Greek study links higher diet inflammatory index scores to increased dementia risk

What you eat may influence your brain health later in life—according to results from a Greek observational study, higher diet inflammatory index (DII) scores were associated with an increased risk for incident dementia among community-dwelling older adults, suggesting a dose-dependent relationship between an inflammatory diet and cognitive decline.

“Aging is accompanied by physiological alterations in both the innate and the adaptive arms of the immune system, a process called immunosenescence,” Nikolaos Scarmeas, MD, PhD, of National and Kapodistrian University of Athens in Greece, and a Fellow of the American Academy of Neurology (AAN), and colleagues explained in Neurology. “One of the hallmarks of immunosenescence is the institution of a chronic low-grade subclinical systemic inflammatory state, characterized by high circulating levels of pro-inflammatory cytokines and mediators, including interleukin (IL)-1, IL-6, C-reactive protein (CRP) and tumor necrosis factor (TNF). This process is mainly mediated by chronically activated macrophages and monocytes, and contributes to many aging-associated phenotypes (hence the term ’inflammaging’). Brain-wise, inflammaging has been associated with cognitive impairment, Alzheimer’s disease (AD), and cerebral small vessel disease (CSVD), a component of vascular dementia (VaD), hence potentially contributing to the most common causes of dementia and cognitive decline.”

Evidence suggests foods, nutrients, and non-nutrient food ingredients can potentially modulate the inflammatory status of an individual “both acutely and chronically,” they added, and therefore, an anti-inflammatory diet—including more servings of fruit, vegetables, beans, and tea or coffee—may represent a modifiable risk factor for inflammaging and subsequent dementia and late-life cognitive impairment.

To explore this possibility, Scarmeas and colleagues conducted an analysis of the relationship between DII scores and dementia incidence among a non-sex-specific cohort of community dwelling, non-demented adults. In this observational study, they found that “higher DII scores were associated with an increase in the risk for dementia incidence. The gradual risk increase for higher DII tertiles, suggests a potential dose–response relationship between the inflammatory potential of diet and the risk for incident dementia. The observed associations remained unchanged and significant even after excluding from the analyses participants who reported an energy intake that could be considered nonacceptable due to potential dietary intake misreporting.”

The study authors concluded that, if there is indeed a dose-response relationship between inflammatory food intake and dementia risk, dietary interventions may prove invaluable in decreasing the risk of dementia and late-life cognitive decline.

“There may be some potent nutritional tools in your home to help fight the inflammation that could contribute to brain aging,” Scarmeas said in an AAN press release on the study. “Diet is a lifestyle factor you can modify, and it might play a role in combating inflammation, one of the biological pathways contributing to risk for dementia and cognitive impairment later in life.”

For their analysis, Scarmeas and colleagues recruited participants from the Hellenic Longitudinal Investigation of Aging and Diet (HELIAD) cohort, a population-based, multidisciplinary study examining the epidemiology of dementia and other aging-associated neuropsychiatric conditions among older community-dwelling adults in Greece. Participants were selected through random sampling of individuals 65 years of age or older; individuals with baseline dementia or missing cognitive follow-up data were excluded from the analysis.

Dietary intake was recorded using a semi-quantitative food frequency questionnaire (FFQ) validated for the Greek population; FFQ data was then used to develop a DII score for each patient. The DII score “considers literature-derived associations of 45 food parameters with levels of pro- and anti-inflammatory cytokines in the blood; higher values indicated a more pro-inflammatory diet,” the study authors explained.

The final analysis consisted of 1,059 individuals with a mean age of 73.1 years; 40.3% were male, and mean education was 8.2 years. Of the 1,059 patients, 62 developed incident dementia over a mean follow-up of 3.05 years—53 developed Alzheimer’s disease, five vascular dementia, four Lewy body dementia, and one developed dementia due to an underlying psychiatric disorder.

Participants were divided into groups based on DII score: “Those in the group with the lowest scores of -1.76 and lower, indicating a more anti-inflammatory diet, ate an average per week of 20 servings of fruit, 19 of vegetables, four of beans or other legumes and 11 of coffee or tea per week,” according to the AAN press release. “Those in the group with the highest scores, 0.21 and above, indicating a more inflammatory diet, ate an average per week of nine servings of fruit, 10 of vegetables, two of legumes and nine of coffee or tea.”

“Each additional unit of DII was associated with a 21% increase in the risk for dementia incidence (HR=1.21 [1.03–1.42]; P=0.023),” the study authors found. “Compared to participants in the lowest DII tertile, participants in the highest one (maximal pro-inflammatory diet potential) were three ([1.2–7.3]; P=0.014) times more likely to develop incident dementia. The test for trend was also significant, indicating a potential dose-response relationship (P=0.014).” The average DII score for participants who developed dementia was −0.06; the average score for participants without dementia was −0.70.

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The study authors noted that their findings replicate and expand on results from a previous prospective, U.S. population based study of a cohort of 7,085 women ages 65-79 years, which found that higher DII scores were linked to higher risk of mild cognitive impairment or probable dementia, as well as greater cognitive decline and earlier onset of cognitive impairment. Scarmeas and colleagues argued that their findings support the generalizability of the U.S. study’s results to a non-sex-specific population of older adults without baseline dementia; “however,” they added, “their validity and reproducibility need to be further explored and ascertained by future research.”

Researchers also pointed out that, while immunosenescence and inflammaging are aging-related processes present in the majority of people, “genetic, environmental, lifestyle, and nutritional factors are responsible for their interindividual heterogeneity. Increasing evidence has revealed that complex interactions between food components and histone modification, DNA methylation, non-coding RNA expression, and chromatin remodeling, influence the inflammaging phenotype. Therefore, dietary interventions might prove a valuable tool in decreasing the risk for dementia and late-life cognitive impairment by counteracting inflammaging and modulating its phenotypic expression, through epigenetic and other mechanisms.”

Scarmeas and colleagues concluded that the development of “widely-applicable and reliable method to characterize individuals’ diet based on their inflammatory potential” should be a major priority in plans for healthy aging and strategies designed to maintain cognitive health.

Study limitations included loss to follow-up; the possibility of disease misclassification bias; the relatively short follow-up period; assessment of dietary intake via FFQ may be subject to measurement error; and the observational nature of the study limits its ability to establish causation.

  1. Higher diet inflammatory index (DII) scores were associated with an increase in the risk for dementia incidence among community-dwelling adults ages 65 years or older in Greece, and the risk gradually increased for higher DII tertiles, suggesting a potential dose–response relationship between the inflammatory potential of diet and the risk for incident dementia.

  2. The findings suggest that dietary interventions might prove a valuable tool in decreasing the risk for dementia and late-life cognitive impairment by counteracting inflammaging among older adults.

John McKenna, Associate Editor, BreakingMED™

The HELIAD study was supported by grants from the Alzheimer’s Association, the ESPA-EU program Excellence Grant ARISTEIA, and the Ministry of Health and Social Solidarity, Greece. It was not supported by any industry

Scarmeas reported personal fees from Merck Consumer Health and Eisai and and personal fees from NIH unrelated to the current study.

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