COPENHAGEN – The location of cerebral microbleeds appears to be strongly associated with dementia subtypes, perhaps reflecting the disorders’ underlying pathologies.
"This regional association with dementia subtypes is consistent with the hypothesis that lobar cerebral microbleeds reflect cerebral amyloid angiopathy, which is consistent with Alzheimer’s disease, while those in deep areas reflect hypertensive arteriopathy, which is important in vascular dementia," Lenore Launer, Ph.D., said at the Alzheimer’s Association International Conference 2014.
Dr. Lenore Launer
Dr. Launer, chief of the neuroepidemiology section in the laboratory of epidemiology and population science at the National Institute on Aging, and her colleagues examined the relationship between incident microbleeds and dementia in the AGES (Age, Gene/Environment Susceptibility) Reykjavik Study.
The population-based study is a project of the Icelandic Heart Association. It was established in 1967 and has followed more than 9,000 people, all of whom were born between 1907 and 1935. In 2000, the group partnered with the National Institute on Aging to further study diseases of old age, with an emphasis on imaging.
Since then, participants have undergone extensive phenotyping and repeat brain imaging to look specifically at cerebral microbleeds, infarcts, white-matter hyperintensities, and whole-brain volume.
Dr. Launer’s study comprised 2,482 people who were without stroke or dementia at baseline and who had complete brain MRI data during two 5-year periods: 2002-2006 and 2007-2011.
At baseline, patients’ mean age was 75 years. About 25% were carriers of the apolipoprotein E epsilon 4 allele. Hypertension was common (77% of patients). Almost a third of patients (29%) had brain infarct–like lesions, 11% had white-matter hyperintensities, and 16% had cerebral microbleeds.
Over the study period, 458 (18%) of the cohort’s patients developed new microbleeds, with 30% of those developing multiple bleeds. Of those new microbleeds, 64% were strictly lobar, with 1-15 bleeds per person. The remainder were deep lesions, numbering 1-19 per person.
There were 111 new dementia cases; of those, 83 were diagnosed as Alzheimer’s and 17 as vascular dementia. The rest were designated as "other dementia."
Two multivariate regression analyses examined the relationship between microbleed location and dementia subtype. Both controlled for a number of clinical and demographic factors. The first analysis included age, gender, and baseline cerebral microbleeds. The second analysis included all of those factors, plus education, depression, baseline vascular risk factors (hypertension, smoking, diabetes, body mass index, and total cholesterol), and baseline MRI markers (infarcts, total brain volume, and hyperintense lesions).
In the fully adjusted model, microbleed location showed a significant relationship with dementia subtypes. Lobar microbleeds were associated with a doubling in the risk of Alzheimer’s disease, while deep bleeds increased the risk of vascular dementia sixfold.
"It’s difficult to disentangle the temporal relationship here," Dr. Launer said. "But incident cerebral microbleeds may indicate more severe small-vessel disease, and be the thing that pushes a person off the cliff into the clinical presentation of dementia."
The Icelandic Heart Association and the National Institute on Aging sponsored the study. As a government employee, Dr. Launer has no financial disclosures.
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