Dietary diversity is associated with longitudinal changes in hippocampal volume among Japanese community dwellers

Dementia, particularly Alzheimer's disease (AD), is a growing global health concern with no known cure, highlighting the need for effective preventive strategies. Lifestyle factors, including diet, are suspected to play a role in dementia incidence. While the Mediterranean diet has been suggested as potentially protective, evidence from randomized controlled trials remains insufficient. The Japanese diet, characterized by diverse seasonal ingredients and abundant seafood, is associated with high healthy life expectancy and dietary diversity. Previous research by the authors indicated a link between higher dietary diversity and better cognitive function in older Japanese individuals, using the Mini-Mental State Examination. However, this method has limitations. This study aimed to use a more objective measure by focusing on structural neuroimaging, specifically examining the hippocampus—a key structure for memory processing and known to atrophy in dementia—to investigate the relationship between dietary diversity and hippocampal volume changes over time in a large sample of Japanese community dwellers. This research addresses a gap in the literature by using a large sample size (n=1683) and following participants longitudinally to assess actual changes in hippocampal volume in relation to dietary diversity, unlike previous smaller studies that often relied on single time point measurements.

Existing research has shown mixed results regarding the relationship between diet and hippocampal volume. Some studies have reported positive associations between adherence to the Mediterranean diet and larger hippocampal volumes, while others have linked Western diets to smaller hippocampal volumes over time. The long-term Healthy Eating Score has also been positively associated with hippocampal volume. However, most of these studies were limited by relatively small sample sizes (n<1000), with only one study directly measuring brain volume changes. No previous study had investigated the effect of dietary diversity specifically on hippocampal volume in a large-scale, longitudinal design. This study aimed to address these limitations by focusing on dietary diversity and employing a large sample size with a 2-year follow-up period to observe changes in hippocampal volume.

Data were drawn from the National Institute for Longevity Sciences-Longitudinal Study of Aging (NILS-LSA), a long-term study of community-dwelling Japanese adults. Participants (n=1683, aged 40-89) from the sixth and seventh waves of the NILS-LSA were included, having undergone 3D MRI scans. Exclusion criteria included those who didn't participate in both waves, had MRI issues, a history of dementia or head surgery, new cerebrovascular lesions, or incomplete data. Dietary intake was assessed using 3-day dietary records, with dietitians verifying and clarifying data. Dietary diversity was calculated using the Quantitative Index for Dietary Diversity (QUANTIDD), based on 13 food groups. Nutritional supplement intake was excluded from analysis due to data limitations. MRI data were processed using FreeSurfer software to estimate hippocampal and total grey matter volumes. Longitudinal changes in volumes were calculated as both volume difference (cm³) and percentage decrease. The general linear model was used to assess the association between dietary diversity (divided into quintiles by sex) and brain volume changes, adjusting for age, sex, education, smoking, alcohol intake, physical activity, and comorbidities (Model 1) and then further adjusting for baseline brain volume (Model 2). Statistical significance was set at p<0.05, with p<0.1 considered marginally significant.

The average annual percentage decrease in hippocampal volume was 0.50%, and for total grey matter, it was 0.39%. Baseline characteristics showed that higher dietary diversity was significantly associated with older age, less smoking, and a higher prevalence of hypertension, dyslipidaemia, and diabetes. Individuals with higher dietary diversity also had lower baseline hippocampal and total grey matter volumes. Multivariate-adjusted analyses (Model 1) showed that the percentage decrease in hippocampal volume was significantly associated with dietary diversity (p=0.030; p for trend = 0.003). Higher dietary diversity quintiles showed progressively smaller hippocampal volume decreases over the two years. Even after adjusting for baseline hippocampal volume (Model 2), the association remained significant. A similar trend was observed for total grey matter volume, although the association wasn't as strong (marginally significant). Analyses of food and nutrient intake showed that those with higher dietary diversity consumed less cereal but more of other food groups and higher quantities of protein, sodium, and various micronutrients.

This large-scale longitudinal study provides strong evidence suggesting a link between greater dietary diversity and slower hippocampal volume decline in a community-dwelling Japanese population. The observed annual hippocampal atrophy rate in this cohort is consistent with previous meta-analyses. The finding that higher dietary diversity is associated with less hippocampal shrinkage is important because it suggests a potential modifiable lifestyle factor for preventing age-related cognitive decline. While baseline differences in hippocampal volume existed across dietary diversity groups, the longitudinal analysis showing a significant association between dietary diversity and hippocampal volume change over time strongly suggests that dietary diversity may play a protective role. Future research could investigate the specific mechanisms by which dietary diversity exerts this effect, potentially exploring the role of various micronutrients or specific food groups. It's crucial to note the observational nature of this study, limiting causal inferences. Future randomized controlled trials would strengthen these findings.

This study provides evidence suggesting that increased dietary diversity is associated with reduced hippocampal atrophy in middle-aged and older Japanese adults. The findings highlight the potential of dietary diversity as a modifiable lifestyle factor for maintaining brain health and preventing cognitive decline. Further research, ideally employing randomized controlled trials, is needed to confirm causality and explore the underlying mechanisms. Future studies could also explore the optimal level of dietary diversity for maximal neuroprotective effects and examine potential interactions with other lifestyle factors.

This study's observational design limits the ability to draw causal conclusions; it is possible that other unmeasured factors confound the relationship between dietary diversity and hippocampal volume. The reliance on self-reported dietary data is subject to recall bias. While the study used a large sample size, the participants were primarily of Japanese descent, limiting the generalizability to other populations. Finally, the study did not account for the cognitive effects of nutritional supplements, potentially underestimating the impact of total dietary diversity.