title: Microbleeds, Mortality, and Stroke in Alzheimer Disease: The MISTRAL Study.
abstract: OBJECTIVE
  Microbleeds are more prevalent in patients with Alzheimer disease (AD) compared with the general elderly population. In addition, microbleeds have been found to predict mortality in AD.
  
  
  OBJECTIVE
  To investigate whether microbleeds in AD increase the risk for mortality, stroke (including intracerebral hemorrhage), and cardiovascular events.
  
  
  METHODS
  The MISTRAL (do MIcrobleeds predict STRoke in ALzheimer's disease) Study is a longitudinal cohort study within the memory clinic-based Amsterdam Dementia Cohort. We selected all patients with AD with a baseline visit between January 2, 2002, and December 16, 2009, and microbleeds (n = 111) and matched those (1:2) for age, sex, and magnetic resonance imaging scanner to 222 patients with AD without microbleeds. After a minimal follow-up of 3 years, information on all-cause mortality, stroke-related mortality, and cardiovascular mortality was obtained between November 1, 2012, and May 1, 2014. In addition, we obtained information on the occurrence of incident stroke or transient ischemic attack, cardiovascular events, and nursing home admittance.
  
  
  METHODS
  Stroke-related mortality, incident stroke, and intracerebral hemorrhage.
  
  
  RESULTS
  Patients had a mean (SD) age of 71.2 (7.8) years and 127 (42%) were female. Compared with having no microbleeds, microbleeds in lobar locations were associated with an increased risk for stroke-related mortality (hazard ratio [HR], 33.9; 95% CI, 2.5-461.7), whereas nonlobar microbleeds were associated with an increased risk for cardiovascular mortality (HR, 12.0; 95% CI, 3.2-44.7). In addition, lobar microbleeds were associated with an increased risk for incident stroke (HR, 3.8; 95% CI, 1.5-10.1) and nonlobar microbleeds with an increased risk for cardiovascular events (HR, 6.2; 95% CI, 1.5-25.0). Even higher risks for incident stroke and cardiovascular events were found in patients using antithrombotic medication. All 5 patients with an intracerebral hemorrhage had lobar microbleeds at baseline; 4 of them used antithrombotics.
  
  
  CONCLUSIONS
  In patients with AD, the presence of nonlobar microbleeds was associated with an increased risk for cardiovascular events and cardiovascular mortality. Patients with lobar microbleeds had an increased risk for stroke and stroke-related mortality, indicating that these patients should be treated with the utmost care.
authors: Alzheimer Center, Department of Neurology, Neuroscience Campus Amsterdam, VU University Medical Center, Amsterdam, the Netherlands.
authors: Marije R
authors: MR
authors: Benedictus
authors: Alzheimer Center, Department of Neurology, Neuroscience Campus Amsterdam, VU University Medical Center, Amsterdam, the Netherlands.
authors: Niels D
authors: ND
authors: Prins
authors: Alzheimer Center, Department of Neurology, Neuroscience Campus Amsterdam, VU University Medical Center, Amsterdam, the Netherlands.
authors: Jeroen D C
authors: JD
authors: Goos
authors: Alzheimer Center, Department of Neurology, Neuroscience Campus Amsterdam, VU University Medical Center, Amsterdam, the Netherlands.
authors: Philip
authors: P
authors: Scheltens
authors: Department of Radiology, Neuroscience Campus Amsterdam, VU University Medical Center, Amsterdam, the Netherlands.
authors: Frederik
authors: F
authors: Barkhof
authors: Alzheimer Center, Department of Neurology, Neuroscience Campus Amsterdam, VU University Medical Center, Amsterdam, the Netherlands3Department of Epidemiology and Biostatistics, Neuroscience Campus Amsterdam, VU University Medical Center, Amsterdam, the Ne.
authors: Wiesje M
authors: WM
authors: van der Flier
mesh_terms: D000368:Aged; D000544:Alzheimer Disease / Q000453:epidemiology / Q000401:mortality* / Q000473:pathology; D002318:Cardiovascular Diseases / Q000453:epidemiology / Q000401:mortality*; D002543:Cerebral Hemorrhage / Q000453:epidemiology / Q000401:mortality* / Q000473:pathology; D015897:Comorbidity; D005260:Female; D006801:Humans; D002546:Ischemic Attack, Transient / Q000453:epidemiology / Q000401:mortality* / Q000473:pathology; D008137:Longitudinal Studies; D008297:Male; D009426:Netherlands / Q000453:epidemiology; D020521:Stroke / Q000453:epidemiology / Q000401:mortality* / Q000473:pathology