Association of Ischemic Stroke Incidence, Severity, and Recurrence With Dementia in the Atherosclerosis Risk in Communities Cohort Study

Abstract

Importance: Ischemic stroke is associated with increased risk of dementia, but the association of stroke severity and recurrence with risk of impaired cognition is not well known.

Objective: To examine the risk of dementia after incident ischemic stroke and assess how it differed by stroke severity and recurrence.

Design, setting, and participants: The Atherosclerosis Risk in Communities (ARIC) study is an ongoing prospective cohort of 15 792 community-dwelling individuals from 4 US states (Mississippi, Maryland, Minnesota, and North Carolina). Among them, 15 379 participants free of stroke and dementia at baseline (1987 to 1989) were monitored through 2019. Data were analyzed from April to October 2021. Associations between dementia and time-varying ischemic stroke incidence, frequency, and severity were studied across an average of 4.4 visits over a median follow-up of 25.5 years with Cox proportional hazards models adjusted for sociodemographic characteristics, apolipoprotein E, and vascular risk factors.

Exposures: Incident and recurrent ischemic strokes were classified by expert review of hospital records, with severity defined by the National Institutes of Health Stroke Scale (NIHSS; minor, ≤5; mild, 6-10; moderate, 11-15; and severe, ≥16).

Main outcomes and measures: Dementia cases adjudicated through expert review of in-person evaluations, informant interviews, telephone assessments, hospitalization codes, and death certificates. In participants with stroke, dementia events in the first year after stroke were not counted.

Results: At baseline, the mean (SD) age of participants was 54.1 (5.8) years, and 8485 of 15 379 participants (55.2%) were women. A total of 4110 participants (26.7%) were Black and 11 269 (73.3%) were White. A total of 1378 ischemic strokes (1155 incident) and 2860 dementia cases were diagnosed 1 year or more after incident stroke in participants with stroke, or at any point after baseline in participants without stroke, were identified through December 31, 2019. NIHSS scores were available for 1184 of 1378 ischemic strokes (85.9%). Risk of dementia increased with both the number and severity of strokes. Compared with no stroke, risk of dementia by adjusted hazard ratio was 1.76 (95% CI, 1.49-2.00) for 1 minor to mild stroke, 3.47 (95% CI, 2.23-5.40) for 1 moderate to severe stroke, 3.48 (95% CI, 2.54-4.76) for 2 or more minor to mild strokes, and 6.68 (95% CI, 3.77-11.83) for 2 or more moderate to severe strokes.

Conclusions and relevance: In this study, risk of dementia significantly increased after ischemic stroke, independent of vascular risk factors. Results suggest a dose-response association of stroke severity and recurrence with risk of dementia.

Figure 1.. Flowchart of Participants Selected for Analysis

Figure 2.. Extended Kaplan-Meier Curves of Dementia by National Institutes of Health Stroke Scale (NIHSS) Severity of Incident Ischemic Stroke (N = 15 379)

Extended Kaplan-Meier curves generated using the Simon and Makuch method. Severity of incident ischemic stroke is treated as a time-varying exposure. Consequently, participants do not enter the risk set for ≤10 or ≥11 until the age of incident stroke. Differences in the rates of dementia were statistically significant when comparing participants with stroke to those without stroke (log-rank P < .001; Gehan-Breslow-Wilcoxon P < .001). Rates of dementia among participants >80 years were substantially increased among participants with more severe stroke (NIHSS ≥11) vs without stroke (log-rank trend P < .001; Gehan-Breslow-Wilcoxon trend P < .001). Dementia diagnosis was determined by adjudicated review, telephone interviews, informant interviews, hospitalization records, and death certificates. Only dementia diagnoses with a date more than 1 year poststroke were counted.

Figure 3.. Adjusted Hazard Ratios (aHRs) of Dementia by National Institutes of Health Stroke Scale (NIHSS) Severity of Each Ischemic Stroke Compared With Not Having a Stroke (N = 15 379)

^aIndicates a statistically significant interaction was detected between high school education (P = .01) and minor to mild stroke (NIHSS ≤ 10). HRs and 95% CIs were calculated from cause-specific, multivariable Cox proportional hazards regression models. All models were adjusted for age, sex, race and center, education, apolipoprotein E (APOE) alleles, and global cognition as time-invariant covariates. Body mass index (calculated as weight in kilograms divided by height in meters squared), systolic blood pressure, and total cholesterol at baseline were also included as time-invariant covariates. Atrial fibrillation, cigarette use, diabetes, antihypertensive medication use, and statin use were included as time-varying covariates.