Trajectory of Cognitive Decline After Incident Stroke

Abstract

Importance: Cognitive decline is a major cause of disability in stroke survivors. The magnitude of survivors' cognitive changes after stroke is uncertain.

Objective: To measure changes in cognitive function among survivors of incident stroke, controlling for their prestroke cognitive trajectories.

Design, setting, and participants: Prospective study of 23,572 participants 45 years or older without baseline cognitive impairment from the Reasons for Geographic and Racial Differences in Stroke (REGARDS) cohort, residing in the continental United States, enrolled 2003-2007 and followed up through March 31, 2013. Over a median follow-up of 6.1 years (interquartile range, 5.0-7.1 years), 515 participants survived expert-adjudicated incident stroke and 23,057 remained stroke free.

Exposure: Time-dependent incident stroke.

Main outcomes and measures: The primary outcome was change in global cognition (Six-Item Screener [SIS], range, 0-6). Secondary outcomes were change in new learning (Consortium to Establish a Registry for Alzheimer Disease Word-List Learning; range, 0-30), verbal memory (Word-List Delayed Recall; range, 0-10), and executive function (Animal Fluency Test; range, ≥0), and cognitive impairment (SIS score <5 [impaired] vs ≥5 [unimpaired]). For all tests, higher scores indicate better performance.

Results: Stroke was associated with acute decline in global cognition (0.10 points [95% CI, 0.04 to 0.17]), new learning (1.80 points [95% CI, 0.73 to 2.86]), and verbal memory (0.60 points [95% CI, 0.13 to 1.07]). Participants with stroke, compared with those without stroke, demonstrated faster declines in global cognition (0.06 points per year faster [95% CI, 0.03 to 0.08]) and executive function (0.63 points per year faster [95% CI, 0.12 to 1.15]), but not in new learning and verbal memory, compared with prestroke slopes. Among survivors, the difference in risk of cognitive impairment acutely after stroke, compared with immediately before stroke, was not statistically significant (odds ratio, 1.32 [95% CI, 0.95 to 1.83]; P = .10); however, there was a significantly faster poststroke rate of incident cognitive impairment compared with the prestroke rate (odds ratio, 1.23 per year [95% CI, 1.10 to 1.38]; P < .001). For a 70-year-old black woman with average values for all covariates at baseline, stroke at year 3 was associated with greater incident cognitive impairment: absolute difference of 4.0% (95% CI, -1.2% to 9.2%) at year 3 and 12.4% (95% CI, 7.7% to 17.1%) at year 6.

Conclusions and relevance: Incident stroke was associated with an acute decline in cognitive function and also accelerated and persistent cognitive decline over 6 years.

Figure 1. Participant Cohort

Abbreviations: SIS=Six-Item Screener test of global cognitive function. *Categories for missing data on covariates are not mutually exclusive. Missing data for covariates included diabetes (n=909), alcohol use (n=459), 4-item CES-D (n=191), waist circumference (n=184), smoking (n=98), baseline history of self-reported stroke (n=80), blood pressure (n=74), health status (n=43), and education (n=15).

Figure 2. Predicted Mean Change in Cognitive Function Test Scores before and after Acute Stroke: REGARDS Study, 2003–2013

Participant-specific (conditional) predicted values of cognition were calculated for a 70 year-old black woman with the average values of all covariates at baseline (high school education, stroke belt residence, income <$20,000, never smoker, no alcohol use, SBP 135 mm Hg, diabetes present, waist circumference 95 cm, no self-reported stroke, CES-D score of 0.9 points, fair health status, and SIS score of 5 points). Random effects for this prediction were set to zero. Linear mixed-effects models included a random intercept, random slope, calendar time, and adjust for time-varying incident stroke, time since incident stroke, and baseline values of cognitive scores, age, sex, race, race*time (Word-List Learning and Word-List Delayed Recall only), education, region, systolic blood pressure, cigarette smoking, waist circumference, diabetes, self-reported stroke, depressive symptoms, income, alcohol use, and self-reported health status. The grey line shows the trajectory for stroke-free adults. The blue line shows the trajectory for adults with incident stroke. The red line shows the prestroke rate of cognitive decline due to cognitive aging. The SIS analysis included 515 participants with incident stroke and 23,057 participants without incident stroke during follow-up. The WLL analysis included 107 participants with incident stroke and 10,214 participants without incident stroke during follow-up. The WLD analysis included 102 participants with incident stroke and 9,951 participants without incident stroke during follow-up. The AFT analysis included 120 participants with incident stroke and 11,093 participants without incident stroke during follow-up. The small increase in AFT scores at the time of stroke was not significant.