Tau pathology in cognitively normal older adults

Abstract

Introduction: Tau pathology, a hallmark of Alzheimer's disease, is observed in the brains of virtually all individuals over 70 years.

Methods: Using ¹⁸F-AV-1451 (¹⁸F-flortaucipir) positron emission tomography, we evaluated tau pathology in 54 cognitively normal participants (mean age: 77.5 years, SD: 8.9) from the Baltimore Longitudinal Study of Aging. We assessed associations between positron emission tomography signal and age, sex, race, and amyloid positivity. We investigated relationships between regional signal and retrospective rates of change in regional volumes and cognitive function adjusting for age, sex, and amyloid status.

Results: Greater age, male sex, black race, and amyloid positivity were associated with higher ¹⁸F-AV-1451 retention in distinct brain regions. Retention in the entorhinal cortex was associated with lower entorhinal volume (β = -1.124, SE = 0.485, P = .025) and a steeper decline in memory performance (β = -0.086, SE = 0.039, P = .029).

Discussion: Assessment of medial temporal tau pathology will provide insights into early structural brain changes associated with later cognitive impairment and Alzheimer's disease.

Keywords: AV-1451; Cognition; Cognitively normal; FTP; Flortaucipir; Longitudinal; PET; T807; Tau; Volume.

Fig. 1

Predictors of ¹⁸F-AV-1451 tau tracer retention among cognitively normal older adults. In these dual-coded representations of voxelwise linear regression results, color indicates the estimated regression coefficient (indicated along the horizontal axis of the color bar) and transparency corresponds to the absolute t value (with 0 as completely transparent and ≥5 as completely opaque, as indicated along the vertical axis of the color bar). Voxels that reach significance (uncorrected P < .001, cluster size ≥400 voxels) are circumscribed by black contour to help with the interpretation of transparency. (A) Age by amyloid status interaction. (B) Main effect of age in amyloid+ individuals. (C) Main effect of age in amyloid− individuals. (D) Main effect of amyloid positivity. (E) Main effect of male sex. (F) Main effect of black race. Color bars on the left and right correspond to panels A–C and D–F, respectively.

Fig. 2

Entorhinal ¹⁸F-AV-1451 tau tracer retention is associated with steeper retrospective longitudinal decline in the composite memory score. (A) Individual-level memory change predicted by linear mixed effects model. (B) Rate of decline (z-score/decade) in memory performance as a function of ¹⁸F-AV-1451 tau tracer retention in the entorhinal cortex. Fitted values for rate of change are plotted for each individual in the sample.