Hormone therapy in perimenopause may protect against Alzheimer’s disease

Hormone therapy may promote better memory and cognitive function and larger brain volumes among women carrying APOE4, a genetic risk factor for Alzheimer’s disease.

“The associations were particularly evident when hormone replacement therapy was introduced early — during the transition to menopause, known as perimenopause,” Rasha N. M. Saleh, MD, a senior research associate at the University of East Anglia Norwich Medical School in Norwich, England, said in a press release. “This is really important because there have been very limited drug options for Alzheimer’s disease for 20 years and there is an urgent need for new treatments. The effects of hormone replacement therapy in this observation study, if confirmed in an intervention trial, would equate to a brain age that is several years younger.”

Saleh and colleagues used data from the European Prevention of Alzheimer’s Dementia (EPAD) Longitudinal Cohort Study (LCS) Innovative Medicines Initiative, which began in 2015 and was released publicly in October 2020. The researchers divided EPAD participants by APOE genotype and determined current or previous use of estrogen only or combination estrogen and progestogens, noting the age of hormone therapy (HT) initiation.

Participants underwent multiple cognitive tests to assess attention, memory, language and visuo-construction and MRIs to evaluate the medial temporal lobe, which includes the hippocampus, parahippocampus, entorhinal cortex and amygdala.

Among women with APOE, those carrying APOE4 who previously or currently used HT had better delayed memory index scores compared with APOE4 carriers who did not use HT and non-APOE4 carriers using HT.

They also had larger left entorhinal (P = .002), left amygdala (P = .003) and right amygdala (P = .005) volumes vs. APOE4 carriers who did not use HT and non-APOE4 carriers using HT.

Among non-APOE4 carriers, HT was associated with smaller amygdala volumes (right P = .03; left P = .039).

Assessment of the age at the start of HT revealed that earlier initiation was associated with larger right hippocampal (standardized beta = –0.555; P = .035) and left hippocampal (standardized beta = –0.577; P = .028) volumes in APOE4 carriers only. Age at HT initiation was not associated with entorhinal or amygdala volumes.

“These results highlight the importance of personalized medicine in the prevention of Alzheimer’s disease,” Saleh and colleagues wrote. “This work provides the rationale for the conduct of a randomized controlled trial which examines the impact of early (perimenopause or early post-menopause) hormone replacement therapy introduction on cognition and brain atrophy according to APOE4 carrier status to confirm the observed associations.”

References:

• HRT could ward off Alzheimer’s among at-risk women. www.uea.ac.uk/news/-/article/hrt-could-ward-off-alzheimers-among-at-risk-women. Published Jan. 14, 2023. Accessed Jan. 17, 2023.
• Saleh RNM, et al. Alzheimers Res Ther. 2023;doi:10.1186/s13195-022-01121-5.