This review highlights recent advances in premotor and nonmotor features in Parkinson's disease, focusing on these issues in the context of prodromal and early-stage Parkinson's disease.
Although ...Parkinson's disease patients experience a wide range of nonmotor symptoms throughout the disease course, studies demonstrate that nonmotor features are not solely a late manifestation. Indeed, disturbances of smell, sleep, mood, and gastrointestinal function may herald Parkinson's disease or related synucleinopathies and precede these neurodegenerative conditions by 5 or more years. In addition, other nonmotor symptoms such as cognitive impairment are now recognized in incident or de-novo Parkinson's disease cohorts. Many of these nonmotor features reflect disturbances in nondopaminergic systems and early involvement of peripheral and central nervous systems, including olfactory, enteric, and brainstem neurons as in Braak's proposed pathological staging of Parkinson's disease. Current research focuses on identifying potential biomarkers that may detect persons at risk for Parkinson's disease and permit early intervention with neuroprotective or disease-modifying therapeutics.
Recent studies provide new insights into the frequency, pathophysiology, and importance of nonmotor features in Parkinson's disease as well as the recognition that these nonmotor symptoms occur in premotor, early, and later phases of Parkinson's disease.
A diagnosis of motor Parkinson's disease (PD) is preceded by a prolonged premotor phase with accumulating neuronal damage. Here we examined the temporal relation between α-synuclein (α-syn) T cell ...reactivity and PD. A longitudinal case study revealed that elevated α-syn-specific T cell responses were detected prior to the diagnosis of motor PD, and declined after. The relationship between T cell reactivity and early PD in two independent cohorts showed that α-syn-specific T cell responses were highest shortly after diagnosis of motor PD and then decreased. Additional analysis revealed significant association of α-syn-specific T cell responses with age and lower levodopa equivalent dose. These results confirm the presence of α-syn-reactive T cells in PD and show that they are most abundant immediately after diagnosis of motor PD. These cells may be present years before the diagnosis of motor PD, suggesting avenues of investigation into PD pathogenesis and potential early diagnosis.
The prodromal phase of dementia with Lewy bodies (DLB) includes (1) mild cognitive impairment (MCI), (2) delirium-onset, and (3) psychiatric-onset presentations. The purpose of our review is to ...determine whether there is sufficient information yet available to justify development of diagnostic criteria for each of these. Our goal is to achieve evidence-based recommendations for the recognition of DLB at a predementia, symptomatic stage. We propose operationalized diagnostic criteria for probable and possible mild cognitive impairment with Lewy bodies, which are intended for use in research settings pending validation for use in clinical practice. They are compatible with current criteria for other prodromal neurodegenerative disorders including Alzheimer and Parkinson disease. Although there is still insufficient evidence to propose formal criteria for delirium-onset and psychiatric-onset presentations of DLB, we feel that it is important to characterize them, raising the index of diagnostic suspicion and prioritizing them for further investigation.
To evaluate microstructural characteristics of the corpus callosum using diffusion tensor imaging (DTI) and their relationships to cognitive impairment in Parkinson disease (PD).
Seventy-five ...participants with PD and 24 healthy control (HC) participants underwent structural MRI brain scans including DTI sequences and clinical and neuropsychological evaluations. Using Movement Disorder Society criteria, PD participants were classified as having normal cognition (PD-NC, n = 23), mild cognitive impairment (PD-MCI, n = 35), or dementia (PDD, n = 17). Cognitive domain (attention/working memory, executive function, language, memory, visuospatial function)
scores were calculated. DTI scalar values, including fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (AD), and radial diffusivity (RD), were established for 5 callosal segments on a midsagittal plane, single slice using a topographically derived parcellation method. Scalar values were compared among participant groups. Regression analyses were performed on cognitive domain
scores and DTI metrics.
Participants with PD showed increased AD values in the anterior 3 callosal segments compared to healthy controls. Participants with PDD had significantly increased AD, MD, and RD in the anterior 2 segments compared to participants with PD-NC and most anterior segment compared to participants with PD-MCI. FA values did not differ significantly between participants with PD and participants with HC or among PD cognitive groups. The strongest associations for the DTI metrics and cognitive performance occurred in the most anterior and most posterior callosal segments, and also reflected fronto-striatal and posterior cortical type cognitive deficits, respectively.
Microstructural white matter abnormalities of the corpus callosum, as measured by DTI, may contribute to PD cognitive impairment by disrupting information transfer across interhemispheric and callosal-cortical projections.
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