CSF neurochemical profile and cognitive changes in Parkinson's disease with mild cognitive impairment

Federico Paolini Paoletti; Lorenzo Gaetani; Giovanni Bellomo; Elena Chipi; Nicola Salvadori; Chiara Montanucci; Andrea Mancini; Marta Filidei; Pasquale Nigro; Simone Simoni; Nicola Tambasco; Massimiliano Di Filippo; Lucilla Parnetti

doi:10.1038/s41531-023-00509-w

CSF neurochemical profile and cognitive changes in Parkinson's disease with mild cognitive impairment

NPJ Parkinsons Dis. 2023 Apr 24;9(1):68. doi: 10.1038/s41531-023-00509-w.

Authors

Affiliations

¹ Section of Neurology, Department of Medicine and Surgery, University of Perugia, Perugia, Italy.
² Laboratory of Clinical Neurochemistry, Section of Neurology, Department of Medicine and Surgery, University of Perugia, Perugia, Italy.
³ Section of Neurology, Department of Medicine and Surgery, University of Perugia, Perugia, Italy. lucilla.parnetti@unipg.it.
⁴ Laboratory of Clinical Neurochemistry, Section of Neurology, Department of Medicine and Surgery, University of Perugia, Perugia, Italy. lucilla.parnetti@unipg.it.

^# Contributed equally.

Abstract

Pathophysiological substrate(s) and progression of Parkinson's disease (PD) with mild cognitive impairment (PD-MCI) are still matter of debate. Baseline cerebrospinal fluid (CSF) neurochemical profile and cognitive changes after 2 years were investigated in a retrospective series of PD-MCI (n = 48), cognitively normal PD (PD-CN, n = 40), prodromal Alzheimer's disease (MCI-AD, n = 25) and cognitively healthy individuals with other neurological diseases (OND, n = 44). CSF biomarkers reflecting amyloidosis (Aβ42/40 ratio, sAPPα, sAPPβ), tauopathy (p-tau), neurodegeneration (t-tau, NfL, p-NfH), synaptic damage (α-syn, neurogranin) and glial activation (sTREM2, YKL-40) were measured. The great majority (88%) of PD-MCI patients was A-/T-/N-. Among all biomarkers considered, only NfL/p-NfH ratio was significantly higher in PD-MCI vs. PD-CN (p = 0.02). After 2 years, one-third of PD-MCI patients worsened; such worsening was associated with higher baseline levels of NfL, p-tau, and sTREM2. PD-MCI is a heterogeneous entity requiring further investigations on larger, longitudinal cohorts with neuropathological verification.