The burden of microstructural damage modulates cortical activation in elderly subjects with MCI and leuko‐araiosis. A DTI and fMRI study

Abstract

The term leuko-araiosis (LA) describes a common chronic affection of the cerebral white matter (WM) in the elderly due to small vessel disease with variable clinical correlates. To explore whether severity of LA entails some adaptive reorganization in the cerebral cortex we evaluated with functional MRI (fMRI) the cortical activation pattern during a simple motor task in 60 subjects with mild cognitive impairment and moderate or severe (moderate-to-severe LA group, n = 46) and mild (mild LA group, n = 14) LA extension on visual rating. The microstructural damage associated with LA was measured on diffusion tensor data by computation of the mean diffusivity (MD) of the cerebral WM and by applying tract based spatial statistics (TBSS). Subjects were examined with fMRI during continuous tapping of the right dominant hand with task performance measurement. Moderate-to-severe LA group showed hyperactivation of left primary sensorimotor cortex (SM1) and right cerebellum. Regression analyses using the individual median of WM MD as explanatory variable revealed a posterior shift of activation within the left SM1 and hyperactivation of the left SMA and paracentral lobule and of the bilateral cerebellar crus. These data indicate that brain activation is modulated by increasing severity of LA with a local remapping within the SM1 and increased activity in ipsilateral nonprimary sensorimotor cortex and bilateral cerebellum. These potentially adaptive changes as well lack of contralateral cerebral hemisphere hyperactivation are in line with sparing of the U fibers and brainstem and cerebellar WM tracts and the emerging microstructual damage of the corpus callosum revealed by TBSS with increasing severity of LA.

Sitagliptin attenuated brain damage and cognitive impairment in mice with chronic cerebral hypo-perfusion through suppressing oxidative stress and inflammatory reaction

“…arteriosclerosis), subsequently leads to WML [4,11]. To date, the treatment of VCI remains a formidable challenge to clinicians [1,2,12]. Although the precise mechanisms of VCI remain unclear, hypertension is still a major risk for cerebrovascular disease and VCI [8].…”

“…Abbreviations: BBB, blood-brain barrier; BCAS, bilateral carotid artery stenosis; BDNF, brain-derived neurotrophic factor; CHP, chronic cerebral hypoperfusion; CREB, cAMP response element-binding protein; DPP-4, dipeptidyl peptidase-4; GAFA, glial fibrillary acidic protein; GLP-1, glycogen-like peptide-1; GLP-1R, glycogen-like peptide-1 receptor; IBA-1, ionized calcium binding adaptor molecule-1; MCP, monocyte chemoattractant protein; MMP, matrix metalloproteinase; MRI, Magnetic resonance imaging; NRT, novel recognition test; TNF, tumour necrosis factor; VID, vascular impairment dementia D ementia, a syndrome of acquired intellectual deficit resulting in significant impairment of social and occupational function, has become a growing epidemic that imposes an economic burden on an ageing society [1][2][3][4]. Cerebrovascular insufficiency caused by atherosclerosis is the most likely cause of ischemic white matter lesions (WML) that result in cognition and memory impairment known as vascular cognitive impairment (VCI) [1,[5][6][7].…”

Disconnections of Cortico-Subcortical Pathways Related to Cognitive Impairment in Patients with Leukoaraiosis: A Preliminary Diffusion Tensor Imaging Study

“…As a result, a potential weakness of the current study was the inter-dependence of the data within subjects in the preprocessing of DTI maps. In contrast to regional analysis of DTI data, the promising tract-based spatial statistics is a more recently described technique, which offers the advantage of whole brain voxel-wise analysis with the preservation of spatial information [28]. Second, the severity of LA was generally rated visually according to the Fazekas scale, with 3 different categories (mild, moderate, and severe).…”

Prediction of Impaired Performance in Trail Making Test in MCI Patients With Small Vessel Disease Using DTI Data

“…Diffusion tensor imaging (DTI) is a well-established technique for in-vivo characterization of directional and overall diffusivity of water molecules in WM tracts which has been successfully employed to unveil microstructural changes and their connection to neurophysiological mechanisms underlying various neurodegenerative disorders (for a review, see Goveas et al [16]) as well as in elderly subjects with variable cognitive status [14], [17]. In this context, machine learning techniques have recently been identified as promising tools in neuroimaging data analysis (for a review, see Orrù et al [18]).…”