Sex, tau, and cortical thinning in the temporal lobe: Findings from the Harvard Aging Brain Study: Neuroimaging / Optimal neuroimaging measures for tracking disease progression. (7th December 2020)

• Record Type: Journal Article
• Authors: Manning, Lyssa K; Properzi, Michael J; Scott, Matthew R; Hampton, Olivia L; Rubinstein, Zoe B; Mayblyum, Danielle V; Hanseeuw, Bernard J; Schultz, Aaron P; Rentz, Dorene M; Johnson, Keith A; Sperling, Reisa A; Buckley, Rachel F
• Is Part Of: Alzheimer's & dementia. Volume 16(2020)Supplement 4
• Page Start: n/a
• Page End: n/a
• Publication Date: 2020-12-07
• Subjects: Alzheimer's disease -- Periodicals; Alzheimer Disease -- Periodicals; Dementia -- Periodicals; Démence; Maladie d'Alzheimer; Périodique électronique (Descripteur de forme); Ressource Internet (Descripteur de forme); 616.83
• DOI: 10.1002/alz.040031
• Languages: English
• ISSNs: 1552-5260

Abstract

Abstract: Background: Recent work suggests regional tau burden is proximal to cortical thinning in clinically‐normal older adults. Clinically‐normal older females show higher levels of temporal tau burden than males, but it remains to be seen whether the association between tau pathology and cortical thinning is significantly impacted by biological sex. We hypothesized that females with higher tau burden would show faster cortical thinning than their male counterparts. Method: 123 clinically‐normal older adults from the Harvard Aging Brain Study ( clinical dementia rating = 0; age (SD) = 73.6(6.1); female = 58%) underwent cross‐sectional Pittsburgh Compound‐B (PiB)‐PET, Flortaucipir (FTP)‐PET and longitudinal MRI (2.95 years; range = 1.3‐5.3 years post‐tau scan). FTP‐PET was introduced after onset of the study, so the first FTP‐PET scan was used as 'baseline'. We selected temporal tau ROIs based on our previous results (HABS & ADNI) showing sex differences in tau signal (e.g. entorhinal, inferior temporal, fusiform, middle temporal). We conducted iterative linear mixed models examining the interaction of sex*time*tauROI on cortical thinning across 34 ROIs, covarying for baseline age*time. To assess the impact of PiB on this relationship, we also examined PiB+ and PiB− groups separately (based on HABS PiB DVR cut‐off = 1.186). Result: Females with higher inferior temporal tau burden showed significantly faster cortical thinning than males in the entorhinal cortex only, t = −2.40, p = 0.02 (see Figure 1). This result was significant in the PiB+ group (n = 33: t = −2.28, p = 0.03), but not PiB− (n = 90: t = −1.60, p = 0.11), suggesting this relationship was driven by a sex effect in PiB+ individuals (see Figure 2). We also found a similar association using fusiform tau ( p = 0.03). Conclusion: In the context of high inferior temporal tau burden, females exhibit significantly faster entorhinal cortical thinning than males. This result suggests that sex may moderate the effect of tau burden on cortical thinning, and for a given level of tau burden, females may be more susceptible to cortical atrophy in temporal lobe structures. We did not adjust for multiple comparisons, so replication is required in another cohort. This relationship between tau pathology and entorhinal neurodegeneration in females provides further insight into how sex‐related cortical structural vulnerability may correspond to pathology over time.