title: Hyperinsulinemia and elevated systolic blood pressure independently predict white matter hyperintensities with associated cognitive decrement in the middle-aged offspring of dementia patients.
abstract: Cerebrovascular disease is an independent risk factor for dementia that may also be synergistic with Alzheimer's disease. In recent years attention has switched from cerebral infarcts to microvascular disease as the primary cause of cerebrovascular cognitive decline, with damage to the white matter the primary mechanism. Uncertainties remain regarding the risks posed by different types vascular threat, the extent to which cerebrovascular damage occurs in middle age, and whether relatively "normal" amounts of white matter damage are accompanied by meaningful degrees of cognitive decline. We explored these issues via laboratory, cardiovascular, cognitive, and magnetic resonance imaging (MRI) data in 67 middle-aged cognitively normal offspring of dementia patients. The sample was enriched for vascular risk. Plasma insulin, 24-h systolic blood pressure, body mass index, age, and % small dense LDL cholesterol were the strongest correlates of MRI white matter hyperintensity (WMH) volume. With shared variance controlled for, 24 h systolic BP, plasma insulin, and age remained as significant predictors of WMH volume. An interaction variable (24 h BP * insulin) did not improve the prediction of WMH. WMH volume correlated negatively with cognition. No evidence for an ApoE ε4 effect emerged for either WMH or cognition. Hypertension and hyperinsulinemia appear to pose independent, consequential threats to the cerebral small vessel vasculature in middle age, reflected in the presence of areas of WMH on MRI scans. Our data show that even modest WMH volumes in middle age are associated with cognitive decrement, underscoring the importance of aggressive treatment and lifestyle modifications to address vascular risk throughout adulthood.
authors.affiliation: Yale University School of Medicine, New Haven, CT, USA. keith.hawkins@yale.edu.|Olin Neuropsychiatry Research Center, Hartford, CT, USA. keith.hawkins@yale.edu.
authors.forename: Keith A
authors.initials: KA
authors.lastname: Hawkins
authors.affiliation: Yale University School of Medicine, New Haven, CT, USA.|Olin Neuropsychiatry Research Center, Hartford, CT, USA.
authors.forename: Nazli
authors.initials: N
authors.lastname: Emadi
authors.affiliation: Yale University School of Medicine, New Haven, CT, USA.|Olin Neuropsychiatry Research Center, Hartford, CT, USA.
authors.forename: Godfrey D
authors.initials: GD
authors.lastname: Pearlson
authors.affiliation: Yale University School of Medicine, New Haven, CT, USA.|Oxford Center for Functional MRI of the Brain, University of Oxford, Oxford, UK.
authors.forename: Anderson M
authors.initials: AM
authors.lastname: Winkler
authors.affiliation: Hartford Hospital, Hartford, CT, USA.|University of Connecticut, Storrs, CT, USA.
authors.forename: Beth
authors.initials: B
authors.lastname: Taylor
authors.affiliation: St. Francis Hospital and Medical Center, Hartford, CT, USA.
authors.forename: Latha
authors.initials: L
authors.lastname: Dulipsingh
authors.affiliation: Olin Neuropsychiatry Research Center, Hartford, CT, USA.|Institute of Living, Hartford, CT, 06106, USA.
authors.forename: Diana
authors.initials: D
authors.lastname: King
authors.affiliation: Yale University School of Medicine, New Haven, CT, USA.
authors.forename: Brian
authors.initials: B
authors.lastname: Pittman
authors.affiliation: Institute of Living, Hartford, CT, 06106, USA.
authors.forename: Karen
authors.initials: K
authors.lastname: Blank
mesh_terms: D001794:Blood Pressure / Q000502:physiology; D016241:Child of Impaired Parents; D060825:Cognitive Dysfunction / Q000097:blood / Q000000981:diagnostic imaging* / Q000453:epidemiology; D003430:Cross-Sectional Studies; D003704:Dementia / Q000097:blood / Q000000981:diagnostic imaging* / Q000453:epidemiology; D005260:Female; D006801:Humans; D006946:Hyperinsulinism / Q000097:blood / Q000000981:diagnostic imaging* / Q000453:epidemiology; D006973:Hypertension / Q000097:blood / Q000000981:diagnostic imaging* / Q000453:epidemiology; D008279:Magnetic Resonance Imaging / Q000639:trends; D008297:Male; D008875:Middle Aged; D011237:Predictive Value of Tests; D066127:White Matter / Q000000981:diagnostic imaging* / Q000378:metabolism
keywords: Cerebrovascular disease; Cognition; Dementia risk; Hypertension; Type 2 diabetes; White matter hyperintensity volume