Brain structure and verbal function across adulthood while controlling for cerebrovascular risks

Abstract

The development and decline of brain structure and function throughout adulthood is a complex issue, with cognitive aging trajectories influenced by a host of factors including cerebrovascular risk. Neuroimaging studies of age-related cognitive decline typically reveal a linear decrease in gray matter (GM) volume/density in frontal regions across adulthood. However, white matter (WM) tracts mature later than GM, particularly in regions necessary for executive functions and memory. Therefore, it was predicted that a middle-aged group (MC: 35-45 years) would perform best on a verbal working memory task and reveal greater regional WM integrity, compared with both young (YC: 18-25 years) and elder groups (EC: 60+ years). Diffusion tensor imaging (DTI) and magnetoencephalography (MEG) were obtained from 80 healthy participants. Objective measures of cerebrovascular risk and cognition were also obtained. As predicted, MC revealed best verbal working memory accuracy overall indicating some maturation of brain function between YC and MC. However, contrary to the prediction fractional anisotropy values (FA), a measure of WM integrity, were not greater in MC (i.e., there were no significant differences in FA between YC and MC but both groups showed greater FA than EC). An overall multivariate model for MEG ROIs showed greater peak amplitudes for MC and YC, compared with EC. Subclinical cerebrovascular risk factors (systolic blood pressure and blood glucose) were negatively associated with FA in frontal callosal, limbic, and thalamic radiation regions which correlated with executive dysfunction and slower processing speed, suggesting their contribution to age-related cognitive decline. Hum Brain Mapp 38:3472-3490, 2017. © 2017 Wiley Periodicals, Inc.

Keywords: DTI; MEG; blood pressure; blood sugar; cerebrovascular risk; development; fractional anisotropy; normal aging; verbal memory; working memory.

Figure 1

Verbal Sternberg working memory task. [Color figure can be viewed at http://wileyonlinelibrary.com]

Figure 2

Verbal working memory performance and cerebrovascular risk factors by groups. Histograms reveal group differences in task performance (top row) and for two common cerebrovascular risk factors (bottom row): systolic blood pressure and blood glucose level (A1c). Standard deviation is shown as error bars for each group. Red lines indicate significant group differences at P < 0.05. The dashed arc in the upper left panel depicts an inverted U‐shaped function across age, which was predicted. [Color figure can be viewed at http://wileyonlinelibrary.com]

Figure 3

Box plots for FX (FA, RD, and AD). A comparison between DTI parameters for the Fornix. Red bars represent group differences. [Color figure can be viewed at http://wileyonlinelibrary.com]

Figure 4

Examples of correlation plots for results presented in Table 3. In particular, the correlation between limbic and thalamic radiations and cerebrovascular risk, as well as performance on verbal working memory task (timing). [Color figure can be viewed at http://wileyonlinelibrary.com]

Figure 5

A. Timecourses for each ROI (left parahippocamal, left inferior parietal, and left inferior frontal gyrus) and time periods of interest (T1, T2, and T3) for each of the 3 age groups (YC = blue tracing, MC = red tracing, and EC = green tracing) are shown. An “*” indicates significant difference in latency in T2, with EC > YC and MC, P = 0.009). B. DKT atlas with ROIs outlined and labeled. C. MEG difference plots using whole‐brain dSPM analysis methods (minimum norm estimates). Top row: blue color represents greater activation levels for MC compared with YC, except in the right medial temporal lobe. Second row: Yellow‐orange color reveals regions of greater activity for MC compared with EC. Third row shows greater activity for YC compared with EC across extensive regions of cortex. Difference plots were constructed for 200–400 ms intervals, poststimulus. Amplitude in fT. Left hemisphere is shown on the left side of these plots.

Figure 6

Left panel: Scalp field maps for YC, MC, and EC at 0, 100, 200, 300, 400, and 500 ms (top view). Right panel: Composite overlay of the waveforms for YC (red tracing), MC (blue tracing), and EC (green tracing) from −200 to 500 ms.