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Low-fat dietary pattern and dementia mortality: a secondary analysis of the Women's Health Initiative dietary modification randomized clinical trial with long-term follow-up
Journal article   Peer reviewed

Low-fat dietary pattern and dementia mortality: a secondary analysis of the Women's Health Initiative dietary modification randomized clinical trial with long-term follow-up

Rowan T Chlebowski, Stephen Rapp, Aaron K Aragaki, JoAnn E Manson, Kathy Pan, Marian L Neuhouser, Karen C Johnson, Linda G Snetselaar, Victor W Henderson, Lihong Qi, …
Menopause (New York, N.Y.)
06/09/2026
DOI: 10.1097/GME.0000000000002808
PMID: 42262514

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Abstract

In the Women's Health Initiative (WHI) Dietary Modification (DM) randomized trial, the dietary intervention significantly reduced breast cancer mortality and, in a subgroup of women 65 years old or above, significantly lowered possible cognitive impairment based on Modified Mini-State Examination (3MSE) scores. Based on this background, we examined the dietary intervention association with long-term dementia mortality. The WHI DM clinical trial randomized 48,835 postmenopausal US women, aged 50-79 years, with dietary fat intake ≥32% of energy and anticipated ≥3-year survival. Cognitive function was not an eligibility criterion. Randomization was to a low-fat dietary pattern intervention (40%; n=19,541) with goals to reduce fat intake and increase fruit, vegetable, and grain intake or a usual diet comparison (60%; n=29,294). All dietary targets were significantly reduced. Mortality findings were confirmed by central medical record review enhanced by serial National Death Index findings. Dementia mortality was examined after an 8.5-year (median) dietary intervention and 20-year cumulative follow-up. Dietary intervention did not influence dementia mortality (n=1,386) (HR: 0.94, 95% CI: 0.85-1.05), with similar findings for Alzheimer (HR: 1.00, 95% CI 0.85-1.17) and non-Alzheimer dementia mortality (HR: 0.90, 95% CI 0.77-1.05). Of 13 subgroup analyses, with dietary intervention, there was a trend for lower dementia mortality in younger women (50-59 y, HR: 0.73, 95% CI: 0.44-1.21; 60-69 y, HR: 0.85, 95% CI: 0.72-1.01; 70-79 y, HR: 1.06, 95% CI: 0.91-1.23; P-trend 0.03). A low-fat eating pattern did not reduce dementia mortality in postmenopausal women.
 Dementia mortality Women’s Health Initiative Postmenopausal women Low-fat dietary pattern Randomize trial

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