Associations Between Stroke Type, Ischemic Stroke Subtypes, and Poststroke Cognitive Trajectories

Deborah A Levine^{1

2}, Rachael T Whitney¹, Wen Ye³, Emily M Briceño⁴, Alden L Gross⁵, Bruno J Giordani⁶, Jeremy B Sussman^{1

7}, Ronald M Lazar⁸, Virginia J Howard⁹, Hugo J Aparicio¹⁰, Alexa S Beiser^{10

11}, Mitchell S V Elkind¹², Rebecca F Gottesman¹³, Silvia Koton^{5

14}, Sarah T Pendlebury¹⁵, Adam S Kollipara¹, Mellanie V Springer², Sudha Seshadri¹⁶, Jose R Romero¹⁰, Annette L Fitzpatrick¹⁷, W T Longstreth Jr^{17

18}, Rodney A Hayward^{1

7}

Affiliations

¹ Departments of Internal Medicine (D.A.L., R.T.W., J.B.S., A.S.K., R.A.H.), University of Michigan, Ann Arbor.
² Neurology (D.A.L., M.V.S.), University of Michigan, Ann Arbor.
³ Biostatistics (W.Y.), University of Michigan, Ann Arbor.
⁴ Physical Medicine and Rehabilitation (E.M.B.), University of Michigan, Ann Arbor.
⁵ Department of Epidemiology, Johns Hopkins University, Baltimore, MD (A.L.G., S.K.).
⁶ Psychiatry (B.J.G.), University of Michigan, Ann Arbor.
⁷ VA Ann Arbor Healthcare System, MI (J.B.S., R.A.H.).
⁸ Departments of Neurology (R.M.L.), University of Alabama at Birmingham.
⁹ Epidemiology (V.J.H.), University of Alabama at Birmingham.
¹⁰ Departments of Neurology (H.J.A., A.S.B., J.R.R.), Boston University, MA.
¹¹ Biostatistics (A.S.B.), Boston University, MA.
¹² Department of Neurology, Columbia University, New York, NY (M.S.V.E.).
¹³ Stroke Branch, National Institute of Neurological Disorders and Stroke, Bethesda, MD (R.F.G.).
¹⁴ Department of Nursing, Tel Aviv University, Israel (S.K.).
¹⁵ Nuffield Department of Clinical Neurosciences, University of Oxford, United Kingdom; National Institute for Health and Care Research (NIHR) Biomedical Research Centre, Departments of Medicine and Geratology, Oxford University Hospitals National Health Service (NHS) Foundation Trust, United Kingdom (S.T.P.).
¹⁶ Department of Neurology, University of Texas San Antonio (S.S.).
¹⁷ Departments of Epidemiology (A.L.F., W.T.L.), University of Washington, Seattle.
¹⁸ Neurology (W.T.L.), University of Washington, Seattle.

PMID: 40062407
PMCID: PMC12101623 (available on 2026-04-01)
DOI: 10.1161/STROKEAHA.124.047640

Associations Between Stroke Type, Ischemic Stroke Subtypes, and Poststroke Cognitive Trajectories

Deborah A Levine et al. Stroke. 2025 Apr.

. 2025 Apr;56(4):898-907.

doi: 10.1161/STROKEAHA.124.047640. Epub 2025 Mar 10.

Authors

Affiliations

¹ Departments of Internal Medicine (D.A.L., R.T.W., J.B.S., A.S.K., R.A.H.), University of Michigan, Ann Arbor.
² Neurology (D.A.L., M.V.S.), University of Michigan, Ann Arbor.
³ Biostatistics (W.Y.), University of Michigan, Ann Arbor.
⁴ Physical Medicine and Rehabilitation (E.M.B.), University of Michigan, Ann Arbor.
⁵ Department of Epidemiology, Johns Hopkins University, Baltimore, MD (A.L.G., S.K.).
⁶ Psychiatry (B.J.G.), University of Michigan, Ann Arbor.
⁷ VA Ann Arbor Healthcare System, MI (J.B.S., R.A.H.).
⁸ Departments of Neurology (R.M.L.), University of Alabama at Birmingham.
⁹ Epidemiology (V.J.H.), University of Alabama at Birmingham.
¹⁰ Departments of Neurology (H.J.A., A.S.B., J.R.R.), Boston University, MA.
¹¹ Biostatistics (A.S.B.), Boston University, MA.
¹² Department of Neurology, Columbia University, New York, NY (M.S.V.E.).
¹³ Stroke Branch, National Institute of Neurological Disorders and Stroke, Bethesda, MD (R.F.G.).
¹⁴ Department of Nursing, Tel Aviv University, Israel (S.K.).
¹⁵ Nuffield Department of Clinical Neurosciences, University of Oxford, United Kingdom; National Institute for Health and Care Research (NIHR) Biomedical Research Centre, Departments of Medicine and Geratology, Oxford University Hospitals National Health Service (NHS) Foundation Trust, United Kingdom (S.T.P.).
¹⁶ Department of Neurology, University of Texas San Antonio (S.S.).
¹⁷ Departments of Epidemiology (A.L.F., W.T.L.), University of Washington, Seattle.
¹⁸ Neurology (W.T.L.), University of Washington, Seattle.

PMID: 40062407
PMCID: PMC12101623 (available on 2026-04-01)
DOI: 10.1161/STROKEAHA.124.047640

Abstract

Background: It is unclear how poststroke cognitive trajectories differ by stroke type and ischemic stroke subtype. We studied associations between stroke types (ischemic and hemorrhagic), ischemic stroke subtypes (cardioembolic, large artery atherosclerotic, lacunar/small vessel, and cryptogenic/other determined causes), and poststroke cognitive decline.

Methods: We pooled participants from 4 US cohort studies (1971-2019). Outcomes were change in global cognition (primary) and changes in executive function and memory (secondary). Outcomes were standardized as T scores (mean [SD], 50 [10]); a 1-point difference represents a 0.1 SD difference in cognition. The median follow-up for the primary outcome was 6.0 (interquartile range, 3.2-9.2) years. Linear mixed-effects models estimated changes in cognition after stroke.

Results: We identified 1143 dementia-free individuals with acute stroke during follow-up: 1061 (92.8%) ischemic, 82 (7.2%) hemorrhagic, 49.9% female, and 30.8% Black. The median age at stroke was 74.1 (interquartile range, 68.6-79.3) years. On average, ischemic stroke survivors showed declines in global cognition (-0.35 [95% CI, -0.43 to -0.27] points/y; P<0.001), executive function (-0.48 [95% CI, -0.59 to -0.36] points/y; P<0.001), and memory (-0.27 [95% CI, -0.36 to -0.19] points/y; P<0.001). Poststroke declines in global cognition, executive function, and memory did not differ between hemorrhagic and ischemic stroke survivors. Differences in poststroke cognitive slope between hemorrhagic and ischemic stroke survivors were global cognition (0.02 [95% CI, -0.21 to 0.26] points/y; P=0.85), executive function (-0.13 [95% CI, -0.48 to 0.23] points/y; P=0.48), and memory (0.19 [95% CI, -0.05 to 0.43] points/y; P=0.12). On average, small vessel stroke survivors showed declines in global cognition (-0.33 [95% CI, -0.49 to -0.16] points/y; P<0.001), executive function (-0.44 [95% CI, -0.68 to -0.19] points/y; P<0.001), and memory (-0.19 [95% CI, -0.35 to -0.03] points/y; P=0.02). Poststroke cognitive declines did not differ between small vessel survivors and survivors of other ischemic stroke subtypes.

Conclusions: Stroke survivors had cognitive decline in multiple domains. Declines did not differ by stroke type or ischemic stroke subtype.

Keywords: blood pressure; cholesterol; cognition; glucose; stroke.

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Conflict of interest statement

Drs Levine, Aparicio, Gross, Briceño, Beiser, Seshadri, Romero, Hayward, Giordani, Springer, and Lazar report funding from the National Institutes of Health. Dr Levine reports personal fees from Northeastern University. Dr Aparicio reports compensation from the Alzheimer’s Association and grants from the American Academy of Neurology. Dr Pendlebury reports funding from the National Institute for Health Research Oxford Biomedical Research Centre. Dr Gottesman reports funding from the National Institute of Neurological Disorders and Stroke Intramural Research Program. Dr Sussman reports compensation from the State of Michigan Department of Health and Human Services for consultant services. Dr Lazar reports compensation from DiaMedica Therapeutics Inc for consultant services, compensation from EISAI INC for consultant services, and employment by the Department of Neurology, University of Alabama at Birmingham. Dr Springer reports travel support from Oregon Health and Science University. Dr Romero reports compensation from the Population Health Research Institute for data and safety monitoring services, service as Chair of Diversity, Equity and Inclusion committee for the American Stroke Association, and compensation from Brainomix for other services. Dr Fitzpatrick reports compensation from the National Institutes of Health Office of the Director for data and safety monitoring services. The other authors report no conflicts.

Update of

Associations Between Stroke Type, Ischemic Stroke Subtypes, and Post-Stroke Cognitive Trajectories.
Levine DA, Whitney RT, Ye W, Briceño EM, Gross AL, Giordani BJ, Sussman JB, Lazar RM, Howard VJ, Aparicio HJ, Beiser AS, Elkind MSV, Gottesman RF, Koton S, Pendlebury ST, Kollipara AS, Springer MV, Seshadri S, Romero JR, Fitzpatrick AL, Longstreth WT Jr, Hayward RA. Levine DA, et al. medRxiv [Preprint]. 2024 May 1:2024.04.29.24306600. doi: 10.1101/2024.04.29.24306600. medRxiv. 2024. Update in: Stroke. 2025 Apr;56(4):898-907. doi: 10.1161/STROKEAHA.124.047640. PMID: 38903102 Free PMC article. Updated. Preprint.

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Associations Between Stroke Type, Ischemic Stroke Subtypes, and Poststroke Cognitive Trajectories

Affiliations

Associations Between Stroke Type, Ischemic Stroke Subtypes, and Poststroke Cognitive Trajectories

Authors

Affiliations

Abstract

Conflict of interest statement

Update of

References

MeSH terms

Grants and funding

LinkOut - more resources

Full Text Sources

Medical