👤 Aleix Sala-Vila

Early-onset dementia (EOD, defined as diagnosis < age 65) imposes a high socio-economic burden. It is less prevalent and less investigated than late-onset dementia (LOD). Observational data indicate that many EOD cases are associated with potentially modifiable risk factors, yet the relationship between diet and EOD has been under-explored. Omega-3 fatty acids are promising dietary factors for dementia prevention; however, existing research has primarily focused on cohorts aged >65. We examined the associations between omega-3 blood levels (which objectively reflect dietary intake) and incident EOD by leveraging data from the UK Biobank cohort. We included participants aged 40-64, free of dementia at baseline and for whom plasma omega-3 levels and relevant covariates were available. We modeled the relationships between the three omega-3 exposures (total omega-3, DHA, and non-DHA omega-3) and incident EOD with quintiles (Q) and continuous linear relationships. We constructed Cox proportional hazards adjusting for sex, age at baseline and APOE-ε4 allele load, besides other lifestyle variables reported to relate to incident EOD. We also assessed the interaction between each exposure of interest and APOE-ε4 allele load. The study included 217,122 participants. During the mean follow-up of 8.3 years, 325 incident EOD cases were ascertained. Compared to participants at Q1 of total omega-3, those at Q4 and Q5 showed a statistically significantly lower risk of EOD (Q4, hazard ratio [95 % confidence interval] = 0.62 [0.43, 0.89]; Q5, 0.60 [0.42, 0.86]). A statistically significant inverse association was also observed for total omega-3 as a continuous variable. Compared to participants at Q1 of DHA, those at Q5 of non-DHA showed a significant lower risk of EOD. A statistically significant lower risk was observed in Q3, Q4 and Q5 of non-DHA omega-3. Finally, we observed no evidence of interaction omega-3 × APOE-ε4 allele load. This study expands the evidence of a beneficial association of omega-3 and LOD to EOD as well. These findings suggest that an increased intake of omega-3 fatty acids earlier in life may slow the development of EOD. Additional research is needed to confirm our findings, particularly in more diverse populations. Show less

Cognitive decline, and more specifically Alzheimer's disease, continues to increase in prevalence globally, with few, if any, adequate preventative approaches. Several tests of cognition are utilized in the diagnosis of cognitive decline that assess executive function, short- and long-term memory, cognitive flexibility, and speech and motor control. Recent studies have separately investigated the genetic component of both cognitive health, using these measures, and circulating fatty acids. We aimed to examine the potential moderating effect of main species of ω-3 polyunsaturated fatty acids (PUFAs) on an individual's genetically conferred risk of cognitive decline. The Offspring cohort from the Framingham Heart Study was cross-sectionally analyzed in this genome-wide interaction study (GWIS). Our sample included all individuals with red blood cell ω-3 PUFA, genetic, cognitive testing (via Trail Making Tests [TMTs]), and covariate data (N = 1620). We used linear mixed effects models to predict each of the 3 cognitive measures (TMT A, TMT B, and TMT D) by each ω-3 PUFA, single nucleotide polymorphism (SNP) (0, 1, or 2 minor alleles), ω-3 PUFA by SNP interaction term, and adjusting for sex, age, education, APOE ε4 genotype status, and kinship (relatedness). Our analysis identified 31 unique SNPs from 24 genes reaching an exploratory significance threshold of 1×10 In this GWIS of ω-3 PUFA species on cognitive outcomes, we identified 8 unique genes with plausible biology suggesting individuals with specific polymorphisms may have greater potential to benefit from increased ω-3 PUFA intake. Additional replication in prospective settings with more diverse samples is needed. Show less