Cerebral Metabolism Related to Cognitive Impairments in Multiple System Atrophy

Abstract

Objective: We aimed to characterize the cognitive profiles in multiple system atrophy (MSA) and explore the cerebral metabolism related to the cognitive decline in MSA using 18F-fluorodeoxyglucose (18F-FDG) Positron Emission Tomography (PET).Methods: In this study, 105 MSA patients were included for cognitive assessment and 84 of them were enrolled for 18F-FDG PET analysis. The comprehensive neuropsychological tests covered five main domains including execution, attention, memory, language, and visuospatial function. The cognitive statuses were classified to MSA with normal cognition (MSA-NC) and MSA with cognitive impairment (MSA-CI), including dementia (MSA-D), and mild cognitive impairment (MSA-MCI). With 18F-FDG PET imaging, the cerebral metabolism differences among different cognitive statuses were analyzed using statistical parametric mapping and post-hoc analysis.Results: Among 84 MSA patients, 52 patients were found with MSA-CI, including 36 patients as MSA-MCI and 16 patients as MSA-D. In detail, the cognitive impairments were observed in all the five domains, primarily in attention, executive function and memory. In 18F-FDG PET imaging, MSA-D and MSA-MCI patients exhibited hypometabolism in left middle and superior frontal lobe compared with MSA-NC (p < 0.001). The normalized regional cerebral metabolic rate of glucose (rCMRglc) in left middle frontal lobe showed relative accuracy in discriminating MSA-CI and MSA-NC [areas under the curve (AUC) = 0.750; 95%CI = 0.6391–0.8609].Conclusions: Cognitive impairments were not rare in MSA, and the hypometabolism in frontal lobe may contribute to such impairments.

The Frontal and Cerebellar Metabolism Related to Cognitive Dysfunction in Multiple System Atrophy

“…Motor disability was evaluated by the Unified Parkinson’s Disease Rating Scale III (UPDRS III) in all participants in a Med-Off state, which means that the patients were off anti-parkinsonism drugs for more than 12 h. Global cognitive status and cognitive dysfunction in five domains covering attention, executive function, memory, visuospatial function, and language were assessed using Mini-Mental State Examination (MMSE) and a series of comprehensive neuropsychological tests, which were as follows: attention by the Symbol Digit Modalities Test (SDMT; Sheridan et al, 2006 ) and part A of Trail-Making Test (TMT-A; Zhao et al, 2013 ); executive function by the part C of Stroop Color-Word Test (CWT-C; Steinberg et al, 2005 ) and part B of Trail-Making Test (TMT-B; Zhao et al, 2013 ); memory function by the Auditory Verbal Learning Test (AVLT; Guo et al, 2009 ) and delayed recall task of the Rey-Osterrieth Complex Figure Test (CFT-delay recall) ( Caffarra et al, 2002 ); visuospatial function by copy task of Rey-Osterrieth Complex Figure Test (CFT; Caffarra et al, 2002 ) and the Clock Drawing Test (CDT; Ricci et al, 2016 ); and language ability by Animal Verbal Fluency Test (AVFT) and Boston Naming Test (BNT; Lucas et al, 2005 ). To eliminate dimensional differences in tests and quantify impairments of cognition, neuropsychological results of each test of all patients were transformed into Z -score using the mean and SD of the norm data from healthy controls of similar age and education in the Shanghai area ( Wu et al, 2018 ; Shen et al, 2021 ): Z -score = (test score - mean score of norm data)/SD of norm data (when data was a score) or Z -score = (mean time of norm data - test time)/SD of norm data (when data were a time metrics) ( Wu et al, 2018 ). Z -score less than −1.5 was defined to be the impairment in each test and Z -score of each cognition domain was calculated using the average Z -score of two tests in the same cognition domain.…”

“…The 18 F-fluorodeoxyglucose ( 18 F-FDG) positron emission tomography (PET) imaging can reflect the cerebral metabolic changes and disclose disease-specific alterations (Eckert et al, 2005(Eckert et al, , 2008. In our previous report, MSA-CI exhibited lower glucose metabolism in the left middle and superior frontal lobe, compared with MSA-NC (Shen et al, 2021). Nevertheless, the cerebral metabolic changes related to detailed cognitive performances in MSA remain to be further explored.…”

“…Although dementia is a non-supporting item according to the second consensus statement on the diagnosis of MSA ( Gilman et al, 2008 ), accumulating data showed great evidence for possible cognitive decline in MSA. Specifically, nearly half of the patients with MSA presented with cognitive impairments in some epidemiological data, with a broad spectrum of injury ( Brown et al, 2010 ; Stankovic et al, 2014 ; Shen et al, 2021 ). At present, however, the underlying mechanisms of cognitive impairments in MSA are still far from being clearly understood.…”

Quantitative cellular changes in multiple system atrophy brains

“…In the frontal cortex, a significant decrease in the total number of neurons in the brains of MSA patients with executive dysfunction was observed, compared to those without cognitive impairment [50]. Similarly, an [ 18 F]FDG PET study has found decreased frontal lobe glucose metabolism in MSA patients with dementia relative to MSA patients with only mild or moderate cognitive impairment, supporting the notion that frontal neurodegenerative changes in the later stages of the disease eventually cause cognitive dysfunction [77]. A further link between frontal lobe pathology and cognitive dysfunction is established by the recent observation of a significant loss of neurons in the mediodorsal thalamus (MDT), suggesting the occurrence of parallel neurodegeneration in the prefrontal cortical‐MDT pathway [54].…”