Impairment In Parkinson's Disease Research Articles

Motor Cortical Neuronal Hyperexcitability Associated with α-Synuclein Aggregation.

Dysfunction of the cerebral cortex is thought to underlie motor and cognitive impairments in Parkinson disease (PD). While cortical function is known to be suppressed by abnormal basal ganglia output following dopaminergic degeneration, it remains to be determined how the deposition of Lewy pathology disrupts cortical circuit integrity and function. Moreover, it is also unknown whether cortical Lewy pathology and midbrain dopaminergic degeneration interact to disrupt cortical function in late-stage. To begin to address these questions, we injected α-synuclein (αSyn) preformed fibrils (PFFs) into the dorsolateral striatum of mice to seed αSyn pathology in the cortical cortex and induce degeneration of midbrain dopaminergic neurons. Using this model system, we reported that αSyn aggregates accumulate in the motor cortex in a layer- and cell-subtype-specific pattern. Particularly, intratelencephalic neurons (ITNs) showed earlier accumulation and greater extent of αSyn aggregates relative to corticospinal neurons (CSNs). Moreover, we demonstrated that the intrinsic excitability and inputs resistance of αSyn aggregates-bearing ITNs in the secondary motor cortex (M2) are increased, along with a noticeable shrinkage of cell bodies and loss of dendritic spines. Last, neither the intrinsic excitability of CSNs nor their thalamocortical input was altered by a partial striatal dopamine depletion associated with αSyn pathology. Our results documented motor cortical neuronal hyperexcitability associated with αSyn aggregation and provided a novel mechanistic understanding of cortical circuit dysfunction in PD.

Hippocampus and olfactory impairment in Parkinson disease: a comparative exploratory combined volumetric/functional MRI study.

Patients with Parkinson's Disease (PD) commonly experience Olfactory Dysfunction (OD). Our exploratory study examined hippocampal volumetric and resting-state functional magnetic resonance imaging (rs-fMRI) variations in a Healthy Control (HC) group versus a cognitively normal PD group, further categorized into PD with No/Mild Hyposmia (PD-N/MH) and PD with Severe Hyposmia (PD-SH). We calculated participants' relative Total Hippocampal Volume (rTHV) and performed Spearman's partial correlations, controlled for age and gender, to examine the correlation between rTHV and olfactory performance assessed by the Odor Stick Identification Test for the Japanese (OSIT-J) score. Mann-Whitney U tests assessed rTHV differences across groups and subgroups, rejecting the null hypothesis for p < 0.05. Furthermore, a seed-based rs-fMRI analysis compared hippocampal connectivity differences using a one-way ANCOVA covariate model with controls for age and gender. Spearman's partial correlations indicated a moderate positive correlation between rTHV and OSIT-J in the whole study population (ρ = 0.406; p = 0.007), PD group (ρ = 0.493; p = 0.008), and PD-N/MH subgroup (ρ = 0.617; p = 0.025). Mann-Whitney U tests demonstrated lower rTHV in PD-SH subgroup compared to both HC group (p = 0.013) and PD-N/MH subgroup (p = 0.029). Seed-to-voxel rsfMRI analysis revealed reduced hippocampal connectivity in PD-SH subjects compared to HC subjects with a single cluster of voxels. Although the design of the study do not allow to make firm conclusions, it is reasonable to speculate that the progressive involvement of the hippocampus in PD patients is associated with the progression of OD.

Pathobiology of Cognitive Impairment in Parkinson Disease: Challenges and Outlooks.

Cognitive impairment (CI) is a characteristic non-motor feature of Parkinson disease (PD) that poses a severe burden on the patients and caregivers, yet relatively little is known about its pathobiology. Cognitive deficits are evident throughout the course of PD, with around 25% of subtle cognitive decline and mild CI (MCI) at the time of diagnosis and up to 83% of patients developing dementia after 20 years. The heterogeneity of cognitive phenotypes suggests that a common neuropathological process, characterized by progressive degeneration of the dopaminergic striatonigral system and of many other neuronal systems, results not only in structural deficits but also extensive changes of functional neuronal network activities and neurotransmitter dysfunctions. Modern neuroimaging studies revealed multilocular cortical and subcortical atrophies and alterations in intrinsic neuronal connectivities. The decreased functional connectivity (FC) of the default mode network (DMN) in the bilateral prefrontal cortex is affected already before the development of clinical CI and in the absence of structural changes. Longitudinal cognitive decline is associated with frontostriatal and limbic affections, white matter microlesions and changes between multiple functional neuronal networks, including thalamo-insular, frontoparietal and attention networks, the cholinergic forebrain and the noradrenergic system. Superimposed Alzheimer-related (and other concomitant) pathologies due to interactions between α-synuclein, tau-protein and β-amyloid contribute to dementia pathogenesis in both PD and dementia with Lewy bodies (DLB). To further elucidate the interaction of the pathomechanisms responsible for CI in PD, well-designed longitudinal clinico-pathological studies are warranted that are supported by fluid and sophisticated imaging biomarkers as a basis for better early diagnosis and future disease-modifying therapies.

Incidence and risk factors of institutionalisation in Parkinson's disease and atypical parkinsonism

IntroductionThe basic epidemiology of institutionalisation (the need for long-term care in an institution) in parkinsonism is unclear. We aimed to identify the incidence of, and risk factors for, institutionalisation in Parkinson's disease (PD) and atypical parkinsonism (AP). MethodsWe analysed data from a prospective population-based incidence cohort of parkinsonism in North-East Scotland (the PINE study). 556 newly-diagnosed participants (PD, N = 200; AP, N = 98; controls, N = 258), recruited between 2002 and 2009, were prospectively followed life-long with data collection on place of residence. We determined the incidence and baseline predictors of institutionalisation using Cox regression. ResultsThe median follow-up time was 9.3, 4.4, and 10.8 years in PD, AP, and controls respectively. 70 (35 %) PD, 53 (54 %) AP, and 43 (16 %) controls became institutionalised. The incidence rates of institutionalisation in PD, AP, and controls were 5.1, 20.8, and 1.8 per 100 person-years respectively. The median time to institutionalisation was 11.8 years in PD and 3.5 years in AP. Multivariable Cox regression showed that AP (HR versus PD = 3.05 [95 % CI 1.90,4.91]), increasing age (HR for 10-year increase = 1.82 [95 % CI 1.40,2.36]), poorer cognition (HR for MMSE<24 versus MMSE>27 = 2.62 [95 % CI 1.45, 4.73]), more-severe parkinsonian impairment (UPDRS part 3) (HR for 10-point increase = 1.25 [95 % CI 1.05, 1.48]) were independently associated with higher hazards of institutionalisation. Sex, co-morbidity, smoking history, and living alone were not associated with institutionalisation. ConclusionInstitutionalisation is much more frequent in parkinsonism, particularly in AP, than in controls. AP, older age, severe parkinsonian impairment, and poorer cognition were independent baseline predictors of institutionalisation.

A fixel-based analysis of white matter reductions early detects Parkinson disease with mild cognitive impairment

BackgroundWhite matter (WM) tract alterations are early signs of cognitive impairment in Parkinson disease (PD) patients. Fixel-based analysis (FBA) has advantages over traditional diffusion tensor imaging in managing complex and crossing fibers. We used FBA to measure fiber-specific changes in patients with PD mild cognitive impairment (PD-MCI) and PD normal cognition (PD-NC). MethodsSeventy-one patients with PD without dementia were included: 39 PD-MCI and 32 PD-NC. All underwent diffusion-weighted imaging, clinical examinations, and tests to evaluate their cognitive function globally and in five cognitive domains. FBA was used to investigate fiber-tract alterations and compare PD-MCI with PD-NC subjects. Correlations with each cognitive test were analyzed. ResultsPatients with PD-MCI were significantly older (P = 0.044), had a higher male-to-female ratio (P = 0.006) and total Unified Parkinson's Disease Rating Scale score (P = 0.001). All fixel-based metrics were significantly reduced within the body of the corpus callosum and superior corona radiata in PD-MCI patients (family-wise error-corrected P value < 0.05) compared with PD-NC patients. The cingulum, superior longitudinal fasciculi, and thalamocortical circuit exhibited predominantly fiber-bundle cross-section (FC) changes. In regression analysis, reduced FC values in cerebellar circuits were associated with poor motor function in PD-MCI patients and poor picture-naming ability in PD-NC patients. ConclusionsPD-MCI patients have significant WM alterations compared with PD-NC patients. FBA revealed these changes in various bundle tracts, helping us to better understand specific WM changes that are functionally implicated in PD cognitive decline. FBA is potentially useful in detecting early cognitive decline in PD.

Cholinergic centro-cingulate network in Parkinson disease and normal aging.

Decreased cholinergic binding within the recently identified centro-cingulate brain network robustly has been shown to robustly correlate with the severity of cognitive impairment in Parkinson disease (PD). This network with key hubs within the cingulum, operculum and peri-central cortical regions also correlates with elements of parkinsonian motor impairments, including postural instability and gait difficulties, such as falls or freezing. MRI neuroimaging studies have shown that the anterior midcingulate cortex is a key node for cognitive aspects of movement generation, i.e., intentional motor control. Recent evidence also suggests a novel aspect of organization of primary motor cortex, describing "effector" regions for fine movement control intercalated with interlinked "inter-effector" regions devoted to whole-body control. A distinguishing feature of inter-effector regions is tight linkage to the cingular and opercular regions. Such inter-effector regions have been proposed to be part of a greater somato-cognitive action network necessary for integration of goals and movement. Recent evidence also points to vulnerabilities of cholinergic nerve terminals in the centro-cingulate network in older non-PD adults. These features of normal aging underscore that cortical cholinergic terminal losses in age-associated neurodegenerative disorders are likely not exclusively the result of disease-specific etiologies but also related to otherwise normal aging. Practical implications of this overlap are that addressing disease-specific and general aging etiologies involved in neurodegeneration, may be of benefit in age-associated neurodegenerative disorders where significant cholinergic systems degeneration is present.

Spinal cord stimulation for gait impairment in Parkinson Disease: scoping review and mechanistic considerations.

Advanced Parkinson's Disease (PD) is associated with Parkinson's Disease gait impairment (PDg), which increases the risk for falls and is often treatment-refractory. Subthalamic nucleus (STN) and globus pallidus pars interna (GPi) deep brain stimulation (DBS) often fails to improve axial symptoms like PDg. Spinal cord stimulation (SCS) has been suggested to improve PDg. SCS may benefit PDg by disrupting pathologic beta-oscillations and hypersynchrony in cortico-striatal-thalamic circuits to override excessive inhibition of brainstem locomotor regions. SCS may potentially improve locomotion by acting at any of these levels, either alone or in combination. We conducted a comprehensive literature search and scoping review, identifying 106 patients in whom SCS was evaluated for PDg. Among the identified patients, 63% carried a pain diagnosis. Overall, the most common stimulation location was thoracic (78%), most commonly T9-T10. Burst (sub-perception) was the most common stimulation modality (59%). Prior treatment with DBS was used in 25%. Motor outcomes were assessed by the Unified Parkinson Disease Rating Scale (UPDRS) III-motor, UPDRS, the Timed Up and Go (TUG), and/or 10-/20-meter walking tests.Among these patients, 95 (90%) had PDg amelioration and improved motor outcomes. Despite small sample sizes, patient heterogeneity, and unblinded evaluations complicating interpretations of efficacy and safety, SCS may be beneficial for at least a subset of PDg. Further research is required to clarify the role of SCS for PDg and the patients most suitable to benefit from this intervention.

Correlation of hypothalamic-pituitary adrenal disorders with cognitive impairment in Parkinsons disease and vascular parkinsonism

Correlation of hypothalamic-pituitary adrenal disorders with cognitive impairment in Parkinsons disease and vascular parkinsonism

Predictive value of abbreviated olfactory tests in prodromal Parkinson disease

There is disagreement in the literature whether olfaction may show specific impairments in Parkinson Disease (PD) and if olfactory tests comprised of selected odors could be more specific for diagnosis. We sought to validate previously proposed subsets of the University of Pennsylvania Smell Identification Test (UPSIT) odors for predicting conversion to PD in an independent, prodromal cohort. Conversion to PD was assessed in 229 participants in the Parkinson At Risk Study who completed baseline olfactory testing with the UPSIT and up to 12 years of clinical and imaging evaluations. No commercially available or proposed subset performed better than the full 40-item UPSIT. The proposed “PD-specific” subsets also did not perform better than expected by chance. We did not find evidence for selective olfactory impairment in Parkinson disease. Shorter odor identification tests, including commercially available 10–12 item tests, may have utility for ease of use and cost, but not for superior predictive value.

Impact of the Dopamine System on Long-Term Cognitive Impairment in Parkinson Disease: An Exploratory Study.

Little is known about the impact of the dopamine system on development of cognitive impairment (CI) in Parkinson disease (PD). We used data from a multi-site, international, prospective cohort study to explore the impact of dopamine system-related biomarkers on CI in PD. PD participants were assessed annually from disease onset out to 7 years, and CI determined by applying cut-offs to four measures: (1) Montreal Cognitive Assessment; (2) detailed neuropsychological test battery; (3) Movement Disorder Society-Unified Parkinson's Disease Rating Scale (MDS-UPDRS) cognition score; and (4) site investigator diagnosis of CI (mild cognitive impairment or dementia). The dopamine system was assessed by serial Iodine-123 Ioflupane dopamine transporter (DAT) imaging, genotyping, and levodopa equivalent daily dose (LEDD) recorded at each assessment. Multivariate longitudinal analyses, with adjustment for multiple comparisons, determined the association between dopamine system-related biomarkers and CI, including persistent impairment. Demographic and clinical variables associated with CI were higher age, male sex, lower education, non-White race, higher depression and anxiety scores and higher MDS-UPDRS motor score. For the dopamine system, lower baseline mean striatum dopamine transporter values (P range 0.003-0.005) and higher LEDD over time (P range <0.001-0.01) were significantly associated with increased risk for CI. Our results provide preliminary evidence that alterations in the dopamine system predict development of clinically-relevant, cognitive impairment in Parkinson's disease. If replicated and determined to be causative, they demonstrate that the dopamine system is instrumental to cognitive health status throughout the disease course. Parkinson's Progression Markers Initiative is registered with ClinicalTrials.gov (NCT01141023).

Amyloid plaque burden and dual tasking impairments on the Timed up and go test in Parkinson disease (P5-11.006)

<h3>Objective:</h3> Dual tasking (DT) impairments in Parkinson disease (PD) are a correlate of fall risk. Their biological basis may reflect multiple underlying pathological causes. <h3>Background:</h3> Low-level amyloid-beta (Abeta) plaque burden is known to correlate with gait and cognitive impairments in PD. It is possible that Abeta plaque burden may exacerbate fall risk by worsening dual tasking cost, though this has not been evaluated to date. <h3>Design/Methods:</h3> In a cross-sectional cohort of 20 participants with PD, we explored the association between Abeta plaque burden and dual task cost (DTC) on the timed up and go test (TUG). TUG gait parameters were assessed using Ambulatory Parkinson’s disease monitoring (APDM) OPAL wearable sensors. Baseline TUG testing was followed by TUG testing during which the participant performed a cognitive task. DTC was calculated as the percentage difference in seconds between the two tasks. Regional Abeta plaque burden was assessed by [11C]Pittsburgh compound B (PiB) positron emission tomography (PET) imaging. Bivariate Pearson’s r statistic was calculated between DTC and PiB distribution volume ratio (DVR) in different regions of interest. <h3>Results:</h3> DTC during the TUG show no significant correlations with PiB DVR in the total cortical mantle (r=0.061, p=0.797), visuospatial cortex (r=0.061, p=0.798), striatum (r=0.033, p=0.890), or thalamus (r=0.041, p=0.865) but did correlate with elevated PiB DVR in the substantia nigra (r=0.535, p=0.015). <h3>Conclusions:</h3> DTC in PD does not correlate with supratentorial amyloid plaque burden but may reflect mixed neurodegenerative pathology, including Abeta plaque burden, in the substantia nigra. <b>Disclosure:</b> Ms. Harrie has nothing to disclose. The institution of Dr. Hampstead has received research support from NIH. The institution of Dr. Hampstead has received research support from Department of Veterans Affairs. Dr. Hampstead has received intellectual property interests from a discovery or technology relating to health care. Dr. Hampstead has received publishing royalties from a publication relating to health care. Catherine Lewis has nothing to disclose. Ms. Herreshoff has received personal compensation in the range of $50,000-$99,999 for serving as a Consultant for Huxley Medical Inc. Dr. Kotagal has received personal compensation in the range of $500-$4,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for Movement Disorders Society. The institution of Dr. Kotagal has received research support from NIH. The institution of Dr. Kotagal has received research support from VA Healthcare System.

Identifying clinical features and blood biomarkers associated with mild cognitive impairment in Parkinson's Disease using machine learning.

A broad list of variables associated with mild cognitive impairment (MCI) in Parkinson's Disease (PD) has been investigated separately. However, there is no study including all of them to assess variable importance yet. Shapley variable importance cloud (ShapleyVIC) can robustly assesses variable importance while accounting for correlation between variables. 1) To prioritise the important variables associated with PD-MCI; 2) To explore new blood biomarkers related to PD-MCI. ShapleyVIC-assisted variable selection was used to identify a subset of variables from 41 variables potentially associated with PD-MCI in a cross-sectional study. Backward selection was used to further identify the variables that associated with PD-MCI. Relative risk was used to quantify the association of final predictors and PD-MCI in the final multivariable log-binomial regression model. Among 41 variables analysed, 22 variables were identified as significantly important variables associated with PD-MCI and 8 variables were subsequently selected in the final model, indicating shorter education year, history of hypertension, higher MDS-UPDRS motor score, higher levels of TG, APOA1, and SNCA rs6826785 non-carrier were associated with increased risk of PD-MCI (p<0.05). Our study highlighted the strong association between TG, APOA1, SNCA rs6826785 and PD-MCI by machine learning approach. Screening and management of high TG and ApoA1 levels might help prevent the cognitive impairment in early PD patients. SNCA rs6826785 could be a novel therapeutic target for PD-MCI. ShapleyVIC-assisted variable selection is a novel and robust alternative to traditional approaches for future clinical study to prioritize the variables of interests.

Prognosis of the probability of development and progression of the disease under the influence of factors causing cerebral vascular disorders in vascular parkinsonism

Cerebrovascular disease, according to many studies, causes 1 to 15% of cases of Parkinsonism. “...200 out of every 100,000 people in the world have the disease...”. Parkinson’s disease is a chronically stable progressive, unavoidable disease, second only in prevalence among the elderly and among neurodegenerative diseases worldwide. The number of elderly people worldwide has increased by 48% since 2000 and is expected to continue to increase by 56% between 2015 and 2030. According to the International Parkinson’s Foundation, the number of Parkinson’s disease cases worldwide will exceed 10 million by 2020. In particular, prediction of severe complications based on the analysis of neurological, neurophysiological, neuroimaging features of the clinical course of vascular Parkinsonism, prevention of cognitive and motor disorders, assessment of the patient’s disability index through key quality of life indicators, diagnostic and treatment algorithms, and determination of differential approach measures are of particular importance. A number of scientific studies are being conducted worldwide to clarify the features of optimization of multivariate analysis of cerebral vascular impairment in parkinsonism.

Olfactory impairment in Parkinson disease using culture-relevant products: making the case for a Moroccan Smell Identification Test (MoroSIT)

Introduction: Olfactory problems are frequent in Parkinson disease. Their early onset relative to motor problems makes them a potential biomarker for the disease, yet no culture-specific standardized tests exist in Morocco.&#x0D; Aim: To use indigenous plant extracts generated in our laboratory to investigate olfactory impairment in patients with Parkinson disease.&#x0D; Method: Our study is a cross-sectional case-controlled analytical investigation in a group of 69 patients with Parkinson disease and another group of 66 healthy volunteers in order to assess odor threshold, odor identification, and odor discrimination in these two groups using Mentha pulegium and Lavandula latifolia extracts.&#x0D; Results: We found a marked decrease of the threshold of odor detection in patients compared to controls (p&lt;0.001). A statistically significant difference was found between the ability to discriminate odors, with more patients with Parkinson disease unable to distinguish between odors (p&lt;0.001). For the odor identification test, 70% of control subjects versus 36% of patients were able to correctly identify the test products. The difference was statistically significant (p&lt;0.001).&#x0D; Conclusions: Our study points to the potential for the elaboration of a standardized smell identification screening battery using indigenous products with which patients are familiar.

Relationship between Plasma Level of Beta-amyloid, Alpha-synuclein, and Tau Protein with Cognitive Impairment in Parkinson Disease

Background: Most people with Parkinson’s disease will develop dementia along with their illness development. There are several overlapping brain pathological features in patients with Parkinson's and Alzheimer's disease. These features are related with beta-amyloid findings, alpha-synuclein and tau protein.&#x0D; Aim: This study was designed to determine the relationship between beta-amyloid, alpha-synuclein and tau protein plasma level with cognitive impairment in Parkinson’s disease. &#x0D; Materials and Methods: This was an observational with case-control design study. Total of 62 patients with Parkinson’s disease and 20 healthy controls were included in this study. Parkinson’s disease group was divided into 2 subgroups, patient with and without cognitive impairment based on Montreal Cognitive Assessment Indonesian version (MoCA-Ina) score. The plasma levels of beta-amyloid, alpha-synuclein, and tau protein were measured by using enzyme-linked immunoassay technique. Student’s t-test was used to analyze normally distributed data of plasma level differences between groups (Parkinson’s disease group; control group) and subgroups (Parkinson disease with and without cognitive impairment). If the data was not normally distributed, we used Mann-Whitney test. The level of significancy was &lt;0.05 (p value &lt;0.05). &#x0D; Results: The result demonstrated significant differences in beta-amyloid, alpha-synuclein, and tau protein plasma level between Parkinson’s disease and control group (p&lt;0.05). We also found significant differences of beta-amyloid plasma level between Parkinson’s with and without cognitive impairment subgroups (p&lt;0.05), but none in other parameters (p&gt;0.05). &#x0D; Conclusion: Low plasma levels of beta-amyloid 42 (Aβ42) are associated with cognitive impairment in patients with Parkinson’s disease.

Alterations in white matter fiber in Parkinson disease across different cognitive stages

Cognitive impairment in Parkinson disease (PD) leads to substantial disability. Unlike external manifestations such as tremor, the decay of cognitive function is often an underlying process, and its neuroanatomic substrates are not yet fully elucidated. Knowledge regarding cognitive-related alterations in white matter (WM) pathways helps us understand the mechanisms of cognitive decline in patients with PD. Previous voxel-based analyses with Diffusion tensor imaging (DTI) metrics, such as fractional anisotropy (FA) and mean diffusivity (MD) have uncovered white matter differences in groupwise, but the conclusions were inconsistent. That was partially due to white matter fibers that are known to affect cognition, such as the corpus callosum (CC) and superior longitudinal fasciculus that cross in voxel, and are hard to interpreted by the abovementioned metrics. Furthermore, cognitive decay is a continuous process, it is difficult to reflect the continuous changes of white matter fibers between groups comparison. In the present work, we chose the constrained spherical deconvolution (CSD) and the fixel model, which avoided the effect of crossing fibers. To compare the white matter fiber in different cognitive stages of patients with PD, the results found that the CC, the cingulum bundle (CB), and the corticospinal tract (CST) showed the same trend in the decline of cognitive function, and this change may lead to the impairment of cognitive function. Our findings can help physicians determine the cognitive stage of PD from the perspective of white matter fiber and provide a reference for clinical trials and predictions.

Diffusion along perivascular spaces reveals evidence supportive of glymphatic function impairment in Parkinson disease

BackgroundReduced diffusion along perivascular spaces in adults with Alzheimer's-disease-related-dementias has been reported and attributed to reduced glymphatic function. ObjectivesTo apply quantitative measures of diffusion along, and orthogonal to, perivascular spaces in a cohort of older adults with and without clinical symptoms of alpha-synuclein related neurodegeneration. Methods181 adults with Parkinson disease (PD) or essential tremor (ET) additionally sub-classified by the presence of cognitive impairment underwent 3 T MRI. Diffusion-tensor-imaging (spatial resolution = 2x2x2 mm; b-value = 1000 s/mm2; directions = 33) measures of diffusion (mm2/s) parallel and orthogonal to perivascular spaces at the level of the medullary veins, and the ratio of these measures (ALPS-index), were calculated. Regions were identified by a board-certified neuroradiologist from T1-weighted and T2-weighted MRI. Evaluations of motor impairment and mild cognitive impairment (MCI) were interpreted by a board-certified neurologist and neuropsychologist, respectively. Multiple regression with false discovery rate correction was applied to understand how diffusion metrics related to (i) disease category (PD vs. ET), (ii) cognition (MCI status), and (iii) white matter disease severity from the Fazekas score. ResultsThe ALPS-index was reduced in PD compared to ET participants (p = 0.037). No association between the ALPS-index and MCI status, but an inverse association between the ALPS-index and Fazekas score (p = 0.002), was observed. The ALPS-index was inversely associated with age (p = 0.007). ConclusionDiffusion aberrations near perivascular spaces are evident in patients with alpha-synuclein related neurodegenerative disorders, and are related to age and white matter disease severity.

Functional Role of the Cerebellum in Parkinson Disease: A PET Study.

To test for cerebellar involvement in motor and nonmotor impairments in Parkinson disease (PD) and to determine patterns of metabolic correlations with supratentorial brain structures, we correlated clinical motor, cognitive, and psychiatric scales with cerebellar metabolism. We included 90 patients with PD. Motor, cognitive, and psychiatric domains were assessed, and resting-state 18FDG-PET metabolic imaging was performed. The motor, cognitive, and psychiatric scores were entered separately into a principal component analysis. We looked for correlations between these 3 principal components and cerebellar metabolism. Furthermore, we extracted the mean glucose metabolism value for each significant cerebellar cluster and looked for patterns of cerebrum-cerebellum metabolic correlations. Severity of impairment was correlated with increased metabolism in the anterior lobes and vermis (motor domain); the right crus I, crus II, and declive (cognitive domain); and the right crus I and crus II (psychiatric domain). No results survived multiple testing corrections regarding the psychiatric domain. Moreover, we found distributed and overlapping, but not identical, patterns of metabolic correlations for motor and cognitive domains. Specific supratentorial structures (cortical structures, basal ganglia, and thalamus) were strongly correlated with each of the cerebellar clusters. These results confirm the role of the cerebellum in nonmotor domains of PD, with differential but overlapping patterns of metabolic correlations suggesting the involvement of cerebello-thalamo-striatal-cortical loops.

Will Artificial Intelligence Outperform the Clinical Neurologist in the Near Future? No.

Will Artificial Intelligence Outperform the Clinical Neurologist in the Near Future? No.

Reduced Regional NREM Sleep Slow-Wave Activity Is Associated With Cognitive Impairment in Parkinson Disease

Growing evidence implicates a distinct role of disturbed slow-wave sleep in neurodegenerative diseases. Reduced non-rapid eye movement (NREM) sleep slow-wave activity (SWA), a marker of slow-wave sleep intensity, has been linked with age-related cognitive impairment and Alzheimer disease pathology. However, it remains debated if SWA is associated with cognition in Parkinson disease (PD). Here, we investigated the relationship of regional SWA with cognitive performance in PD. In the present study, 140 non-demented PD patients underwent polysomnography and were administered the Montréal Cognitive Assessment (MoCA) to screen for cognitive impairment. We performed spectral analysis of frontal, central, and occipital sleep electroencephalography (EEG) derivations to measure SWA, and spectral power in other frequency bands, which we compared to cognition using linear mixed models. We found that worse MoCA performance was associated with reduced 1–4 Hz SWA in a region-dependent manner (F2, 687 =11.67, p < 0.001). This effect was driven by reduced regional SWA in the lower delta frequencies, with a strong association of worse MoCA performance with reduced 1–2 Hz SWA (F2, 687 =18.0, p < 0.001). The association of MoCA with 1–2 Hz SWA (and 1–4 Hz SWA) followed an antero-posterior gradient, with strongest, weaker, and absent associations over frontal (rho = 0.33, p < 0.001), central (rho = 0.28, p < 0.001), and occipital derivations, respectively. Our study shows that cognitive impairment in PD is associated with reduced NREM sleep SWA, predominantly in lower delta frequencies (1–2 Hz) and over frontal regions. This finding suggests a potential role of reduced frontal slow-wave sleep intensity in cognitive impairment in PD.