Higher blood pressure predicts lower regional grey matter volume: Consequences on short-term information processing

Abstract

Hypertension is a risk factor for diffuse brain atrophy. Yet, there is little evidence that higher blood pressure predicts focal brain atrophy, as indicated by a lower volume of regional brain tissue. This voxel-based morphometry study tested (a) whether higher blood pressure predicts lower regional grey or white matter volume and (b) whether a blood-pressure-related reduction in regional brain tissue volume predicts poorer neuropsychological test performance. Participants were 76 men (M age = 61.33, SD = 4.95 years) and 58 women (M age = 59.86, SD = 5.10 years) without a cardiovascular, cerebrovascular, or neuropsychiatric disease. Results showed that among men, higher resting systolic blood pressure predicted lower grey matter volume in the supplementary motor area and adjacent superior frontal gyrus, the anterior cingulate cortex, and middle temporal gyrus. Among men, lower grey matter volume in the supplementary motor area also predicted a slower time to complete the Trail Making Part B Test of executive control and a poorer recall of items from the Four-word Short-term Memory Test of working memory. These relationships were independent of age, total brain tissue volume, educational history, severity of carotid atherosclerosis, and the extent of periventricular and subcortical white matter lesions. Among women, no statistically significant relationships were found between blood pressure, regional brain tissue volume, and cognitive function. These findings suggest a functional relationship among men between higher blood pressure, lower regional grey matter volume, and poorer cognitive function that is independent of other risk factors and confounding medical conditions.

Fig. 1

Profiled in color are brain regions in which higher age (blue–green) and a sex-by-systolic blood pressure interaction (red–yellow) predicted a lower grey matter volume. The sex-by-blood pressure interaction was explained by men (n = 76), but not women (n = 53), showing a lower regional grey matter volume as a function of higher systolic blood pressure (see Fig. 3). Color-scaled t values (legends at lower right) were derived from a general linear model of voxel-wise grey matter volume that included total brain tissue volume as a nuisance variable. Montreal Neurological Institute coordinate values below each section of a grey matter template refer to the distance in millimeters relative to the midline for sagittal sections in this figure (+ = right; − = left) and to the anterior commissure for coronal sections in Fig. 2 (+ = anterior; − = posterior). In each section, white matter and cerebrospinal fluid are blackened.

Fig. 2

Profiled in color are brain regions in which higher age (blue–green) and a sex-by-systolic blood pressure interaction (red–yellow) predicted a lower grey matter volume. The sex-by-blood pressure interaction was explained by men (n = 76), but not women (n = 53), showing a lower regional grey matter volume as a function of higher systolic blood pressure (see Fig. 3). Color-scaled t values (legends at lower right) were derived from a general linear model of voxel-wise grey matter volume that included total brain tissue volume as a nuisance variable. Montreal Neurological Institute coordinate values below each section of a grey matter template refer to the distance in millimeters relative to the midline for sagittal sections in Fig. 1 (+ = right; − = left) and to the anterior commissure for coronal sections in this figure (+ = anterior; − = posterior). In each section, white matter and cerebrospinal fluid are blackened.

Fig. 3

Higher resting systolic blood pressure among men (n = 76), but not women (n = 58), predicted lower grey matter volumes in Brodmann areas 6, 8, 24, and 21. Grey matter volumes (shown along the y-axes) represent the sum of all volume values from those voxels within a 6 mm radius of the x, y, and z coordinates for the region in which sex and systolic blood pressure interacted to predict grey matter volume (see Table 2 for the coordinates for each region of interaction). Correlation coefficients off of each dotted line are for men (closed circles, solid lines) and women (open circles, dashed lines).

Fig. 4

Lower grey matter volume in Brodmann area 6 of the supplementary motor area was associated with higher resting systolic pressure and poorer performance on the Trail Making Test Part B (panel A) and the Four-word Short-term Memory Test (panel B) among 76 men. Shown along the x-axis of both panels are grey matter volume values for all voxels in a 6 mm radius surrounding the region of the supplementary motor area where higher systolic blood pressure predicted lower grey matter volume (Montreal Neurological Institute coordinates are x = −6, y = 23, z = 55). Shown along the y-axis in panel A are standardized Trail Making Test Part B completion times, adjusted for Trail Making Test Part A completion times (see Methods). Lower standardized Trail Making Test Part B completion times indicate better performance. Shown along the y-axis in panel B is the number of correctly recalled items after a 5-s distracting interval from the Four-word Short-term Memory Test.