Dataset Information

The Global Cognition, Frontal Lobe Dysfunction and Behavior Changes in Chinese Patients with Multiple System Atrophy.

ABSTRACT:

Background

Studies on cognition in multiple system atrophy (MSA) patients are limited.

Methods

A total of 110 MSA patients were evaluated using Addenbrooke's Cognitive Examination-Revised (ACE-R), Frontal Assessment Battery (FAB), Frontal Behavioral Inventory (FBI), and Unified MSA Rating Scale (UMSARS) tests. Fifty-five age-, sex-, education- and domicile-matched healthy controls were recruited to perform the FAB and ACE-R scales.

Results

Approximately 32.7% of the patients had global cognitive deficits with the most impaired domain being verbal fluency and visuospatial ability (26.4%), followed by memory (24.5%), language (20%) and orientation/attention (20%) based on a cut-off score of ACE-R ≤ 70. A total of 41.6% of the patients had frontal lobe dysfunction, with inhibitory control (60.9%) as the most impaired domain based on a cut-off score of FAB ≤14. Most patients (57.2%) showed moderate frontal behavior changes (FBI score 4-15), with incontinence (64.5%) as the most impaired domain. The binary logistic regression model revealed that an education level < 9 years (OR:13.312, 95% CI:2.931-60.469, P = 0.001) and UMSARS ≥ 40 (OR: 2.444, 95%CI: 1.002-5.962, P< 0.049) were potential determinants of abnormal ACE-R, while MSA-C (OR: 4.326, 95%CI: 1.631-11.477, P = 0.003), an education level < 9 years (OR:2.809 95% CI:1.060-7.444, P = 0.038) and UMSARS ≥ 40 (OR:5.396, 95%CI: 2.103-13.846, P < 0.0001) were potential determinants of abnormal FAB.

Conclusions

Cognitive impairment is common in Chinese MSA patients. MSA-C patients with low education levels and severe motor symptoms are likely to experience frontal lobe dysfunction, while MSA patients with low education levels and severe motor symptoms are likely to experience global cognitive deficits. These findings strongly suggest that cognitive impairment should not be an exclusion criterion for the diagnosis of MSA.

SUBMITTER: Cao B

PROVIDER: S-EPMC4591982 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:Multiple system atrophy (MSA) is a rare neurodegenerative disease characterized by neuronal loss and gliosis, with oligodendroglial cytoplasmic inclusions (GCIs) containing α-synuclein being the primary pathological hallmark. Clinical presentations of MSA overlap with other parkinsonian disorders, such as Parkinson's disease (PD), dementia with Lewy bodies (DLB), and progressive supranuclear palsy (PSP), posing challenges in early diagnosis. Numerous studies have reported alterations in DNA methylation in neurodegenerative diseases, with candidate loci being identified in various parkinsonian disorders including MSA, PD, and PSP. Although MSA and PSP present with substantial white matter pathology, alterations in white matter have also been reported in PD. However, studies comparing the DNA methylation architectures of white matter in these diseases are lacking. We therefore aimed to investigate genome-wide DNA methylation patterns in the frontal lobe white matter of individuals with MSA (n = 17), PD (n = 17), and PSP (n = 16) along with controls (n = 15) using the Illumina EPIC array, to identify shared and disease-specific DNA methylation alterations. Genome-wide DNA methylation profiling of frontal lobe white matter in the three parkinsonian disorders revealed substantial commonalities in DNA methylation alterations in MSA, PD, and PSP. We further used weighted gene correlation network analysis to identify disease-associated co-methylation signatures and identified dysregulation in processes relating to Wnt signaling, signal transduction, endoplasmic reticulum stress, mitochondrial processes, RNA interference, and endosomal transport to be shared between these parkinsonian disorders. Our overall analysis points toward more similarities in DNA methylation patterns between MSA and PD, both synucleinopathies, compared to that between MSA and PD with PSP, which is a tauopathy. Our results also highlight several shared DNA methylation changes and pathways indicative of converging molecular mechanisms in the white matter contributing toward neurodegeneration in all three parkinsonian disorders.