Tract-specific white matter degeneration in aging: the Rotterdam Study.

BACKGROUND:Loss of brain white matter microstructure is presumed to be an early sign of neurodegenerative disease. Yet, little is known on microstructural changes of various white matter tracts with normal aging. METHODS:In 4532 nondemented elderly persons, we studied age-related changes in tract-specific diffusion characteristics for 25 tracts using probabilistic tractography. We studied how diffusion differs across tracts with aging, whether this depends on macrostructural white matter changes, and whether cardiovascular risk factors affect microstructure. RESULTS:With increasing age, loss of microstructural organization occurred in association, commissural and limbic tracts. White matter lesions and atrophy each partially explained this loss. We observed worse microstructure with severe hypertension, current smoking and diabetes mellitus, independent from age and macrostructural white matter changes. CONCLUSIONS:Microstructure of white matter tracts changes with age, and may mark neurodegeneration more sensitively than white matter lesion load and atrophy. Cardiovascular factors relate to loss in microstructural organization.