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From Clinical Neuroscience (R.A.C., T.R.B., Y.S., M.O., C.A.C., H.S.M.), and Basic Medical Sciences (D.J.M., F.A.H.), St. George's University of London, UK; Department of Psychology (R.G.M.), Institute of Psychiatry, King's College, University of London, UK.
Address correspondence and reprint requests to Dr. Hugh Markus, Clinical Neuroscience, St. George's University of London, Cranmer Terrace, London SW17 0RE, UK; e-mail: h.markus{at}sgul.ac.uk
Background: Damage to white matter tracts, resulting in "cerebral disconnection," may underlie age-related cognitive decline.
Methods: Using diffusion tensor MRI (DTI) to investigate white matter damage, and magnetic resonance spectroscopy (MRS) to look at its underlying pathologic basis, the authors investigated the relationship between white matter structure and cognition in 106 healthy middle-aged and elderly adults. Fractional anisotropy (FA) and mean diffusivity (MD) values, whole brain white matter histograms, and regions of interest placed in the white matter of the centrum semiovale were analyzed. Correlations with executive function, working memory, and information-processing speed were performed.
Results: There was a progressive reduction in FA and increase in diffusivity with age in both region of interest (r = 0.551, p < 0.001), and whole brain histograms (r = 0.625, p < 0.001). DTI values correlated with performance in all three cognitive domains. After controlling for age, DTI parameters correlated with working memory but not with the other two cognitive domains. MRS studies found a correlation of N-acetyl aspartate, a neuronal marker, with DTI parameters (r = 0.253, p < 0.05).
Conclusion: The results are consistent with white matter damage due to axonal loss, causing age- related cognitive decline. Working memory may be particularly dependent on complex networks dependent on white matter connections.
Supported by UK Charity Research into Ageing grant 227.
Disclosure: The authors report no conflicts of interest.
Received June 28, 2005. Accepted in final form October 11, 2005.
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