MIND Diet Linked to Lower Dementia Risk via Reduced Hippocampal Sclerosis: Study

An autopsy study published in the Journal of American Medical Association revealed that higher adherence to the Mediterranean–Dietary Approaches to Stop Hypertension Intervention for Neurodegenerative Delay (MIND) diet was associated with lower odds of hippocampal sclerosis and less dementia at death, suggesting the diet’s protective effect may be partly mediated through reduced hippocampal damage.

Severe neuronal loss and astrogliosis in coronal sections of the mid-hippocampus cornu ammonis 1 or subiculum is known as hippocampal sclerosis (HS). This pathology is linked to dementia, Alzheimer's disease, and limbic-predominant age-related transactive response DNA-binding protein 43 encephalopathy neuropathological change (LATE-NC). In humans, nothing is known about the relationship between food and HS or HS and LATE-NC. Thus, this study examined the relationship between HS and HS with LATE-NC and the MIND diet.

Autopsied patients from the ongoing Rush Memory and Aging Project cohort research were included in this investigation. Researchers included participants with neuropathological and nutritional data from 2004 to 2024. Analysis of the data was place between April 3, 2024, and May 13, 2025. The average MIND diet scores were calculated using all verified food frequency questionnaires that were given every year for up to 18 years before to death.

Hematoxylin and eosin staining was used to determine the presence of HS, while TDP-43 immunohistochemistry was used to identify the presence of LATE-NC in eight different brain areas. A semiquantitative measure was used to evaluate the degree of hippocampus neuronal loss in a group of 300 patients. The scale ranged from 0, which indicates no neuronal loss, to 5, which is classified as none to mild, moderate, and severe neuronal loss.

Of the 809 participants (mean [SD] age at death, 91.3 [6.1] years; mean [SD] follow-up, 7.2 [4.4] years; 538 [72%] female; mean [SD] follow-up, 7.2 [4.4] years), 82 (10.1%) had HS; 71 (9%) had both HS and LATE-NC; and in the scored subset, 35 (12%) and 43 (14%) had severe hippocampus neuronal loss.

After adjusting for age at death, sex, education, total calories, APOE-ε4 status, AD, and vascular pathologies, higher MIND diet scores were linked to decreased risks of HS (odds ratio [OR], 0.78; 95% CI, 0.65 to 0.95) and HS with LATE-NC (OR, 0.79; 95% CI, 0.64 to 0.97).

The MIND diet was linked to a 21% indirect connection through HS (β = -0.05; 95% CI, -0.10 to -0.01; P =.02) and a lower incidence of dementia at the time of death (β = -0.26; 95% CI, -0.36 to -0.15; P <.001) in mediation analyses. Less hippocampus neuronal loss was linked to a higher MIND diet score (P for trend =.01).

Overall, MIND diet adherence throughout follow-up was linked to a decreased risk of HS, HS with LATE-NC, and hippocampus neuronal loss in this cohort analysis of autopsied subjects. According to these results, the MIND diet may lessen negative effects on brain health.

Reference:

Agarwal, P., Agrawal, S., Wagner, M., Cherian, L. J., Aggarwal, N. T., James, B. D., Holland, T. M., Bennett, D. A., Barnes, L. L., Leurgans, S. E., & Schneider, J. A. (2025). MIND diet and hippocampal sclerosis among community-based older adults. JAMA Network Open, 8(8), e2526089. https://doi.org/10.1001/jamanetworkopen.2025.26089