Predictors of brain morphology for the men of the NHLBI twin study

Background and Purpose - Cross-sectional studies show that cerebrovascular risk factors are associated with increased brain atrophy, accumulation of abnormal cerebral white matter signals, and clinically silent stroke. We extend these findings by examining the relationship between midlife cerebrovascular risk factors and later-life differences in brain atrophy, amount of abnormal white matter, and stroke on MRI. Methods - Subjects were the 414 surviving members of the prospective National Heart, Lung, and Blood Institute Twin Study, who have been examined on 4 separate occasions, spanning the 25 years between 1969-1973 and 1995-1997. Quantitative measures of brain volume, volume of abnormal white matter signal (WMHI), and volume of stroke, when present, were obtained from those participating in the fourth examination. Results - The mean±SD age of the subjects was 47.2±3.0 years at initial examination and 72.5±2.9 years at final examination. Average blood pressure (BP) levels were normal, although 32% of the subjects had received or were currently taking antihypertensive medications. As a group, 31% had symptomatic cardiovascular disease, 11% had symptomatic cerebrovascular disease, and 8% had symptomatic peripheral vascular disease. Both Systolic and diastolic BP levels at initial examination were inversely related to brain volume and positively related to WMHI volume. Multiple regression analysis identified BP-related measures and vascular risk factors as significant predictors of brain and WMHI volumes. In addition, the magnitude of orthostatic BP change was significantly associated with WMHI volume. Subjects with extensive amounts of WMHI had significantly higher systolic BP at the final examination and a higher prevalence of symptomatic cardiovascular and cerebrovascular disease, without significant differences in the prevalence of hypertension treatment. Conclusions - Midlife BP measures are significantly associated with later-life brain and WMHI volumes and the prevalence of symptomatic vascular disease. Since WMHI share cerebrovascular risk factors and extensive WMHI are associated with symptomatic vascular disease, extensive WMHI may be a subclinical expression of cerebrovascular disease. Careful treatment of midlife BP elevations may diminish these later-life brain changes.