Associations of cerebral amyloid beta and tau with cognition from midlife

INTRODUCTION: Understanding early neuropathological changes and their associations with cognition may aid dementia prevention. This study investigated associations of cerebral amyloid and tau positron emission tomography (PET) retention with cognition in a predominately middle-aged community-based cohort and examined factors that may modify these relationships. METHODS: ¹¹C-Pittsburgh compound B amyloid and ¹⁸F-flortaucipir tau PET imaging were performed. Associations of amyloid and tau PET with cognition were evaluated using linear regression. Interactions with age, apolipoprotein E (APOE) ε4 status, and education were examined. RESULTS: Amyloid and tau PET were not associated with cognition in the overall sample (N = 423; mean: 57 ± 10 years; 50% female). However, younger age (< 55 years) and APOE ε4 were significant effect modifiers, worsening cognition in the presence of higher amyloid and tau. DISCUSSION: Higher levels of Aβ and tau may have a pernicious effect on cognition among APOE ε4 carriers and younger adults, suggesting a potential role for targeted early interventions. Highlights: Risk and resilience factors influenced cognitive vulnerability due to Aβ and tau. Higher fusiform tau associated with poorer visuospatial skills in younger adults. APOE ε4 interacted with Aβ and tau to worsen cognition across multiple domains.