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

OBJECTIVES: 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. METHODS: 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. RESULTS: 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). CONCLUSIONS: A low-fat eating pattern did not reduce dementia mortality in postmenopausal women.

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Journal
Menopause The Journal of The North American Menopause Society
Published
2026-06-09
DOI
https://doi.org/10.1097/gme.0000000000002808
Primary Topic
Nutritional Studies and Diet
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article
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article

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

Karen Johnson, Aaron K. Aragaki, Laura D. Baker, Kathy Pan et al.
Menopause The Journal of The North American Menopause Society
Nutritional Studies and Diet
article

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

Karen Johnson, Aaron K. Aragaki, Laura D. Baker, Kathy Pan, L Qi, J E Manson, Jean Wactawski-Wende, Kathleen M. Hayden, Marian L. Neuhouser, Victor W. Henderson, Rowan T. Chlebowski, Margaret D. Pichardo, Linda G. Snetselaar, Ross L. Prentice, Orena Garcia, Stephen Rapp
article en

Abstract

OBJECTIVES: 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. METHODS: 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. RESULTS: 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). CONCLUSIONS: A low-fat eating pattern did not reduce dementia mortality in postmenopausal women.

Menopause The Journal of The North American Menopause Society
University of Iowa (US), Brigham and Women's Hospital (US), Kaiser Permanente (US), Harvard University (US), University of Tennessee Health Science Center (US), University of Washington (US), Fred Hutch Cancer Center (US), Stanford Health Care (US), Penn Center for AIDS Research (US), Wake Forest University (US), University at Buffalo, State University of New York (US), University of California, Davis (US), Stanford University (US)
Good health and well-being
Openalex Percentile: Top 6%
Nutritional Studies and Diet
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