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Uncovering pathology, subjective cognitive complaints, and sex in early Alzheimer's disease

Sophie Boutin,B. Houzé,A. Pichet Binette,S. Brambati

Published 2025 in Journal of Alzheimer's Disease

ABSTRACT

Background Subjective cognitive complaints may correlate with cerebral amyloid-β (Aβ) levels in the early phases of Alzheimer's disease (AD). The relationship between sex, AD pathology, and complaints remains unclear. Objective Our study aims to (1) explore the relationship between Aβ pathology, assessed with two complementary measures, and subjective cognitive complaints across multiple domains in cognitively unimpaired (CU) individuals and those with mild cognitive impairment (MCI); (2) assess which subjective cognitive complaints can differentiate Aβ-positive from Aβ-negative individuals, CU from MCI, and progressors from non-progressors; and (3) evaluate sex differences in these relationships. Methods In 418 CU older adults and 408 with MCI from the ADNI cohort, we examined associations between Aβ, subjective cognitive complaints and sex, controlling for age, education, depression, and anxiety. Results In CU individuals, higher Aβ levels correlated with more severe language and visuospatial complaints. MCI individuals with elevated Aβ reported more severe memory, language, and planning complaints. Memory, language, planning, and organization complaints predicted risk of MCI and clinical progression. Sex differences emerged in the association between Aβ and visuospatial complaints, and in complaint types predicting Aβ positivity and cognitive impairment. Conclusions Subjective cognitive complaints in memory and non-memory domains (language, visuospatial, and executive functions) may signal cognitive decline risk due to their association with AD biomarkers and clinical progression. Sex differences highlight the need for personalized approaches in AD early diagnosis and disease progression monitoring.

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