Featured ArticleBeta-amyloid and cognitive decline in late middle age: Findings from the Wisconsin Registry for Alzheimer's Prevention study

IntroductionThe present study investigated the relationship between beta-amyloid (Aβ) and cognition in a late middle-aged cohort at risk for Alzheimer's disease (AD).MethodsOne eighty-four participants (mean age = 60; 72% parental history of AD) completed a [C-11]Pittsburgh compound B positron emission tomography scan and serial cognitive evaluations. A global measure of Aβ burden was calculated, and composite scores assessing learning, delayed memory, and executive functioning were computed.ResultsHigher Aβ was associated with classification of psychometric mild cognitive impairment (MCI) at follow-up (P < .01). Linear mixed effects regression results indicated higher Aβ was associated with greater rates of decline in delayed memory (P < .01) and executive functioning (P < .05). Apolipoprotein E (APOE) ε4 status moderated the relationship between Aβ and cognitive trajectories (P values <.01).DiscussionIn individuals at risk for AD, greater Aβ in late middle age is associated with increased likelihood of MCI at follow-up and steeper rates of cognitive decline.