Background: The biological basis of cognitive ageing is unknown. One underlying process might be disruption of white matter tracts connecting cortical regions. White matter lesions (WML) seen on structural MRI may disrupt cortical connections, but diffusion tensor MRI (DT-MRI) parameters – mean diffusivity () and fractional anisotropy (FA) – may reflect more subtle changes in white matter integrity. Here the relationships between WML load, DT-MRI parameters and cognition in a large cohort of elderly subjects with a very narrow age range were investigated. Methods: 105 community-dwelling volunteers underwent MRI and neuropsychological assessment. Seventy-two (68.6%) were female, and their mean age was 78.4 (SD 1.5) years. Scans were rated for WML load. and FA were measured from regions of interest in normal-appearing frontal and occipital white matter, and centrum semiovale. Results: and FA differed significantly among the three brain regions studied (p ≪ 0.01). increased with age (r = 0.22 to 0.35, p < 0.03), and was negatively correlated with FA (r = –0.20 to –0.51, p < 0.05) in all three regions. There was a trend towards increased WML load correlating with poorer cognitive function, and this was statistically significant for the Mini-Mental State Examination (ρ = –0.23, p = 0.02). was generally negatively correlated with cognitive test score, and FA was positively correlated. This pattern was more consistent for than for FA, and particularly for verbal fluency (: r = –0.22 to –0.27, p < 0.03), which measures executive function. Conclusions: DT-MRI parameters, in particular , are sensitive to early ultrastructural changes underlying cognitive ageing. Executive function may be the cognitive domain most sensitive to age-related decline in white matter tract integrity.
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