Deep versus Periventricular White Matter Lesions and Cognitive Function in a Community Sample of Middle-Aged Participants

AbstractThe 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)

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Tract-Specific Fractional Anisotropy Predicts Cognitive Outcome in a Community Sample of Middle-Aged Participants with White Matter Lesions

Journal of Cerebral Blood Flow & Metabolism ◽

10.1038/jcbfm.2014.26 ◽

2014 ◽

Vol 34 (5) ◽

pp. 861-869 ◽

Cited By ~ 10

Author(s):

Juan José Soriano-Raya ◽

Júlia Miralbell ◽

Elena López-Cancio ◽

Núria Bargalló ◽

Juan Francisco Arenillas ◽

...

Keyword(s):

White Matter ◽

Fractional Anisotropy ◽

Predictive Value ◽

Diffusion Tensor ◽

Community Sample ◽

White Matter Lesions ◽

Cognitive Outcome ◽

Cerebral White Matter ◽

High Grade ◽

Middle Aged

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.

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Silent cerebral white matter lesions and cognitive function in middle-aged essential hypertensive patients*1

American Journal of Hypertension ◽

10.1016/j.amjhyper.2004.02.014 ◽

2004 ◽

Vol 17 (6) ◽

pp. 529-534 ◽

Cited By ~ 41

Author(s):

C SIERRA

Keyword(s):

Cognitive Function ◽

White Matter ◽

White Matter Lesions ◽

Cerebral White Matter ◽

Middle Aged ◽

Hypertensive Patients ◽

Cerebral White Matter Lesions

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Relationship between small cerebral white matter lesions and cognitive function in patients with Alzheimer's disease and amnestic mild cognitive impairment

Geriatrics and Gerontology International ◽

10.1111/ggi.12176 ◽

2013 ◽

Vol 14 (4) ◽

pp. 819-826 ◽

Cited By ~ 12

Author(s):

Taeko Makino ◽

Hiroyuki Umegaki ◽

Yusuke Suzuki ◽

Madoka Yanagawa ◽

Zen Nonogaki ◽

...

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Cognitive Impairment ◽

Mild Cognitive Impairment ◽

Cognitive Function ◽

White Matter ◽

White Matter Lesions ◽

Amnestic Mild Cognitive Impairment ◽

Cerebral White Matter ◽

Cerebral White Matter Lesions

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Abstract WMP78: The Efficacy of Angiotensin II Peptide Vaccination Against White Matter Lesions of Vascular Dementia in Rats

Stroke ◽

10.1161/str.51.suppl_1.wmp78 ◽

2020 ◽

Vol 51 (Suppl_1) ◽

Author(s):

Kouji Wakayama ◽

Munehisa Shimamura ◽

Hironori Nakagami ◽

Ryuichi Morishita

Keyword(s):

Endothelial Cells ◽

Cognitive Function ◽

Angiotensin Ii ◽

White Matter ◽

Western Blot ◽

Vascular Dementia ◽

White Matter Lesions ◽

Ang Ii ◽

Peptide Vaccination ◽

Brdu Assay

Background & Purposes: There had been no attempt to show the efficacy of therapeutic vaccination in vascular dementia. A rat model of vascular dementia was prepared by bilateral common carotid artery ligation (2VO). The purpose of this study is to investigate whether pre-exposure Angiotensin II (Ang II) peptide vaccination exhibits the protective effects against white matter lesions (WML) in 2VO rats. Methods: After subcutaneous injection of Ang II peptide vaccine (10μg/200μl) or saline (200μl) to Wistar rats (male) at the time point of 6, 8 and 10 week-old, 2VO or sham surgery was performed at 12 week-old. Cognitive function was evaluated after 14 days of 2VO using the novel object recognition (NOR) test. Anti-Ang II antibody (Ab) level was quantified using ELISA. Histological examinations of WML and demyelination in the corpus callosum (CC) were evaluated using immunohistochemistry (IHC), 5-bromodeoxyuridine (BrdU) assay and Klüver-Barrera staining. Western blot analyses of VCAM-1, FGF2, phospho-CREB and CREB using proteins extracted from CC were performed to investigate the mechanism of restoration of WML by Ang II vaccination. Results: Histological examinations presented that exacerbation of WML and demyelination observed in saline treated (S) rats was ameliorated in Ang II vaccinated (V) rats. The results of NOR test indicated that cognitive dysfunction observed in S rats was improved in V rats at 14 days after 2VO. Expression of VCAM-1 in CC of S rats was significantly reduced in V rats at 7 days after 2VO. BrdU assay exhibited that vaccination accelerated the differentiation of oligodendrocyte progenitor cells (OPCs) in WML from 14 days to 28 days of 2VO. Western blot presented that both CREB phosphorylation and FGF2 expression in CC were increased in V rats compared with S rats at 14 days after 2VO. Double IHC showed that FGF2 expressing cells were mostly endothelial cells and astrocytes in WML. Conclusions: Ang II vaccination restored WML as well as cognitive function in 2VO rats. Our findings suggested that Ang II vaccination ameliorated cerebrovascular endothelial dysfunction which could accelerate the OPCs differentiation through increased expression of FGF2 in endothelial cells or astrocytes in 2VO rats.

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