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

Background and Purpose-Cross-sectional studies show that cerebrovascular ri sk factors are associated with increased brain atrophy, accumulation of abn ormal cerebral white matter signals, and clinically silent stroke. We exten d these findings by examining the relationship between midlife cerebrovascu lar risk factors and later-life differences in brain atrophy, amount of abn ormal 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 s eparate occasions, spanning the 25 years between 1969-1973 and 1995-1997. Q uantitative measures of brain volume, volume of abnormal white matter signa l (WMHI), and volume of stroke, when present, were obtained from those part icipating in the fourth examination. Results-The mean+/-SD age of the subjects was 47.2+/-3.0 years at initial e xamination and 72.5+/-2.9 years at final examination. Average blood pressur e (BP) levels were normal, although 32% of the subjects had received or wer e currently taking antihypertensive medications. As a group, 31% had sympto matic cardiovascular disease, 11% had symptomatic cerebrovascular disease, and 8% had symptomatic peripheral vascular disease. Both systolic and diast olic BP levels at initial examination were inversely related to brain volum e and positively related to WMHI volume. Multiple regression analysis ident ified BP-related measures and vascular risk factors as significant predicto rs of brain and WMHI volumes. In addition, the magnitude of orthostatic BP change was significantly associated with WMHI volume. Subjects with extensi ve amounts of WMHI had significantly higher systolic BP at the final examin ation and a higher prevalence of symptomatic cardiovascular and cerebrovasc ular disease, without significant differences in the prevalence of hyperten sion treatment. Conclusions-Midlife BP measures are significantly associated with later-lif e brain and WMHI volumes and the prevalence of symptomatic vascular disease . Since WMHI share cerebrovascular risk factors and extensive WMHI are asso ciated with symptomatic vascular disease, extensive WMHI may be a subclinic al expression of cerebrovascular disease. Careful treatment of midlife BP e levations may diminish these later-life brain changes.