstract":"<jats:p>Background: Neuropsychiatric symptoms, also known as behavioral and psychological symptoms of dementia (BPSD), affect the majority of patients with dementia, and result in a greater cognitive and functional impairment. Objective: To investigate associations between BPSD and amyloid cerebral deposition as measured by 18F-Florbetapir-PET quantitative uptake in elderly subjects with and without cognitive impairment. Methods: Participants with cognitive impairment [mild cognitive impairment (MCI) or Alzheimer\u2019s disease (AD)] and healthy controls (HC) from the ADNI cohort (Alzheimer Disease Neuroimaging Initiative) who underwent an 18F-florbetapir PET scan between May 2010 and March 2014 were included. Clinical assessments included the Clinical Dementia Rating, the Mini-Mental State Examination (MMSE), and the Neuropsychiatric Inventory. Freesurfer software was used to extract PET counts based on T1-based structural ROI (frontal, cingulate, parietal, and temporal). Spearman\u2019s partial correlation scores between BPSD severity and regional amyloid uptake were calculated. Results: Data for 657 participants [age\u200a=\u200a72.6 (7.19); MMSE\u200a=\u200a27.4 (2.67)] were analyzed, including 230 HC [age\u200a=\u200a73.1 (6.02); MMSE\u200a=\u200a29 (1.21)], 308 MCI [age\u200a=\u200a71.5 (7.44); MMSE\u200a=\u200a28.0 (1.75)], and 119 AD subjects [age\u200a=\u200a74.7 (8.05); MMSE\u200a=\u200a23.1 (2.08)]. Considering all diagnostic groups together, positive significant correlations were found between anxiety and 18F-florbetapir uptake in the frontal (r\u200a=\u200a0.102; p\u200a=\u200a0.009), cingulate (r\u200a=\u200a0.083; p\u200a=\u200a0.034), and global cerebral uptake (r\u200a=\u200a0.099; p\u200a=\u200a0.011); between irritability and frontal (r\u200a=\u200a0.089; p\u200a=\u200a0.023), cingulate (r\u200a=\u200a0.085; p\u200a=\u200a0.030), parietal (r\u200a=\u200a0.087; p\u200a=\u200a0.025), and global cerebral uptake (r\u200a=\u200a0.093; p\u200a=\u200a0.017); in the MCI subgroup, between anxiety and frontal (r\u200a=\u200a0.126; p\u200a=\u200a0.03) and global uptake (r\u200a=\u200a0.14; p\u200a=\u200a0.013); in the AD subgroup, between irritability and parietal uptake (r\u200a=\u200a0.201; p\u200a=\u200a0.03). Conclusion: Anxiety and irritability are associated with greater amyloid deposition in the neurodegenerative process leading to AD.<\/jats:p>","DOI":"10.3233\/jad-150181","type":"journal-article","created":{"date-parts":[[2015,11,27]],"date-time":"2015-11-27T08:35:17Z","timestamp":1448613317000},"page":"387-398","source":"Crossref","is-referenced-by-count":63,"title":["Associations between Neuropsychiatric Symptoms and Cerebral Amyloid Deposition in Cognitively Impaired Elderly People"],"prefix":"10.1177","volume":"49","author":[{"given":"David","family":"Bensamoun","sequence":"first","affiliation":[{"name":"Centre Memoire de Ressources et de Recherche, Institut Claude Pompidou, EA CoBTek, University of Nice Sophia Antipolis, Nice, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"name":"for the Alzheimer\u2019s Disease Neuroimaging Initiative","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Renaud","family":"Guignard","sequence":"additional","affiliation":[{"name":"Department of Nuclear Medicine, H\u00f4pital de La Tour, Meyrin, GE, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ansgar J.","family":"Furst","sequence":"additional","affiliation":[{"name":"Department of Psychiatry and Behavioral Sciences, Department of Neurology and Neurological Sciences, Stanford University, Stanford, USA; War Related Illness and Injury Study Center, VA Palo Alto, Palo Alto, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexandre","family":"Derreumaux","sequence":"additional","affiliation":[{"name":"Centre Memoire de Ressources et de Recherche, Institut Claude Pompidou, EA CoBTek, University of Nice Sophia Antipolis, Nice, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Valeria","family":"Manera","sequence":"additional","affiliation":[{"name":"Centre Memoire de Ressources et de Recherche, Institut Claude Pompidou, EA CoBTek, University of Nice Sophia Antipolis, Nice, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jacques","family":"Darcourt","sequence":"additional","affiliation":[{"name":"Nuclear Medicine Department, Antoine Lacassagne Center, Nice, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michel","family":"Benoit","sequence":"additional","affiliation":[{"name":"Department of Psychiatry, University Hospital of Nice, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Philippe H.","family":"Robert","sequence":"additional","affiliation":[{"name":"Centre Memoire de Ressources et de Recherche, Institut Claude Pompidou, EA CoBTek, University of Nice Sophia Antipolis, Nice, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Renaud","family":"David","sequence":"additional","affiliation":[{"name":"Centre Memoire de Ressources et de Recherche, Institut Claude Pompidou, EA CoBTek, University of Nice Sophia Antipolis, Nice, France"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"179","reference":[{"key":"10.3233\/JAD-150181_ref1","doi-asserted-by":"crossref","first-page":"708","DOI":"10.1176\/appi.ajp.157.5.708","article-title":"Mental and behavioral disturbances in dementia: Findings from the Cache County Study on Memory in Aging","volume":"157","author":"Lyketsos","year":"2000","journal-title":"Am J Psychiatry"},{"key":"10.3233\/JAD-150181_ref2","doi-asserted-by":"crossref","first-page":"233","DOI":"10.1176\/jnp.12.2.233","article-title":"Validation of the NPI-Q, a brief clinical form of the Neuropsychiatric Inventory","volume":"12","author":"Kaufer","year":"2000","journal-title":"J Neuropsychiatry Clin Neurosci"},{"key":"10.3233\/JAD-150181_ref3","doi-asserted-by":"crossref","first-page":"167","DOI":"10.1136\/jnnp.69.2.167","article-title":"Cerebral correlates of psychotic symptoms in Alzheimer\u2019s disease","volume":"69","author":"Mega","year":"2000","journal-title":"J Neurol Neurosurg Psychiatr"},{"key":"10.3233\/JAD-150181_ref4","doi-asserted-by":"crossref","first-page":"16","DOI":"10.1159\/000089215","article-title":"Relationship between delusions and regional cerebral blood flow in Alzheimer\u2019s disease","volume":"21","author":"Nakano","year":"2006","journal-title":"Dement Geriatr Cogn Disord"},{"key":"10.3233\/JAD-150181_ref5","doi-asserted-by":"crossref","first-page":"864","DOI":"10.1002\/gps.1163","article-title":"Brain perfusion correlates of the apathy inventory dimensions of Alzheimer\u2019s disease","volume":"19","author":"Benoit","year":"2004","journal-title":"Int J Geriatr Psychiatry"},{"key":"10.3233\/JAD-150181_ref6","doi-asserted-by":"crossref","first-page":"328","DOI":"10.1016\/j.neulet.2008.06.053","article-title":"The relationship between depressive symptoms and prefrontal hypoperfusion demonstrated by eZIS in patients with DAT","volume":"441","author":"Akiyama","year":"2008","journal-title":"Neurosci Lett"},{"key":"10.3233\/JAD-150181_ref7","first-page":"218","article-title":"Frontal lobe hypoperfusion and depressive symptoms in Alzheimer disease","volume":"33","author":"Levy-Cooperman","year":"2008","journal-title":"J Psychiatry Neurosci"},{"key":"10.3233\/JAD-150181_ref8","doi-asserted-by":"crossref","first-page":"56","DOI":"10.1176\/jnp.13.1.56","article-title":"Psychiatric symptoms associated with cortical-subcortical dysfunction in Alzheimer\u2019s disease","volume":"13","author":"Lopez","year":"2001","journal-title":"J Neuropsychiatry Clin Neurosci"},{"key":"10.3233\/JAD-150181_ref9","doi-asserted-by":"crossref","first-page":"412","DOI":"10.1016\/j.biopsych.2004.11.035","article-title":"Regional cerebral metabolism in early Alzheimer\u2019s disease with clinically significant apathy or depression","volume":"57","author":"Holthoff","year":"2005","journal-title":"Biol Psychiatry"},{"key":"10.3233\/JAD-150181_ref10","doi-asserted-by":"crossref","first-page":"37","DOI":"10.1159\/000257761","article-title":"Metabolic compensation and depression in Alzheimer\u2019s disease","volume":"29","author":"Caroli","year":"2010","journal-title":"Dement Geriatr Cogn Disord"},{"key":"10.3233\/JAD-150181_ref11","doi-asserted-by":"crossref","first-page":"619","DOI":"10.1001\/archneur.1991.00530180075020","article-title":"Neuropathologic and neurochemical correlates of psychosis in primary dementia","volume":"48","author":"Zubenko","year":"1991","journal-title":"Arch Neurol"},{"key":"10.3233\/JAD-150181_ref12","doi-asserted-by":"crossref","first-page":"355","DOI":"10.1002\/ana.72","article-title":"Orbitofrontal and anterior cingulate cortex neurofibrillary tangle burden is associated with agitation in Alzheimer disease","volume":"49","author":"Tekin","year":"2001","journal-title":"Ann Neurol"},{"key":"10.3233\/JAD-150181_ref13","doi-asserted-by":"crossref","first-page":"144","DOI":"10.1159\/000090674","article-title":"Neuropathologic correlates of apathy in Alzheimer\u2019s disease","volume":"21","author":"Marshall","year":"2006","journal-title":"Dement Geriatr Cogn Disord"},{"key":"10.3233\/JAD-150181_ref14","doi-asserted-by":"crossref","first-page":"559","DOI":"10.1159\/000137671","article-title":"Neuropsychiatric correlates of cerebrospinal fluid biomarkers in Alzheimer\u2019s disease","volume":"25","author":"Skogseth","year":"2008","journal-title":"Dement Geriatr Cogn Disord"},{"key":"10.3233\/JAD-150181_ref15","doi-asserted-by":"crossref","first-page":"302","DOI":"10.1176\/appi.neuropsych.12060156","article-title":"Apathy is associated with increased amyloid burden in mild cognitive impairment","volume":"25","author":"Marshall","year":"2013","journal-title":"J Neuropsychiatry Clin Neurosci"},{"key":"10.3233\/JAD-150181_ref16","doi-asserted-by":"crossref","first-page":"275","DOI":"10.1001\/jama.2010.2008","article-title":"Use of florbetapir-PET for imaging beta-amyloid pathology","volume":"305","author":"Clark","year":"2011","journal-title":"JAMA"},{"key":"10.3233\/JAD-150181_ref17","doi-asserted-by":"crossref","first-page":"449","DOI":"10.1136\/jnnp-2013-306110","article-title":"Apathy correlates with prefrontal amyloid \u03b2 deposition in Alzheimer\u2019s disease","volume":"85","author":"Mori","year":"2014","journal-title":"J Neurol Neurosurg Psychiatr"},{"key":"10.3233\/JAD-150181_ref18","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":"1994","journal-title":"Neurology"},{"key":"10.3233\/JAD-150181_ref19","doi-asserted-by":"crossref","first-page":"578","DOI":"10.1002\/ana.23650","article-title":"Amyloid deposition, hypometabolism, and longitudinal cognitive decline","volume":"72","author":"Landau","year":"2012","journal-title":"Ann Neurol"},{"key":"10.3233\/JAD-150181_ref20","doi-asserted-by":"crossref","first-page":"531","DOI":"10.1002\/gps.1317","article-title":"The course of neuropsychiatric symptoms in dementia. Part II: Relationships among behavioural sub-syndromes and the influence of clinical variables","volume":"20","author":"Aalten","year":"2005","journal-title":"Int J Geriatr Psychiatry"},{"key":"10.3233\/JAD-150181_ref21","doi-asserted-by":"crossref","first-page":"457","DOI":"10.1159\/000110738","article-title":"Neuropsychiatric syndromes in dementia. Results from the European Alzheimer Disease Consortium: Part I","volume":"24","author":"Aalten","year":"2007","journal-title":"Dement Geriatr Cogn Disord"},{"key":"10.3233\/JAD-150181_ref22","doi-asserted-by":"crossref","first-page":"493","DOI":"10.1097\/JGP.0b013e3181953b82","article-title":"Depression and anxiety symptoms are associated with cerebral FDDNP-PET binding in middle-aged and older nondemented adults","volume":"17","author":"Lavretsky","year":"2009","journal-title":"Am J Geriatr Psychiatry"},{"key":"10.3233\/JAD-150181_ref23","doi-asserted-by":"crossref","first-page":"911","DOI":"10.1017\/S0033291712001870","article-title":"Anxiety is related to Alzheimer cerebrospinal fluid markers in subjects with mild cognitive impairment","volume":"43","author":"Ramakers","year":"2013","journal-title":"Psychol Med"},{"key":"10.3233\/JAD-150181_ref24","doi-asserted-by":"crossref","first-page":"266","DOI":"10.1016\/0166-2236(90)90107-L","article-title":"Functional architecture of basal ganglia circuits: Neural substrates of parallel processing","volume":"13","author":"Alexander","year":"1990","journal-title":"Trends Neurosci"},{"key":"10.3233\/JAD-150181_ref25","doi-asserted-by":"crossref","first-page":"251","DOI":"10.1007\/978-3-642-02912-7","volume-title":"Behavioral neurobiology of anxiety and its treatment","author":"Stein","year":"2010"},{"key":"10.3233\/JAD-150181_ref26","doi-asserted-by":"crossref","first-page":"114","DOI":"10.1016\/j.jad.2014.01.022","article-title":"Neural structures, functioning and connectivity in generalized anxiety disorder and interaction with neuroendocrine systems: A systematic review","volume":"158","author":"Hilbert","year":"2014","journal-title":"J Affect Disord"},{"key":"10.3233\/JAD-150181_ref27","doi-asserted-by":"crossref","first-page":"1458","DOI":"10.1016\/j.neuroimage.2005.11.011","article-title":"Levels of appraisal: A medial prefrontal role in high-level appraisal of emotional material","volume":"30","author":"Kalisch","year":"2006","journal-title":"Neuroimage"},{"key":"10.3233\/JAD-150181_ref28","doi-asserted-by":"crossref","first-page":"202","DOI":"10.1002\/da.20901","article-title":"Pilot multimodal twin imaging study of generalized anxiety disorder","volume":"29","author":"Hettema","year":"2012","journal-title":"Depress Anxiety"},{"key":"10.3233\/JAD-150181_ref29","doi-asserted-by":"crossref","first-page":"1913","DOI":"10.1016\/j.neurobiolaging.2013.01.002","article-title":"The effects of small vessel disease and amyloid burden on neuropsychiatric symptoms: A study among patients with subcortical vascular cognitive impairments","volume":"34","author":"Kim","year":"2013","journal-title":"Neurobiol Aging"},{"key":"10.3233\/JAD-150181_ref30","doi-asserted-by":"crossref","first-page":"484","DOI":"10.1176\/appi.neuropsych.11120375","article-title":"Diffusion tensor imaging of neuropsychiatric symptoms in mild cognitive impairment and Alzheimer\u2019s dementia","volume":"24","author":"Tighe","year":"2012","journal-title":"J Neuropsychiatry Clin Neurosci"},{"key":"10.3233\/JAD-150181_ref31","doi-asserted-by":"crossref","first-page":"72","DOI":"10.1196\/annals.1401.026","article-title":"Role of orbitofrontal cortex connections in emotion","volume":"1121","author":"Rempel-Clower","year":"2007","journal-title":"Ann N Y Acad Sci"},{"key":"10.3233\/JAD-150181_ref32","doi-asserted-by":"crossref","first-page":"549","DOI":"10.1016\/j.neuropsychologia.2009.10.016","article-title":"Irritability in pre-clinical Huntington\u2019s disease","volume":"48","author":"Kl\u00f6ppel","year":"2010","journal-title":"Neuropsychologia"},{"key":"10.3233\/JAD-150181_ref33","doi-asserted-by":"crossref","first-page":"1186","DOI":"10.1176\/appi.ajp.2013.12070917","article-title":"Neural mechanisms of frustration in chronically irritable children","volume":"170","author":"Deveney","year":"2013","journal-title":"Am J Psychiatry"},{"key":"10.3233\/JAD-150181_ref34","doi-asserted-by":"crossref","first-page":"1348","DOI":"10.1111\/j.1532-5415.2006.00854.x","article-title":"Four components describe behavioral symptoms in 1,120 individuals with late-onset Alzheimer\u2019s disease","volume":"54","author":"Hollingworth","year":"2006","journal-title":"J Am Geriatr Soc"},{"key":"10.3233\/JAD-150181_ref35","doi-asserted-by":"crossref","first-page":"87","DOI":"10.1016\/j.arr.2011.06.005","article-title":"Apolipoprotein E genotypes and neuropsychiatric symptoms and syndromes in late-onset Alzheimer\u2019s disease","volume":"11","author":"Panza","year":"2012","journal-title":"Ageing Res Rev"},{"key":"10.3233\/JAD-150181_ref36","doi-asserted-by":"crossref","first-page":"474","DOI":"10.1016\/j.neuroimage.2013.04.048","article-title":"Mapping the effects of ApoE4, age and cognitive status on 18F-florbetapir PET measured regional cortical patterns of beta-amyloid density and growth","volume":"78","author":"Murphy","year":"2013","journal-title":"Neuroimage"},{"key":"10.3233\/JAD-150181_ref37","doi-asserted-by":"crossref","unstructured":"American Psychiatric Association, American Psychiatric Association, DSM-5 Task Force (2013) Diagnostic and Statistical Manual of Mental Disorders: DSM-5., American Psychiatric Association, Washington, D.C.","DOI":"10.1176\/appi.books.9780890425596"},{"key":"10.3233\/JAD-150181_ref38","doi-asserted-by":"crossref","first-page":"1035","DOI":"10.1002\/gps.1203","article-title":"Behavioural and psychological syndromes in Alzheimer\u2019s disease","volume":"19","author":"Mirakhur","year":"2004","journal-title":"Int J Geriatr Psychiatry"},{"key":"10.3233\/JAD-150181_ref39","doi-asserted-by":"crossref","first-page":"1157","DOI":"10.3233\/JAD-2010-101212","article-title":"Grouping and trajectories of the neuropsychiatric symptoms in patients with Alzheimer\u2019s disease, part I: Symptom clusters","volume":"22","author":"Garre-Olmo","year":"2010","journal-title":"J Alzheimers Dis"}],"container-title":["Journal of Alzheimer's Disease"],"original-title":[],"link":[{"URL":"https:\/\/content.iospress.com\/download?id=10.3233\/JAD-150181","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,4,28]],"date-time":"2026-04-28T10:01:24Z","timestamp":1777370484000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.sagepub.com\/doi\/full\/10.3233\/JAD-150181"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2015,11,27]]},"references-count":39,"journal-issue":{"issue":"2"},"URL":"https:\/\/doi.org\/10.3233\/jad-150181","relation":{"has-review":[{"id-type":"doi","id":"10.3410\/f.725861261.793576048","asserted-by":"object"}]},"ISSN":["1387-2877","1875-8908"],"issn-type":[{"value":"1387-2877","type":"print"},{"value":"1875-8908","type":"electronic"}],"subject":[],"published":{"date-parts":[[2015,11,27]]}}}