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In dementia, apathy is associated with higher morbidity, mortality and caregiver distress. However, the significance of MBI-apathy in dementia-free persons, including its associations with AD biomarkers, remains unclear. This study aimed to determine whether MBI-apathy is associated with biomarker evidence of amyloid-beta (A\u03b2) and tau [phosphorylated (p-tau) and total (t-tau)] in CSF. Because MBI predicts incident dementia better than NPS without MBI, we aimed to determine the association between apathy and AD biomarkers when it occurred as part of the MBI syndrome and when it did not.<\/jats:p>\n                  <jats:p>Dementia-free participants with mild cognitive impairment or normal cognition from the Alzheimer's Disease Neuroimaging Initiative were stratified by NPS status (MBI-apathy, non-apathy MBI, non-MBI NPS and no-NPS) based on the Neuropsychiatric Inventory (NPI) or NPI-Questionnaire (NPI-Q). Linear regressions modelled cross-sectional associations between NPS status (predictor) and CSF biomarker ratios (A\u03b242\/A\u03b240, p-tau181\/A\u03b242 and t-tau\/A\u03b242; primary outcomes) and levels (A\u03b240, A\u03b242, p-tau181 and t-tau; exploratory outcomes), adjusting for age, sex, apolipoprotein E4, education, Mini-Mental State Examination and NPI version. Hierarchical linear mixed-effects (LME) models assessed longitudinal associations over 2 years, incorporating random intercepts and slopes to account for repeated measures. Fixed effects included NPS status, all covariates from the linear regression model, and an interaction term between NPS status and time.<\/jats:p>\n                  <jats:p>Among 477 participants (176 cognitively normal), 52 had MBI-apathy. Primary cross-sectional analyses showed that, compared with the no-NPS group, MBI-apathy was associated with higher CSF p-tau181\/A\u03b242 [11.25% (2.56%\u201320.68%); adjusted P = 0.018] and t-tau181\/A\u03b242 [10.26% (2.42%\u201318.70%); adjusted P = 0.018]. Exploratory analyses revealed that MBI-apathy was associated with higher CSF p-tau181 [5.98% (0.50%\u201311.77%); P = 0.032]. Primary LME models showed that MBI-apathy was associated with higher CSF p-tau181\/A\u03b242 [11.34% (2.55%\u201320.88%); adjusted P = 0.022] and t-tau181\/A\u03b242 [10.34% (2.41\u201318.88%); adjusted P = 0.022] over 2 years. Exploratory LME models revealed that MBI-apathy was associated with higher CSF p-tau181 [6.03% (0.56%\u201311.81%); P = 0.032] and t-tau [4.96% (0.07%\u201310.09%); P = 0.049] over 2 years.<\/jats:p>\n                  <jats:p>MBI-apathy was significantly associated with core AD biomarkers cross-sectionally and longitudinally, over 2 years, underscoring its relevance as a marker of AD pathological burden. An overall MBI composite score might reflect a broader spectrum of pathology and warrants further investigation.<\/jats:p>","DOI":"10.1093\/brain\/awaf194","type":"journal-article","created":{"date-parts":[[2025,6,1]],"date-time":"2025-06-01T07:35:30Z","timestamp":1748763330000},"page":"4345-4358","source":"Crossref","is-referenced-by-count":14,"title":["Mild behavioural impairment-apathy and core Alzheimer's disease cerebrospinal fluid biomarkers"],"prefix":"10.1093","volume":"148","author":[{"given":"Daniella","family":"Vellone","sequence":"first","affiliation":[{"name":"Faculty of Graduate Studies, University of Calgary , Calgary, Alberta T2N 1N4 ,","place":["Canada"]},{"name":"Hotchkiss Brain Institute, Cumming School of Medicine, University of Calgary , Calgary, Alberta T2N 4N1 ,","place":["Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rebeca","family":"Leon","sequence":"additional","affiliation":[{"name":"Hotchkiss Brain Institute, Cumming School of Medicine, University of Calgary , Calgary, Alberta T2N 4N1 ,","place":["Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8858-4076","authenticated-orcid":false,"given":"Zahra","family":"Goodarzi","sequence":"additional","affiliation":[{"name":"Faculty of Graduate Studies, University of Calgary , Calgary, Alberta T2N 1N4 ,","place":["Canada"]},{"name":"Mathison Centre for Mental Health Research and Education, Cumming School of Medicine, University of Calgary , Calgary, Alberta T2N 4Z6 ,","place":["Canada"]},{"name":"Department of Community Health Sciences, Cumming School of Medicine, University of Calgary , Calgary, Alberta T2N 4N1 ,","place":["Canada"]},{"name":"Department of Medicine, Cumming School of Medicine, University of Calgary , Calgary, Alberta T2N 4N1 ,","place":["Canada"]},{"name":"O\u2019Brien Institute for Public Health, Cumming School of Medicine, University of Calgary , Calgary, Alberta T2N 4Z6 ,","place":["Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2556-3224","authenticated-orcid":false,"given":"Nils D","family":"Forkert","sequence":"additional","affiliation":[{"name":"Hotchkiss Brain Institute, Cumming School of Medicine, University of Calgary , Calgary, Alberta T2N 4N1 ,","place":["Canada"]},{"name":"Department of Clinical Neurosciences, Cumming School of Medicine, University of Calgary , Calgary, Alberta T2N 4N1 ,","place":["Canada"]},{"name":"Department of Radiology, Cumming School of Medicine, University of Calgary , Calgary, Alberta T2N 4N1 ,","place":["Canada"]},{"name":"Alberta Children\u2019s Hospital Research Institute, University of Calgary , Calgary, Alberta T3B 6A8 ,","place":["Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eric E","family":"Smith","sequence":"additional","affiliation":[{"name":"Hotchkiss Brain Institute, Cumming School of Medicine, University of Calgary , Calgary, Alberta T2N 4N1 ,","place":["Canada"]},{"name":"Department of Community Health Sciences, Cumming School of Medicine, University of Calgary , Calgary, Alberta T2N 4N1 ,","place":["Canada"]},{"name":"Department of Clinical Neurosciences, Cumming School of Medicine, University of Calgary , Calgary, Alberta T2N 4N1 ,","place":["Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5529-3731","authenticated-orcid":false,"given":"Zahinoor","family":"Ismail","sequence":"additional","affiliation":[{"name":"Hotchkiss Brain Institute, Cumming School of Medicine, University of Calgary , Calgary, Alberta T2N 4N1 ,","place":["Canada"]},{"name":"Mathison Centre for Mental Health Research and Education, Cumming School of Medicine, University of Calgary , Calgary, Alberta T2N 4Z6 ,","place":["Canada"]},{"name":"Department of Community Health Sciences, Cumming School of Medicine, University of Calgary , Calgary, Alberta T2N 4N1 ,","place":["Canada"]},{"name":"O\u2019Brien Institute for Public Health, Cumming School of Medicine, University of Calgary , Calgary, Alberta T2N 4Z6 ,","place":["Canada"]},{"name":"Department of Clinical Neurosciences, Cumming School of Medicine, University of Calgary , Calgary, Alberta T2N 4N1 ,","place":["Canada"]},{"name":"Department of Psychiatry, Cumming School of Medicine, University of Calgary , Calgary, Alberta T2N 4N1 ,","place":["Canada"]},{"name":"Department of Pathology and Laboratory Medicine, University of Calgary , Calgary, Alberta T2N 4N1 ,","place":["Canada"]},{"name":"Faculty of Health and Life Sciences, Clinical and Biomedical Sciences, University of Exeter , Exeter EX1 2HZ ,","place":["UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2025,6,2]]},"reference":[{"key":"2025120423110853800_awaf194-B1","volume-title":"Dementia facts & figures","author":"Alzheimer\u2019s Disease 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