Small Brain Lesions and Incident Stroke and Mortality: A Cohort Study

Ann Intern Med. 2015 Jul 7;163(1):22-31. doi: 10.7326/M14-2057.


Background: Although cerebral lesions 3 mm or larger on imaging are associated with incident stroke, lesions smaller than 3 mm are typically ignored.

Objective: To examine stroke risks associated with subclinical brain lesions (<3 mm only, ≥3 mm only, and both sizes) and white matter hyperintensities (WMHs).

Design: Community cohort from the ARIC (Atherosclerosis Risk in Communities) Study.

Setting: Two ARIC sites with magnetic resonance imaging (MRI) data from 1993 to 1995.

Participants: 1884 adults aged 50 to 73 years with MRI, no prior stroke, and average follow-up of 14.5 years.

Measurements: Lesions on MRI (by size), WMH score (scale of 0 to 9), incident stroke, all-cause mortality, and stroke-related mortality. Hazard ratios (HRs) were estimated with proportional hazards models.

Results: Compared with no lesions, stroke risk tripled with lesions smaller than 3 mm only (HR, 3.47 [95% CI, 1.86 to 6.49]), doubled with lesions 3 mm or larger only (HR, 1.94 [CI, 1.22 to 3.07]), was 8-fold higher with lesions of both sizes (HR, 8.59 [CI, 4.69 to 15.73]), and doubled with a WMH score of at least 3 (HR, 2.14 [CI, 1.45 to 3.16]). Risk for stroke-related death tripled with lesions smaller than 3 mm only (HR, 3.05 [CI, 1.04 to 8.94]) and was 7 times higher with lesions of both sizes (HR, 6.97 [CI, 2.03 to 23.93]).

Limitation: Few strokes (especially hemorrhagic) and few participants with lesions smaller than 3 mm only or lesions of both sizes.

Conclusion: Very small cerebrovascular lesions may be associated with increased risks for stroke and death; presence of lesions smaller than 3 mm and 3 mm or larger may result in a particularly striking risk increase. Larger studies are needed to confirm findings and provide more precise estimates.

Primary funding source: National Heart, Lung, and Blood Institute.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Aged
  • Brain / pathology*
  • Brain Infarction / complications
  • Brain Infarction / pathology*
  • Cause of Death
  • Female
  • Humans
  • Incidence
  • Longitudinal Studies
  • Magnetic Resonance Imaging
  • Male
  • Middle Aged
  • Prospective Studies
  • Risk Factors
  • Stroke / epidemiology*
  • Stroke / mortality