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

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)...

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Published in:	Neurology Vol. 88; no. 22; p. 2089
Main Authors:	Ding, Jie, Sigurðsson, Sigurður, Jónsson, Pálmi V, Eiriksdottir, Gudny, Meirelles, Osorio, Kjartansson, Olafur, Lopez, Oscar L, van Buchem, Mark A, Gudnason, Vilmundur, Launer, Lenore J
Format:	Journal Article
Language:	English
Published:	United States 30.05.2017
Subjects:	Aged Aged, 80 and over Brain - diagnostic imaging Cerebral Hemorrhage - diagnostic imaging Cerebral Hemorrhage - epidemiology Cognitive Dysfunction - diagnostic imaging Cognitive Dysfunction - epidemiology Dementia - diagnostic imaging Dementia - epidemiology Executive Function Female Follow-Up Studies Humans Iceland Incidence Linear Models Longitudinal Studies Magnetic Resonance Imaging Male Memory Multivariate Analysis Neuropsychological Tests Prevalence Sensitivity and Specificity
ISSN:	1526-632X, 1526-632X
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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.
AbstractList	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.OBJECTIVETo 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.METHODSIn 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.RESULTSIn 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.CONCLUSIONSMixed 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. 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.
Author	Ding, Jie Jónsson, Pálmi V Eiriksdottir, Gudny van Buchem, Mark A Kjartansson, Olafur Lopez, Oscar L Sigurðsson, Sigurður Meirelles, Osorio Gudnason, Vilmundur Launer, Lenore J
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Icelandic Heart Association (S.S., G.E., O.K., V.G.), Kopavogur; Faculty of Medicine (P.V.J., V.G.), University of Iceland, Reykjavik; Department of Psychiatry and Neurology (O.L.L.), University of Pittsburgh, Pennsylvania; and Department of Radiology (M.A.v.B.), Leiden University Medical Center, the Netherlands – sequence: 4 givenname: Gudny surname: Eiriksdottir fullname: Eiriksdottir, Gudny organization: From the Laboratory of Epidemiology and Population Sciences (J.D., O.M., L.J.L.), National Institute on Aging, NIH, Bethesda, MD; Icelandic Heart Association (S.S., G.E., O.K., V.G.), Kopavogur; Faculty of Medicine (P.V.J., V.G.), University of Iceland, Reykjavik; Department of Psychiatry and Neurology (O.L.L.), University of Pittsburgh, Pennsylvania; and Department of Radiology (M.A.v.B.), Leiden University Medical Center, the Netherlands – sequence: 5 givenname: Osorio surname: Meirelles fullname: Meirelles, Osorio organization: From the Laboratory of Epidemiology and Population Sciences (J.D., O.M., L.J.L.), National Institute on Aging, NIH, Bethesda, MD; Icelandic Heart Association (S.S., G.E., O.K., V.G.), Kopavogur; Faculty of Medicine (P.V.J., V.G.), University of Iceland, Reykjavik; Department of Psychiatry and Neurology (O.L.L.), University of Pittsburgh, Pennsylvania; and Department of Radiology (M.A.v.B.), Leiden University Medical Center, the Netherlands – sequence: 6 givenname: Olafur surname: Kjartansson fullname: Kjartansson, Olafur organization: From the Laboratory of Epidemiology and Population Sciences (J.D., O.M., L.J.L.), National Institute on Aging, NIH, Bethesda, MD; Icelandic Heart Association (S.S., G.E., O.K., V.G.), Kopavogur; Faculty of Medicine (P.V.J., V.G.), University of Iceland, Reykjavik; Department of Psychiatry and Neurology (O.L.L.), University of Pittsburgh, Pennsylvania; and Department of Radiology (M.A.v.B.), Leiden University Medical Center, the Netherlands – sequence: 7 givenname: Oscar L surname: Lopez fullname: Lopez, Oscar L organization: From the Laboratory of Epidemiology and Population Sciences (J.D., O.M., L.J.L.), National Institute on Aging, NIH, Bethesda, MD; Icelandic Heart Association (S.S., G.E., O.K., V.G.), Kopavogur; Faculty of Medicine (P.V.J., V.G.), University of Iceland, Reykjavik; Department of Psychiatry and Neurology (O.L.L.), University of Pittsburgh, Pennsylvania; and Department of Radiology (M.A.v.B.), Leiden University Medical Center, the Netherlands – sequence: 8 givenname: Mark A surname: van Buchem fullname: van Buchem, Mark A organization: From the Laboratory of Epidemiology and Population Sciences (J.D., O.M., L.J.L.), National Institute on Aging, NIH, Bethesda, MD; Icelandic Heart Association (S.S., G.E., O.K., V.G.), Kopavogur; Faculty of Medicine (P.V.J., V.G.), University of Iceland, Reykjavik; Department of Psychiatry and Neurology (O.L.L.), University of Pittsburgh, Pennsylvania; and Department of Radiology (M.A.v.B.), Leiden University Medical Center, the Netherlands – sequence: 9 givenname: Vilmundur surname: Gudnason fullname: Gudnason, Vilmundur organization: From the Laboratory of Epidemiology and Population Sciences (J.D., O.M., L.J.L.), National Institute on Aging, NIH, Bethesda, MD; Icelandic Heart Association (S.S., G.E., O.K., V.G.), Kopavogur; Faculty of Medicine (P.V.J., V.G.), University of Iceland, Reykjavik; Department of Psychiatry and Neurology (O.L.L.), University of Pittsburgh, Pennsylvania; and Department of Radiology (M.A.v.B.), Leiden University Medical Center, the Netherlands – sequence: 10 givenname: Lenore J surname: Launer fullname: Launer, Lenore J email: LaunerL@nia.nih.gov organization: From the Laboratory of Epidemiology and Population Sciences (J.D., O.M., L.J.L.), National Institute on Aging, NIH, Bethesda, MD; Icelandic Heart Association (S.S., G.E., O.K., V.G.), Kopavogur; Faculty of Medicine (P.V.J., V.G.), University of Iceland, Reykjavik; Department of Psychiatry and Neurology (O.L.L.), University of Pittsburgh, Pennsylvania; and Department of Radiology (M.A.v.B.), Leiden University Medical Center, the Netherlands. LaunerL@nia.nih.gov
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SubjectTerms	Aged Aged, 80 and over Brain - diagnostic imaging Cerebral Hemorrhage - diagnostic imaging Cerebral Hemorrhage - epidemiology Cognitive Dysfunction - diagnostic imaging Cognitive Dysfunction - epidemiology Dementia - diagnostic imaging Dementia - epidemiology Executive Function Female Follow-Up Studies Humans Iceland Incidence Linear Models Longitudinal Studies Magnetic Resonance Imaging Male Memory Multivariate Analysis Neuropsychological Tests Prevalence Sensitivity and Specificity
Title	Space and location of cerebral microbleeds, cognitive decline, and dementia in the community
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