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Space and location of cerebral microbleeds, cognitive decline, and dementia in the community.

ABSTRACT: To assess the association of the number and anatomic location of cerebral microbleeds (CMBs), visible indicators of microvascular damage on MRI, with incident cognitive disease in the general population of older people.In the longitudinal population-based Age, Gene/Environment Susceptibility (AGES)-Reykjavik Study, 2,602 participants 66 to 93 years of age and free of prevalent dementia underwent brain MRI and cognitive testing of verbal memory, processing speed, and executive function at baseline and a mean of 5.2 years later. Adjudicated incident dementia cases were diagnosed according to international guidelines.In the multiple linear regression models adjusted for demographic, genetic, cardiovascular risk, and other cerebrovascular MRI markers, the presence of CMBs located in deep or mixed (deep and lobar) areas was associated with a greater decline in all 3 cognitive domains. Mixed CMBs were the strongest correlate for decline in memory and speed. Compared to those with no CMBs, participants with ?3 CMBs had a steeper decline in a composite measure of global cognitive function, memory, and speed. Among those with ?3 deep or mixed CMBs, associations were strongest for memory; the association with speed was strongest in those having ?3 strictly lobar CMBs. People with ?3 CMBs, regardless of their locations, had a higher incidence of all-cause dementia and vascular dementia.Mixed or a higher load of CMBs, with some specificity for location, is associated with accelerated cognitive decline in older people. These findings suggest a role for hypertensive vasculopathy and the combined effect of hypertensive and cerebral amyloid angiopathy in the pathogenesis of cognitive deterioration.

SUBMITTER: Ding J

PROVIDER: S-EPMC5447401 | biostudies-other | 2017 May

REPOSITORIES: biostudies-other

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Space and location of cerebral microbleeds, cognitive decline, and dementia in the community.

Ding Jie J Sigurðsson Sigurður S Jónsson Pálmi V PV Eiriksdottir Gudny G Meirelles Osorio O Kjartansson Olafur O Lopez Oscar L OL van Buchem Mark A MA Gudnason Vilmundur V Launer Lenore J LJ

Neurology 20170503 22

<h4>Objective</h4>To assess the association of the number and anatomic location of cerebral microbleeds (CMBs), visible indicators of microvascular damage on MRI, with incident cognitive disease in the general population of older people.<h4>Methods</h4>In the longitudinal population-based Age, Gene/Environment Susceptibility (AGES)-Reykjavik Study, 2,602 participants 66 to 93 years of age and free of prevalent dementia underwent brain MRI and cognitive testing of verbal memory, processing speed, ...[more]

PMID: 28468844

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Project description:ImportanceCerebral microbleeds are hypothesized downstream markers of brain damage caused by vascular and amyloid pathologic mechanisms. To date, whether their presence is associated with cognitive deterioration in the general population remains unclear.ObjectiveTo determine whether microbleeds, and more specifically microbleed count and location, are associated with an increased risk for cognitive impairment and dementia in the general population.Design, setting, and participantsThe Rotterdam Study, a prospective population-based study set in the general community, assessed the presence, number, and location of microbleeds at baseline (August 2005 to December 2011) on magnetic resonance imaging studies of the brain in 4841 participants 45 years or older. Participants underwent neuropsychological testing at 2 points a mean (SD) of 5.9 (0.6) years apart and were followed up for incident dementia throughout the study period until January 1, 2013. The association of microbleeds with cognitive decline and dementia was studied using multiple linear regression, linear mixed-effects modeling, and Cox proportional hazards.ExposuresCerebral microbleed presence, location, and number.Main outcomes and measuresCognitive decline measured by a decrease in neuropsychological test battery scores (Mini-Mental State Examination, Letter Digit Substitution Task, Word Fluency Test, Stroop test, 15-word Verbal Learning Test, and Purdue Pegboard Test) and compound scores (eg, G factor, executive function, information processing speed, memory, motor speed) and dementia.ResultsIn total, 3257 participants (1758 women [54.7%]; mean [SD] age, 59.6 [7.8] years) underwent baseline and follow-up cognitive testing. Microbleed prevalence was 15.3% (median [interquartile range] count, 1 [1-88]). The presence of more than 4 microbleeds was associated with cognitive decline. Lobar (with or without cerebellar) microbleeds were associated with a decline in executive functions (mean difference in z score, -0.31; 95% CI, -0.51 to -0.11; P = .003), information processing (mean difference in z score, -0.44; 95% CI, -0.65 to -0.22; P < .001), and memory function (mean difference in z score, -0.34; 95% CI, -0.64 to -0.03; P = .03), whereas microbleeds in other brain regions were associated with a decline in information processing and motor speed (mean difference in z score, -0.61; 95% CI, -1.05 to -0.17; P = .007). After a mean (SD) follow-up of 4.8 (1.4) years, 72 participants developed dementia, of whom 53 had Alzheimer dementia. The presence of microbleeds was associated with an increased risk for dementia after adjustment for age, sex, and educational level (hazard ratio, 2.02; 95% CI, 1.25-3.24), including Alzheimer dementia (hazard ratio, 2.10; 95% CI, 1.21-3.64).Conclusions and relevanceIn the general population, a high microbleed count was associated with an increased risk for cognitive deterioration and dementia. Microbleeds thus mark the presence of diffuse vascular and neurodegenerative brain damage.

Project description:Background and purposeThe burden of amyloid β is greater in patients with dementia with Lewy bodies than in those with Parkinson disease dementia, and an increased amyloid β load is closely related to a higher incidence of cerebral microbleeds. Here, we investigated the prevalence and topography of cerebral microbleeds in patients with dementia with Lewy bodies and those with Parkinson disease dementia to examine whether cerebral microbleeds are more prevalent in patients with dementia with Lewy bodies than in those with Parkinson disease dementia.Materials and methodsThe study population consisted of 42 patients with dementia with Lewy bodies, 88 patients with Parkinson disease dementia, and 35 controls who underwent brain MR imaging with gradient recalled-echo. Cerebral microbleeds were classified as deep, lobar, or infratentorial.ResultsThe frequency of cerebral microbleeds was significantly greater in patients with dementia with Lewy bodies (45.2%) than in those with Parkinson disease dementia (26.1%) or in healthy controls (17.1%; P = .017). Lobar cerebral microbleeds were observed more frequently in the dementia with Lewy bodies group (40.5%) than in the Parkinson disease dementia (17%; P = .004) or healthy control (8.6%; P = .001) group, whereas the frequencies of deep and infratentorial cerebral microbleeds did not differ among the 3 groups. Logistic regression analyses revealed that, compared with the healthy control group, the dementia with Lewy bodies group was significantly associated with the presence of lobar cerebral microbleeds after adjusting for age, sex, nonlobar cerebral microbleeds, white matter hyperintensities, and other vascular risk factors (odds ratio, 4.39 [95% CI, 1.27-15.25]). However, compared with the healthy control group, the Parkinson disease dementia group was not significantly associated with lobar cerebral microbleeds.ConclusionsThis study showed that patients with dementia with Lewy bodies had a greater burden of cerebral microbleeds and exhibited a lobar predominance of cerebral microbleeds than did patients with Parkinson disease dementia.

Dataset Information

Space and location of cerebral microbleeds, cognitive decline, and dementia in the community.

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Space and location of cerebral microbleeds, cognitive decline, and dementia in the community.

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