Cardiometabolic Trajectories Preceding Dementia in Community-Dwelling Older Individuals
Authors: Zimu Wu, Lachlan Cribb, Rory Wolfe, Raj C. Shah, Suzanne G. Orchard, Alice Owen, Robyn L. Woods, Swarna Vishwanath, Trevor T.-J. Chong, Kerry M. Sheets, Anne M. Murray, Joanne Ryan
Journal: JAMA Network Open (2025)

Importance Poor cardiometabolic health is a risk factor associated with cognitive impairment in later life, but it remains unclear whether cardiometabolic trajectories can serve as early markers associated with dementia. Objective To compare cardiometabolic trajectories that precede dementia diagnosis with those among individuals without dementia. Design, Setting, and Participants This case-control study analyzed a sample drawn from community-dwelling participants in the Aspirin in Reducing Events in the Elderly (ASPREE) study. Recruitment through primary care physicians occurred between March 2010 and December 2014, with participants followed up for a maximum of 11 years. Dementia cases were matched on sociodemographic characteristics and time of diagnosis to dementia-free controls. Data analysis was performed between February and June 2024. Exposures Body mass index (BMI), waist circumference, systolic and diastolic blood pressure, glucose levels, high- and low-density lipoprotein (HDL and LDL) and total cholesterol levels, and triglyceride levels were measured repeatedly between 2010 and 2022. Main Outcomes and Measures Dementia ( Diagnostic and Statistical Manual of Mental Disorders [ Fourth Edition ] criteria) was adjudicated by an international expert panel. Results Among 5390 participants (mean [SD] age, 76.9 [4.8] years; 2915 women [54.1%]), there were 2655 individuals (49.3%) with less than 12 years of education. The study included 1078 dementia cases and 4312 controls. Up to a decade before diagnosis, dementia cases compared with controls had lower BMI for all years from −7 years (marginal estimate, 27.52 [95% CI, 27.24 to 27.79] vs 28.00 [95% CI, 27.86 to 28.14]; contrast P = 002) to 0 years (marginal estimate, 26.09 [95% CI, 25.81 to 26.36] vs 27.22 [95% CI, 27.09 to 27.36]; contrast P &amp;amp;lt; .001) and lower waist circumference for all years from −10 years (marginal estimate, 95.45 cm [95% CI, 94.33 to 96.57 cm] vs 97.35 cm [95% CI, 96.79 to 97.92 cm]; contrast P = .003) to 0 years (marginal estimate, 93.90 [95% CI, 93.15 cm to 94.64 cm] vs 96.67 cm [95% CI, 96.30 to 97.05 cm]; contrast P &amp;amp;lt; .001); cases also had a faster decline in BMI (linear change β, −0.13 [95% CI, −0.19 to −0.08]) and waist circumference (linear change β, −0.30 cm [95% CI, −0.51 to −0.08 cm]). Compared with controls, cases generally had higher HDL levels, in particular from 5 years (marginal estimate, 62.57 mg/dL [95% CI, 61.59 to 63.56 mg/dL] vs 60.84 mg/dL [95% CI, 60.35 to 61.34 mg/dL]; contrast P = .002) to 3 years (marginal estimate, 62.78 mg/dL [95% CI, 61.82 to 63.74 mg/dL] vs 61.08 mg/dL [95% CI, 60.60 to 61.56 mg/dL]; contrast P = .002) before dementia but with a decline in levels just before diagnosis (linear change β, −0.47 mg/dL [95% CI, −0.86 to −0.07 mg/dL]). Dementia cases had lower systolic blood pressure and triglyceride levels in the decade before diagnosis and higher LDL and total cholesterol levels, but these were not significantly different from controls. Conclusions and Relevance In this study of older individuals, decline in BMI, waist circumference, and HDL occurred up to a decade before dementia diagnosis. These findings provide insights into cardiometabolic changes preceding dementia and the potential for early monitoring and intervention.