Region-specific association of subjective cognitive decline with tauopathy independent of global β-amyloid burden

Abstract

IMPORTANCE: The ability to explore associations between reports of subjective cognitive decline (SCD) and biomarkers of early Alzheimer disease (AD) pathophysiologic processes (accumulation of neocortical β-amyloid [Aβ] andtau) provides an important opportunity to understand the basis of SCD and AD risk. OBJECTIVE: To examine associations between SCD and global Aβ and tau burdens in regions of interest in clinically healthy older adults. DESIGN, SETTING, AND PARTICIPANTS: This imaging substudy of the Harvard Aging Brain Study included 133 clinically healthy older participants (Clinical Dementia Rating Scale global scores of 0) participating in the Harvard Aging Brain Study who underwent cross-sectional flortaucipir F18 (previously known as AV1451, T807) positron emission tomography (FTP-PET) imagingfor tau and Pittsburgh compound B carbon 11-labeled PET(PiB-PET) imagingfor Aβ. The following 2 regions for tau burden were identified: the entorhinal cortex, which exhibits early signs of tauopathy, and the inferior temporal region, which is more closely associated with AD-related pathologic mechanisms. Data were collected from June 11, 2012, through April 7, 2016. MAIN OUTCOMES AND MEASURES: Subjective cognitive decline was measured using a previously published method of z-transforming subscales from the Memory Functioning Questionnaire, the Everyday Cognition battery, and a 7-item questionnaire. The Aβ level was measured according to a summary distribution volume ratio of frontal, lateral temporal and parietal, and retrosplenial PiB-PET tracer uptake. The FTP-PET measures were computed as standardized uptake value ratios. Linear regression models focused on main and interactive effects of Aβ, entorhinal cortical, and inferior temporal tau on SCD, controlling for age, sex, educational attainment, and Geriatric Depression Scale score. RESULTS: Of the 133 participants, 75 (56.3%) were women and 58 (43.6%) were men; mean (SD) age was 76 (6.9) years (range, 55-90 years). Thirty-nine participants (29.3%) exhibited a high Aβ burden. Greater SCD was associated with increasing entorhinal cortical tau burden (β = 0.35; 95% CI, 0.19-.52; P