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Davies Medical Research Scholarship"],"award-info":[{"award-number":["William H. Davies Medical Research Scholarship"]}]}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Journal of Alzheimer\u2019s Disease"],"published-print":{"date-parts":[[2026,9]]},"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Mild behavioral impairment (MBI), characterized by later-life emergence of persistent neuropsychiatric symptoms (NPS), is an early clinical indicator of dementia risk. Global MBI has been associated with Alzheimer's disease (AD) pathology; studies have also explored MBI domains. Prior work has linked MBI-apathy to AD cerebrospinal fluid (CSF) biomarkers, but whether associations are detectable using plasma-based biomarkers such as phosphorylated tau (p-tau) is unknown. Establishing such relationships is critical, as plasma biomarkers are more accessible than CSF.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>\n                      To explore cross-sectional and longitudinal associations between MBI-apathy and plasma p-tau\n                      <jats:sub>181<\/jats:sub>\n                      levels using Alzheimer's Disease Neuroimaging Initiative data.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      Older adults with normal cognition or mild cognitive impairment were categorized as MBI-apathy (n\u2009=\u200969), non-MBI NPS (n\u2009=\u2009112), and no-NPS (n\u2009=\u2009215) based on Neuropsychiatric Inventory scores and symptom persistence over one year. Linear regression modelled cross-sectional associations between NPS group and plasma p-tau\n                      <jats:sub>181<\/jats:sub>\n                      , adjusting for age, sex, education, apolipoprotein E4 status, and Mini-Mental State Examination score. Hierarchical linear mixed-effects modelling assessed associations over two and three years, including time-by-NPS group interactions.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      MBI-apathy was associated with significantly higher plasma p-tau\n                      <jats:sub>181<\/jats:sub>\n                      levels at baseline (24.05% [6.06\u201345.08%]; adjusted\n                      <jats:italic toggle=\"yes\">p<\/jats:italic>\n                      \u2009=\u20090.014), and over two (26.46% [7.24\u201349.12%]; adjusted\n                      <jats:italic toggle=\"yes\">p<\/jats:italic>\n                      \u2009=\u20090.012) and three years (29.28% [10.17\u201351.72%]; adjusted\n                      <jats:italic toggle=\"yes\">p<\/jats:italic>\n                      \u2009=\u20090.004) compared to no-NPS. No significant associations were observed for non-MBI NPS. In sensitivity analyses, non-MBI apathy was not associated with plasma p-tau\n                      <jats:sub>181<\/jats:sub>\n                      at baseline (\u22129.96% [\u221232.69\u201320.44%]; unadjusted\n                      <jats:italic toggle=\"yes\">p<\/jats:italic>\n                      \u2009=\u20090.478).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>\n                      MBI-apathy is associated with elevated plasma p-tau\n                      <jats:sub>181<\/jats:sub>\n                      cross-sectionally and longitudinally, supporting MBI-apathy as a potential proxy marker of tau pathology for early AD detection.\n                    <\/jats:p>\n                  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