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Self‐reported history of estrogen hormone therapy differentiates rates of amyloid accumulation (PiB‐PET) relative to males: Findings from the Harvard Aging Brain Study
Author(s) -
Rubinstein Zoe B.,
Buckley Rachel F.,
Scott Matthew R.,
Manning Lyssa K.,
Mayblyum Danielle V.,
Thibault Emma G.,
Jacobs Heidi I.L.,
Farrell Michelle E.,
Properzi Michael J.,
Rabin Jennifer S.,
Chhatwal Jasmeer P.,
Lois Cristina,
Rentz Dorene,
Price Julie C.,
Schultz Aaron P.,
Sperling Reisa A.,
Johnson Keith A.
Publication year - 2021
Publication title -
alzheimer's and dementia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 6.713
H-Index - 118
eISSN - 1552-5279
pISSN - 1552-5260
DOI - 10.1002/alz.056069
Subject(s) - medicine , pittsburgh compound b , hormone therapy , estrogen , longitudinal study , psychology , endocrinology , dementia , oncology , pathology , disease , cancer , breast cancer
Background Women’s Health Initiative Memory Study (WHIMS) findings suggest that hormone therapy increases risk of dementia. Conversely, evidence from the Kronos Early Estrogen Prevention Study (KEEPS) implicates estrogen hormone therapy (HT) as protective against ß‐amyloid (Aß) burden. We sought to explore if self‐reported HT use is associated with rates of Aß accumulation in an observational sample of clinically‐unimpaired older adults. Method 134 participants (Age=73yrs±5.8) underwent at least three timepoints of Pittsburgh compound‐B (PiB)‐PET scans over an average of 9.7 years. Longitudinal PiB‐PET was examined as aggregate neocortical DVR (composite reference region: whole cerebellum + eroded white matter). Concurrent with baseline PiB‐PET, female participants self‐reported if they ever took HT. Participants were thus identified as: females who never used HT (HT‐:n=36), females who have ever taken HT to any extent (HT+:n=42), and males (M:n=56). We examined the relationship between these three groups and longitudinal PiB‐PET using linear mixed models, adjusting for baseline age, and with random slopes and intercepts. Post‐hoc analyses adjusted for APOE ε4 status and examined interactions between HT and baseline PiB‐PET on change in PiB‐PET from baseline. Result While we found no significant sex (male/female) difference in PiB‐PET accumulation (t=1.5, p >0.05,Fig 1A), we observed significant HT group differences with HT‐ exhibiting approximately half the PiB‐PET rate of change than M (t=2.3, p =0.02) and HT+ (t=1.8, p =0.07; Fig 1B). There was no significant slope difference between M and HT+ (t=0.32, p =0.75). These differences survived after covarying for APOE ε4. A three‐way interaction with baseline PiB‐PET revealed a greater slope difference between HT‐ and M (t=2.1, p =0.04) in those with higher baseline PiB‐PET relative to lower baseline PiB‐PET (Fig 2). Conclusion HT‐ showed significantly slower rates of Aß accumulation than males and a trend‐level slower rate compared to HT+; these differences appear heightened with greater baseline Aß burden. With similar ages across HT groups (p=0.20), these differences did not appear to be a function of chronological age. It remains unclear whether the introduction of estrogen, a mediating commonality, or collider bias is driving these results. Our findings, in conjunction with other studies, suggest the relationship between HT and Aß is complicated and necessitates examination of HT type and duration.