Risk Factors for Poststroke Cognitive Decline: The REGARDS Study (Reasons for Geographic and Racial Differences in Stroke)

Abstract

Background and purpose: Poststroke cognitive decline causes disability. Risk factors for poststroke cognitive decline independent of survivors' prestroke cognitive trajectories are uncertain.

Methods: Among 22 875 participants aged ≥45 years without baseline cognitive impairment from the REGARDS cohort (Reasons for Geographic and Racial Differences in Stroke), enrolled from 2003 to 2007 and followed through September 2015, we measured the effect of incident stroke (n=694) on changes in cognitive functions and cognitive impairment (Six-Item Screener score <5) and tested whether patient factors modified the effect. Median follow-up was 8.2 years.

Results: Incident stroke was associated with acute declines in global cognition, new learning, verbal memory, and executive function. Acute declines in global cognition after stroke were greater in survivors who were black (P=0.04), men (P=0.04), and had cardioembolic (P=0.001) or large artery stroke (P=0.001). Acute declines in executive function after stroke were greater in survivors who had <high school education versus college graduates (P=0.01). Incident stroke was associated with faster declines in global cognition and executive function but not new learning or verbal memory compared with prestroke slopes. Faster declines in global cognition over years after stroke were greater in survivors who were older (P<0.01), resided outside the Stroke Belt (P=0.005), or had cardioembolic stroke (P=0.01). Faster declines in executive function over years after stroke were greater in survivors who were older (P<0.01) or lacked hypertension (P=0.03).

Conclusions: Incident stroke alters a patient's cognitive trajectory, and this effect is greater with increasing age and cardioembolic stroke. Race, sex, geography, and hypertension status may modify the risk of poststroke cognitive decline.

Keywords: cognition; geography; humans; risk factors; stroke; survivors.

Figure 1. Predicted Mean Changes in Cognition Test Scores Before and After Acute Stroke by Baseline Age: REGARDS Study, 2003 to 2015

We calculated participant-specific (conditional) predicted values for each cognitive score over follow-up time for a 70 year-old black woman living in the Stroke Belt conditional on her experiencing or not experiencing an incident stroke mid-way through the follow-up period (at year 4 for SIS and at year 3 for secondary outcomes). Random effects for this subject-specific prediction were set to zero. Refer to Table 1 for detailed results. The black dashed line indicates the slope for adults without incident stroke. The red line indicates the slope for adults with incident stroke. The blue dashed (reference) line indicates the slope before incident stroke. This line is included to visualize the effects of stroke on the slope of the post-stroke cognitive trajectory relative to control subjects (those without stroke). The SIS analysis is shown in Panel 1A (Age 65) and 1B (Age 75). The adjusted difference in acute decline in global cognition after stroke between participants age 75 and participants age 65: −0.04 points (95% CI, −0.01 to 0.02); P=0.19. The adjusted difference in slope after incident stroke between participants age 75 and participants age 65: −0.04 points per year (95% CI, −0.06 to −0.03); P<0.001. The AFT analysis is shown in Panel 1C (Age 65) and 1D (Age 75). The adjusted difference in acute decline in executive function after stroke between participants age 75 and participants age 65: 0.51 points (95% CI, −0.04 to 1.4); P=0.25. The adjusted difference in slope after incident stroke between participants age 75 and participants age 65: −0.58 points per year (95% CI, −0.94 to −0.22); P=0.002. Values of covariates at baseline were some college education, Stroke Belt residence, income $20,000-$34,999, never smoker, no alcohol use, SBP 120 mmHg, no diabetes present, waist circumference 95 cm, no self-reported stroke, 4-item CES-D score of 0.9 points, fair health status, BMI overweight, mixed urban/rural area, physical activity 1–3 per week, no hypertension, no diabetes, no hyperlipidemia and SIS score of 5 points for SIS prediction and AFT score of 17 points for AFT prediction (mean baseline cognitive scores).