Association Between Triglycerides and Risk of Dementia in Community-Dwelling Older Adults: A Prospective Cohort Study

Abstract

Background and objectives: It has been suggested that higher triglyceride levels were associated with a lower risk of Alzheimer disease. This study aimed to examine the association of triglycerides with dementia and cognition change in community-dwelling older adults.

Methods: This prospective longitudinal study used data from the Aspirin in Reducing Events in the Elderly (ASPREE) randomized trial of adults aged 65 years or older without dementia or previous cardiovascular events at enrollment. The main outcome was incident dementia. Other outcomes included changes in composite cognition and domain-specific cognition (global cognition, memory, language and executive function, and psychomotor speed). The association between baseline triglycerides and dementia risk was estimated using Cox proportional hazard models adjusting for relevant risk factors. Linear mixed models were used to investigate cognitive change. The analysis was repeated in a subcohort of participants with available APOE-ε4 genetic data with additional adjustment for APOE-ε4 carrier status and an external cohort (UK Biobank) with similar selection criteria applied.

Results: This study included 18,294 ASPREE participants and 68,200 UK Biobank participants (mean age: 75.1 and 66.9 years; female: 56.3% and 52.7%; median [interquartile range] triglyceride: 106 [80-142] mg/dL and 139 [101-193] mg/dL), with dementia recorded in 823 and 2,778 individuals over a median follow-up of 6.4 and 12.5 years, respectively. Higher triglyceride levels were associated with lower dementia risk in the entire ASPREE cohort (hazard ratio [HR] with doubling of triglyceride: 0.82, 95% CI 0.72-0.94). Findings were similar in the subcohort of participants with APOE-ε4 genetic data (n = 13,976) and in the UK Biobank cohort (HR was 0.82 and 0.83, respectively, all p ≤ 0.01). Higher triglycerides were also associated with slower decline in composite cognition and memory over time (p ≤ 0.05).

Discussion: Older adults with higher triglyceride levels within the normal to high-normal range had a lower dementia risk and slower cognitive decline over time compared with individuals with lower triglyceride levels. Higher triglyceride levels may be reflective of better overall health and/or lifestyle behaviors that would protect against dementia development. Future studies are warranted to investigate whether specific components within the total circulating pool of plasma triglycerides may promote better cognitive function, with the hope of informing the development of new preventive strategies.

Figure 1. Association Between Baseline TG Levels and Risk of Incident Dementia in the ASPREE and UK Biobank

The figure shows restricted cubic splines for the association between TG levels and risk of incident dementia in ASPREE and UK Biobank. The scale of the primary Y-axis (left hand) reflects the values for the adjusted HRs for incident dementia (reference: TG = 100 mg/dL). The scale of the secondary Y-axis (right hand) shows the number of participants at different levels of TG. The solid red line shows multivariable HR with black dash lines denoting corresponding 95% CIs derived from restricted cubic splines regression with 3 knots. The light blue solid line was the reference line for HR of 1.0. The gray bar denotes population distribution based on TG. Cubic splines were adjusted for age, sex, race, country, smoking, alcohol consumption, education level, family history of dementia, diabetes, hypertension, waist circumference, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, statin use, other lipid-lowering medication use, and composite cognitive score at baseline and randomized aspirin in the ASPREE cohorts and adjusted for age, sex, race, smoking, alcohol consumption, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, waist circumference, systolic and diastolic blood pressure, diabetes, and medications for lipid-lowering, blood pressure-lowering, and glucose-lowering in the UK Biobank cohort. *Analysis further adjusted for the carrier status of APOE-ε4 allele. ASPREE = Aspirin in Reducing Events in the Elderly; HR = hazard ratio; TG = triglyceride.

Figure 2. Risk of Incident Dementia by TG Categories

Circles denote adjusted HRs for incident dementia, and error bars denote the corresponding 95% CIs. Adjustment was made for age, sex, race, country, smoking, alcohol consumption, education level, family history of dementia, diabetes, hypertension, waist circumference, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, statin use, other lipid-lowering medication use, and composite cognitive score at baseline and randomized aspirin in the ASPREE cohorts and adjusted for age, sex, race, smoking, alcohol consumption, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, waist circumference, systolic and diastolic blood pressure, diabetes, and medications for lipid-lowering, blood pressure-lowering, and glucose-lowering in the UK Biobank cohort. The TG values at 10th, 50th, and 90th percentile in the overall ASPREE cohort and the subcohort of participants with genotyped data were 62, 106, and 186 mg/dL and in the UK Biobank cohort were 78, 139, and 261 mg/dL. ASPREE = Aspirin in Reducing Events in the Elderly; HR = hazard ratio; TG = triglyceride.

Figure 3. Subgroup Analysis of Dementia by Baseline Characteristics

HR for incident dementia with doubling triglycerides. The size of the squares representing the point estimates of the HRs is proportional to the inverse of the variance of the estimate. Analyses were adjusted for age, sex, race, country, smoking, alcohol consumption, education level, family history of dementia, diabetes, hypertension, waist circumference, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, statin, other lipid-lowering medications, and composite cognitive score at baseline and randomized aspirin, unless used as a stratifying variable. FH = family history; HDL = high-density lipoprotein; HR = hazard ratio; LDL = low-density lipoprotein; WC = waist circumference.