Cognitive processing speed in older adults: relationship with white matter integrity.

Kerchner, Geoffrey A; Racine, Caroline A; Hale, Sandra; Wilheim, Reva; Laluz, Victor; Miller, Bruce L; Kramer, Joel H · 2012 · DOAJ

DOI: 10.1371/journal.pone.0050425

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Summary

This study investigates the neural mechanisms underlying age-related declines in cognitive processing speed, specifically examining the role of white matter integrity. While cognitive slowing is a well-documented phenomenon in aging that impacts daily functioning, such as driving ability, its precise biological causes remain unclear. The authors hypothesized that microstructural degradation of cerebral white matter, detectable via diffusion tensor imaging (DTI), mediates this decline, independent of other age-related changes like gray matter atrophy or white matter lesions. The researchers employed a cross-sectional design involving 131 cognitively normal adults aged 55–87. To isolate pure cognitive processing speed from motor performance, the team developed a novel battery of seven computerized, non-verbal, binary choice reaction time tasks. These tasks required visuospatial judgments (e.g., abstract matching, mental rotation, visual search) but involved simple button presses. Performance was quantified as a composite z-score relative to a young adult control group. Participants underwent 3T MRI, including DTI sequences. Data were analyzed using tract-based spatial statistics (TBSS) to assess diffusion metrics, primarily fractional anisotropy (FA), mean diffusivity (MD), and radial diffusivity (DR). The study also controlled for gray and white matter volume via voxel-based morphometry and white matter lesion load. Results confirmed that cognitive processing speed slowed significantly with age. Crucially, this slowing correlated strongly with reduced white matter integrity. Specifically, lower FA (indicating less organized white matter) and higher MD and DR correlated with slower reaction times. These associations were most prominent in frontal and parietal white matter, particularly within the genu and body of the corpus callosum, the superior longitudinal fasciculus, and the inferior fronto-occipital fasciculus. Importantly, statistical mediation analysis demonstrated that loss of white matter integrity fully mediated the relationship between age and processing speed. Furthermore, this relationship persisted after controlling for gray and white matter atrophy and was not explained by white matter lesion volume. In contrast, white matter integrity did not correlate with verbal episodic memory performance, suggesting specificity to processing speed. The findings establish that age-related cognitive slowing is distinct from other aging processes, such as memory decline or gross tissue atrophy, and is primarily driven by microstructural white matter degradation. By using a rigorous, motor-independent assessment of processing speed, the study provides robust evidence that white matter integrity is a key determinant of cognitive efficiency in older adults. This highlights the potential utility of DTI metrics in predicting functional decline and underscores the importance of white matter health in maintaining cognitive performance during aging.

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• cognitive aging