DOI: 10.1002/alz.074224 ISSN: 1552-5260

Associations between Distinct Trajectories of Cardiometabolic Risk Factors (Hypertension, Hypercholesterolemia, and Diabetes) over 15 Years Preceding Dementia and Incidence of Dementia

Dianxu Ren, Oscar L. Lopez, Jennifer H Lingler, Yvette Conley
  • Psychiatry and Mental health
  • Cellular and Molecular Neuroscience
  • Geriatrics and Gerontology
  • Neurology (clinical)
  • Developmental Neuroscience
  • Health Policy
  • Epidemiology



Cardiometabolic Risk Factors (Hypertension, Hypercholesterolemia, and Diabetes) have been reported inconsistently to associate with dementia, with both increased and decreased risks. The purpose of this study was to examine longitudinal distinct trajectories of cardiometabolic risk factors over 15 years preceding dementia with incident dementia using the large national dataset from National Alzheimer’s Coordinating Center (NACC).


We used NACC dataset from 2005 to December 2020 and performed a nested case‐control study (up to 1 to 5 match). The sample included 720 cases of all‐causes dementia with at least 5–years follow‐up time preceding dementia diagnosis, and 2526 non‐dementia controls matched on age, sex, race, education and baseline cognitive status. Group‐based trajectory models were applied to identify longitudinal distinct trajectory groups of binary status measures (absent/inactive vs. recent/active) of hypertension, hypercholesterolemia and diabetes among this sample. Conditional logistic regression models were used to evaluate the effect of distinct trajectories of each cardiometabolic risk factor, APOE genotype and the interaction between them with incident dementia.


For the case group (n = 720), mean age at enrollment was 75.5 years and average education in years was 15.6, participants were more female (58.7%), non‐Hispanic white (87.1%) and healthy cognitive status at initial visit (61.9%). All three binary outcome trajectory models identified similar three trajectory groups over 15 years preceding dementia: “low‐flat,” “low‐to‐high,” and “high‐flat”. Conditional logistic regression model revealed no significant main effects of hypercholesterolemia and hypertension as well as no interaction between them and APOE genotype on the incidence of dementia. However, there is borderline significant effect of diabetes trajectory group on the incidence of dementia. Comparing to “low‐flat” diabetes trajectory group, “high‐flat” group were more likely to develop dementia [OR = 1.32, 95% CI (0.99‐1.76), P = 0.056] after controlling APOE genotype.


Our findings suggest the existence of distinct trajectories of cardiometabolic risk factors preceding incident dementia. Active diabetes status may play an important role for developing dementia especially those who are with long‐term diabetes are with greater risk for the incidence of dementia.

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