Ischemic Stroke Incidence and Severity and Poststroke Cognitive Decline and Incident Dementia
Year: 2026
Type: article
Abstract: Importance: The association between stroke severity and dementia is well established. However, reports on trajectories of cognitive decline comparing stroke survivors with individuals without stroke in large cohorts are insufficient. Objectives: To examine associations of ischemic stroke incidence and severity with cognitive decline and dementia risk and to explore whether vascular risk factors modify these associations. Design, Setting, and Participants: This cohort study pooled longitudinal data on cognitive function of participants aged 45 years or older and without stroke and dementia at baseline from 3 US prospective cohorts: the Atherosclerosis Risk in Communities study (1987-2019), Framingham Offspring Study (1971-2019), and Reasons for Geographic and Racial Differences in Stroke study (2003-2019). First definite ischemic strokes were reported in each cohort using consistent protocols, with severity defined using the National Institutes of Health Stroke Scale (NIHSS). The data analysis was completed February 27, 2026. Exposure: Incident ischemic stroke categorized as minor (NIHSS 0-5), mild to moderate (NIHSS 6-10), or moderate to severe (NIHSS ≥11). Main Outcomes and Measures: The primary outcomes were decline in global cognition and incident dementia. Secondary outcomes were changes in memory and executive function. Multivariable linear mixed-effects models were used to test the association of stroke incidence and severity with cognitive decline. Results: A total of 42 342 participants from the pooled cohorts were included (mean [SD] age, 61.3 [9.8] years; 55.0% female). Longitudinal cognitive testing data were available for a median of 11.1 years (range, 0-29.7 years) with 397 344 person-years of observation for dementia incidence. Stroke severity data were available for 1055 of 1505 first-ever ischemic stroke survivors (70.1%). Compared with participants with no stroke, adjusted hazard ratios for incident dementia were 1.93 (95% CI, 1.52-2.45) for NIHSS 0 to 5, 3.26 (95% CI, 1.93-5.53) for NIHSS 6 to 10, and 5.06 (95% CI, 2.71-9.45) for NIHSS 11 or higher. Over the follow-up, higher stroke severity was associated with progressively steeper cognitive declines across all domains, with more prevalent dose-response associations for global cognition (ranging from a mean -0.18 [95% CI, -0.19 to -0.18] points per year for no stroke to -0.58 [95% CI, -0.73 to -0.42] points per year for moderate to severe stroke) and memory (ranging from a mean -0.15 [95% CI, -0.16 to -0.14] points per year for no stroke to -0.36 [95% CI, -0.51 to -0.21] points per year for moderate to severe stroke) than for executive function (ranging from a mean -0.33 [95% CI, -0.34 to -0.32] points per year for no stroke to -0.52 [95% CI, -0.66 to -0.39] points per year for moderate to severe stroke). Conclusions and Relevance: This large cohort study of participants from 3 prospective cohorts found that greater stroke severity was associated with substantially elevated dementia risk and accelerated decline in global cognition, memory, and executive function. These findings underscore the critical importance of stroke prevention, particularly severe stroke, and identifying mechanisms that may link stroke to cognitive decline.
Source: JAMA Network Open
Authors: Silvia Koton, Alden L. Gross, Hugo J. Aparicio, Alexa S. Beiser, Emily M. Briceño, Josef Coresh, Mitchell S. V. Elkind, Bruno J. Giordani, Rebecca F. Gottesman, Rodney A. Hayward, Virginia J. Howard, Michelle C. Johansen, Ronald M. Lazar, Mellanie V. Springer, Robert J. Stanton, Jeremy Sussman, Hang Wang, Rachael T. Whitney, Wen Ye, Deborah A. Levine
Institutions: Johns Hopkins University, Tel Aviv University, New York University, Boston University, University of Michigan, American Heart Association, National Institute of Neurological Disorders and Stroke, VA Ann Arbor Healthcare System, University of Alabama at Birmingham, Johns Hopkins Medicine, University of Cincinnati
Language: English
Subfield: Psychiatry and Mental health
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $3,000
Funders: U.S. Department of Health and Human Services, Brain Research Foundation, McKnight Foundation, Evelyn F. McKnight Brain Research Foundation, Northwestern University, Eisai, National Institutes of Health, National Institute on Aging, National Heart, Lung, and Blood Institute, National Institute on Deafness and Other Communication Disorders, National Institute of Neurological Disorders and Stroke
Awards: G1194882026, G124418500, VCID and Stroke in a Bi-racial National Cohort, G1518371162, ARIC Neurocognitive Study (ARIC-NCS) Renewal, G1623886336, G1632931450, G1671748052, G1735617348, G17707931, G1773517813, G1851406594, G1924893021, G2103396735, G2195207551, G2287024733, G2339050794, G2784128823, G2883369658, G2889674361, G2991237628, G3263181819, G351949366, G354227350, G3642446616, G3931319179, G3938966547, G3978702139, G421917476, G4397751285, G4498387036, G456869620, ARIC Neurocognitive Study (ARIC-NCS) Renewal UNC 4 of 5, G4782323294, G4819198047, G4846232932, G4961862235, G4976486911, ARIC Neurocognitive Study (ARIC-NCS) Renewal 4 of 5, G5104152550, The Effect of Vascular Risk Factors on Risk of Alzheimer's Disease and Related Dementias after Stroke (STROKE COG), G5267790454, G5364873420, G54938809, G557577377, Aortic Dysfunction, Pulsatile Stress and Target Organ Damage in Framingham, G5792112273, G583528397, G5954722477, G6265038979, G6418484092, ARIC Neurocognitive Study (ARIC-NCS) Renewal 2 of 5, ARIC Neurocognitive Study (ARIC-NCS), G6811927220, G6978868085, G7114400168, G7243995979, G7276788223, G748486544, G7491785057, G8008717573, G8773483559, G8946053683, G9000005794, G9000008877, G9000028535, G9000076324, G9000079369, G9000086042, Johns Hopkins Alzheimer's Disease Research Center, G939786002
OpenAlex ID: W7154612933
