Alterations In Parkinson's Disease Research Articles

Increased prevalence of vertebrobasilar dolichoectasia in Parkinson's disease and its effect on white matter microstructure and network.

This study aimed to investigate the prevalence of vertebrobasilar dolichoectasia (VBD) in Parkinson's disease (PD) patients and analyze its role in gray matter changes, white matter (WM) microstructure and network alterations in PD. This is a cross-sectional study including 341 PD patients. Prevalence of VBD in these PD patients was compared with general population. Diffusion tensor imaging and T1-weighted imaging analysis were performed among 174 PD patients with or without VBD. Voxel-based morphometry analysis was used to estimate gray matter volume changes. Tract-based spatial statistics and region of interest-based analysis were used to evaluate WM microstructure changes. WM network analysis was also performed. Significantly higher prevalence of VBD in PD patients was identified compared with general population. Lower fractional anisotropy and higher diffusivity, without significant gray matter involvement, were found in PD patients with VBD in widespread areas. Decreased global and local efficiency, increased hierarchy, decreased degree centrality at left Rolandic operculum, increased betweenness centrality at left postcentral gyrus and decreased average connectivity strength between and within several modules were identified in PD patients with VBD. VBD is more prevalent in PD patients than general population. Widespread impairments in WM microstructure and WM network involving various motor and nonmotor PD symptom-related areas are more prominent in PD patients with VBD compared with PD patients without VBD.

Alterations of Cortical Structure and Neurophysiology in Parkinson's Disease Are Aligned with Neurochemical Systems.

Parkinson's disease (PD) affects the structural integrity and neurophysiological signaling of the cortex. These alterations are related to the motor and cognitive symptoms of the disease. How these changes are related to the neurochemical systems of the cortex is unknown. We used T1-weighted magnetic resonance imaging (MRI) and magnetoencephalography (MEG) to measure cortical thickness and task-free neurophysiological activity in patients with idiopathic PD (nMEG = 79, nMRI = 65) and matched healthy controls (nMEG = 65, nMRI = 37). Using linear mixed-effects models, we examined the topographical alignment of cortical structural and neurophysiological alterations in PD with cortical atlases of 19 neurotransmitter receptor and transporter densities. We found that neurophysiological alterations in PD occur primarily in brain regions rich in acetylcholinergic, serotonergic, and glutamatergic systems, with protective implications for cognitive and psychiatric symptoms. In contrast, cortical thinning occurs preferentially in regions rich in noradrenergic systems, and the strength of this alignment relates to motor deficits. This study shows that the spatial organization of neurophysiological and structural alterations in PD is relevant for nonmotor and motor impairments. The data also advance the identification of the neurochemical systems implicated. The approach uses novel nested atlas modeling methodology that is transferrable to research in other neurological and neuropsychiatric diseases and syndromes. ANN NEUROL 2024;95:802-816.

Molecular characterization of the circadian clock in patients with Parkinson's disease-CLOCK4PD Study protocol.

Circadian rhythms (CRs) orchestrate intrinsic 24-hour oscillations which synchronize an organism's physiology and behaviour with respect to daily cycles. CR disruptions have been linked to Parkinson's Disease (PD), the second most prevalent neurodegenerative disorder globally, and are associated to several PD-symptoms such as sleep disturbances. Studying molecular changes of CR offers a potential avenue for unravelling novel insights into the PD progression, symptoms, and can be further used for optimization of treatment strategies. Yet, a comprehensive characterization of the alterations at the molecular expression level for core-clock and clock-controlled genes in PD is still missing. The proposed study protocol will be used to characterize expression profiles of circadian genes obtained from saliva samples in PD patients and controls. For this purpose, 20 healthy controls and 70 PD patients will be recruited. Data from clinical assessment, questionnaires, actigraphy tracking and polysomnography will be collected and clinical evaluations will be repeated as a follow-up in one-year time. We plan to carry out sub-group analyses considering several clinical factors (e.g., biological sex, treatment dosages, or fluctuation of symptoms), and to correlate reflected changes in CR of measured genes with distinct PD phenotypes (diffuse malignant and mild/motor-predominant). Additionally, using NanoStringⓇ multiplex technology on a subset of samples, we aim to further explore potential CR alterations in hundreds of genes involved in neuropathology pathways. CLOCK4PD is a mono-centric, non-interventional observational study aiming at the molecular characterization of CR alterations in PD. We further plan to determine physiological modifications in sleep and activity patterns, and clinical factors correlating with the observed CR changes. Our study may provide valuable insights into the intricate interplay between CR and PD with a potential to be used as a predictor of circadian alterations reflecting distinct disease phenotypes, symptoms, and progression outcomes.

Itga5-PTEN signaling regulates striatal synaptic strength and motor coordination in Parkinson's disease.

Background: Parkinson's disease (PD) is marked by the loss of dopaminergic neurons in the substantia nigra pars compacta, leading to motor and cognitive dysfunctions. The molecular mechanisms underlying synaptic alterations in PD remain elusive, with a focus on the role of Itga5 in synaptic integrity and motor coordination and TAT-Itga5 was designed to suppress PTEN activity in this investigation. Methods: This study utilized MPTP-induced PD animal models to investigate the expression and role of Itga5 in the striatum. Techniques included quantitative PCR, Western blotting, immunostaining, CRISPR-CasRx-mediated knockdown, electrophysiological assays, behavioral tests, and mass spectrometry. Results: Itga5 expression was significantly reduced in MPTP-induced PD models. In these models, a marked decrease in dendritic spine density and a shift towards thinner spines in striatal GABA neurons were observed, suggesting impaired synaptic integration. Knockdown of Itga5 resulted in reduced dendritic branching, decreased mushroom spines, and increased thin spines, altering synaptic architecture. Electrophysiological analyses revealed changes in action potential and spontaneous excitatory postsynaptic currents, indicating altered synaptic transmission. Motor behavior assessments showed that Itga5 deficiency led to impairments in fine motor control and coordination. Furthermore, Itga5 was found to interact with PTEN, affecting AKT signaling crucial for synaptic development and motor coordination. Conclusion: The study demonstrates that Itga5 plays a critical role in maintaining synaptic integrity and motor coordination in PD. The Itga5-PTEN-AKT pathway represents a potential therapeutic target for addressing synaptic and motor dysfunctions in PD.

Analysis of spontaneous speech in Parkinson's disease by natural language processing

IntroductionPatients with Parkinson's disease (PD) encounter a variety of speech-related problems, including dysarthria and language disorders. To elucidate the pathophysiological mechanisms for linguistic alteration in PD, we compared the utterance of patients and that of healthy controls (HC) using automated morphological analysis tools. MethodsWe enrolled 53 PD patients with normal cognitive function and 53 HC, and assessed their spontaneous speech using natural language processing. Machine learning algorithms were used to identify the characteristics of spontaneous conversation in each group. Thirty-seven features focused on part-of-speech and syntactic complexity were used in this analysis. A support-vector machine (SVM) model was trained with ten-fold cross-validation. ResultsPD patients were found to speak less morphemes on one sentence than the HC group. Compared to HC, the speech of PD patients had a higher rate of verbs, case particles (dispersion), and verb utterances, and a lower rate of common noun utterances, proper noun utterances, and filler utterances. Using these conversational changes, the respective discrimination rates for PD or HC were more than 80%. ConclusionsOur results demonstrate the potential of natural language processing for linguistic analysis and diagnosis of PD.

Optical coherence tomography angiography measurements in Parkinson's disease: A systematic review and meta-analysis.

Optical coherence tomography angiography (OCT-A) is an ocular imaging technology that has emerged as a non-invasive tool to evaluate retinal microvascular changes in neurodegenerative diseases including Parkinson's disease (PD) and Alzheimer's disease. While several studies have reported on the presence of pathologic retinal microvascular alterations in PD, the utility of OCT-A as a biomarker for PD evaluation is still unclear. A systematic review and meta-analysis were performed to explore the current evidence for the role of OCT-A in PD published up until June 2022. PubMed, Scopus, and Web of Science databases were used to systematically identify relevant papers and a meta-analysis was conducted using Stata16 software according to the level of heterogeneity applying a random- or fixed-effect model. Thirteen studies of 925 eyes in the PD group and 1501 eyes in the control group assessing OCT-A findings in PD patients were included. The meta-analyses revealed that the foveal region of PD patients had a significantly lower vessel density in the superficial capillary plexus (SCP) compared to healthy controls but that there were no significant differences in the foveal avascular zone, the SCP in whole, parafoveal, and perifoveal regions, and deep capillary plexus. OCT-A metrics may act as a potential biomarker for a more accurate and early PD diagnosis. Still, the OCT-A algorithms and interchangeability between OCT-A devices require further standardization to draw clinical conclusions regarding their utility.

Soluble TREM2 in body fluid in Alzheimer's disease and Parkinson's disease.

Previous studies showed conflicting results regarding soluble triggering receptor expressed on myeloid cells 2 (sTREM2) level alteration in body fluid in Alzheimer's disease (AD) and Parkinson's disease (PD). We applied the STATA 12.0 software to compute standard mean difference (SMD) and 95% confidence interval (CI). The study showed elevated sTREM2 level in cerebrospinal fluid (CSF) in AD, mild cognitive impairment (MCI), and preclinical AD (pre-AD) patients, compared to healthy controls (HCs) with random effects models (AD: SMD 0.28, 95% CI 0.12 to 0.44, I2 = 77.6%, p < 0.001; MCI: SMD 0.29, 95% CI 0.09 to 0.48, I2 = 89.7%, p < 0.001; pre-AD: SMD 0.24, 95% CI 0.00 to 0.48, I2 = 80.8%, p < 0.001). The study showed no significant difference in sTREM2 level in plasma between AD patients and HCs with a random effects model (SMD 0.06, 95% CI - 0.16 to 0.28, I2 = 65.6%, p = 0.008). The study showed no significant difference in sTREM2 level in CSF or plasma between PD patients and HCs with random effects models (CSF: SMD 0.33, 95% CI - 0.02 to 0.67, I2 = 85.6%, p < 0.001; plasma: SMD 0.37, 95% CI - 0.17 to 0.92, I2 = 77.8%, p = 0.011). In conclusion, the study highlighted the CSF sTREM2 as a promising biomarker in the different clinical stages of AD. More studies were essential to explore the CSF and plasmatic concentrations of sTREM2 alteration in PD.

Cluster analysis reveals distinct patterns of saccade impairment and their relation to cognitive profiles in Parkinson's disease.

Saccade performance has been reported to be altered in Parkinson's disease (PD), however, with a large variability between studies as both motor and cognitive impairment interfere with oculomotor control. The aim of this study was to identify different patterns in saccade alterations in PD using a data-driven approach and to explore their relationship with cognitive phenotypes. Sixty-one participants with PD and 25 controls performed eye-tracking (horizontal and vertical prosaccades, antisaccades) and neuropsychological testing. Hierarchical cluster analysis was applied to the eye-tracking data to subsequently compare the clusters based on demographical, clinical and cognitive characteristics. The three identified clusters of saccade alterations differed in cognitive profiles from healthy controls, but not in PD-related motor symptoms or demographics. The rate of directive errors in the antisaccade task was increased in clusters 1 and 2. Further, cluster 1 was defined by a general disinhibition of reflexive saccades and executive dysfunction in the neuropsychological evaluation. In cluster 2, prolonged saccade latencies and hypometria were accompanied by multidomain cognitive impairment. The cluster 3 showed increased antisaccade latency and vertical hypometria despite lack of evidence for cognitive impairment. Our results suggest that there may be at least two opposing patterns of saccade alterations associated with cognitive impairment in PD, which may explain some of the contradictory results of previous studies.

Global Alterations of Whole Brain Structural Connectome in Parkinson's Disease: A Meta-analysis.

Recent graph-theoretical studies of Parkinson's disease (PD) have examined alterations in the global properties of the brain structural connectome; however, reported alterations are not consistent. The present study aimed to identify the most robust global metric alterations in PD via a meta-analysis. A comprehensive literature search was conducted for all available diffusion MRI structural connectome studies that compared global graph metrics between PD patients and healthy controls (HC). Hedges' g effect sizes were calculated for each study and then pooled using a random-effects model in Comprehensive Meta-Analysis software, and the effects of potential moderator variables were tested. A total of 22 studies met the inclusion criteria for review. Of these, 16 studies reporting 10 global graph metrics (916 PD patients; 560 HC) were included in the meta-analysis. In the structural connectome of PD patients compared with HC, we found a significant decrease in clustering coefficient (g = -0.357, P = 0.005) and global efficiency (g = -0.359, P < 0.001), and a significant increase in characteristic path length (g = 0.250, P = 0.006). Dopaminergic medication, sex and age of patients were potential moderators of global brain network changes in PD. These findings provide evidence of decreased global segregation and integration of the structural connectome in PD, indicating a shift from a balanced small-world network to 'weaker small-worldization', which may provide useful markers of the pathophysiological mechanisms underlying PD.

Gray and white matter alterations in different predominant side and type of motor symptom in Parkinson's disease.

BackgroundParkinson's disease (PD) is highly heterogeneous reflected by different affected side of body and type of motor symptom. We aim to explore clinical characteristics and underlying brain structure alterations in PD with different predominant sides and motor types.MethodsWe recruited 161 PD patients and 50 healthy controls (HC). Patients were classified into four subtypes according to their predominant side and motor type: left akinetic/rigid‐dominant (LAR), left tremor‐dominant (LTD), right akinetic/rigid‐dominant (RAR), and right tremor‐dominant (RTD). All participants assessed motor and cognitive performances, then underwent T1‐weighted and diffusion tensor imaging scanning. A general linear model was used to compare neuroimaging parameters among five groups.ResultsAmong four PD subtypes, patients of LAR subtype experienced the worst motor impairment, and only this subtype showed worse cognitive performance compared with HC. Compared with HC and other subtypes, LAR subtype showed a significant reduction in cortical thickness of the right caudal‐anterior‐cingulate gyrus and fractional anisotropy of the right cingulum bundle.ConclusionsWe demonstrated that LAR subtype had the worst clinical performance, which the severer damage in the right cingulate region might be the underlying mechanism. This study underscores the importance of classifying PD subtypes based on both the side and type of motor symptom for clinical intervention and research to optimize behavioral outcomes in the future.

Spiritual care for the management of Parkinson's disease: Where we are and how far can we go.

An increasing number of studies have investigated the neural networks and brain regions activated by different aspects of religious faith or spiritual practice. The extent to which religiousness and spirituality are dependent on the integrity of neural circuits is a question unique to neurological illnesses. Several studies have reported that neural networks and brain areas represent the various components of religious faith or spiritual activity in recent decades. In addition to research in healthy people, another strategy is to observe if neurological abnormalities caused by stroke, tumour, brain damage, or degenerative sickness are accompanied by an alteration in religiosity or spirituality. Similarly, Parkinson's disease (PD), an ailment characterized by dopaminergic neuron malfunction, has been utilized to explore the role of dopaminergic networks in the practice, experience, and maintenance of religious or spiritual beliefs. Case-control and priming studies have demonstrated a decline in spirituality and religion in people with PD due to dopaminergic degeneration. These studies could not adequately control for confounding variables and lacked methodological rigour. Using qualitative and quantitative assessments, a mixed-method approach might shed additional light on putative religious beliefs alterations in PD. In the current review paper, we discussed the recent research on the impact of PD on spiritual beliefs and spirituality.

Parkinson Disease: Epidemiology, Pathology, and Clinical Diagnosis

Parkinson disease (PD) is the second most common neurodegenerative disorder after Alzheimer disease. PD predominantly affects elderly people, and most countries are now facing a marked demographic change, with a progressively larger proportion of the population reaching old age. Thus, PD is expected to cause an increasing social and economic burden on society in the near future. The causes of PD are still mostly unknown. There has been a substantial progress in our understanding of the genetic basis of PD in the past 15 years; however, these mutations explain only a small fraction of all PD cases and other non-genetic factors may play a role. This review covers the epidemiology, pathology, and clinical diagnosis of PD. Figures show age-specific incidence of PD, age-specific prevalence of PD, PD risks for exposures reported in high-quality studies, PD and atypical parkinsonism clinical features, and neuroimaging alterations in PD and atypical parkinsonism. Tables list factors associated with increased or decreased risk of PD, Braak staging scheme of α-synuclein pathology in PD, United Kingdom Parkinson’s Disease Society Brain Bank clinical diagnostic for PD, National Institute of Neurological Disorders and Stroke diagnostic criteria for PD, differential diagnosis of parkinsonian syndromes, and “atypical” atypical parkinsonism.

Parkinson Disease: Epidemiology, Pathology, and Clinical Diagnosis

Parkinson disease (PD) is the second most common neurodegenerative disorder after Alzheimer disease. PD predominantly affects elderly people, and most countries are now facing a marked demographic change, with a progressively larger proportion of the population reaching old age. Thus, PD is expected to cause an increasing social and economic burden on society in the near future. The causes of PD are still mostly unknown. There has been a substantial progress in our understanding of the genetic basis of PD in the past 15 years; however, these mutations explain only a small fraction of all PD cases and other non-genetic factors may play a role. This review covers the epidemiology, pathology, and clinical diagnosis of PD. Figures show age-specific incidence of PD, age-specific prevalence of PD, PD risks for exposures reported in high-quality studies, PD and atypical parkinsonism clinical features, and neuroimaging alterations in PD and atypical parkinsonism. Tables list factors associated with increased or decreased risk of PD, Braak staging scheme of α-synuclein pathology in PD, United Kingdom Parkinson’s Disease Society Brain Bank clinical diagnostic for PD, National Institute of Neurological Disorders and Stroke diagnostic criteria for PD, differential diagnosis of parkinsonian syndromes, and “atypical” atypical parkinsonism.

Basal ganglia atrophy-associated causal structural network degeneration in Parkinson's disease.

Parkinson's disease (PD) is a progressive neurodegenerative disease characterized by both motor and non‐motor symptoms. A convergent pathophysiological hallmark of PD is an early selective vulnerability within the basal ganglia circuit. However, the causal interactions between basal ganglia atrophy and progressive structural network alterations in PD remain unaddressed. Here, we adopted voxel‐based morphometry method to measure gray matter (GM) volume for each participant (n = 84 PD patients and n = 70 matched healthy controls). Patients were first divided into three stages according to the Hoehn and Yahr (H&Y) and the Part III of Unified Parkinson's Disease Rating Scale scores respectively to analyze the stage‐specific GM atrophy patterns. Then, the modulation of early caudate atrophy over other brain structures was evaluated using the whole‐brain voxel‐wise and region‐of‐interest‐wise causal structural covariance network approaches. We found that GM atrophy progressively expands from the basal ganglia to the angular gyrus, temporal areas, and eventually spreads through the subcortical–cortical networks as PD progresses. Notably, we identified a shared caudate‐associated degeneration network including the basal ganglia, thalamus, cerebellum, sensorimotor cortex, and cortical association areas with the PD progressive factors. These findings suggest that the early structural vulnerability of basal ganglia in PD may play a pivotal role in the modulation of motor and non‐motor circuits at the structural level. Our work provides evidence for a novel mechanism of network degeneration that underlies the pathology of PD and may have potential clinical applications in the development of early predictors of PD onset and progress.

Role of toll-like receptor 4 and sex in 6-hydroxydopamine–induced behavioral impairments and neurodegeneration in mice

Parkinson's disease (PD) is a neurodegenerative disease characterized by progressive loss of the nigrostriatal dopaminergic neurons that are associated with motor alterations and non-motor manifestations (such as depression). Neuroinflammation is a process with a critical role in the pathogenesis of PD. In this regard, toll-like receptor 4 (TLR4) is a central mediator of immune response in PD. Moreover, there are gender-related differences in the incidence, prevalence, and clinical features of PD. Therefore, we aimed to elucidate the role of TLR4 in the sex-dependent response to dopaminergic denervation induced by 6-hydroxydopamine (6-OHDA) in mice. Female and male adult wildtype (WT) and TLR4 knockout (TLR4−/−) mice were administered with unilateral injection of 6-OHDA in the dorsal striatum, and non-motor and motor impairments were evaluated for 30 days, followed by biochemistry analysis in the substantia nigra pars compacta (SNc), dorsal striatum, and dorsoventral cortex. Early non-motor impairments (i.e., depressive-like behavior and spatial learning deficits) induced by 6-OHDA were observed in the male WT mice but not in male TLR4−/− or female mice. Motor alterations were observed after administration of 6-OHDA in both strains, and the lack of TLR4 was also related to motor commitment. Moreover, ablation of TLR4 prevented 6-OHDA–induced dopaminergic denervation and microgliosis in the SNc, selectively in female mice. These results reinforced the existence of sex-biased alterations in PD and indicated TLR4 as a promising therapeutic target for the motor and non-motor symptoms of PD, which will help counteract the neuroinflammatory and neurodegenerative processes.

Choroidal Thickness Correlates with Clinical and Imaging Metrics of Parkinson's Disease: A Pilot Study.

Parkinson's disease (PD) is marked clinically by motor symptoms and pathologically by Lewy bodies and dopamine neuron loss in the substantia nigra pars compacta (SNc). Higher iron accumulation, assessed by susceptibility MRI, also is observed as PD progresses. Recently, evidence has suggested that PD affects the retina. To better understand retinal alterations in PD and their association to clinical and SNc iron-related imaging metrics. Ten PD and 12 control participants (2 eyes each) from an ongoing PD imaging biomarker study underwent enhanced depth imaging optical coherence tomography evaluation. Choroidal (vascular) thickness and nerve layers were measured in 4 subregions [superior, temporal, inferior, and nasal] and at 3 foveal distances (1, 1.5, and 3 mm). These metrics were compared between PD and control groups. For significantly different metrics, their associations with clinical [levodopa equivalent daily dosage (LEDD), motor and visuospatial function] and SNc susceptibility MRI metrics [R2* and quantitative susceptibility mapping (QSM)] were explored. Compared to control participants, PD participants had a thicker choroid (p = 0.005), but no changes in nerve layers. Higher mean choroidal thickness was associated with lower LEDD (p < 0.01) and better visuospatial function (p < 0.05). Subregion analyses revealed higher choroidal thickness correlated with lower LEDD and better motor and visuospatial measures. Higher mean choroidal thickness also was associated with lower nigral iron MRI (p < 0.05). A small cohort of PD research participants displayed higher choroidal thickness that was related to better clinical performance and less nigral pathology. These intriguing findings warrant further investigation.

REM sleep without atonia and nocturnal body position in prediagnostic Parkinson's disease

BackgroundSleep disturbances are features of Parkinson's disease (PD), that can already occur before PD diagnosis. The most investigated prodromal PD sleep disorder is REM sleep behavior disorder (RBD). The relation between other polysomnographic (PSG) alterations and the prediagnostic stages of PD, however, is less clear. MethodsWe performed a retrospective case–control study to characterize polysomnographic alterations in PD and prediagnostic PD. We included 63 PD subjects (33 subjects that underwent a video-PSG before PD diagnosis [13 with and 20 without RBD] and 30 subjects that underwent a PSG after PD diagnosis) and 30 controls. PSGs were analyzed for sleep stages, different RSWA variables, body position, arousals, periodic limb movements, and REM density. ResultsHigher subscores of all RSWA variables were observed in subjects with PD and prediagnostic PD (with and without RBD). Total RSWA, tonic RSWA and chin RSWA severity were significant predictors for all PD and prediagnostic PD groups. Our study also shows a higher percentage of nocturnal supine body position in all PD and prediagnostic PD groups. Supine body position percentage is the highest in the PD group and has a positive correlation with time since diagnosis. ConclusionsThese findings suggest that increased total, tonic and chin RSWA as well as nocturnal supine body position are already present in prediagnostic PD, independently of RBD status. Prospective longitudinal studies are necessary to confirm the additional value of these PSG abnormalities as prodromal PD biomarkers.

The Effect of Parkinson's Disease on Otoacoustic Emissions and Efferent Suppression of Transient Evoked Otoacoustic Emissions.

Purpose Several studies have demonstrated increased auditory thresholds in patients with Parkinson's disease (PD) based on subjective tonal audiometry. However, the pathophysiological mechanisms underlying auditory dysfunction in PD remain elusive. The primary aim of this study was to investigate cochlear and olivocochlear function in PD using objective measurements and to assess the effect of dopaminergic medication on auditory function. Method Eighteen patients with PD and 18 gender- and age-matched healthy controls (HCs) were included. Patients with PD participated in medication on and off conditions. Linear mixed models were used to determine the effect of PD on tonal audiometry, transient evoked and distortion product otoacoustic emissions (OAEs), and efferent suppression (ES). Results Tonal audiometry revealed normal auditory thresholds in patients with PD for their age across all frequencies. OAE signal amplitudes demonstrated a significant interaction effect between group (PD vs. HC) and frequency, indicating decreased OAEs at low frequencies and increased OAEs at high frequencies in patients with PD. No significant differences were found between patients with PD and HCs regarding ES. In addition, no significant effect of medication status was found on auditory measurements in patients with PD. Conclusions Altered OAEs support the hypothesis of cochlear alterations in PD. No evidence was found for the involvement of the medial olivocochlear system. Altogether, OAEs may provide an objective early indicator of auditory alterations in PD and should complement subjective tonal audiometry when assessing and monitoring auditory function in PD.

Impaired Structural Connectivity in Parkinson's Disease Patients with Mild Cognitive Impairment: A Study Based on Probabilistic Tractography.

Background: Probabilistic tractography, in combination with graph theory, has been used to reconstruct the structural whole-brain connectome. Threshold-free network-based statistics (TFNBS) is a useful technique to study structural connectivity in neurodegenerative disorders; however, there are no previous studies using TFNBS in Parkinson's disease (PD) with and without mild cognitive impairment (MCI).Materials and Methods: Sixty-two PD patients, 27 of whom classified as PD-MCI, and 51 healthy controls (HC) underwent diffusion-weighted 3T magnetic resonance imaging. Probabilistic tractography, using FMRIB Software Library (FSL), was used to compute the number of streamlines (NOS) between regions. NOS matrices were used to find group differences with TFNBS, and to calculate global and local measures of network integrity using graph theory. A binominal logistic regression was then used to assess the discrimination between PD with and without MCI using non-overlapping significant tracts. Tract-based spatial statistics were also performed with FSL to study changes in fractional anisotropy (FA) and mean diffusivity.Results: PD-MCI showed 37 white matter connections with reduced connectivity strength compared with HC, mainly involving temporal/occipital regions. These were able to differentiate PD-MCI from PD without MCI with an area under the curve of 83–85%. PD without MCI showed disrupted connectivity in 18 connections involving frontal/temporal regions. No significant differences were found in graph measures. Only PD-MCI showed reduced FA compared with HC.Discussion: TFNBS based on whole-brain probabilistic tractography can detect structural connectivity alterations in PD with and without MCI. Reduced structural connectivity in fronto-striatal and posterior cortico-cortical connections is associated with PD-MCI.Impact statementOur data help to clarify that whole-brain connectome analysis based on probabilistic tractography is a useful and sensitive approach to explore the role of white matter damages as a relevant pathological substrate of cognitive deficits in Parkinson's disease (PD). Our results might add some evidence regarding the involvement of mostly posterior cortical regions and their connections in PD patients with worse cognitive prognosis. Therefore, a threshold-free network-based statistics approach might indicate that structural connectivity abnormalities are not a global phenomenon, and suggests the implication of regional and predominantly posterior structural network disruption underlying cognitive impairment in PD.

Bidirectional Correlations Between Dopaminergic Function and Motivation in Parkinson's Disease.

To test the hypothesis that striatal dopamine function influences motivational alterations in Parkinson disease (PD), we compared vesicular monoamine transporter 2 (VMAT2) and dopamine transporter (DaT) imaging data in PD patients with impulse control disorders (ICDs), apathy, or neither. We extracted striatal binding ratios (SBR) from VMAT2 PET imaging (18F-AV133) and DaTscans from the Parkinson's Progression Markers Initiative (PPMI) multicenter observational study. Apathy and ICDs were assessed using the Movement Disorders Society-revised Unified Parkinson's Disease Rating Scale (MDS-UPDRS) and the Questionnaire for Impulsive-Compulsive Disorders in Parkinson's Disease (QUIP), respectively. We used analysis of variance (ANOVA) and log-linear mixed-effects (LME) regression to model SBRs with neurobehavioral metrics. Among 23 participants (mean age 62.7 years, mean disease duration 1.8 years) with VMAT2 imaging data, 5 had apathy, 5 had an ICD, and 13 had neither. ANOVA indicated strong groupwise differences in VMAT2 binding in right anterior putamen [F(2,20) = 16.2, p < 0.0001), right posterior putamen [F(2,20) = 16.9, p < 0.0001), and right caudate [F(2,20) = 6.8, p = 0.006)]. Post-hoc tests and repeated-measures analysis with LME regression also supported right striatal VMAT2 elevation in the ICD group and reduction in the apathy group relative to the group with neither ICD nor apathy. DaT did not exhibit similar correlations, but normalizing VMAT2 with DaT SBR strengthened bidirectional correlations with ICD (high VMAT2/DaT) and apathy (low VMAT2/DaT) in all striatal regions bilaterally. Our findings constitute preliminary evidence that striatal presynaptic dopaminergic function helps describe the neurobiological basis of motivational dysregulation in PD, from high in ICDs to low in apathy.