Send to

Choose Destination
Metab Brain Dis. 2017 Jun;32(3):849-857. doi: 10.1007/s11011-017-9980-9. Epub 2017 Mar 3.

Hyperinsulinemia and elevated systolic blood pressure independently predict white matter hyperintensities with associated cognitive decrement in the middle-aged offspring of dementia patients.

Author information

Yale University School of Medicine, New Haven, CT, USA.
Olin Neuropsychiatry Research Center, Hartford, CT, USA.
Yale University School of Medicine, New Haven, CT, USA.
Olin Neuropsychiatry Research Center, Hartford, CT, USA.
Oxford Center for Functional MRI of the Brain, University of Oxford, Oxford, UK.
Hartford Hospital, Hartford, CT, USA.
University of Connecticut, Storrs, CT, USA.
St. Francis Hospital and Medical Center, Hartford, CT, USA.
Institute of Living, Hartford, CT, 06106, USA.


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.


Cerebrovascular disease; Cognition; Dementia risk; Hypertension; Type 2 diabetes; White matter hyperintensity volume

[Indexed for MEDLINE]

Supplemental Content

Full text links

Icon for Springer
Loading ...
Support Center