Abstract
Cerebral small-vessel damage manifests as white matter hyperintensities and cerebral atrophy on brain MRI and is associated with aging, cognitive decline and dementia. We sought to examine the interrelationship of these imaging biomarkers and the influence of hypertension in older individuals. We used a multivariate spatial covariance neuroimaging technique to localize the effects of white matter lesion load on regional gray matter volume and assessed the role of blood pressure control, age and education on this relationship. Using a case-control design matching for age, gender, and educational attainment we selected 64 participants with normal blood pressure, controlled hypertension or uncontrolled hypertension from the Northern Manhattan Study cohort. We applied gray matter voxel-based morphometry with the scaled subprofile model to (1) identify regional covariance patterns of gray matter volume differences associated with white matter lesion load, (2) compare this relationship across blood pressure groups, and (3) relate it to cognitive performance. In this group of participants aged 60–86 years, we identified a pattern of reduced gray matter volume associated with white matter lesion load in bilateral temporal-parietal regions with relative preservation of volume in the basal forebrain, thalami and cingulate cortex. This pattern was expressed most in the uncontrolled hypertension group and least in the normotensives, but was also more evident in older and more educated individuals. Expression of this pattern was associated with worse performance in executive function and memory. In summary, white matter lesions from small-vessel disease are associated with a regional pattern of gray matter atrophy that is mitigated by blood pressure control, exacerbated by aging, and associated with cognitive performance.
Highlights
White matter hyperintensities (WMH) observed on T2 MRI are frequently discovered incidentally but are more prevalent with increased age, hypertension, and other cerebrovascular risk factors (Fazekas, 1989; DeCarli et al, 1995; de Leeuw et al, 2001)
In this study we identify regional differences in gray matter volume (GMV) associated with WMH lesion load in a group of cognitively normal older adults and investigate the effects of blood pressure control, age, sex, education, and overall intelligence on this relationship, as well as examine the association between the WMH-associated GMV (WMH∼GMV) pattern and domainspecific cognitive performance
There were no differences between the study participants and the overall Northern Manhattan Study (NOMAS) population in age, ethnic distribution, smoking status, diabetes status, cognitive scores or Center for Epidemiologic Studies Depression Scale (CESD)
Summary
White matter hyperintensities (WMH) observed on T2 MRI are frequently discovered incidentally but are more prevalent with increased age, hypertension, and other cerebrovascular risk factors (Fazekas, 1989; DeCarli et al, 1995; de Leeuw et al, 2001). The origins of WMHs are thought to be heterogeneous, ischemic small-vessel disease is one established etiology (DeCarli et al, 2005), and extensive lesions are associated with an increased risk of stroke (Fazekas et al, 1993), gait disturbance (Whitman et al, 2001), cognitive impairment and decline (de Groot et al, 2000), and dementia (Barber et al, 1999). WMH and hypertension increase the risk of all-cause dementia (Barber et al, 1999; Launer et al, 2000), Alzheimer’s disease (Hofman et al, 1997), and are independently linked to cognitive decline (van Swieten et al, 1991), with aspects of frontal lobe-mediated executive functions, memory, and processing speed preferentially affected (Junqué et al, 1990; Prins et al, 2005). Since cognitive changes in aging may be mediated by gray matter loss (Raji et al, 2012), it is important to understand how WMH relate to gray matter volume, and which risk factors modify this relationship
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