White matter grade and ventricular volume on brain MRI as markers of longevity in the cardiovascular health study

Abstract

High white matter grade (WMG) on magnetic resonance imaging (MRI) is a risk factor for dementia, stroke and disability. Higher ventricular size is a marker of brain “atrophy.” In the Cardiovascular Health Study (CHS) (n = 3245) mean age 75 years, 50% black and 40% men, we evaluated WM and ventricular grade (VG), total, cardiovascular and noncardiovascular mortality and longevity before and after adjusting for numerous determinants of longevity over an approximate 10–12 years of follow-up. A low WMG and VG was a marker for low total, cardiovascular and noncardiovascular mortality and for increased longevity over 10+ years of follow-up. We estimated that a 75-year-old with WMG below median would have about a 5–6 years greater longevity and for VG about 3 years, than above the median even after adjustment for numerous risk factors. Low WMG and VG on MRI is a powerful determinant of long-term survival among older individuals.

Introduction

The identification of objective markers of longevity among older individuals is important for both the study of the determinants of longevity and identification of potential therapeutic agents. Epidemiological studies, including the Cardiovascular Health Study (CHS), have shown that high ventricular grade (VG) and white matter grade (WMG) on magnetic resonance imaging (MRI) of the brain were predictors of dementia, which is associated with increased mortality [2], [57], [16], [24], [25], [54].

High WMG is likely related to small vessel vascular disease in the brain [37], [43]. Risk factors for high WMG include age, higher systolic blood pressure (SBP), carotid intimal medial thickness, and lower forced expiratory volume in 1 s (FEV1) [33], [19]. A strong and direct linear relationship with SBP and WMG has been demonstrated for both men and women [33]. Many clinical features have also been correlated with high WMG in CHS, especially impaired cognition and lower extremity function [33]. High WMG was also an independent predictor of the risk of stroke and dementia [24], [23], [20], [56], [4]. Risk factors for high VG included white race, male sex, age, higher WMG and retinopathy [30]. High VG has also been associated with poorer cognitive and physical function and increased risk of dementia [25], [30]. Preliminary data from CHS have suggested a lower mortality rate in 5-year follow-up for persons with lower ventricular size or WMG [32], [31]. Longer-term follow-up and the independence of the associations of high WMG and ventricular size with mortality have not been examined. The leukoaraiosis and disability in the elderly (LADIS) study is evaluating age-related white matter change as an independent predictor of transition to disability in 639 subjects. They are using the Fazakas scale to quantify white matter lesions [42], [12].

In this report from the CHS we evaluated measures of ventricular volume and white matter grade based on magnetic resonance imaging among 3245 CHS participants age 65+, mean age 75, in 1992–1994 and subsequent total mortality and survivorship through 30 June 2002.

We have tested the hypothesis that lower ventricular and/or WMG is inversely associated with total mortality and directly related to survivorship, and that the association persists after adjustment for clinical or subclinical cardiovascular disease (CVD), hypertension, diabetes, apolipoprotein E₄ (ApoE₄) and other measures in the CHS which have been related to survivorship.