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. 2023;93(2):727-741.
doi: 10.3233/JAD-221240.

Associations Between Midlife Menopausal Hormone Therapy Use, Incident Diabetes, and Late Life Memory in the Wisconsin Longitudinal Study

Victoria J Williams  1   2 , Rebecca Koscik  1   2   3 , Kamil Sicinski  4 , Sterling C Johnson  1   2   3   5 , Pamela Herd  6 , Sanjay Asthana  1   2   3   5
Affiliations

Associations Between Midlife Menopausal Hormone Therapy Use, Incident Diabetes, and Late Life Memory in the Wisconsin Longitudinal Study

Victoria J Williams et al. J Alzheimers Dis. 2023.

Abstract

Background: Prior research suggests a link between menopausal hormone therapy (MHT) use, memory function, and diabetes risk. The menopausal transition is a modifiable period to enhance long-term health and cognitive outcomes, although studies have been limited by short follow-up periods precluding a solid understanding of the lasting effects of MHT use on cognition.

Objective: We examined the effects of midlife MHT use on subsequent diabetes incidence and late life memory performance in a large, same-aged, population-based cohort. We hypothesized that the beneficial effects of MHT use on late life cognition would be partially mediated by reduced diabetes risk.

Methods: 1,792 women from the Wisconsin Longitudinal Study (WLS) were included in analysis. We employed hierarchical linear regression, Cox regression, and causal mediation models to test the associations between MHT history, diabetes incidence, and late life cognitive performance.

Results: 1,088/1,792 women (60.7%) reported a history of midlife MHT use and 220/1,792 (12.3%) reported a history of diabetes. MHT use history was associated with better late life immediate recall (but not delayed recall), as well as a reduced risk of diabetes with protracted time to onset. Causal mediation models suggest that the beneficial effect of midlife MHT use on late life immediate recall were at least partially mediated by diabetes risk.

Conclusion: Our data support a beneficial effect of MHT use on late life immediate recall (learning) that was partially mediated by protection against diabetes risk, supporting MHT use in midlife as protective against late life cognitive decline and adverse health outcomes.

Keywords: Adult onset diabetes mellitus; Alzheimer’s disease; estrogen; immediate memory; mediation; menopause.

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Conflict of interest statement

CONFLICT OF INTEREST

Victoria J. Williams is an Associate Editor of this journal but was not involved in the peer-review process nor had access to any information regarding its peer-review. Victoria J. Williams owns stock equity in Niji Corporation and receives scientific consulting fees from Amylyx Pharmaceuticals and Cognito Therapeutics. The remaining authors have no conflicts of interest to report.

Figures

Fig. 1.
Fig. 1.
Flow chart of overall participant retention data across all Wisconsin Longitudinal Study (WLS) data collection waves (1957, 1975, 1993, 2004, and 2011), as well as sample selection for the current study. The current study excluded males, individuals who were not in the 80% randomly selected for cognitive testing, those with a history of stroke, those with Type I Diabetes, those with diabetes incidence prior to starting MHT, and those missing primary endpoints. The final sample size included 1,792 women.
Fig. 2.
Fig. 2.
Cox cumulative hazard ratio plotting time to diabetes onset age in years by history of Menopausal Hormone Therapy (MHT) use. Risk of incident diabetes was lower among women with reported history of MHT use compared to no MHT use.
Fig. 3.
Fig. 3.
Causal mediation analyses evaluating the mediating effects of diabetes on the association between MHT use and late life immediate recall performance. Diabetes was observed to partially mediate the association between MHT use and Late Life Immediate Recall. Average Causal Mediating Effect (ACME); Average Direct Effect (ADE).
See this image and copyright information in PMC

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