Associations Between Vascular Risk Factor Levels and Cognitive Decline Among Stroke Survivors

Author:

Levine Deborah A.123,Chen Bingxin4,Galecki Andrzej T.15,Gross Alden L.6,Briceño Emily M.17,Whitney Rachael T.1,Ploutz-Snyder Robert J.4,Giordani Bruno J.8,Sussman Jeremy B.139,Burke James F.10,Lazar Ronald M.11,Howard Virginia J.12,Aparicio Hugo J.1314,Beiser Alexa S.131415,Elkind Mitchell S. V.1617,Gottesman Rebecca F.18,Koton Silvia619,Pendlebury Sarah T.2021,Sharma Anu1,Springer Mellanie V.23,Seshadri Sudha1422,Romero Jose R.1314,Hayward Rodney A.139

Affiliation:

1. Department of Internal Medicine and Cognitive Health Services Research Program, University of Michigan, Ann Arbor

2. Department of Neurology and Stroke Program, University of Michigan, Ann Arbor

3. Institute for Healthcare Policy and Innovation, University of Michigan, Ann Arbor

4. Department of Nursing, University of Michigan, Ann Arbor

5. Department of Biostatistics, University of Michigan, Ann Arbor

6. Department of Epidemiology, Johns Hopkins Bloomberg School Public Health, Baltimore, Maryland

7. Department of Physical Medicine and Rehabilitation, University of Michigan, Ann Arbor

8. Department of Psychiatry and Michigan Alzheimer’s Disease Center, University of Michigan, Ann Arbor

9. VA Ann Arbor Healthcare System, Ann Arbor, Michigan

10. Department of Neurology, Ohio State University College of Medicine, Columbus

11. Department of Neurology and Evelyn F. McKnight Brain Institute, Heersink School of Medicine, University of Alabama at Birmingham

12. Department of Epidemiology, University of Alabama at Birmingham School of Public Health

13. Department of Neurology, Boston University School of Medicine, Boston, Massachusetts

14. Framingham Heart Study, National Heart, Lung, and Blood Institute, Framingham, Massachusetts

15. Department of Biostatistics, Boston University School of Public Health, Boston, Massachusetts

16. Department of Neurology, Vagelos College of Physicians and Surgeons, Columbia University, New York, New York

17. Department of Epidemiology, Mailman School of Public Health, Columbia University, New York, New York

18. Stroke Branch, National Institute of Neurological Disorders and Stroke, Bethesda, Maryland

19. Department of Nursing, The Stanley Steyer School of Health Professions, Tel Aviv University, Tel Aviv, Israel

20. Wolfson Centre for Prevention of Stroke and Dementia, Nuffield Department of Clinical Neurosciences, University of Oxford, Oxford, United Kingdom

21. NIHR Biomedical Research Centre, Departments of Medicine and Geratology, Oxford University Hospitals NHS Foundation Trust, Oxford, United Kingdom

22. Department of Neurology and Glenn Biggs Institute for Alzheimer’s and Neurodegenerative Diseases, Joe R. and Teresa Lozano Long School of Medicine, University of Texas San Antonio

Abstract

ImportanceIncident stroke is associated with accelerated cognitive decline. Whether poststroke vascular risk factor levels are associated with faster cognitive decline is uncertain.ObjectiveTo evaluate associations of poststroke systolic blood pressure (SBP), glucose, and low-density lipoprotein (LDL) cholesterol levels with cognitive decline.Design, Setting, and ParticipantsIndividual participant data meta-analysis of 4 US cohort studies (conducted 1971-2019). Linear mixed-effects models estimated changes in cognition after incident stroke. Median (IQR) follow-up was 4.7 (2.6-7.9) years. Analysis began August 2021 and was completed March 2023.ExposuresTime-dependent cumulative mean poststroke SBP, glucose, and LDL cholesterol levels.Main Outcomes and MeasuresThe primary outcome was change in global cognition. Secondary outcomes were change in executive function and memory. Outcomes were standardized as t scores (mean [SD], 50 [10]); a 1-point difference represents a 0.1-SD difference in cognition.ResultsA total of 1120 eligible dementia-free individuals with incident stroke were identified; 982 (87.7%) had available covariate data and 138 (12.3%) were excluded for missing covariate data. Of the 982, 480 (48.9%) were female individuals, and 289 (29.4%) were Black individuals. The median age at incident stroke was 74.6 (IQR, 69.1-79.8; range, 44.1-96.4) years. Cumulative mean poststroke SBP and LDL cholesterol levels were not associated with any cognitive outcome. However, after accounting for cumulative mean poststroke SBP and LDL cholesterol levels, higher cumulative mean poststroke glucose level was associated with faster decline in global cognition (−0.04 points/y faster per each 10–mg/dL increase [95% CI, −0.08 to −0.001 points/y]; P = .046) but not executive function or memory. After restricting to 798 participants with apolipoprotein E4 (APOE4) data and controlling for APOE4 and APOE4 × time, higher cumulative mean poststroke glucose level was associated with a faster decline in global cognition in models without and with adjustment for cumulative mean poststroke SBP and LDL cholesterol levels (−0.05 points/y faster per 10–mg/dL increase [95% CI, −0.09 to −0.01 points/y]; P = .01; −0.07 points/y faster per 10–mg/dL increase [95% CI, −0.11 to −0.03 points/y]; P = .002) but not executive function or memory declines.Conclusions and RelevanceIn this cohort study, higher poststroke glucose levels were associated with faster global cognitive decline. We found no evidence that poststroke LDL cholesterol and SBP levels were associated with cognitive decline.

Publisher

American Medical Association (AMA)

Subject

General Medicine

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