Brain networks associated with cognitive reserve in healthy young and old adults

Abstract

In order to understand the brain networks that mediate cognitive reserve, we explored the relationship between subjects' network expression during the performance of a memory test and an index of cognitive reserve. Using H2(15)O positron emission tomography, we imaged 17 healthy older subjects and 20 young adults while they performed a serial recognition memory task for nonsense shapes under two conditions: low demand, with a unique shape presented in each study trial; and titrated demand, with a study list size adjusted so that each subject recognized shapes at 75% accuracy. A factor score that summarized years of education, and scores on the NART and the WAIS-R Vocabulary subtest was used as an index of cognitive reserve. The scaled subprofile model was used to identify a set of functionally connected regions (or topography) that changed in expression across the two task conditions and was differentially expressed by the young and elderly subjects. The regions most active in this topography consisted of right hippocampus, posterior insula, thalamus, and right and left operculum; we found concomitant deactivation in right lingual gyrus, inferior parietal lobe and association cortex, left posterior cingulate, and right and left calcarine cortex. Young subjects with higher cognitive reserve showed increased expression of the topography across the two task conditions. Because this topography, which is responsive to increased task demands, was differentially expressed as a function of reserve level, it may represent a neural manifestation of innate or acquired reserve. In contrast, older subjects with higher cognitive reserve showed decreased expression of the topography across tasks. This suggests some functional reorganization of the network used by the young subjects. Thus, for the old subjects this topography may represent an altered, compensatory network that is used to maintain function in the face of age-related physiological changes.

Figure 1

Top: Samples of the shapes used in the nonverbal recognition task. A probe item is denoted by a surrounding rectangle. Bottom: Schematic of the nonverbal recognition task for study list sizes of 1 and 3.

Figure 2

The common (A) and age-related (B) covariance patterns (topographies) noted in the 20 young and 17 healthy elderly subjects. Weights for regions with most marked participation in the topography have been overlaid on standard Tailarach-transformed axial MRI sections, with positive weights indicated in red and negative weights indicated in blue. Radiological convention is used. (A) Common topography. This topography consisted of positive loadings in the right and left anterior cingulate and left orbital frontal cortex, with associated negative loadings in left association cortex and right cerebellum and vermis. (B) Age-related topography. This topography consisted of positive loadings in the right hippocampus, posterior insula, thalamus, and right and left operculum; negative loadings in right lingual gyrus, inferior parietal lobe and association cortex, left posterior cingulate, and right and left calcarine cortex.

Figure 3

Subjects’ expression, as measured by the subject scaling factor of the common and age-related topographies in the young and old groups. (A) Common topography. Note that mean expression is comparable across the two groups, but that the range is greater in the younger group. (B) Age-related topography. Note that mean expression of this topography is lower in the young than the old subjects.

Figure 4

Correlation between expression of the differential topography and the cognitive reserve factor in the young and old subjects. Note that this correlation is positive in the young group and negative in the old group.