Dementia Risk Significantly Increased After Ischemic Stroke

The association was found independent of vascular risk factors, suggesting a dose-response association between stroke severity and recurrence with risk of dementia.

A recent study found risk of dementia to be significantly increased following ischemic stroke, independent of vascular risk factors. Investigators further posited the potential of a dose-response association of stroke severity and recurrence with risk of dementia.1

A total of 15,379 participants were included from the ongoing Atherosclerosis Risk in Communities (ARIC) prospective cohort study, with a mean age of 54.1 years (standard deviation, 5.8) at baseline. A total of 4110 patients (26.7%) were Black and 11,269 (73.3%) were White. Additionally, 8485 participants (55.2%) were women.

Led by Silvia Koton, PhD, MOccH, RN, FAHA, head, Herczeg Institute on Aging, head, PhD program, department of nursing, the Stanley Steyer School of Health Profession, Tel Aviv University, in Tel Aviv, Israel; and adjunct faculty, department of epidemiology, Johns Hopkins University School of Public Health, in Baltimore, Maryland, investigators concluded that risk of dementia increased with both the number of strokes as well as the severity of strokes. There were National Institutes of Health Stroke Scale (NIHSS) scores available for 1184 of the 1378 strokes (85.9%), with minor strokes defined as a score of 5 or less, mild as a score between 6-10, moderate as a score between 11-15, and severe as a score of 16 or greater.

Among 1378 ischemic strokes and 2860 incident dementia cases in the cohort, risk of dementia by adjusted HR 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, when compared with participants without stroke. Dementia cases were identified through December 31, 2019, and diagnosed 1 year or more after incident stroke for participants with stroke, or at any point after baseline for those that did not have stroke.

Koton et al further found that the median time between ischemic stroke and incident dementia was 7.2 years (interquartile range, 3.7-12.4). In those with stroke, the proportion of dementia risk attributable to stroke was 17.4% (95% CI, 4.8-28.6), which increased with frequency, at 9.1% for 1 stroke (95% CI, –6.4 to 22.5) compared with 53.0% for 2 or more strokes (95% CI, 35.1-65.3). The proportion of dementia risk further increased with stroke severity, at 7.0% for NIHSS scores of 5 or less (95% CI, –12.5 to 21.3) and 50.0% for NIHSS score of 16 or higher (95% CI, 8.3-72.9). After adjusting for sociodemographic characteristics, apolipoprotein E, and vascular risk factors, dementia incidence rates were 0.47 (95% CI, 0.44-0.50) in patients without stroke and 1.21 (95% CI, 1.05-1.40) in patients with stroke.

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“Risk of stroke, and thus recurrent stroke and dementia, is increased in individuals with more vascular risk factors. An estimated 39% of recurrent strokes and 10% of poststroke dementia cases are attributable to vascular risk factors present before the stroke,” Koton et al wrote. “By evaluating these risk factors and their changes and treatment over time, we demonstrated that the risk of dementia was elevated independent of these risk factors for both first and recurrent strokes. Even when risk is reduced poststroke by secondary prevention, the effect of these risk factors (likely present for decades) remains important for dementia risk. In fact, even intensive risk-factor management within the first year after stroke does not improve cognitive outcomes,  indicating the likely need to manage risk factors over years to best impact cognition both poststroke and in the general population.”

The ARIC study included 15,792 community-dwelling individuals from 4 US states: Mississippi, Maryland, Minnesota, and North Carolina. The 15,379 participants included in current analyses were free of stroke and dementia at baseline (1987 to 1989) and were monitored through 2019, when 8544 participants (55.6%) were deceased, and 447 of the 6835 living participants (6.5%) were no longer participating in telephone or in-person assessments.

Limitations were cited as a lack of consistent data in the immediate period poststroke, as well as lack of neuroimaging from the intervening period. Attrition rates were also noted and the potential for survivorship to impact dementia rates, particularly in those with severe of recurrent strokes. Investigators also stated there may have been an underestimation in the rate of early poststroke dementia due to the exclusion of acute changes in cognitive function after early stroke.

1. Koton S, Pike JR, Johansen M, et al. Association of ischemic stroke incidence, severity, and recurrence with dementia in the Atherosclerosis Risk in Communities Cohort Study. JAMA Neurol. Published online January 24, 2022. doi:10.1001/jamaneurol.2021.5080