B. Gwen Windham, MD, MHS; Michael E. Griswold, PhD; Steven R. Wilkening, MD, MS; Dan Su, MS; Jonathan Tingle, BS; Laura H. Coker, PhD; David Knopman, MD; Rebecca F. Gottesman, MD, PhD; Dean Shibata, MD; Thomas H. Mosley, PhD
Acknowledgment: The authors thank the staff and participants of the ARIC study for their important contributions.
Financial Support: The ARIC study is carried out as a collaborative study supported by contracts HHSN268201100005C, HHSN268201100006C, HHSN268201100007C, HHSN268201100008C, HHSN268201100009C, HHSN268201100010C, HHSN268201100011C, and HHSN268201100012C from the National Heart, Lung, and Blood Institute (NHLBI). Neurocognitive data are collected under contracts 2U01HL096812, 2U01HL096814, 2U01HL096899, 2U01HL096902, and 2U01HL096917 from the National Institutes of Health (NIH) (NHLBI, National Institute of Neurological Disorders and Stroke, National Institute on Aging, and National Institute on Deafness and Other Communication Disorders), and previous brain MRI examinations were funded by grant R01-HL70825 from the NHLBI.
Disclosures: Dr. Windham reports grants from the NIH/NHLBI/National Institute on Aging during the conduct of the study. Mr. Tingle reports grants from the NHLBI during the conduct of the study. Dr. Knopman reports personal fees from the DIAN (Dominantly Inherited Alzheimer Network) study and Lundbeck outside the submitted work. Dr. Gottesman reports that she as an Associate Editor of Neurology with the American Academy of Neurology outside the submitted work. Dr. Mosley reports grants from the NIH during the conduct of the study. Authors not named here have disclosed no conflicts of interest. Disclosures can also be viewed at www.acponline.org/authors/icmje/ConflictOfInterestForms.do?msNum=M18-0295.
Editors' Disclosures: Christine Laine, MD, MPH, Editor in Chief, reports that her spouse has stock options/holdings with Targeted Diagnostics and Therapeutics. Darren B. Taichman, MD, PhD, Executive Editor, reports that he has no financial relationships or interests to disclose. Cynthia D. Mulrow, MD, MSc, Senior Deputy Editor, reports that she has no relationships or interests to disclose. Jaya K. Rao, MD, MHS, Deputy Editor, reports that she has stock holdings/options in Eli Lilly and Pfizer. Catharine B. Stack, PhD, MS, Deputy Editor, Statistics, reports that she has stock holdings in Pfizer, Johnson & Johnson, and Colgate-Palmolive. Christina C. Wee, MD, MPH, Deputy Editor, reports employment with Beth Israel Deaconess Medical Center. Sankey V. Williams, MD, Deputy Editor, reports that he has no financial relationships or interests to disclose. Yu-Xiao Yang, MD, MSCE, Deputy Editor, reports that he has no financial relationships or interest to disclose.
Reproducible Research Statement: Study protocol and data set: Protocols and data for the ARIC and ARIC Brain MRI studies may be obtained by approved persons through written agreements with the ARIC Steering Committee and the research sponsor (NIH and NHLBI) (e-mail, email@example.com). Statistical code: Available from Dr. Griswold (e-mail, firstname.lastname@example.org).
Corresponding Author: B. Gwen Windham, MD, MHS, University of Mississippi Medical Center, 2500 North State Street, Jackson, MS 39216; e-mail, email@example.com.
Current Author Addresses: Drs. Windham, Wilkening, Griswold, and Mosley; Miss Su; and Mr. Tingle: University of Mississippi Medical Center, 2500 North State Street, Jackson, MS 39216.
Dr. Coker: Wake Forest University School of Medicine, Medical Center Boulevard, Winston-Salem, NC 27103.
Dr. Knopman: Mayo Clinic, 200 First Street SW, Rochester, MN 55905.
Dr. Gottesman: Johns Hopkins Medicine, Phipps 446D, 600 North Wolfe Street, Baltimore, MD 21287.
Dr. Shibata: University of Washington, 1959 NE Pacific Street, Seattle, WA 98195.
Author Contributions: Conception and design: B.G. Windham, M.E. Griswold, S.R. Wilkening, R.F. Gottesman.
Analysis and interpretation of the data: B.G. Windham, M.E. Griswold, S.R. Wilkening, D. Su, J. Tingle, D. Knopman, R.F. Gottesman, T.H. Mosley.
Drafting of the article: B.G. Windham, M.E. Griswold.
Critical revision of the article for important intellectual content: B.G. Windham, M.E. Griswold, S.R. Wilkening, L.H. Coker, D. Knopman, R.F. Gottesman, D. Shibata, T.H. Mosley.
Final approval of the article: B.G. Windham, M.E. Griswold, S.R. Wilkening, D. Su, J. Tingle, L.H. Coker, D. Knopman, R.F. Gottesman, D. Shibata, T.H. Mosley.
Provision of study materials or patients: L.H. Coker.
Statistical expertise: M.E. Griswold, D. Su, J. Tingle.
Obtaining of funding: L.H. Coker, T.H. Mosley.
Administrative, technical, or logistic support: M.E. Griswold, T.H. Mosley.
Collection and assembly of data: J. Tingle, L.H. Coker, D. Shibata, T.H. Mosley.
Smaller (<3-mm) infarctions are associated with stroke and stroke mortality, but relationships with cognitive decline are unknown.
To characterize the relationships of smaller, larger, and both smaller and larger infarctions in middle age with 20-year cognitive decline.
Longitudinal cohort study.
Two ARIC (Atherosclerosis Risk in Communities) study sites with magnetic resonance imaging data (1993 to 1995) and up to 5 cognitive assessments over 20 years.
Stroke-free participants aged 50 years or older.
Infarctions were categorized as none, smaller only, larger only (3 to 20 mm), or both smaller and larger. Global cognitive Z scores were derived from 3 cognitive tests administered up to 5 times. Mixed-effects models estimated adjusted associations between infarctions and cognitive decline. Results are the average difference in standardized cognitive decline associated with infarctions versus no infarctions.
Among 1884 participants (mean age, 62 years; 60% women; 50% black), 1611 (86%) had no infarctions, 50 (3%) had smaller infarctions only, 185 (10%) had larger infarctions only, and 35 (2%) had both. Participants with both smaller and larger infarctions had steeper cognitive decline by more than half an SD (difference, −0.57 SD [95% CI, −0.89 to −0.26 SD]) compared with those who had no infarctions. Amounts of cognitive decline associated with only smaller infarctions and only larger infarctions were similar and were not statistically different from that associated with no infarctions.
Few participants had only smaller infarctions or both smaller and larger infarctions, and the data lacked counts of smaller infarctions and volumes of white matter hyperintensities.
The substantial cognitive decline from middle age associated with having both smaller and larger infarctions, but not larger infarctions alone, suggests that the combination of smaller and larger infarctions may escalate risk for cognitive decline later in life in stroke-free persons.
National Institutes of Health.
Windham BG, Griswold ME, Wilkening SR, et al. Midlife Smaller and Larger Infarctions, White Matter Hyperintensities, and 20-Year Cognitive Decline: A Cohort Study. Ann Intern Med. [Epub ahead of print 27 August 2019]171:389–396. doi: 10.7326/M18-0295
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Published: Ann Intern Med. 2019;171(6):389-396.
Published at www.annals.org on 27 August 2019
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