Clinical outcomes of delayed mechanical thrombectomy: Descriptive analysis and development of a screening tool.

BACKGROUND AND PURPOSE: Limited data guide the selection of patients with large vessel occlusion ischaemic stroke who may benefit from referral to a distant tertiary centre for mechanical thrombectomy (MT). We aimed to characterize this population, describe clinical outcomes and develop a screening system to identify patients most likely to benfit from delayed mechanical thrombectomy (MT). METHODS: We undertook a retrospective cohort analysis enrolling patients transferred from regional sites to one of two MT comprehensive stroke units with a time from non-contrast computed tomography (NCCT) of the brain to reperfusion of 4 h or more. We describe Alberta Stroke Programme Early Computed Tomography Score (ASPECTS), National Institute of Health Stroke Scale (NIHSS) and modified Rankin Scale (mRS) in our patients and compare these patients to those in extended-time-window trials. Lastly, we developed and validated a scoring model to help clinicians identify appropriate patients based on variables associated with poor outcomes. RESULTS: We included 563 patients, 46% of whom received thrombolysis; the median (interquartile range [IQR]) ASPECTS was 8 (7-10) and the median (IQR) NIHSS score was 16 (11-20). The median (IQR) symptom to mechanical reperfusion time was 390 (300-580) min. Eight patients (1%) had a symptomatic haemorrhage. We achieved good clinical outcome (defined as mRS score ≤2) in 299 patients (54%). Age, diabetes, NIHSS score and ASPECTS were used to create a weighted scoring system with a validated area under the curve of 0.83 (95% confidence interval 0.74-0.92). CONCLUSION: Our study shows, in highly selected patients, that delayed MT many hours after baseline NCCT is associated with good clinical outcomes. However, older patients with diabetes, high NIHSS score and low ASPECTS may not benefit from transfer to a hub centre many hours away for MT in this model of care.

A Multi-Step Model of Parkinson's Disease Pathogenesis.

BACKGROUND: Parkinson's disease (PD) may result from the combined effect of multiple etiological factors. The relationship between disease incidence and age, as demonstrated in the cancer literature, can be used to model a multistep pathogenic process, potentially affording unique insights into disease development. OBJECTIVES: We tested whether the observed incidence of PD is consistent with a multistep process, estimated the number of steps required and whether this varies with age, and examined drivers of sex differences in PD incidence. METHODS: Our validated probabilistic modeling process, based on medication prescribing, generated nationwide age- and sex-adjusted PD incidence data spanning 2006-2017. Models of log(incidence) versus log(age) were compared using Bayes factors, to estimate (1) if a linear relationship was present (indicative of a multistep process); (2) the relationship's slope (one less than number of steps); (3) whether slope was lower at younger ages; and (4) whether slope or y-intercept varied with sex. RESULTS: Across >15,000 incident cases of PD, there was a clear linear relationship between log(age) and log(incidence). Evidence was strongest for a model with an initial slope of 5.2 [3.8, 6.4], an inflexion point at age 45, and beyond this a slope of 6.8 [6.4, 7.2]. There was evidence for the intercept varying by sex, but no evidence for slope being sex-dependent. CONCLUSIONS: The age-specific incidence of PD is consistent with a process that develops in multiple, discrete steps - on average six before age 45 and eight after. The model supports theories emphasizing the primacy of environmental factors in driving sex differences in PD incidence. © 2021 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Test-retest reliability and sample size estimates after MRI scanner relocation.

OBJECTIVE: Many factors can contribute to the reliability and robustness of MRI-derived metrics. In this study, we assessed the reliability and reproducibility of three MRI modalities after an MRI scanner was relocated to a new hospital facility. METHODS: Twenty healthy volunteers (12 females, mean age (standard deviation) â€‹= â€‹41 (11) years, age range [25-66]) completed three MRI sessions. The first session (S1) was one week prior to the 3T GE HDxt scanner relocation. The second (S2) occurred nine weeks after S1 and at the new location; a third session (S3) was acquired 4 weeks after S2. At each session, we acquired structural T1-weighted, pseudo-continuous arterial spin labelled, and diffusion tensor imaging sequences. We used longitudinal processing streams to create 12 summary MRI metrics, including total gray matter (GM), cortical GM, subcortical GM, white matter (WM), and lateral ventricle volume; mean cortical thickness; total surface area; average gray matter perfusion, and average diffusion tensor metrics along principal white matter pathways. We compared mean MRI values and variance at the old scanner location to multiple sessions at the new location using Bayesian multi-level regression models. K-fold cross validation allowed identification of important predictors. Whole-brain analyses were used to investigate any regional differences. Furthermore, we calculated within-subject coefficient of variation (wsCV), intraclass correlation coefficient (ICC), and dice similarity index (SI) of cortical segmentations across scanner relocation and within-site. Additionally, we estimated sample sizes required to robustly detect a 4% difference between two groups across MRI metrics. RESULTS: All global MRI metrics exhibited little mean difference and small variability (bar cortical gray matter perfusion) both across scanner relocation and within-site repeat. T1- and DTI-derived tissue metrics showed â€‹< â€‹|0.3|% mean difference and <1.2% variance across scanner location and <|0.4|% mean difference and <0.8% variance within the new location, with between-site intraclass correlation coefficient (ICC) â€‹> â€‹0.80 and within-subject coefficient of variation (wsCV) â€‹< â€‹1.4%. Mean cortical gray matter perfusion had the highest between-session variability (6.7% [0.3, 16.7], estimate [95% uncertainty interval]), and hence the smallest ICC (0.71 [0.44,0.92]) and largest wsCV (13.4% [5.4, 18.1]). No global metric exhibited evidence of a meaningful mean difference between scanner locations. However, surface area showed evidence of a mean difference within-site repeat (between S2 and S3). Whole-brain analyses revealed no significant areas of difference between scanner relocation or within-site. For all metrics, we found no support for a systematic difference in variance across relocation sites compared to within-site test-retest reliability. Necessary sample sizes to detect a 4% difference between two independent groups varied from a maximum of n â€‹= â€‹362 per group (cortical gray matter perfusion), to total gray matter volume (n â€‹= â€‹114), average fractional anisotropy (n â€‹= â€‹23), total gray matter volume normalized by intracranial volume (n â€‹= â€‹19), and axial diffusivity (n â€‹= â€‹3 per group). CONCLUSION: Cortical gray matter perfusion was the most variable metric investigated (necessitating large sample sizes to identify group differences), with other metrics showing substantially less variability. Scanner relocation appeared to have a negligible effect on variability of the global MRI metrics tested. This manuscript reports within-site test-retest variability to act as a tool for calculating sample size in future investigations. Our results suggest that when all other parameters are held constant (e.g., sequence parameters and MRI processing), the effect of scanner relocation is indistinguishable from within-site variability, but may need to be considered depending on the question being investigated.

Childbirth and Delayed Parkinson's Onset: A Reproducible Nonbiological Artifact of Societal Change.

BACKGROUND: Uncontrolled studies have reported associations between later Parkinson's disease onset in women and a history of giving birth, with age at onset delayed by nearly 3 years per child. We tested this association in two independent data sets, but, as a control to test for nonbiological explanations, also included men with PD. METHODS: We analyzed valid cases from the Parkinson's Progressive Markers Initiative incident sample (145 women, 276 men) and a prevalent sample surveyed by the New Zealand Brain Research Institute (210 women, 394 men). RESULTS: The association was present in both women and men in the Parkinson's Progressive Markers Initiative study, and absent in both in the New Zealand Brain Research Institute study. This is consistent with generational differences common to men and women, which confound with age at onset in incident-dominant samples. CONCLUSIONS: Despite being replicable in certain circumstances, associations between childbirth and later PD onset are an artifact of generational cohort differences. © 2020 International Parkinson and Movement Disorder Society.

Parkinson's disease across ethnicities: A nationwide study in New Zealand.

BACKGROUND: New Zealand is an ethnically diverse country with a unified national prescribing system. This provides a good framework to use drug-tracing methodology to establish the prevalence and incidence of Parkinson's disease across different ethnic groups. The objective of this study was to determine the prevalence and incidence of Parkinson's disease in the major ethnic groups in New Zealand. METHODS: Information on Parkinson's disease-related medications was extracted from the national Pharmaceutical Collection of community-dispensed medications for the period January 1, 2005, to December 31, 2014. Diagnoses for a large subset of individuals were independently determined through national mortality and hospital admissions data sets. We used a Bayesian model, accommodating uncertainty and bias, to estimate the number of people with Parkinson's disease. RESULTS: We found the highest rate of Parkinson's disease in the European ethnic group and the lowest rate in the indigenous Maori. The 2006-2013 age-standardized incidence (per 100,000 population per year) was European, 33; Asian, 28; Pasifika, 27; Maori, 20. The 2013 age-standardized prevalence (per 100,000 population) was European, 223; Asian, 174; Pasifika, 160; Maori, 114. CONCLUSIONS: There is a differential occurrence of Parkinson's disease across the major ethnic groups within the New Zealand population, with indigenous Maori showing the lowest incidence. Varying susceptibility profiles, gene-environment interactions, and inequalities in accessing health care may play a role in the variation in rates of Parkinson's disease in New Zealand. © 2018 International Parkinson and Movement Disorder Society.

Response to "Parkinson's disease mild cognitive impairment classifications and neurobehavioral symptoms".

A recent paper, "Parkinson's disease mild cognitive impairment classifications and neurobehavioral symptoms" (McDermott et al., 2017), provides an interesting comparison of the influence of different criteria for Parkinson's disease with mild cognitive impairment (PD-MCI) on progression to dementia (PDD). Unfortunately, McDermott et al. (2017) incorrectly stated that "only 21% of PD-MCI participants (identified with a 1.5 SD cut-off) converted to PDD within four years" (p.6) in our study (Wood et al., 2016). However, the important point made by Wood et al. (2016) was that the proportion of conversions to PDD was 51% when the PD-MCI diagnosis required a minimum of two 1.5 SD impairments within any single cognitive domain, whereas additional PD-MCI patients classified with one impairment at 1.5 SD in each of the two domains (but never two impairments in the same domain) had a non-significant risk of dementia relative to non-MCI patients (11% vs. 6% converted, respectively). Our PDD conversion rate was 38% when combining both 1.5 SD criteria (21/56 PD-MCI patients vs. 4/65 non-MCI patients converted); McDermott et al. (2017) found a 42% conversion rate over three years for similarly described PD-MCI patients (10/24 PD-MCI patients vs. 0/27 non-MCI patients converted). Our study was also part of a multinational study (n = 467) showing that PD-MCI has predictive validity beyond known demographic and PD-specific factors of influence (Hoogland et al., 2017). All three studies found that multiple cognitive domain impairments are common in PD-MCI. Nonetheless, the research community needs to clarify the association between PD-MCI subtypes and, especially, the optimal cognitive markers for dementia risk in PD patients.

Cross-Sectional and Longitudinal Association of Clinical and Neurocognitive Factors With Apathy in Patients With Parkinson Disease.

BACKGROUND AND OBJECTIVES: A robust understanding of the natural history of apathy in Parkinson disease (PD) is foundational for developing effective clinical management tools. However, large longitudinal studies are lacking while the literature is inconsistent about even cross-sectional associations. We aimed to determine the longitudinal predictors of apathy development in a large cohort of people with PD and its cross-sectional associations and trajectories over time, using sophisticated Bayesian modeling techniques. METHODS: People with PD followed up in the longitudinal New Zealand Parkinson's progression project were included. Apathy was defined using the neuropsychiatric inventory subscale ≥4, and analyses were also repeated using a less stringent cutoff of ≥1. Both MoCA and comprehensive neuropsychological testing were used as appropriate to the model. Depression was assessed using the hospital anxiety and depression scale. Cross-sectional Bayesian regressions were conducted, and a multistate predictive model was used to identify factors that predict the initial onset of apathy in nonapathetic PD, while also accounting for the competing risk of death. The relationship between apathy presence and mortality was also investigated. RESULTS: Three hundred forty-six people with PD followed up for up to 14 years across a total of 1,392 sessions were included. Apathy occurrence did not vary significantly across the disease course (disease duration odds ratio [OR] = 0.55, [95% CI 0.28-1.12], affecting approximately 11% or 22% of people at any time depending on the NPI cutoff used. Its presence was associated with a significantly higher risk of death after controlling for all other factors (hazard ratio [HR] = 2.92 [1.50-5.66]). Lower cognition, higher depression levels, and greater motor severity predicted apathy development in those without motivational deficits (HR [cognition] = 0.66 [0.48-0.90], HR [depression] = 1.45 [1.04-2.02], HR [motor severity] = 1.37 [1.01-1.86]). Cognition and depression were also associated with apathy cross-sectionally, along with male sex and possibly lower dopaminergic therapy level, but apathy still occurred across the full spectrum of each variable (OR [cognition] = 0.58 [0.44-0.76], OR [depression] = 1.43 [1.04-1.97], OR [female sex] = 0.45 [0.22-0.92], and OR [levodopa equivalent dose] = 0.78 [0.59-1.04]. DISCUSSION: Apathy occurs across the PD time course and is associated with higher mortality. Depressive symptoms and cognitive impairment in particular predict its future development in those with normal motivation.

Early-phase amyloid PET reproduces metabolic signatures of cognitive decline in Parkinson's disease.

INTRODUCTION: Recent work suggests that amyloid beta (Aß) positron emission tomography (PET) tracer uptake shortly after injection ("early phase") reflects brain metabolism and perfusion. We assessed this modality in a predominantly amyloid-negative neurodegenerative condition, Parkinson's disease (PD), and hypothesized that early-phase 18F-florbetaben (eFBB) uptake would reproduce characteristic hypometabolism and hypoperfusion patterns associated with cognitive decline in PD. METHODS: One hundred fifteen PD patients across the spectrum of cognitive impairment underwent dual-phase Aß PET, structural and arterial spin labeling (ASL) magnetic resonance imaging (MRI), and neuropsychological assessments. Multiple linear regression models compared eFBB uptake to cognitive performance and ASL MRI perfusion. RESULTS: Reduced eFBB uptake was associated with cognitive performance in brain regions previously linked to hypometabolism-associated cognitive decline in PD, independent of amyloid status. Furthermore, eFBB uptake correlated with cerebral perfusion across widespread regions. DISCUSSION: EFBB uptake is a potential surrogate measure for cerebral perfusion/metabolism. A dual-phase PET imaging approach may serve as a clinical tool for assessing cognitive impairment. Highlights: Images taken at amyloid beta (Aß) positron emission tomography tracer injection may reflect brain perfusion and metabolism.Parkinson's disease (PD) is a predominantly amyloid-negative condition.Early-phase florbetaben (eFBB) in PD was associated with cognitive performance.eFBB uptake reflects hypometabolism-related cognitive decline in PD.eFBB correlated with arterial spin labeling magnetic resonance imaging measured cerebral perfusion.eFBB distinguished dementia from normal cognition and mild cognitive impairment.Findings were independent of late-phase Aß burden.Thus, eFBB may serve as a surrogate measure for brain metabolism/perfusion.

A perceptual discrimination task results in greater facilitation of voluntary saccades in Parkinson's disease patients.

Many studies have shown that Parkinson's disease (PD) affects not only the ability to generate voluntary saccades but also the ability to suppress reflexive saccades (hyper-reflexivity). To further investigate these apparently contradictory effects of PD on the saccade system we adapted a well-known dual-task paradigm (Deubel, 2008) to measure saccades with and without a peripheral discrimination task. Previously we reported that the concurrent performance of a perceptual discrimination task abnormally reduced the latencies of reflexive saccades in PD. Here we report the effects of the concurrent discrimination task on the generation of voluntary saccades in a PD and a control group. As expected, when saccades were performed without the discrimination task the PD group made voluntary saccades with longer latencies and smaller gain than the control group. The concurrent performance of the perceptual discrimination task facilitated the initiation of voluntary saccades in both groups, but, surprisingly, this facilitatory effect was stronger in the PD group than in the control group. In addition, in the PD group voluntary saccades were abnormally facilitated by the peripheral symbol-changes that occur during saccade planning in this paradigm. The results of this study may help to clarify apparently contradictory oculomotor abnormalities observed in PD.

Cross-sectional area of the anterior belly of the digastric muscle: comparison of MRI and ultrasound measures.

Changes in morphometry of head and neck muscles have received little attention in research relative to limb muscles. While recent literature suggests that high-frequency ultrasound transducers can provide superior spatial resolution compared to that of magnetic resonance imaging (MRI), no studies have compared these imaging methods for investigating the submental muscle group. This preliminary study sought to compare ultrasound and MRI as a method of quantifying the cross-sectional area (CSA) of the submental muscle group. Measurements were taken from coronal ultrasound and MRI images in 11 healthy participants. Comparisons were limited to the anterior belly of the digastric muscle because of differences in imaging resolution. Ultrasound CSA measurements were smaller than MRI measurements (p = 0.01) by 10 % (95% CI = -18 to -2). Correlations were significant and relatively high (left: r = 0.909, p < 0.001; right: r = 0.776, p = 0.005). Ultrasound imaging has the advantages of natural participant positioning, superior clarity of muscle borders of the submental muscles, requires less acquisition time, and is a less expensive method of imaging compared to MRI. This preliminary study has shown that ultrasound is a viable imaging modality for quantitative measurements of the anterior belly of the digastric muscle and has advantages over MRI beyond cost and accessibility.

Progressive MRI brain volume changes in ovine models of CLN5 and CLN6 neuronal ceroid lipofuscinosis.

Neuronal ceroid lipofuscinoses (Batten disease) are a group of inherited lysosomal storage disorders characterized by progressive neurodegeneration leading to motor and cognitive dysfunction, seizure activity and blindness. The disease can be caused by mutations in 1 of 13 ceroid lipofuscinosis neuronal (CLN) genes. Naturally occurring sheep models of the CLN5 and CLN6 neuronal ceroid lipofuscinoses recapitulate the clinical disease progression and post-mortem pathology of the human disease. We used longitudinal MRI to assess global and regional brain volume changes in CLN5 and CLN6 affected sheep compared to age-matched controls over 18 months. In both models, grey matter volume progressively decreased over time, while cerebrospinal fluid volume increased in affected sheep compared with controls. Total grey matter volume showed a strong positive correlation with clinical scores, while cerebrospinal fluid volume was negatively correlated with clinical scores. Cortical regions in affected animals showed significant atrophy at baseline (5 months of age) and progressively declined over the disease course. Subcortical regions were relatively spared with the exception of the caudate nucleus in CLN5 affected animals that degenerated rapidly at end-stage disease. Our results, which indicate selective vulnerability and provide a timeline of degeneration of specific brain regions in two sheep models of neuronal ceroid lipofuscinoses, will provide a clinically relevant benchmark for assessing therapeutic efficacy in subsequent trials of gene therapy for CLN5 and CLN6 disease.

A perceptual discrimination task abnormally facilitates reflexive saccades in Parkinson's disease.

Numerous studies have shown that Parkinson's disease (PD) affects the ability to generate voluntary saccades and the ability to suppress reflexive saccades. The effects of PD on the generation of reflexive saccades, however, are not clear. Some studies report impairments, but there are also reports of abnormal facilitation or hyper-reflexivity of the saccade system in PD. Meanwhile, it has been reported that the concurrent performance of a perceptual discrimination task facilitates saccade initiation and reduces saccade latencies in healthy subjects [A. Montagnini & L. Chelazzi (2005)Vis. Res., 45, 3391-3401; L. Trottier & J. Pratt (2005)Vis. Res., 45, 1349-1354]. To investigate the circumstances under which the saccade system may appear hyper-reflexive in PD, we compared reflexive saccades with and without a concurrent perceptual discrimination task in 20 PD patients and 20 controls. Without the discrimination task, the PD group produced reflexive saccades at normal latencies. The discrimination task reduced saccade latencies more in the PD group than in the control group, resulting in abnormally short mean reflexive saccade latencies in the PD group. The discrimination task increased saccade gain in both groups, but saccades in the PD group remained hypometric as compared with saccades in the control group. We conclude that the attentional demands of this paradigm revealed a hypersensitivity to visual inputs in the PD group.

Pharyngeal pressures during swallowing within and across three sessions: within-subject variance and order effects.

No studies have investigated within-subject variation in measures of pharyngeal pressures during swallowing across sessions. This study aimed to document the variation in pharyngeal pressures both within and across three sessions. Twenty healthy participants were recruited for three sessions. For each session, peak or nadir pressures were recorded from the upper pharynx (sensor 1), mid-pharynx (sensor 2), and upper esophageal sphincter (sensor 3) during saliva and 10-ml water bolus swallows. Variance was larger across sessions than within sessions for sensors 1 and 2 but comparable for sensor 3. For all sensors there was a high correlation between the variance across sessions and within session (r = 0.92, p < 0.0001). There were no significant order effects of session or of trial at any sensor with estimated order effects less than 2% and the estimated maximum possible change no larger than 5% for trial and no larger than 12% for session. These data offer direction for longitudinal treatment studies in which pharyngeal pressures are an outcome measurement by (1) providing a basis for power calculations, (2) estimating the likely values of any confounding order effects, and (3) providing suggestions for more reliable data analysis.

Neuropsychiatric Symptoms Are Associated with Dementia in Parkinson's Disease but Not Predictive of it.

BACKGROUND: Neuropsychiatric symptoms in Parkinson's disease (PD) may increase dementia (PDD) risk. The predictive value of these symptoms, however, has not been compared to clinical and demographic predictors of future PDD. OBJECTIVES: Determine if neuropsychiatric symptoms are useful markers of PDD risk. METHODS: 328 PD participants completed baseline neuropsychiatric and MDS-Task Force-Level II assessments. Of these, 202 non-demented individuals were followed-up over a four-years period to detect conversion to PDD; 51 developed PDD. ROC analysis tested associations between baseline neuropsychiatric symptoms and future PDD. The probability of developing PDD was also modeled as a function of neuropsychiatric inventory (NPI)-total score, PD Questionnaire (PDQ)-hallucinations, PDQ-anxiety, and contrasted to cognitive ability, age, and motor function. Leave-one-out information criterion was used to evaluate which models provided useful information when predicting future PDD. RESULTS: The PDD group experienced greater levels of neuropsychiatric symptoms compared to the non-PDD groups at baseline. Few differences were found between the PD-MCI and PD-N groups. Six neuropsychiatric measures were significantly, but weakly, associated with future PDD. The strongest was NPI-total score: AUC = 0.66 [0.57-0.75]. There was, however, no evidence it contained useful out-of-sample predictive information of future PDD (delta ELPD = 1.8 (SD 2.5)); Similar results held for PDQ-hallucinations and PDQ-anxiety. In contrast, cognitive ability (delta ELPD = 36 (SD 8)) and age (delta ELPD = 11 (SD 5)) provided useful predictive information of future PDD. CONCLUSIONS: Cognitive ability and age strongly out-performed neuropsychiatric measures as markers of developing PDD within 4 years. Therefore, neuropsychiatric symptoms do not appear to be useful markers of PDD risk.

Higher perceived stress and exacerbated motor symptoms in Parkinson's disease during the COVID-19 lockdown in New Zealand.

AIMS: Stress plays a key role in Parkinson's disease (PD) by acting on the dopaminergic system and worsening patients' motor function. The impact of New Zealand's strict lockdown measures to contain COVID-19 on perceived stress and PD motor symptoms remains unknown. Here we examined the relationship between perceived levels of stress, changes in physical activity levels and PD motor symptoms during lockdown. METHODS: During lockdown, 134 participants with PD and 49 controls completed a survey assessing perceived stress, self-reported changes in PD motor symptoms and physical activity duration and intensity prior to and during lockdown. RESULTS: Perceived stress was higher in PD than controls, and in those reporting a worsening of tremor, balance/gait, dyskinesia and bradykinesia compared to those indicating no change during the COVID-19 lockdown. These effects were not modulated by physical activity. CONCLUSIONS: Reducing stressors may be an important adjunct treatment strategy to improve motor function in PD.

Volitional Suppression of Parkinsonian Resting Tremor.

BACKGROUND: We have observed in the clinic that a number of patients with Parkinson's disease (PD) can suppress their tremor at will for brief periods, by conscious mental processes. To our knowledge, the ability to consciously diminish one's resting tremor has not yet been reported nor assessed quantitatively. OBJECTIVE: To provide the first detailed systematic investigation of the phenomenon of voluntary tremor suppression in PD. METHODS: We examined changes in tremor characteristics during voluntary tremor suppression in 37 PD patients (on medication) presenting with rest tremor in their upper limb. We measured tremor oscillations with a triaxis accelerometer on the index finger of the most-affected hand (n = 27). With surface electromyography (EMG), we measured changes in neuromuscular activity of the forearm flexor digitorum superficialis and extensor digitorum muscles (n = 15). Participants completed four 1-minute trials, consisting of alternating consecutive 30-second periods of resting tremor and 30-second periods of attempted tremor suppression. RESULTS: Bayesian multilevel modeling revealed that attempted voluntary tremor suppression did indeed reduce tremor amplitude (peak power) of the acceleration signal and increased tremor frequency of the acceleration and EMG signals. Relative EMG power in the 3- to 8-Hz tremor band was also smaller. Tremor suppression was not by enhanced voluntary contraction of the relevant muscle pairs. CONCLUSIONS: We present novel empirical evidence that PD resting tremor can be suppressed by an act of will, as evidenced by significant modulation of key neurophysiological tremor characteristics. These data highlight that it is possible to exert significant conscious control over parkinsonian resting tremor.

Beta Amyloid Deposition Is Not Associated With Cognitive Impairment in Parkinson's Disease.

The extent to which Alzheimer neuropathology, particularly the accumulation of misfolded beta-amyloid, contributes to cognitive decline and dementia in Parkinson's disease (PD) is unresolved. Here, we used Florbetaben PET imaging to test for any association between cerebral amyloid deposition and cognitive impairment in PD, in a sample enriched for cases with mild cognitive impairment. This cross-sectional study used Movement Disorders Society level II criteria to classify 115 participants with PD as having normal cognition (PDN, n = 23), mild cognitive impairment (PD-MCI, n = 76), or dementia (PDD, n = 16). We acquired 18F-Florbetaben (FBB) amyloid PET and structural MRI. Amyloid deposition was assessed between the three cognitive groups, and also across the whole sample using continuous measures of both global cognitive status and average performance in memory domain tests. Outcomes were cortical FBB uptake, expressed in centiloids and as standardized uptake value ratios (SUVR) using the Centiloid Project whole cerebellum region as a reference, and regional SUVR measurements. FBB binding was higher in PDD, but this difference did not survive adjustment for the older age of the PDD group. We established a suitable centiloid cut-off for amyloid positivity in Parkinson's disease (31.3), but there was no association of FBB binding with global cognitive or memory scores. The failure to find an association between PET amyloid deposition and cognitive impairment in a moderately large sample, particularly given that it was enriched with PD-MCI patients at risk of dementia, suggests that amyloid pathology is not the primary driver of cognitive impairment and dementia in most patients with PD.