By Kellyann Niotis, MD
Instructor, Clinical Neurology, Weill Cornell Medical College; Assistant Attending Neurologist, New York-Presbyterian/Weill Cornell Medical Center
SYNOPSIS: Specific dietary patterns, such as the Mediterranean-style diet, have been shown to promote brain health, mitigate neuro-inflammation, and reduce the risk of dementia. This prospective cohort study demonstrated an association between a high inflammatory potential diet and increased risk for incident dementia.
SOURCE: Charisis S, Ntanasi E, Yannakoulia M, et al. Diet inflammatory index and dementia incidence: A population-based study. Neurology 2021;97:e2381-e2391.
With an aging population, the global disability burden of age-related cognitive decline and dementia is expected to soar. Inflammation typically increases with age (“inflammaging”) because of immunosenescence, a physiological process of immune dysfunction that leads to a low-grade systemic inflammatory state. This is thought to contribute to many age-associated diseases, including “cognitive aging,” Alzheimer’s disease (AD), and cerebral small vessel disease.
Diet and nutrition, two well-documented modifiable risk factors for dementia, can mediate systemic inflammatory status. Therefore, characterizing the inflammatory potential of an individual’s diet could help guide personalized nutrition and dietary interventions targeted to combat “inflammaging” and reduce dementia risk. Diet inflammatory index (DII) scores, which consist of 45 food parameters including energy, nutrients, bioactive compounds, and foods/spices validated by systemic inflammatory biomarkers (interleukin [IL]-1β, IL-4, IL-6, IL-10, tumor necrosis factor-α, and C-reactive protein), have been examined in relation to cognition and dementia in few prior studies. Although results are inconsistent among the literature, some suggest that higher DII scores (indicative of higher inflammatory potential) are associated with poorer cognitive performance and increased risk of mild cognitive impairment (MCI) and dementia. However, these studies have notable confounding variables and limitations.
To address the shortcomings of the current literature and further elucidate the relationship between dementia and DII scores, Charisis et al conducted a longitudinal prospective cohort study to investigate the inflammatory potential of diet through a population-based DII and dementia incidence in community-dwelling older adults. Participants from the Hellenic Longitudinal Investigation of Aging and Diet (HELIAD) study were selected through random sampling from community-dwelling individuals ≥ 65 years of age from two centers in Greece. HELIAD is a population-based study designed to estimate the incidence of dementia and other neuropsychiatric conditions in the Greek population with face-to-face evaluations every three years. For the present analyses, the authors included only participants based on the following criteria: no baseline dementia, available follow-up data, and available baseline dietary information.
The primary outcome was incidence of dementia as a function of baseline DII score. Dementia diagnosis was based on standard clinical criteria and reached through diagnostic consensus meetings among study investigators (including neurologists and neuropsychologists). Dietary consumption over the past month was evaluated via a population-validated semiquantitative food frequency questionnaire (FFQ) that was standardized to representative normative dietary intake data from 11 different countries. To obtain DII scores, each food parameter from the FFQ was assigned a value according to its association with inflammatory biomarkers, where higher positive scores indicate greater inflammatory potential. The authors analyzed the relationship between dementia incidence and inflammatory diet potential by treating DII score as a continuous linear variable as well as a nonlinear variable by ranking scores into tertiles, with the first tertile representing maximal anti-inflammatory diet potential.
Of the 3,531 HELIAD participants, 1,059 met inclusion criteria for the present analyses. A significant number of patients (n = 689) were lost to follow-up. Mean follow-up was 3.05 years. During this time, 62 were diagnosed with dementia.
Those who developed dementia were older (77.5 vs. 72.9 years of age, P < 0.001), were less educated (6.1 vs. 8.3 years, P < 0.001), had higher DII scores (-0.06 vs. -0.70, P < 0.027), and were more likely to have MCI at baseline (46.8% vs. 8.8%, P < 0.001) compared to those who did not. Greater inflammatory diet potential was associated with a significantly higher risk for dementia in both continuous and tertile analyses.
For each additional unit of DII score, a 21% increase in risk of incident dementia was observed (hazard ratio, 1.21; 95% confidence interval [CI], 1.03-1.42;
P = 0.023). Participants in the highest DII score tertile were three times more likely to develop incident dementia than those in the lowest tertile, and the authors also demonstrated a potential corresponding dose response relationship (95% CI, 1.2-7.3; P = 0.014). The observed significant associations remained even after adjusting for confounders and potential dietary intake misreporting.
COMMENTARY
Given our aging population and the global disease burden of AD, nutritional interventions have become a focal point in clinical research on primary dementia prevention. This prospective study replicates and expands on previous work by demonstrating that a diet with a higher inflammatory potential is associated with increased risk of MCI and dementia but also is associated with an earlier onset of cognitive impairment. However, the short study duration and large number of participants who became lost to follow-up are important limitations.
Although these findings suggest that dietary modification targeted to lower DII scores may be an effective risk reduction strategy, preventive nutritional interventions may not be universally applicable and may depend on the clinical profile of the individual patient. Future study is needed to corroborate these results and ascertain more precise guidelines on the use of DII scores and diet recommendations to slow and/or prevent cognitive decline and dementia.
