Gray Matter Atrophy And Corresponding Impairments In Connectivity In Patients With Anti-N-Methyl-D-Aspartate Receptor Encephalitis

Anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis is a severe autoimmune disease that is commonly accompanied by cognitive impairment and various neurological and psychiatric symptoms, advanced image analyses help explore the pathogenesis of this disease. Therefore, this study aimed to explore specific structural and functional alterations and their relationship with the clinical symptoms of anti-NMDAR encephalitis. In this study, twenty-two patients with anti-NMDAR encephalitis after the acute stage and 29 controls received cognitive assessments and magnetic resonance imaging. Grey matter atrophy was measured using voxel-based morphometry, and functional alterations in abnormal regions were subsequently investigated using resting state functional connectivity (RSFC). Finally, correlation analyses were performed to explore the associations between imaging alterations and cognitive assessments. The patients demonstrated significant gray matter atrophy in the bilateral triangle part of the inferior frontal gyrus (triIFG.L and triIFG.R) and right precuneus, decreased RSFC between triIFG.L and bilateral Heschl gyrus (HES), decreased RSFC between triIFG.R and HES.R, decreased RSFC between right precuneus and left cerebellum, and increased RSFC between triIFG.R and left superior frontal gyrus. Further correlation analyses showed that the gray matter volume in triIFG.R and decreased RSFC between triIFG.L and HES.R were associated with decreased memory scores, whereas decreased RSFC between triIFG.R and HES.R was marginally correlated with the disease course in patients. In conclusion, this study suggests that cognitive impairments in patients with anti-NMDAR encephalitis may be mainly associated with gray matter atrophy and abnormal RSFC in the triIFG. These findings provide new insights into anti-NMDAR encephalitis pathogenesis and help explore potential treatments.

The Influence of MTHFR Polymorphism on Gray Matter Volume in Patients With Amnestic Mild Cognitive Impairment

The methylenetetrahydrofolate reductase (MTHFR) gene has been associated with Alzheimer’s disease (AD) pathogenesis. Amnestic mild cognitive impairment (aMCI) represents a prodromal stage of dementia and involves a high risk of progression into AD. Although the effects of the apolipoprotein E (APOE) gene on structural alterations in aMCI have been widely investigated, the effects of MTHFR C677T and interaction effects of MTHFR × APOE genotypes on gray matter atrophy in aMCI remain largely unknown. In the present study, 60 aMCI patients and 30 healthy controls were enrolled, and voxel-based morphometry analysis was performed to inspect the effects of diagnosis, different genotypes, and their interactions on gray matter atrophy. The results showed that aMCI patients had significant gray matter atrophy involving the bilateral hippocampus, the right parahippocampal gyrus, and the left superior temporal gyrus compared with healthy controls. Besides, a substantial reduction in gray matter volume was observed in the right hippocampus region in APOE ε4 carriers from the aMCI group, compared with APOE ε4 non-carriers. A significant interaction was found between diagnosis and MTHFR C677T genotype on the right precuneus in healthy controls and aMCI patients not carrying APOE ε4 allele. Our findings may provide new evidence substantiating the genetic effects of MTHFR C677T on brain structural alternation in patients with aMCI.

Odor Identification and Regional Gray Matter Atrophy in Patients with Alzheimer’s Disease, Parkinson’s Disease, and the Healthy Elderly: A Cross-Sectional Structural MRI Study

Multiple associations between impaired olfactory performance and regional cortical and deep gray matter atrophy have been reported in separate studies of patients with Alzheimer’s disease (AD), Parkinson’s disease (PD), and of the healthy elderly. We aimed to evaluate such possible associations among these populations in a unified manner. Twenty AD, twenty PD patients’ and twenty healthy age- and sex-matched controls’ odor identification performance was assessed with the Lithuanian adaptation of the Sniffin’ Sticks 12 odor identification test, followed by morphometric gray matter analysis by MRI using FreeSurfer. AD patients had significantly lower cognitive performance than both PD patients and the healthy elderly, as evaluated with the Mini-Mental State Examination (MMSE). Odor identification performance was significantly worse in AD and PD patients compared with the healthy elderly; AD patients performed slightly worse than PD patients, but the difference was not statistically significant. Among patients with AD, worse odor identification performance was initially correlated with atrophy of multiple cortical and deep gray matter regions known to be involved in olfactory processing, however, only two measures—decreased thicknesses of the right medial and left lateral orbitofrontal cortices—remained significant after adjustment for possible confounders (age, MMSE score, and global cortical thickness). Among patients with PD and the healthy elderly we found no similar statistically significant correlations. Our findings support the key role of the orbitofrontal cortex in odor identification among patients with AD, and suggest that correlations between impaired odor identification performance and regional gray matter atrophy may be relatively more pronounced in AD rather than in PD.