Effects of Homocysteine on white matter diffusion parameters in Alzheimer’s disease

Abstract

BackgroundThe clinical features of Alzheimer’s disease (AD) are related to brain network degeneration, and hyperhomocysteinemia is related to greater white matter hyperintensities. We investigated the changes in four diffusion tensor imaging parameters in the white matter of patients with early stage AD, examined their associations with homocysteine level, and tested the clinical significance of the diffusion tensor imaging parameters and homocysteine level in correlation analysis with cognitive test scores.MethodsWe enrolled 132 patients with AD and analyzed white matter (WM) macrostructural changes using diffusion tensor neuroimaging parameters including fractional anisotropy (FA), mean diffusion (MD), axial diffusivity (axial-D) and radial diffusivity (RD). Two neuroimaging post-processing analyses were performed to provide complementary data. First, we calculated 11 major bundle microstructural integrities using a WM parcellation algorithm, and correlated them with serum homocysteine levels to explore whether the fiber bundles were affected by homocysteine. Second, we used tract-based spatial statistics to explore the anatomical regions associated with homocysteine levels. Changes in cognitive test scores caused by homocysteine served as the major outcome factor.ResultsThe results suggested that homocysteine levels did not have a direct impact on cross-sectional cognitive test scores, but that they were inversely correlated with renal function, B12 and folate levels. Topographies showing independent correlations with homocysteine in FA and MD were more diffusely located compared to the posterior brain regions in axial-D and RD. In the association bundle analysis, homocysteine levels were significantly correlated with the four diffusion parameters even after correcting for confounders, however no association between homocysteine and WM to predict cognitive outcomes was established.ConclusionsIn our patients with AD, homocysteine levels were associated with renal dysfunction and decreased levels of vitamin B12 and folate, all of which require clinical attention as they may have been associated with impaired WM microstructural integrity and modulated cognitive performance in cross-sectional observations.

Association of serum cystatin C with white matter abnormalities in patients with amnestic mild cognitive impairment

“…Several studies have shown the association between WMH and blood levels of molecules, such as cystatin C (CysC), 25‐hydroxyvitamin D and homocysteine, and the presence of lifestyle‐associated diseases, such as hypertension, hyperlipidemia and diabetes mellitus . However, most of these studies have assessed WMH by visual rating, which is not very precise .…”

“…Several studies have shown the association between WMH and blood levels of molecules, such as cystatin C (CysC), 25-hydroxyvitamin D and homocysteine, and the presence of lifestyleassociated diseases, such as hypertension, hyperlipidemia and diabetes mellitus. [8][9][10] However, most of these studies have assessed WMH by visual rating, which is not very precise. [3][4][5] In the present study, we calculated the volume of periventricular hyperintensities (PVH) and deep WMH (DWMH) on T2 fluid-attenuated inversion recovery (FLAIR) MRI using 3D Slicer, a freely available, opensource software package for visualization, registration, segmentation, and quantification of medical data (http://www.slicer.org).…”

Vitamin D, Folate, and Cobalamin Serum Concentrations Are Related to Brain Volume and White Matter Integrity in Urban Adults

“…This is corroborated by a direct association between annual 25(OH)D increase and ALIC volumes at follow-up. While previous studies have linked vitamin D and folate deficiency to WM damage (Sachdev et al, 2002;Bleich and Kornhuber, 2003;Den Heijer et al, 2003;Dufouil et al, 2003;Scott et al, 2004;Censori et al, 2007;De Lau et al, 2009;Pieters et al, 2009;Buell et al, 2010;Prager et al, 2014;Annweiler et al, 2015b;Del Brutto et al, 2015;Moon et al, 2015;Wu et al, 2015;Lee et al, 2017), our study further specified most affected ROIs and target socio-demographic groups. The ALIC connects the thalamus with the frontal lobe, suggesting these nutrients can maintain cognitive functions that are reliant on frontothalamic connectivity, such as executive function (Schoenberg and Scott, 2011;Jacobs et al, 2013).…”

Corrigendum: Vitamin D, Folate, and Cobalamin Serum Concentrations Are Related to Brain Volume and White Matter Integrity in Urban Adults

“…Novel are our findings that folate and 25(OH)D are related to greater white matter integrity, with folate being inversely related to MD in the ALIC region while 25(OH)D being related to higher FA in the cingulum (cingulate gyrus). While previous studies have linked vitamin D and folate deficiency to WM damage (Sachdev et al, 2002;Bleich and Kornhuber, 2003;Den Heijer et al, 2003;Dufouil et al, 2003;Scott et al, 2004;Censori et al, 2007;De Lau et al, 2009;Pieters et al, 2009;Buell et al, 2010;Prager et al, 2014;Annweiler et al, 2015b;Del Brutto et al, 2015;Moon et al, 2015;Wu et al, 2015;Lee et al, 2017), our study further specified most affected ROIs and target socio-demographic groups. The ALIC connects the thalamus with the frontal lobe, suggesting these nutrients can maintain cognitive functions that are reliant on frontothalamic connectivity, such as executive function (Schoenberg and Scott, 2011;Jacobs et al, 2013).…”