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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

  • Rowan T. Chlebowski
  • , Stephen Rapp
  • , Aaron K. Aragaki
  • , Jo Ann E. Manson
  • , Kathy Pan
  • , Marian L. Neuhouser
  • , Karen C. Johnson
  • , Linda G. Snetselaar
  • , Victor W. Henderson
  • , Lihong Qi
  • , Kathleen M. Hayden
  • , Laura D. Baker
  • , Orena Garcia
  • , Margaret D. Pichardo
  • , Jean Wactawski-Wende
  • , Ross L. Prentice
  • The Lundquist Institute
  • Wake Forest University
  • Fred Hutchinson Cancer Research Center
  • Brigham and Women’s Hospital
  • Kaiser Permanente
  • University of Washington
  • University of Tennessee Health Science Center
  • University of Iowa
  • Stanford University
  • University of California at Davis
  • Penn Health System

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish
JournalMenopause
DOIs
StateAccepted/In press - 2026

Keywords

  • Dementia mortality
  • Low-fat dietary pattern
  • Postmenopausal women
  • Randomize trial
  • Women’s Health Initiative

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