medwireNews: In older adults with elevated amyloid-β (Aβ) but no cognitive impairment or Alzheimer disease (AD), tau positron emission tomography (PET) accumulation occurs faster in women than men, suggests a meta-analysis of studies published in JAMA Neurology.
Investigator Rachel Buckley (Massachusetts General Hospital Charlestown HealthCare Center, USA) and colleagues assessed Aβ and tau PET scans from 1376 individuals, with a mean age of 71.9 years, who participated in one of six longitudinal aging and AD studies (the Alzheimer’s Disease Neuroimaging Initiative, Berkeley Aging Cohort Study, BioFINDER 1, Harvard Aging Brain Study, Mayo Clinic Study of Aging, and Wisconsin Registry for Alzheimer Prevention).
Using sex association statistical models over time for analysis, the team says their findings show “that Aβ deposition is associated with sex-specific risk for the downstream accumulation of tau.”
Specifically, among the 401 (29%) participants with high baseline levels of Aβ PET (ranging from 10–24 Centiloids across the studies), the 221 women had significantly faster tau accumulation over a mean 2.8 years of follow-up than the 182 men.
“Sex differences in tau accumulation were regionally specific,” note Buckley et al, with female sex significantly associated with faster tau accumulation in the inferior temporal (β=−0.14), temporal fusiform gyri (β=−0.13), and lateral occipital (β=−0.15) regions compared with male sex.
There was also an interaction of sex with longitudinal tau PET among the 412 (30%) APOEε4 carriers (234 women, 178 men), with female sex being significantly associated with faster inferior temporal gyrus tau accumulation than male sex (β=−0.10). However, Aβ status remained a significant factor in the association between sex and tau accumulation in this brain region after taking into account the effects of APOEε4 carrier status.
Just over half of the patients analyzed were women (55%), and while the women were younger on average than the men at baseline (71.4 vs 72.5 years), there were no between-sex differences in the frequency of high Aβ, APOEε4-carrier status, or mean tau-PET follow-up time. In the group of individuals with low Aβ levels at baseline, there was “little to no tau PET change,” regardless of sex, observe the investigators.
They highlight: “The focus on this preclinical phase of AD was to elucidate disease progression at the time when disease-modifying therapies may be most efficacious (ie, in participants without cognitive impairment but with elevated Aβ).”
They say their findings suggest that the disproportionately higher rates of AD among women than men “are not only driven by survival bias but also an elevated female risk for tauopathy,” and “call for sex-specific timing considerations when administrating anti-Aβ and anti-tau treatments.”
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