Abstract
Parkinson’s disease is associated with cognitive decline, misfolded protein deposition and brain atrophy. We herein hypothesized that structural abnormalities may be mediators between plasma misfolded proteins and cognitive functions. Neuropsychological assessments including five domains (attention, executive, speech and language, memory and visuospatial functions), ultra-sensitive immunomagnetic reduction-based immunoassay (IMR) measured misfolded protein levels (phosphorylated-Tau, Amyloidβ-42 and 40, α-synuclein and neurofilament light chain) and auto-segmented brain volumetry using FreeSurfur were performed for 54 Parkinson’s disease (PD) patients and 37 normal participants. Our results revealed that PD patients have higher plasma misfolded protein levels. Phosphorylated-Tau (p-Tau) and Amyloidβ-42 (Aβ-42) were correlated with atrophy of bilateral cerebellum, right caudate nucleus, and right accumbens area (RAA). In mediation analysis, RAA atrophy completely mediated the relationship between p-Tau and digit symbol coding (DSC). RAA and bilateral cerebellar cortex atrophy partially mediated the Aβ-42 and executive function (DSC and abstract thinking) relationship. Our study concluded that, in PD, p-Tau deposition adversely impacts DSC by causing RAA atrophy. Aβ-42 deposition adversely impacts executive functions by causing RAA and bilateral cerebellum atrophy.
Highlights
54 Parkinson’s disease (PD) patients and 37 normal controls, statistical analysis of clinical characteristics showed no significant difference between age and sex
Our results showed significantly higher plasma p-Tau in PD patients, which correlated with atrophy of the bilateral cerebellar cortex, right caudate nucleus, and right accumbens area (RAA)
Our results demonstrate that atrophy of the nucleus accumbens contributes to executive function impairment, including to digit symbol coding (DSC) and abstract thinking (ABS)
Summary
Parkinson’s disease (PD) is currently the second most common neurodegenerative disease [1], lacking both efficient methods of early diagnosis and a mechanism-based cure [2]. In addition to motor deficits in PD patients, cognitive decline is increasingly emphasized and investigated. Individuals with PD have increased risk of dementia compared to the general population [3]. Such cognitive impairments in PD patients have significant impacts on quality of life and provide daily burdens for caregivers [4]. Detailed neuropsychological assessments are lengthy and cost time, while being heavily dependent on the adherence of patients. The lack of a long-term follow-up regarding cognitive function, early medical or psychological interventions remains challenging and potentially affects the
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