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Cerebral white matter lesions (WMLs) have been consistently related to cognitive dysfunction but the role of white matter (WM) damage in cognitive impairment is not fully determined. Diffusion tensor imaging is a promising tool to explain impaired cognition related to WMLs. We investigated the separate association of high-grade periventricular hyperintensities (PVHs) and deep white matter hyperintensities (DWMHs) with fractional anisotropy (FA) in middle-aged individuals. We also assessed the predictive value to cognition of FA within specific WM tracts associated with high-grade WMLs. One hundred participants from the Barcelona-AsIA Neuropsychology Study were divided into groups based on low- and high-grade WMLs. Voxel-by-voxel FA were compared between groups, with separate analyses for high-grade PVHs and DWMHs. The mean FA within areas showing differences between groups was extracted in each tract for linear regression analyses. Participants with high-grade PVHs and participants with high-grade DWMHs showed lower FA in different areas of specific tracts. Areas showing decreased FA in high-grade DWMHs predicted lower cognition, whereas areas with decreased FA in high-grade PVHs did not. The predictive value to cognition of specific WM tracts supports the involvement of cortico-subcortical circuits in cognitive deficits only in DWMHs.

Background: The contribution of traditional vascular risk factors to cognitive impairment and dementia is well known. However, in order to obtain possible targets for prevention of vascular cognitive impairment (VCI), it may be important to identify other early and noninvasive markers in asymptomatic middle-aged adults. The calculation of middle cerebral artery-pulsatility index (MCA-PI) is an ultrasonologic, noninvasive, validated and easily reproducible technique to assess increased distal resistance to blood flow. This study aims to assess the relationship between MCA-PI, microstructural white matter (WM) integrity and cognition in a middle-aged asymptomatic population., Methods: Ninety-five participants from the Barcelona-Asymptomatic Intracranial Atherosclerosis (AsIA) neuropsychology study were included. Subjects were 50-65 years old, free from dementia and without history of vascular disease. Transcranial color-coded duplex ultrasound examination was performed to assess MCA-PI as a measure of vascular resistance. WM integrity was evaluated by fractional anisotropy (FA) measurements of diffusion tensor images (DTI) acquired on a 3T-MRI. The neuropsychological battery was specifically selected to be sensitive to VCI, and included tests that were grouped into six cognitive domains: executive functioning, attention, verbal fluency, memory, visuospatial skills and psychomotor speed. A multivariate linear regression model adjusted for age, gender, years of education, diabetes and hypertension was performed., Results: MCA-PI was significantly associated with WM disintegration in different tracts (fornix, corticospinal and anterior thalamic), all p < 0.05 uncorrected. Both mean MCA-PI and mean FA of those significant tracts were independently associated with poor performance in attention, psychomotor speed, and visuospatial skills after adjustment for age, gender, years of education, and vascular risk factors (all p < 0.05). MCA-PI was independently associated with lower scores in all cognitive domains, except for visuospatial skills., Conclusions: Our data suggest that MCA-PI may be related to WM disintegration and early vascular cognitive impairment in middle-aged subjects. Although further prospective studies are needed to provide evidence for its validity in longitudinal studies, our results support the proposal of including MCA-PI as part of clinical assessment in order to identify targets for VCI prevention., (© 2014 S. Karger AG, Basel.)

The association of cerebral white matter lesions (WMLs) with cognitive status is not well understood in middle-aged individuals. Our aim was to determine the specific contribution of periventricular hyperintensities (PVHs) and deep white matter hyperintensities (DWMHs) to cognitive function in a community sample of asymptomatic participants aged 50 to 65 years. One hundred stroke- and dementia-free adults completed a comprehensive neuropsychological battery and brain MRI protocol. Participants were classified according to PVH and DWMH scores (Fazekas scale). We dichotomized our sample into low grade WMLs (participants without or with mild lesions) and high grade WMLs (participants with moderate or severe lesions). Analyses were performed separately in PVH and DWMH groups. High grade DWMHs were associated with significantly lower scores in executive functioning (-0.45 standard deviations [SD]), attention (-0.42 SD), verbal fluency (-0.68 SD), visual memory (-0.52 SD), visuospatial skills (-0.79 SD), and psychomotor speed (-0.46 SD). Further analyses revealed that high grade DWMHs were also associated with a three- to fourfold increased risk of impaired scores (i.e.,<1.5 SD) in executive functioning, verbal fluency, visuospatial skills, and psychomotor speed. Our findings suggest that only DWMHs, not PVHs, are related to diminished cognitive function in middle-aged individuals. (JINS, 2012, 18, 1-12).