Higher triglyceride levels — a main energy source for the brain — are associated with lower risk for dementia that is not mediated by age, sex, or APOE-ε4 allele status, a large study of community-dwelling older adults suggests.
The analysis included 18,294 participants, median age 75 years and median triglyceride level 106 mg/dL, from the ASPirin in Reducing Events in the Elderly (ASPREE) study, a placebo-controlled, randomized trial of daily low-dose aspirin in older people without dementia or history of cardiovascular disease (CVD) at recruitment.
Researchers repeated their main analyses in a sub-cohort of 13,976 subjects with APOE-ε4 genetic data, cigna pharmacies and an external cohort of 68,200 participants, mean age 66.9 years and a median non-fasting triglyceride of 139 mg/dL, from the UK biobank, followed for a median of 12.5 years.
The main outcome was incident dementia over 6.4 years and secondary outcomes included changes in composite cognitive function and domain-specific cognition.
Researchers controlled for a number of potential confounders, including age, sex, race, smoking, alcohol consumption, education, family history of dementia, diabetes, hypertension, and statin use.
Every doubling of baseline triglycerides was associated with an 18% lower risk of incident dementia across the entire study cohort (adjusted hazard ratio [aHR], 0.82) and in participants with genotypic data (aHR, 0.82) and a 17% lower risk in the external UK Biobank cohort (aHR, 0.83) (P ≤ .01 for all).
In the entire cohort, the risk for dementia was 15% lower in those with triglyceride levels at 63-106 mg/dL (aHR, 0.85); 24% lower in those at 107-186 mg/dL (aHR, 0.76); and 36% lower for those with levels higher than 187 mg/dL (aHR, 0.64) compared with individuals with levels below 62 mg/dL (P for trend <.001).
The direction and magnitude of the inverse association between triglycerides and dementia risk were not modified by age, sex, or risk factors related to triglycerides or dementia.
In the entire study cohort, higher triglyceride levels were significantly associated with slower decline in global cognition (P = .02), composite cognition (P = .03), and a borderline significantly slower decline in episodic memory (P = .05).
“Triglyceride levels may serve as a useful predictor for dementia risk and cognitive decline in older populations,” the investigators write. Higher triglyceride levels may reflect better overall health and/or lifestyle behaviors that protect against dementia, they add.
The study was led by Zhen Zhou, School of Public Health and Preventive Medicine, Monash University, Melbourne, Australia. It was published online October 25 in Neurology.
The study can’t establish a causal relationship between triglyceride levels and dementia or fully exclude reverse causality. As most ASPREE participants had normal to high normal triglyceride levels, the results can’t be generalized to those with severe hypertriglyceridemia. The findings are unique to older people without CVD and may not be generalizable to other populations.
The study received support from the Royal Australian College of General Practitioners (RACGP)/HCF Research Foundation. Zhou reported receiving salary from the RACGP/HCF Research Foundation. See the original article for disclosures of other authors.
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