In this issue of Neurology, Carmelli et al. document the important relationship of midlife cardiovascular risk factors to brain morphology in 74 monozygotic male-male twin pairs who participated in the National Heart, Lung, and Blood Institute Twin Study.[1] Three risk factors were predictors of greater changes in white matter hyperintensities (WMH) in old age independent of shared genetic and familial influences: higher 1-hour postload glucose level, lower high-density lipoprotein cholesterol, and higher systolic blood pressure at baseline (25 years earlier). Furthermore, a history of coronary heart disease, a lower forced expiratory volume in 1 second/forced vital capacity in midlife, and higher systolic blood pressure and alcohol consumption at follow-up predicted a greater reduction in brain parenchyma. After adjustment for education and clinical stroke, twins with more WMH had lower scores on "memory" and "speed"; cognitive summary scales, more impairment of walking and standing balance, and more depression symptoms than co-twins with fewer WHM. The lower the brain volume the poorer the memory performance.
Cardiovascular risk factors early in life may be an important predictor of cognitive function later in life.[2] For example, in epidemiologic studies, midlife elevation of systolic or diastolic blood pressure may be associated with cognitive impairment or dementia in later years.[3,4] Attention, memory, and new learning may be sensitive to blood pressure level, especially when there are "complicated" hypertensive manifestations such as WMH.[5] Interest in WMH and cognitive function has led to studies on the effects of sustained daytime and nocturnal blood pressure ("nondipping"), nocturnal dips in blood pressure, and hypertension control on the risk of developing WMH.[2] Normally, blood pressure dips during sleep; however, sustained nocturnal blood pressure or exaggerated dips in nocturnal blood pressure may predict small deep infarcts and WMH. On the therapy front, the Systolic Hypertension in Europe (Syst-Eur) trial suggests that the incidence of dementia can be reduced by 50% with treatment of isolated systolic hypertension; importantly, 19 cases of dementia might be prevented if 1,000 patients were treated for 5 years.[6] Other lifestyle or metabolic factors such as smoking, hyperinsulinemia, insulin resistance, diabetes mellitus, and alcohol consumption (protective or at-risk effect) may also affect cognitive function.[4,7-9] Moreover, cardiovascular disease risk factors may even predict AD10 and suggest a connection between neurodegeneration and atherosclerotic disease.[2]
MRI is now important for understanding the effects of cardiovascular risk factors on brain aging and function. MRI volumetric studies suggest that hypertensive patients lose brain volume in key brain areas such as the hippocampus, parahippocampus, and thalamic nuclei. The reduced MRI volume is associated with poorer performance on tests of cognitive function (e.g., memory and language).[11-13] These findings are more likely to occur as we get older as there are interactive effects of age and hypertension.[5,13]
Can we save the brain from the ravages of hypertension and other cardiovascular risk factors that appear to contribute to neurodegenerative and vascular causes of cognitive impairment? We need more prospective studies of the progression of brain morphologic changes that are associated with cognitive and physical function and various risk factors.[1] Furthermore, we must understand mechanisms of interventions that we use to treat the risk factor(s). For example, does treatment of hypertension reduce the risk of cognitive dysfunction by:
We may be able to prevent brain damage associated with modifiable midlife cardiovascular disease risk factors if we treat them.[15] Currently, we should redouble our efforts to detect and control modifiable cardiovascular risk factors that decrease brain volume.