Influence of Small Vessel Disease and Microstructural Integrity on Neurocognitive Functioning in Older Individuals: The DANTE Study Leiden.

BACKGROUND AND PURPOSE Small vessel disease is a major cause of neurocognitive dysfunction in the elderly. Small vessel disease may manifest as white matter hyperintensities, lacunar infarcts, cerebral microbleeds, and atrophy, all of which are visible on conventional MR imaging or as microstructural changes determined by diffusion tensor imaging. This study investigated whether microstructural integrity is associated with neurocognitive dysfunction in older individuals, irrespective of the conventional features of small vessel disease. MATERIALS AND METHODS The study included 195 participants (75 years of age or older) who underwent conventional 3T MR imaging with DTI to assess fractional anisotropy, mean diffusivity, axial diffusivity, and radial diffusivity. Cognitive tests were administered to assess cognitive domains, and the Geriatric Depression Scale-15 and Apathy Scale of Starkstein were used to assess symptoms of depression and apathy, respectively. The association between DTI measures and neurocognitive function was analyzed by using linear regression models. RESULTS In gray matter, a lower fractional anisotropy and higher mean diffusivity, axial diffusivity, and radial diffusivity were associated with worse executive function, psychomotor speed, and overall cognition and, in white matter, also with memory. Findings were independent of white matter hyperintensities, lacunar infarcts, and cerebral microbleeds. However, after additional adjustment for normalized brain volume, only lower fractional anisotropy in white and gray matter and higher gray matter radial diffusivity remained associated with executive functioning. DTI measures were not associated with scores on the Geriatric Depression Scale-15 or the Apathy Scale of Starkstein. CONCLUSIONS Microstructural integrity was associated with cognitive but not psychological dysfunction. Associations were independent of the conventional features of small vessel disease but attenuated after adjusting for brain volume.