Mediterranean Diet and Risk of Dementia and Alzheimer's Disease in the EPIC-Spain Dementia Cohort Study

Abstract

The Mediterranean diet (MD) has shown to reduce the occurrence of several chronic diseases. To evaluate its potential protective role on dementia incidence we studied 16,160 healthy participants from the European Prospective Investigation into Cancer and Nutrition (EPIC)-Spain Dementia Cohort study recruited between 1992-1996 and followed up for a mean (±SD) of 21.6 (±3.4) years. A total of 459 incident cases of dementia were ascertained through expert revision of medical records. Data on habitual diet was collected through a validated diet history method to assess adherence to the relative Mediterranean Diet (rMED) score. Hazard ratios (HR) of dementia by rMED levels (low, medium and high adherence levels: ≤6, 7-10 and ≥11 points, respectively) were estimated using multivariable Cox models, whereas time-dependent effects were evaluated using flexible parametric Royston-Parmar (RP) models. Results of the fully adjusted model showed that high versus low adherence to the categorical rMED score was associated with a 20% (HR = 0.80, 95%CI: 0.60-1.06) lower risk of dementia overall and HR of dementia was 8% (HR = 0.92, 0.85-0.99, p = 0.021) lower for each 2-point increment of the continuous rMED score. By sub-types, a favorable association was also found in women for non-AD (HR per 2-points = 0.74, 95%CI: 0.62-0.89), while not statistically significant in men for AD (HR per 2-points = 0.88, 0.76-1.01). The association was stronger in participants with lower education. In conclusion, in this large prospective cohort study MD was inversely associated with dementia incidence after accounting for major cardiovascular risk factors. The results differed by dementia sub-type, sex, and education but there was no significant evidence of effect modification.

Keywords: Alzheimer’s disease; EPIC-Spain; Mediterranean diet; cohort study; dementia; prospective analysis.

Figure 1

Hazard ratio of dementia according to Mediterranean Diet scores in the EPIC-Spain Dementia Cohort study (N = 16,160), by sex. The dashed lines represent the upper and lower 95% confidence interval limits of the estimates. A non-linear inverse association between risk of dementia and rMED scores was observed among women, but not among men. Hazard ratios of dementia were estimated using Cox proportional hazards regression models, with age as the time scale, stratified by center and age (in 5-year categories), and adjusted by sex, education, energy intake, smoking, BMI category, elevated waist circumference, household and recreational physical activities, hypertension (self-reported), hyperlipidemia (self-reported), coffee and tea consumption (combined), and intake (in g/day per 2000 kcal) of potatoes, eggs, and cakes and biscuits. In women, models were further adjusted by menopausal status, oral contraceptive use, and hormone replacement therapy. Dementia risk was modelled following a restricted cubic spline transformation of the rMED variable with three degrees of freedom (knots were placed at the 33rd and 67th percentiles).

Figure 2

Time-dependent variation in hazard ratio estimates of dementia for participants with high versus low Mediterranean Diet scores (rMED) throughout 25 years of follow-up in the EPIC-Spain Dementia Cohort study (N = 16,160). Hazard ratio estimates of dementia varied depending on follow-up time and cumulative number of cases. Time-varying hazard ratios were calculated using flexible parametric Royston-Parmar survival models, with time on study as the time scale. Models were adjusted by center, sex, education, energy intake, smoking, BMI category, elevated waist circumference, household and recreational physical activities, hypertension (self-reported), hyperlipidemia (self-reported), coffee and tea consumption (combined), and intake (in g/day per 2000 kcal) of potatoes, eggs, and cakes and biscuits.