title: Cerebral microbleeds and risk of incident dementia: the Framingham Heart Study.
abstract: Cerebral microbleeds (CMBs) are MRI markers attributed to the most common cerebral angiopathies in the elderly and in patients with dementia: hypertensive and cerebral amyloid angiopathy. CMB detection in asymptomatic persons may help identify those at risk for dementia and may influence preventive strategies and design of clinical trials testing treatments for dementia. We studied the association of CMB with risk of incident dementia in community dwelling individuals. A total of 1296 dementia-free Framingham Heart Study participants (mean age 72 years; 54% women) with available brain MRI and incident dementia data during a mean follow-up period of 6.7 years were included. Using Cox proportional hazards models, we related CMB presence to incident dementia. Multivariable models were adjusted for age, sex, APOE status, and education, with additional models adjusting for vascular risk factors and MRI markers of ischemic brain injury. CMBs were observed in 10.8% and incident dementia in 85 participants (6.6% over study period). Participants with any CMB had 1.74 times higher risk of dementia (hazard ratio [HR] 1.74, 95% confidence interval [CI] 1.00-3.01), whereas those with deep and mixed CMB had a three-fold increased risk (HR 2.99, 95% CI 1.52-5.90). The associations were independent of vascular risk factors, and for deep and mixed CMB also independent of MRI markers of ischemia (HR 2.44, 95% CI 1.22-4.88). Purely lobar CMBs were not associated with incident dementia. Our findings support a role for hypertensive vasculopathy and the interplay of hypertensive and cerebral amyloid angiopathy in risk of dementia and suggest that CMB presence can identify individuals at risk of dementia.
authors.affiliation: Department of Neurology, School of Public Health at Boston University, Boston, MA, USA; NHLBI's Framingham Heart Study, Framingham, MA, USA. Electronic address: joromero@bmc.org.
authors.forename: José R
authors.initials: JR
authors.lastname: Romero
authors.affiliation: Department of Neurology, School of Public Health at Boston University, Boston, MA, USA; NHLBI's Framingham Heart Study, Framingham, MA, USA; Department of Biostatistics, School of Public Health at Boston University, Boston, MA, USA.
authors.forename: Alexa
authors.initials: A
authors.lastname: Beiser
authors.affiliation: NHLBI's Framingham Heart Study, Framingham, MA, USA; Department of Biostatistics, School of Public Health at Boston University, Boston, MA, USA.
authors.forename: Jayandra J
authors.initials: JJ
authors.lastname: Himali
authors.affiliation: Department of Medicine-Neurology, McMaster University and Population Health Research Institute, Hamilton, Ontario, Canada.
authors.forename: Ashkan
authors.initials: A
authors.lastname: Shoamanesh
authors.affiliation: Department of Neurology, University of California-Davis, Sacramento, CA, USA.
authors.forename: Charles
authors.initials: C
authors.lastname: DeCarli
authors.affiliation: Department of Neurology, School of Public Health at Boston University, Boston, MA, USA; NHLBI's Framingham Heart Study, Framingham, MA, USA.
authors.forename: Sudha
authors.initials: S
authors.lastname: Seshadri
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D001921:Brain / Q000000981:diagnostic imaging; D016657:Cerebral Amyloid Angiopathy / Q000150:complications; D002543:Cerebral Hemorrhage / Q000150:complications* / Q000000981:diagnostic imaging; D003704:Dementia / Q000453:epidemiology / Q000209:etiology*; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D006973:Hypertension / Q000150:complications; D015994:Incidence; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D015233:Models, Statistical; D016016:Proportional Hazards Models; D012306:Risk
keywords: Brain MRI; Cerebral microbleeds; Cerebral small vessel disease; Dementia