Biomarkers for cognitive impairment in alpha-synucleinopathies: an overview of systematic reviews and meta-analyses

Elisa Mantovani; Alice Martini; Alessandro Dinoto; Chiara Zucchella; Sergio Ferrari; Sara Mariotto; Michele Tinazzi; Stefano Tamburin

doi:10.1038/s41531-024-00823-x

Biomarkers for cognitive impairment in alpha-synucleinopathies: an overview of systematic reviews and meta-analyses

NPJ Parkinsons Dis. 2024 Nov 2;10(1):211. doi: 10.1038/s41531-024-00823-x.

Authors

Elisa Mantovani¹, Alice Martini^{2

3}, Alessandro Dinoto⁴, Chiara Zucchella⁵, Sergio Ferrari⁵, Sara Mariotto⁴, Michele Tinazzi⁴, Stefano Tamburin⁶

Affiliations

¹ Department of Neurosciences, Biomedicine and Movement Sciences, University of Verona, Verona, Italy. [email protected].
² School of Psychology, Keele University, Newcastle, UK.
³ Addiction Department, Azienda Sanitaria Friuli Occidentale, Pordenone, Italy.
⁴ Department of Neurosciences, Biomedicine and Movement Sciences, University of Verona, Verona, Italy.
⁵ Section of Neurology, Department of Neurosciences, Verona University Hospital, Verona, Italy.
⁶ Department of Neurosciences, Biomedicine and Movement Sciences, University of Verona, Verona, Italy. [email protected].

Abstract

Cognitive impairment (CI) is common in α-synucleinopathies, i.e., Parkinson's disease, Lewy bodies dementia, and multiple system atrophy. We summarize data from systematic reviews/meta-analyses on neuroimaging, neurophysiology, biofluid and genetic diagnostic/prognostic biomarkers of CI in α-synucleinopathies. Diagnostic biomarkers include atrophy/functional neuroimaging brain changes, abnormal cortical amyloid and tau deposition, and cerebrospinal fluid (CSF) Alzheimer's disease (AD) biomarkers, cortical rhythm slowing, reduced cortical cholinergic and glutamatergic and increased cortical GABAergic activity, delayed P300 latency, increased plasma homocysteine and cystatin C and decreased vitamin B12 and folate, increased CSF/serum albumin quotient, and serum neurofilament light chain. Prognostic biomarkers include brain regional atrophy, cortical rhythm slowing, CSF amyloid biomarkers, Val66Met polymorphism, and apolipoprotein-E ε2 and ε4 alleles. Some AD/amyloid/tau biomarkers may diagnose/predict CI in α-synucleinopathies, but single, validated diagnostic/prognostic biomarkers lack. Future studies should include large consortia, biobanks, multi-omics approach, artificial intelligence, and machine learning to better reflect the complexity of CI in α-synucleinopathies.