Mini Review: Correlations of Cognitive Domains With Cerebrospinal Fluid α-Synuclein Levels in Patients With Parkinson's Disease.

Hidetomo Murakami,Shusaku Omoto,Tadashi Umehara,Kenjiro Ono,Tomotaka Shiraishi,Yasuyuki Iguchi

doi:10.3389/fnagi.2020.616357

Abstract

The level of α-synuclein, a component of Lewy bodies, in cerebrospinal fluid (CSF) in Parkinson's disease (PD) has attracted recent attention. Most meta-analyses conclude that CSF levels of α-synuclein are decreased in PD. Patients with PD present with cognitive impairment, including frontal/executive dysfunction in the early phase and later emergence of visuospatial and mnemonic deficits. To examine whether CSF α-synuclein levels reflect the activities of various cognitive domains, we reviewed reports examining the association of these levels with cognitive performance in each domain in PD. Among 13 cross-sectional studies, five showed that a lower CSF α-synuclein level was associated with worse cognitive function. In four of these five reports, frontal/executive function showed this association, suggesting a link of the pathophysiology with Lewy bodies. In three other reports, a higher CSF α-synuclein level was associated with temporal-parieto-occipital cognitive deterioration such as memory. In the other five reports, the CSF α-synuclein level did not correlate with cognitive performance for any domain. In four longitudinal studies, a higher baseline CSF α-synuclein level was associated with a worse cognitive outcome, including cognitive processing speed, visuospatial function and memory in two, but not with any cognitive outcome in the other two. The different associations may reflect the heterogeneous pathophysiology in PD, including different pathogenic proteins, neurotransmitters. Thus, more studies of the association between cognitive domains and CSF levels of pathogenic proteins are warranted.

Highlights

Parkinson’s disease (PD) is a common neurodegenerative disease that presents with motor and various non-motor symptoms, including cognitive impairment
Skogseth et al (2015) showed that low Cerebrospinal fluid (CSF) α-synuclein was significantly associated with phonemic fluency and attention, but not with posterior cortical domains, such as memory and visuospatial domains, in PD and PD with mild cognitive impairment (PD-MCI)
We have shown that lower CSF α-synuclein is associated with worse performance in a judgement subtest that assesses planning and executive function, but not with subtests assessing other cognitive domains in patients with PD, PD-MCI and PD with dementia (PDD) (Murakami et al, 2019)

Summary

INTRODUCTION

Parkinson’s disease (PD) is a common neurodegenerative disease that presents with motor and various non-motor symptoms, including cognitive impairment Such impairment of frontal/executive function, such as flexibility, planning, and working memory, is common as early cognitive impairment in PD (Williams-Gray et al, 2007; Kehagia et al, 2010). Twelve papers examining associations of CSF α-synuclein levels and cognitive function in single domains were included in the study (Table 1). Three of these reports included two or three associations (Stewart et al, 2014; Compta et al, 2015; Førland et al, 2018), and 13 cross-sectional results were used from the 12 papers (Tables 1A–C). There were 4 longitudinal studies, of which two showed that a higher CSF α-synuclein level predicted worse cognitive outcome (Table 1D) and the other two showed no association (Tables 1E,F)

Results

CONCLUSION AND FUTURE PERSPECTIVE