Midlife smaller and larger infarctions, white matter hyperintensities, and 20-year cognitive decline

B. Gwen Windham, Michael E. Griswold, Steven R. Wilkening, Dan Su, Jonathan Tingle, Laura H. Coker, David Knopman, Rebecca F Gottesman, Dean Shibata, Thomas H. Mosley

Research output: Contribution to journalArticle

Abstract

Background: Smaller (<3-mm) infarctions are associated with stroke and stroke mortality, but relationships with cognitive decline are unknown. Objective: To characterize the relationships of smaller, larger, and both smaller and larger infarctions in middle age with 20-year cognitive decline. Design: Longitudinal cohort study. Setting: 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. Participants: Stroke-free participants aged 50 years or older. Measurements: 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. Results: 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. Limitation: 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. Conclusion: 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.

Original languageEnglish (US)
Pages (from-to)389-396
Number of pages8
JournalAnnals of internal medicine
Volume171
Issue number6
DOIs
StatePublished - Sep 17 2019

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Infarction
Stroke
White Matter
Cognitive Dysfunction

ASJC Scopus subject areas

  • Internal Medicine

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Gwen Windham, B., Griswold, M. E., Wilkening, S. R., Su, D., Tingle, J., Coker, L. H., ... Mosley, T. H. (2019). Midlife smaller and larger infarctions, white matter hyperintensities, and 20-year cognitive decline. Annals of internal medicine, 171(6), 389-396. https://doi.org/10.7326/M18-0295

Midlife smaller and larger infarctions, white matter hyperintensities, and 20-year cognitive decline. / Gwen Windham, B.; Griswold, Michael E.; Wilkening, Steven R.; Su, Dan; Tingle, Jonathan; Coker, Laura H.; Knopman, David; Gottesman, Rebecca F; Shibata, Dean; Mosley, Thomas H.

In: Annals of internal medicine, Vol. 171, No. 6, 17.09.2019, p. 389-396.

Research output: Contribution to journalArticle

Gwen Windham, B, Griswold, ME, Wilkening, SR, Su, D, Tingle, J, Coker, LH, Knopman, D, Gottesman, RF, Shibata, D & Mosley, TH 2019, 'Midlife smaller and larger infarctions, white matter hyperintensities, and 20-year cognitive decline', Annals of internal medicine, vol. 171, no. 6, pp. 389-396. https://doi.org/10.7326/M18-0295
Gwen Windham B, Griswold ME, Wilkening SR, Su D, Tingle J, Coker LH et al. Midlife smaller and larger infarctions, white matter hyperintensities, and 20-year cognitive decline. Annals of internal medicine. 2019 Sep 17;171(6):389-396. https://doi.org/10.7326/M18-0295
Gwen Windham, B. ; Griswold, Michael E. ; Wilkening, Steven R. ; Su, Dan ; Tingle, Jonathan ; Coker, Laura H. ; Knopman, David ; Gottesman, Rebecca F ; Shibata, Dean ; Mosley, Thomas H. / Midlife smaller and larger infarctions, white matter hyperintensities, and 20-year cognitive decline. In: Annals of internal medicine. 2019 ; Vol. 171, No. 6. pp. 389-396.
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abstract = "Background: Smaller (<3-mm) infarctions are associated with stroke and stroke mortality, but relationships with cognitive decline are unknown. Objective: To characterize the relationships of smaller, larger, and both smaller and larger infarctions in middle age with 20-year cognitive decline. Design: Longitudinal cohort study. Setting: 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. Participants: Stroke-free participants aged 50 years or older. Measurements: 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. Results: 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. Limitation: 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. Conclusion: 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.",
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AU - Gwen Windham, B.

AU - Griswold, Michael E.

AU - Wilkening, Steven R.

AU - Su, Dan

AU - Tingle, Jonathan

AU - Coker, Laura H.

AU - Knopman, David

AU - Gottesman, Rebecca F

AU - Shibata, Dean

AU - Mosley, Thomas H.

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N2 - Background: Smaller (<3-mm) infarctions are associated with stroke and stroke mortality, but relationships with cognitive decline are unknown. Objective: To characterize the relationships of smaller, larger, and both smaller and larger infarctions in middle age with 20-year cognitive decline. Design: Longitudinal cohort study. Setting: 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. Participants: Stroke-free participants aged 50 years or older. Measurements: 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. Results: 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. Limitation: 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. Conclusion: 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.

AB - Background: Smaller (<3-mm) infarctions are associated with stroke and stroke mortality, but relationships with cognitive decline are unknown. Objective: To characterize the relationships of smaller, larger, and both smaller and larger infarctions in middle age with 20-year cognitive decline. Design: Longitudinal cohort study. Setting: 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. Participants: Stroke-free participants aged 50 years or older. Measurements: 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. Results: 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. Limitation: 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. Conclusion: 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.

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