Faster rates of tau accumulation in FTP‐PET in females relative to males, and a cross‐sectional influence on faster cognitive decline: Preliminary findings from HABS and ADNI: Neuropsychology/Neuropsychological profiles of dementia: Valid biomarkers?. (7th December 2020)

• Record Type: Journal Article
• Authors: Buckley, Rachel F.; Properzi, Michael J.; Schultz, Aaron P.; Scott, Matthew R.; Jacobs, Heidi I.L.; Farrell, Michelle E.; Kirn, Dylan; Hanseeuw, Bernard J.; Amariglio, Rebecca; Rentz, Dorene; Johnson, Keith A.; Sperling, Reisa A.
• Is Part Of: Alzheimer's & dementia. Volume 16(2020)Supplement 6
• 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.043620
• Languages: English
• ISSNs: 1552-5260

Abstract

Abstract: Background: Clinically normal older females exhibit higher cross‐sectional 18 F‐Flortaucipir (FTP)‐PET signal, but not Aβ‐PET, than males, particularly in temporal regions. What remains unclear is the extent to which these findings represent a real biological phenomenon as opposed to a methodological bias. Here, we explored sex differences in longitudinal tau accumulation, and how contemporaneous rates of FTP‐PET, Aβ‐PET and cognitive change may be modified by sex. Method: We examined 128 clinically‐normal participants from the Harvard Aging Brain Study (HABS; 60% Female, Age=75(6.6)years) with at least two time‐points of contemporaneous FTP‐PET, PiB‐PET and cognition. Also, 153 ADNI participants with at least two time‐points of FTP‐PET (nCN =94/nMCI =59; 50% Female, Age=73(6.4)years), and with prospective longitudinal AV45‐PET and cognition (n=131). Mean follow up was 3.3yrs (range=1.2‐6.2yrs) and 1.4yrs (range=0.6‐3.3yrs), respectively. For FTP‐PET we exclusively examined the inferior temporal lobe (non‐partial volume corrected, cerebellar greyreference ), for Aβ‐PET we used the PiB summary measure in HABS (cerebellar greyreference ) and the AV‐45 summary measure in ADNI (whole cerebellumreference ). For cognition, we used the Preclinical Alzheimer Cognitive Composite (PACC). We examined relationships between contemporaneous longitudinal FTP‐PET, Aβ‐PET, and cognitive performance using linear mixed models, adjusting for age, years of education and random intercept. Result: In HABS, females exhibited faster rates of FTP‐PET accumulation than males, but only with increasing rates of Aβ‐PET accumulation (t=1.93, p =0.003; see Figure 1A). In ADNI, females exhibited faster rates of FTP‐PET accumulation, not moderated by Aβ‐PETchange (t=2.92, p =0.004; see Figure 1B). Sex did not moderate the relationship between FTP‐PET and PACC change in HABS or ADNI (see Figure 2.). We did, however, find that females with higher baseline FTP‐PET resulted in faster PACC decline than men in only clinically‐normal individuals in both cohorts (t=‐1.86ADNI, ‐2.72HABS, p ∼0.02; see Figure 3.). Conclusion: These findings support a female susceptibility to tau as a biological phenomenon of accelerated tau accumulation in AD‐vulnerable regions. A lack of an association between changing tau and changing cognition remains to be understood. It is possible that our models are picking up more on the 'severity of burden' (e.g. baseline tau) to influence faster rates of decline in females, rather than dynamic change per se.