Moving Beyond Depression: Mood Symptoms Across the Spectrum Relate to Tau Pathology in Older Women at Risk for Alzheimer's Disease

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Abstract

We examined how symptoms across the mood spectrum relate to Alzheimer's disease (AD) biomarkers in older women at high risk for AD. Participants included 25 women aged 65+ with mild cognitive deficits and elevated AD genetic risk. The Profile of Mood States Questionnaire measured mood symptoms and a total mood disturbance (TMD) score. Tau burden in the meta-temporal region of interest was measured using MK-6240 Tau positron emission tomography (PET) imaging. A subset (n = 12) also had p-Tau181, and Aß40/42 levels measured in plasma. Higher TMD scores related to higher tau PET standardized uptake value ratio (SUVR). Greater negative mood symptoms correlated with higher tau PET SUVR, while greater vigor correlated with lower SUVR. Similar results were seen with plasma p-Tau181 levels, but not with Aβ40/42 levels. In conclusion, positive and negative mood symptoms related to tau pathology in older women at high risk for AD, highlighting a role of mental well-being in AD risk.

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Ahmadi, N., Dratva, M. A., Heyworth, N., Wang, X., Blennow, K., Banks, S. J., & Sudermann, E. E. (2025). Moving Beyond Depression: Mood Symptoms Across the Spectrum Relate to Tau Pathology in Older Women at Risk for Alzheimer’s Disease. International Journal of Aging and Human Development, 100(1), 3–22. https://doi.org/10.1177/00914150241253257

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