Risk Factors Associated With Incident Cerebral Microbleeds According to Location in Older People: The Age, Gene/Environment Susceptibility (AGES)-Reykjavik Study

JAMA Neurol. 2015 Jun;72(6):682-8. doi: 10.1001/jamaneurol.2015.0174.


Importance: The spatial distribution of cerebral microbleeds (CMBs), which are asymptomatic precursors of intracerebral hemorrhage, reflects specific underlying microvascular abnormalities of cerebral amyloid angiopathy (lobar structures) and hypertensive vasculopathy (deep brain structures). Relatively little is known about the occurrence of and modifiable risk factors for developing CMBs, especially in a lobar location, in the general population of older people.

Objective: To investigate whether lifestyle and lipid factors predict new CMBs in relation to their anatomic location.

Design, setting, and participants: We enrolled 2635 individuals aged 66 to 93 years from the population-based Age, Gene/Environment Susceptibility (AGES)-Reykjavik Study in a brain imaging study. Participants underwent a baseline magnetic resonance imaging (MRI) examination of the brain from September 1, 2002, through February 28, 2006, and returned for a second MRI examination from April 1, 2007, through September 30, 2011.

Exposures: Lifestyle and lipid factors assessed at baseline included smoking, alcohol consumption, body mass index, and serum levels of total cholesterol, high- and low-density lipoprotein cholesterol, and triglycerides.

Main outcomes and measures: Incident CMBs detected on MRIs, which were further categorized as exclusively lobar or as deep.

Results: During a mean follow-up of 5.2 years, 486 people (18.4%) developed new CMBs, of whom 308 had lobar CMBs only and 178 had deep CMBs. In the multivariate logarithm-binomial regression model adjusted for baseline cardiovascular risk factors, including blood pressure, antihypertensive use, prevalent CMBs, and markers of cerebral ischemic small-vessel disease, heavy alcohol consumption (vs light to moderate consumption; relative risk [RR], 2.94 [95% CI, 1.23-7.01]) was associated with incident CMBs in a deep location. Baseline underweight (vs normal weight; RR, 2.41 [95% CI, 1.21-4.80]), current smoking (RR, 1.47 [95% CI, 1.11-1.94]), an elevated serum level of high-density lipoprotein cholesterol (RR per 1-SD increase, 1.13 [95% CI, 1.02-1.25]), and a decreased triglyceride level (RR per 1-SD decrease in natural logarithm-transformed triglyceride level, 1.17 [95% CI, 1.03-1.33]) were significantly associated with an increased risk for lobar CMBs exclusively but not for deep CMBs.

Conclusions and relevance: Lifestyle and lipid risk profiles for CMBs were similar to those for symptomatic intracerebral hemorrhage and differed for lobar and deep CMBs. Modification of these risk factors could have the potential to prevent new-onset CMBs, particularly those occurring in a lobar location.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Aged, 80 and over
  • Alcohol Drinking / epidemiology
  • Cerebral Hemorrhage* / blood
  • Cerebral Hemorrhage* / epidemiology
  • Cerebral Hemorrhage* / etiology
  • Cerebral Hemorrhage* / pathology
  • Cholesterol, HDL / blood*
  • Female
  • Humans
  • Iceland / epidemiology
  • Incidence
  • Life Style*
  • Magnetic Resonance Imaging
  • Male
  • Risk Factors
  • Smoking / epidemiology
  • Thinness / epidemiology
  • Triglycerides / blood*


  • Cholesterol, HDL
  • Triglycerides