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

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.

Fully automated measurement of plasma Aβ42/40 and p‐tau181: Analytical robustness and concordance with cerebrospinal fluid profile along the Alzheimer's disease continuum in two independent cohorts

“…PDD/DLB cases had a CSF A+/T+ profile in 47% of cases, in agreement with previous findings. 23 , 24 , 25 Regarding FTD patients, 42% had CSF A‐/T‐ and the remaining 58% were equally divided between CSF A‐/T+ and A+/T‐.…”

Pathobiology of Cognitive Impairment in Parkinson Disease: Challenges and Outlooks

“…It has been proposed that the development of cognitive decline prior to or simultaneous with the manifestation of motor symptoms should be included in the diagnostic procedures of PD [ 450 , 451 ]. The prospective assessment and validation of PD-CI and a deeper understanding of the interaction of multiple pathogenic factors will be achieved by modern fluid biomarkers (reduced αSyn and Aβ-42 levels, increased p-tau 181, glial fibrillary acidic protein/GFAP/and NfL) as well as in post-mortem brain tissue [ 452 , 453 , 454 , 455 , 456 , 457 , 458 ] that will also enable a differentiation between PD-CI and AD. In order to elucidate these and other open questions, a combined assessment of in vivo neuroimaging and liquid biomarkers in multicentric longitudinal clinico-pathological studies is warranted that also may contribute to the development of meaningful disease-modifying therapies and preventive measures to slow the progression of PD and associated cognitive deterioration.…”

Decoding sTREM2: its impact on Alzheimer’s disease – a comprehensive review of mechanisms and implications

“…This variability might stem from the differing stages of disease among participants, including the inclusion of individuals with preclinical AD in control groups ( Figure 2 ). CSF sTREM2 has shown promise as an indicator of cognitive decline in Parkinson’s disease (PD) ( Qin et al, 2022 ), especially in PD with mild cognitive impairment (PD-MCI), where baseline CSF levels were significantly higher in patients who exhibited cognitive deterioration over a two-year period compared to those who remained cognitively stable ( Paolini Paoletti et al, 2023 ). Remarkably, elevated CSF sTREM2 levels can be detected 12 to 14 years before the estimated onset of symptoms, marking its potential as an early indicator of neuroinflammatory changes ( Li et al, 2024 ).…”