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Independent and joint effects of vascular and cardiometabolic risk factor pairs for risk of all-cause dementia: a prospective population-based study

  • C. Elizabeth Shaaban (a1) (a2), Yichen Jia (a3), Chung-Chou H. Chang (a3) (a4) and Mary Ganguli (a1) (a5) (a6)



To assess independent and joint effects of pairs of vascular and cardiometabolic risk factors (VCMRFs) in relation to risk of all-cause dementia.


Population-based longitudinal cohort study of cognitive impairment. We used an algorithm to select pairs of VCMRFs and tested their joint effects in time-dependent Cox models. We used attributable proportions (AP) to measure the proportion of risk from interactions beyond any additive effect.


Economically depressed small-town population.


Adults age 65+ years with up to 10 yearly study visits (N=1701, median (Q1, Q3) age, 78 (71.0, 83.0), 62.3% female, 94.9% white).


Among 1701 participants free from prevalent dementia with at least one follow-up visit, 109 developed incident all-cause dementia. In pairings of APOE*4 with hypertension (HTN) and congestive heart failure (CHF), the variables contributed independently and additively to all-cause dementia risk. In pairings of APOE*4 with stroke and stroke with CHF, the variables demonstrated independent contributions to all-cause dementia risk; their joint effects showed excess detriment demonstrating synergistic interactions (joint HR [95% CI]: 28.33 [6.74, 119.01] and 50.30 [14.57, 173.57] respectively, fully adjusted models). Physical activity (PA) was independently associated with lower all-cause dementia risk when paired with APOE*4, stroke, and CHF in unadjusted models; these associations did not survive covariate adjustment. The joint effect of low PA and APOE*4 was associated with additively increased all-cause dementia risk (joint HR [95% CI]: 4.61 [2.07, 10.23], fully adjusted model).


Reduction of VCMRFs, including low PA, could be valuable for dementia prevention, especially among APOE*4 carriers.


Corresponding author

Correspondence should be addressed to: C. Elizabeth Shaaban, Department of Epidemiology, Graduate School of Public Health, 130 DeSoto Street, 5121B Public Health Building, Pittsburgh, PA 15261. Phone: (412)-383-2623; E-mail:


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Independent and joint effects of vascular and cardiometabolic risk factor pairs for risk of all-cause dementia: a prospective population-based study

  • C. Elizabeth Shaaban (a1) (a2), Yichen Jia (a3), Chung-Chou H. Chang (a3) (a4) and Mary Ganguli (a1) (a5) (a6)


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