Eat Well, Stay Trim—Your Brain Will Thank You Later

A raft of epidemiological studies links better health in midlife with a sharper mind in old age. Now, brain-imaging data offers an explanation. In the March 12 JAMA Network Open, scientists led by Daria Jensen at the Max Planck Institute for Human Cognitive and Brain Sciences, Leipzig, Germany, attributed the relationship between health and cognition to strengthened connectivity in the aging brain. In a 22-year longitudinal study of more than 600 people, those who had less abdominal fat in midlife had more intact white matter tracts in old age, leading to better performance on tests of working memory and executive function. In addition, a healthier diet in midlife was associated with better functional connectivity between the hippocampus and other brain regions late in life. Separately, a large survey to be published in Nature Medicine next week confirmed that adherence to a healthy diet begets healthier aging

  • Abdominal fat in midlife predicted white-matter damage in old age.
  • Unhealthy diets came with worse functional connectivity.
  • Cardiovascular disease correlated with higher serum NfL.
  • In short: a healthy lifestyle may stave off cognitive decline.

In a JAMA commentary, Sharmili Edwin Thanarajah at Goethe University Frankfurt, Germany, wrote that Jensen et al.’s findings strengthen the case for midlife interventions. “In particular, this study highlighted the relevance of improving the food environment for better brain structure and function in later life,” he wrote.

Gill Livingston at University College London noted that this is the first time midlife body composition has been linked to better brain connectivity and white matter integrity. “The results … add another layer of evidence to the literature and show a mechanism of action through brain changes,” she wrote to Alzforum (comment below). Livingston has worked with some of the authors.

Along similar lines, in the March 11 JAMA Network Open, scientists led by Anisa Dhana at Rush University Medical Center, Chicago, tied cardiovascular health (CVH) in midlife to brain health later. People with better CVH scores had less neurofilament light, a marker of neurodegeneration, in their blood, and NfL did not increase as much over time. This was equally true for men and women, white and black participants.

Both papers add to the evidence that healthy lifestyle choices could delay dementia, a factor that could explain falling dementia prevalence rates worldwide.

Waist, Hips, and White Matter. Sagittal (left), coronal (middle), and transverse (right) statistical maps based on diffusion tensor imaging scans of the Whitehall II cohort. Damage (red) to white-matter tracts (green) at age 70 associated with abdominal fat in midlife. [Courtesy of Jensen et al., JAMA Network Open, 2025.]

Many prior studies have linked metabolic conditions such as diabetes and obesity, as well as poor cardiovascular health, to greater dementia risk (Sep 2014 news; Aug 2020 conference news; Feb 2024 news), but scientists do not know what effects specific lifestyle choices might have on brain structure.

To home in on these factors, Jensen and colleagues turned to the Whitehall II Study, which enrolled more than 10,000 British civil servants and followed them for 30 years. Jensen analyzed data from the imaging substudy of 775 participants. The authors picked the 664 people who had a waist-to-hip ratio measurement when they were about 48 years old, had at least one follow-up measurement of that ratio, and had structural and functional MRI scans at age 70. Waist-to-hip ratio reflects visceral fat in the abdomen, which is linked to the risk of chronic diseases such as diabetes and cancer. About 80 percent of participants were men; most were highly educated.

A high waist-to-hip ratio at baseline was associated with skimpy white matter at age 70, as measured by diffusion tensor imaging (image above). It also came with worse performance on tests of verbal episodic memory, working memory, and executive function. Mediation analysis suggested this white-matter weakness was responsible for difficulties on the digit span test, which measures working memory, and the digit coding test, which measures executive function.

Jensen and colleagues also analyzed the effects of diet among 512 of the substudy participants who provided that information. The Whitehall Study assessed diet quality using the Alternative Healthy Eating Index-2010. Based on 11 dietary components, such as vegetables, fruit, whole grains, sugar, processed food, red meat, sodium, and trans fat, scores on this scale range from 0 to 110, with higher numbers indicating healthier eating. At baseline, scores ranged from 25 to 85, with the cohort averaging 56, indicating generally unhealthy diets. This average did not change during follow-up.

Having a better midlife diet associated with better functional connectivity between the hippocampus and both the occipital lobe and the cerebellum at age 70. In addition, participants who improved their diet over time had better white matter at age 70 than did those who continued to eat less well.

Thanarajah cautioned that the Whitehall data do not prove that diet or body composition affect brain structure, since the data are correlative, meaning other factors could be involved. David Knopman at the Mayo Clinic in Rochester, Minnesota, noted that the authors did not take socioeconomic status into account. “Dietary choices are strongly influenced by socioeconomic circumstances, which themselves are unquestionably strongly related to all health outcomes including cognitive health,” he wrote (comment below).

Bad for the Heart, Bad for the Brain. People with the worst cardiovascular health (green) had a steeper rise in serum NfL over the next 10 years than did those with the best heart health (red). [Courtesy of Dhana et al., JAMA Network Open, 2025.]

Meanwhile, Dhana and colleagues focused on cardiovascular health. They analyzed data from 1,018 participants in the Chicago Health and Aging Project, a longitudinal study of people older than 65 without dementia at baseline. Sixty percent of participants were black, and the rest white. Their average age was 73 at baseline, 60 percent were women, and about a third carried an APOE4 allele.

Baseline cardiovascular health (CVH) was estimated as per the American Heart Association’s Life’s Simple 7 score , which combines an assessment of diet, exercise, body mass index, smoking, dyslipidemia, diabetes, and hypertension. Scores range from 0 to 14, and higher scores are better (Lloyd-Jones et al., 2010).

At baseline, better CVH was associated with having less NfL in the blood. Every 1 point higher CVH was linked to 3.5 percent lower serum NfL, such that those with the highest scores had 19 percent lower NfL than did those with the lowest scores. Those with higher CVH were likelier to be white and well-educated, the authors noted. The relationship between CVH and serum NfL was the same in both sexes and races in this study. The relationship was statistically stronger in APOE4 carriers than non-carriers.

Ten-year longitudinal data were available for 832 participants. Those with the lowest CVH experienced an annual 7 percent rise in their serum NfL; those with the highest CVH, 5 percent (image above). This study did not analyze effects on cognition, but Dhana and colleagues had previously reported that higher CVH associated with slower cognitive decline and a lower risk of Alzheimer’s disease in the same cohort (Dhana et al., 2023).

The authors also examined serum total tau levels, but found no link to cardiovascular health. They noted that NfL often flags neuronal damage caused by poor vascular health, perhaps making it a better indicator of CVH than is t-tau (Wakita et al., 2002; Disanto et al., 2017).

Previously, high risk of cardiovascular disease had been linked to both higher plasma NfL and t-tau, and worse performance on cognitive tests, in the Health and Aging Brain Study–Health Disparities (Jiang et al., 2023).

Knopman said these studies offer valuable insights. “It’s not just overt strokes that matter … cerebrovascular disease also exerts its pathologic effects via gradual, insidious, covert means that are proxied by brain volume loss and nonspecific plasma biomarkers such as NfL,” he wrote.—Madolyn Bowman Rogers

Comments

  1. The study by Jensen and colleagues is carefully done and in line with the literature showing that midlife obesity—and waist-hip ratio, which is a better measure—are associated with future lower cognition. It also shows for the first time an association with good hippocampal connectivity and higher white-matter integrity. The results on obesity or waist-hip ratio add another layer of evidence to the literature, showing a mechanism of action through brain changes, and reinforce the conclusion that midlife weight is important. In particular, white-matter changes mediated the association with cognition.

    The diet component is less clear. Diet is measured through the alternate healthy eating index, incorporating not only healthy eating—vegetables, fruit, whole grains, nuts and legumes, long-chain omega-3 fatty acids that include docosahexaenoic acid and eicosapentaenoic acid, and polyunsaturated fatty acids—but also moderate alcohol, low sugar and low sodium. Diet was associated with the hippocampal but not the white-matter findings. This diet may act directly on the brain, be related to weight or waist-hip ratio, or reflect alcohol intake or sodium that increases hypertension, or a combination of these. It is impossible to know. It clearly is a wide measure with better scores reflecting a healthier lifestyle.…More

    I do not agree that because the participants did not have alcohol dependence, intake was unimportant, as the effect of alcohol on cognition can be important even in the absence of dependence. I agree with the authors’ caveat that the cohort was mainly male, white, British who survived to middle age. Even so, the findings are from a large cohort and add to our understanding, particularly that lower white-matter integrity mediates the effect (i.e., is the pathway of effect) of obesity/waist-hip ratio on cognition. 

    I’d like to note a COI with the Whitehall paper as some of its authors are colleagues.

    View all comments by Gill Livingston

  2. We would all like to believe that we could control our own health by eating healthy. Dietary epidemiological studies such as this one of Jensen et al. sought to validate the protective effects of a healthy diet on cognition and its presumed neurophysiological correlates. The authors found that those who reported following quality diets in midlife and who had lower waist-to-hip ratios had better functional and structural MRI measurements as well as slightly better cognitive performance. While these results are gratifying, the lack of attention to the socioeconomic status of participants lessens my confidence for making causal claims about the benefits of diet on later life cognition. Dietary choices are strongly influenced by socioeconomic circumstances, which themselves are unquestionably strongly related to all health outcomes including cognitive health. If the authors had been able to control for socioeconomics, which they do not mention, would the associations of diet be attenuated?…More

    The straightforward observations of Dhana et al. showing that plasma NfL concentrations were associated with a cardiovascular health score shows that the known effects of vascular disease on brain health can be proxied by the plasma biomarkers. This is reinforced by an article that just appeared in Neurology, which also showed in a large multidisciplinary cohort that NfL and AD specific biomarkers associated with brain volume loss and white-matter hyperintensity burden (Sanchez et al., 2025).

    One of the valuable insights that has emerged in the past few years about the relationship between cerebrovascular disease and brain health is that it is not just overt strokes that matter. Cerebrovascular disease also exerts its pathologic effects via gradual, insidious, covert means, that are proxied by brain volume loss and nonspecific plasma biomarkers, such as NfL.

    References:

    Sanchez E, Coughlan GT, Wilkinson T, Ramirez J, Mirza SS, Baril AA, Dilliott AA, Frank A, Lang AE, Hassan A, Pollock BG, Scott CJ, Marras C, Fischer CE, Seitz D, Andriuta D, Dowlatshahi D, Grimes DA, Tang-Wai DF, Sahlas DJ, Rogaeva EA, Finger E, Robinson JF, Tan K, Binns MA, Tartaglia MC, Borrie MJ, Strong MJ, Ozzoude M, Nanayakkara ND, Goncalves RA, Bartha R, Hegele RA, Farhan SM, Black SE, Kumar S, Symons SP, Haddad SM, Pasternak SH, Arnott SR, Rajji TK, Steeves T, Swardfager W, Ashton NJ, Kvartsberg H, Zetterberg H, Munoz DP, Masellis M, ONDRI Investigators. Association of Plasma Biomarkers With Longitudinal Atrophy and Microvascular Burden on MRI Across Neurodegenerative and Cerebrovascular Diseases. Neurology. 2025 Apr 8;104(7):e213438. Epub 2025 Mar 10 PubMed.

    View all comments by David Knopman
    • User Profile Image Daria Jensen
      University Hospital Leipzig and Max Planck Institute for Human Cognitive and Brain Sciences
    • Posted:

    We thank Drs. Livingston and Knopman for their comments on our study and their evaluation. We agree with Dr Knopman that socioeconomic status is strongly related to dietary quality. Therefore, we’d like to clarify that we did correct all analyses for education status. Thus, in the "Statistical Analysis" section of the paper we state "All analyses were adjusted for age, sex, years of education, MRI scanner model, physical activity, and the Montreal Cognitive Assessment score, all of which were measured at the time of MRI scan. Resting-state fMRI analyses were corrected for head motion and voxelwise gray matter density. AHEI-2010 analyses were adjusted for total energy intake (kcal/d) (eMethods 7 in Supplement 1).…More

    References:

    Jensen DE, Ebmeier KP, Akbaraly T, Jansen MG, Singh-Manoux A, Kivimäki M, Zsoldos E, Klein-Flügge MC, Suri S. Association of Diet and Waist-to-Hip Ratio With Brain Connectivity and Memory in Aging. JAMA Netw Open. 2025 Mar 3;8(3):e250171. PubMed.

    View all comments by Daria Jensen

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References

News Citations

  1. World Alzheimer Report: Preventing Dementia through Lifestyle Changes
  2. Heart Health Is Brain Health, and It Starts in Your 20s
  3. In Diabetes, Tight Blood Sugar Control Staves Off Dementia

Paper Citations

  1. Lloyd-Jones DM, Hong Y, Labarthe D, Mozaffarian D, Appel LJ, Van Horn L, Greenlund K, Daniels S, Nichol G, Tomaselli GF, Arnett DK, Fonarow GC, Ho PM, Lauer MS, Masoudi FA, Robertson RM, Roger V, Schwamm LH, Sorlie P, Yancy CW, Rosamond WD, American Heart Association Strategic Planning Task Force and Statistics Committee. Defining and setting national goals for cardiovascular health promotion and disease reduction: the American Heart Association's strategic Impact Goal through 2020 and beyond. Circulation. 2010 Feb 2;121(4):586-613. Epub 2010 Jan 20 PubMed.
  2. Dhana A, DeCarli CS, Dhana K, Desai P, Holland TM, Evans DA, Rajan KB. Cardiovascular health and cognitive outcomes: Findings from a biracial population-based study in the United States. Alzheimers Dement. 2023 Oct;19(10):4446-4453. Epub 2023 Aug 3 PubMed.
  3. Wakita H, Tomimoto H, Akiguchi I, Matsuo A, Lin JX, Ihara M, McGeer PL. Axonal damage and demyelination in the white matter after chronic cerebral hypoperfusion in the rat. Brain Res. 2002 Jan 4;924(1):63-70. PubMed.
  4. Disanto G, Barro C, Benkert P, Naegelin Y, Schädelin S, Giardiello A, Zecca C, Blennow K, Zetterberg H, Leppert D, Kappos L, Gobbi C, Kuhle J, Swiss Multiple Sclerosis Cohort Study Group. Serum Neurofilament light: A biomarker of neuronal damage in multiple sclerosis. Ann Neurol. 2017 Jun;81(6):857-870. PubMed.
  5. Jiang X, O'Bryant SE, Johnson LA, Rissman RA, Yaffe K, Health and Aging Brain Study (HABS‐HD) Study Team. Association of cardiovascular risk factors and blood biomarkers with cognition: The HABS-HD study. Alzheimers Dement (Amst). 2023;15(1):e12394. Epub 2023 Mar 8 PubMed.

Further Reading

Primary Papers

  1. Jensen DE, Ebmeier KP, Akbaraly T, Jansen MG, Singh-Manoux A, Kivimäki M, Zsoldos E, Klein-Flügge MC, Suri S. Association of Diet and Waist-to-Hip Ratio With Brain Connectivity and Memory in Aging. JAMA Netw Open. 2025 Mar 3;8(3):e250171. PubMed.
  2. Edwin Thanarajah S. Midlife Dietary Quality and Body Composition Relevance for Brain Connectivity and Cognitive Performance in Later Life. JAMA Netw Open. 2025 Mar 3;8(3):e250181. PubMed.
  3. Dhana A, DeCarli CS, Dhana K, Desai P, Ng TK, Evans DA, Rajan KB. Cardiovascular Health and Biomarkers of Neurodegenerative Disease in Older Adults. JAMA Netw Open. 2025 Mar 3;8(3):e250527. PubMed.

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