Mediterranean diet adherence is associated with lower dementia risk, independent of genetic predisposition: findings from the UK Biobank prospective cohort study

Abstract

Background: The identification of effective dementia prevention strategies is a major public health priority, due to the enormous and growing societal cost of this condition. Consumption of a Mediterranean diet (MedDiet) has been proposed to reduce dementia risk. However, current evidence is inconclusive and is typically derived from small cohorts with limited dementia cases. Additionally, few studies have explored the interaction between diet and genetic risk of dementia.

Methods: We used Cox proportional hazard regression models to explore the associations between MedDiet adherence, defined using two different scores (Mediterranean Diet Adherence Screener [MEDAS] continuous and Mediterranean diet Pyramid [PYRAMID] scores), and incident all-cause dementia risk in 60,298 participants from UK Biobank, followed for an average 9.1 years. The interaction between diet and polygenic risk for dementia was also tested.

Results: Higher MedDiet adherence was associated with lower dementia risk (MEDAS continuous: HR = 0.77, 95% CI = 0.65-0.91; PYRAMID: HR = 0.86, 95% CI = 0.73-1.02 for highest versus lowest tertiles). There was no significant interaction between MedDiet adherence defined by the MEDAS continuous and PYRAMID scores and polygenic risk for dementia.

Conclusions: Higher adherence to a MedDiet was associated with lower dementia risk, independent of genetic risk, underlining the importance of diet in dementia prevention interventions.

Keywords: Alzheimer’s; Dementia; Genetics; Mediterranean diet; Polygenic risk; Risk factors; UK Biobank.

Fig. 1

Association between MedDiet adherence and risk of dementia (n = 60,298, including 882 dementia cases). MedDiet adherence level was split into tertiles, with the dashed line reflecting the low MedDiet adherence reference group for each MedDiet score

Fig. 2

Association between MedDiet adherence and risk of dementia in sub-group and sensitivity analyses. MedDiet adherence level was split into tertiles, with the dashed line reflecting the low MedDiet adherence reference group for each MedDiet score. Analyses include: A) Primary analyses for the MEDAS, MEDAS continuous and PYRAMID scores (n = 60,298, including 882 dementia cases); B) Including participants with a minimum of 2 dietary reports (n = 38,794, including 479 dementia cases); C) After excluding participants with extreme energy intakes (n = 59,627, including 867 dementia cases); D) Excluding participants with less than 2 years (n = 59,594, including 843 dementia cases) and 5 years (n = 58,196, including 698 dementia cases) follow up; E) Adjusting for potential mediators, including BMI (n = 60,163, including 876 dementia cases), history of depression (n = 58,837, including 851 dementia cases), or stroke (n = 60,298, including 882 dementia cases); F) Stratified into low (n = 21,009, including 261 dementia cases), medium (n = 20,000, including 313 dementia cases) and high (n = 19,273, including 308 dementia cases) genetic risk categories; G) Stratified into APOE4 carriers (n = 16,644, including 467 dementia cases) and non-carriers (n = 43,651, including 415 dementia cases); H) With imputed missing data (n = 196,335, including 5001 dementia cases); I) Restricted to fatal (n = 59,627, including 260 dementia cases) and non-fatal (n = 60,038, including 622 dementia cases) dementia cases; and J) Stratified into higher (n = 33,281, including 430 dementia cases) and lower (n = 27,007, including 452 dementia cases) education status groups

Fig. 3

Association between MedDiet adherence defined by the MEDAS (A), MEDAS continuous (B) and PYRAMID (C) scores and risk of dementia (n = 60,298, including 882 dementia cases) after sequentially removing each MedDiet component from the total score. Hazard ratios and 95% CIs were estimated per point increased in MedDiet score