Fan, Lei; Sun, Yunyi; Liu, Dandan; Robb, W. Hudson; Pechman, Kimberly R.; Shashikumar, Niranjana; Vyas, Yukti; Landman, Bennett A.; Hohman, Timothy J.; Jefferson, Angela L. (2026).听.听Alzheimer’s & Dementia, 22(6), e71548.听
The relationship between dietary fat and听Alzheimer’s disease (AD)听has remained unclear, with previous studies reporting mixed results. This study examined whether fat intake was associated with changes in brain structure over time and whether those associations differed based on factors such as cognitive status, sex, and听APOE 蔚4听status鈥攁 genetic variant that increases the risk of developing Alzheimer’s disease. The researchers followed 758 participants for an average of 4.6 years, including individuals with normal cognition and those with听mild cognitive impairment (MCI), an early stage of cognitive decline. Among cognitively unimpaired participants, a higher percentage of calories from fat was associated with faster shrinkage of the听temporal lobe, a brain region important for memory. In contrast, among participants with MCI, higher fat intake was associated with slower enlargement of the听inferior lateral ventricle, a change that is often linked to brain atrophy. This association appeared to be driven primarily by women and individuals carrying the APOE 蔚4 genetic variant. The findings suggest that the relationship between dietary fat and brain health may differ depending on a person’s stage of cognitive decline and underlying risk factors. The authors note that, in higher-risk groups, the slower progression of some brain changes may reflect a compensatory response rather than a protective effect of a high-fat diet.
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FIGURE 1
Pfat 脳 Cognitive status and Tfat 脳 Cognitive status on longitudinal structural MRI variables. Lines reflect structural MRI variables corresponding to Pfat and Tfat. The gray shaded area reflects 95% confidence interval. (A) Associations between Tfat and hippocampal volume, stratified by cognitive status; CU participants听尾听=听鈭�18.7,听p听=听0.008; MCI participants听尾听=听11.2, p听=听0.43. (B) Associations between Pfat and temporal lobe volume, stratified by cognitive status; CU participants听尾听=听鈭�47.2,听p听=听0.007; MCI participants听尾听=听50.9,听p听=听0.21. (C) Associations between Pfat and inferior lateral ventricle volume, stratified by cognitive status; CU participants听尾听=听鈭�1.89,听p听=听0.27; MCI participants听尾听=听鈭�22.5,听p听=听0.006. CU, cognitively unimpaired; MCI, mild cognitive impairment; MRI, magnetic resonance imaging; Pfat, percentage of energy from fat; Tfat, total fat intake.