Cognitive aging, executive function, and fractional anisotropy: a diffusion tensor MR imaging study

Abstract

Background and purpose: Fractional anisotropy (FA) is a useful measure of connectivity in the brain that can be derived from the diffusion tensor imaging (DTI) dataset. This study investigated the relationship between FA and selected measures of cognition across a broad age group to explore a possible structural basis for cognitive changes with age.

Methods: FA images were generated from DTI data acquired at 1.5T in 87 healthy subjects (age range, 20-73 years). Relationships between a range of cognitive measures and FA were explored using regional and voxel-based analysis.

Results: Age and regional average FA were significantly associated in the frontal, parietal, and temporal lobes but not in the occipital lobe. This negative relationship was especially prominent in the prefrontal regions of the frontal lobe, where FA declined at a rate of approximately 3% per decade. Decreased FA in the frontal, temporal, and parietal lobes was associated with poorer cognitive performance in executive maze and in an attention-switching task. A voxel-level analysis of these data revealed that the executive function-FA association was particularly strong and regionally delineated over 2 continuous, bilateral areas extending from the prefrontal cortex to the parietal lobe, with projections to the anterior portions of the thalamus.

Conclusions: We demonstrate a relationship between FA and a measure of executive function-a core cognitive component that is a key feature of cognitive aging. We propose that that FA may provide an early means for the detection of age-related cognitive change and suggest a need for prospective data to explore this association.

Fig 1.

Scatterplots displaying the relationship between FA and age (A). FA decreases linearly with age (β = 0.010/year; 95% CI, 0.007–0.013 year; r² = 0.371; P < .001). B, FA and time to completion for the executive maze test. Higher FA is associated with faster completion of the maze, a relationship described by a linear trend (β = −24 seconds per 0.01 FA unit; 95% CI, 16–33 seconds per 0.01 FA; r² = 0.274; P < .001).

Fig 2.

A, A series of axial images at 10-mm intervals showing T-scores (in color) superimposed over a representative high-resolution anatomic magnetization-prepared rapid acquisition of gradient echo (MPRAGE) image in standardized MNI space. Bilateral cluster of voxels are present in the frontal and parietal lobes (sections +28 to +48 mm); in addition, significant voxels connect these regions to the anterior thalamus (sections −2 to +28 mm). B, A series of coronal sections at 10-mm intervals showing the connection between the frontal and parietal significant voxels with the anterior thalamus (section −6 mm). Bilateral clusters of voxels represent brain regions where a significant negative association between FA and age exists. These clusters indicate regions in which FA loss is greatest in advancing age.

Fig 3.

A, A series of axial images at 10-mm intervals showing T-scores (in color) superimposed over a representative high-resolution anatomic MPRAGE image in standardized MNI space. Bilateral cluster of voxels are present in the frontal and parietal lobes (sections +28 to +48 mm), in addition significant voxels connect these regions to the anterior thalamus (sections −2 to +28 mm). B, A series of coronal sections at 10-mm intervals showing the connection between the frontal and parietal significant voxels with the anterior thalamus (section −6 mm). Color voxels represent regions of association between voxel FA and overall time score in an executive function task is significant.

Fig 4.

A maximum intensity projection image displaying the age-related FA changes superimposed over the significant regions of FA associated with altered performance in executive function task. The volume of the age-FA cluster was 29.4 mL versus 49.5 mL in the executive function-FA association cluster.