Sex and cognition: Relationships with tau PET across the Alzheimer’s disease spectrum

Abstract

AbstractBackgroundRecent evidence suggests that tau accumulates differently in the brains of men and women with Alzheimer’s disease (AD), with greater neurofibrillary tangles in women especially in the MCI stage. Women show a reserve in verbal memory but then more rapid decline in this domain once they are symptomatic. Since regional tau deposition is closely tethered to cognitive symptoms, we were interested in how relationships between tau distribution and cognition might differ by sex.MethodData were extracted from the AD Neuroimaging Initiative database for participants (136 women, 139 men) who were amyloid PET positive and had flortaucapir (“tau”) PET, across clinical diagnoses of normal cognition (NC), mild cognitive impairment (MCI) and AD. Vertex‐wise analyses were conducted in FreeSurfer, quantifying the vertices with above‐threshold SUVR and assessing regional distribution. We compared overall burden in men and women, and further investigated results by ApoE status and diagnosis and assessed how regional tau burden related to different cognitive scores.ResultsWomen and men did not differ on overall amount of tau PET uptake, but there was a sex by diagnosis interaction on overall tau SUVr. On further analysis (figure 1) this was driven by higher SUVr in women in the MCI stage (F(1, 85) = 7.313, p = .008). Furthermore, women with a higher tau burden scored worse across verbal memory measures, whereas men with higher tau burdens demonstrated worse performance on processing speed and executive measures. This was reflected in topological representation of the tau burden by cognitive test (figure 2).ConclusionSex differences in the expression of AD correspond to differences in tau especially at the MCI stage. Higher tau in women is reflected in reduced performance in verbal memory, while higher tau in men reflects worse performance on executive measures. These findings point to the differences in trajectories of tau deposition in men and women and the relationship of tau to sex differences in cognitive findings.