Search

BackgroundThe criteria for PD-MCI allow the use of global cognitive tests. Their predictive value for conversion from PD-MCI to PDD, especially compared to comprehensive neuropsychological assessment, is unknown.MethodsThe MDS PD-MCI Study Group combined four datasets containing global cognitive tests as well as a comprehensive neuropsychological assessment to define PD-MCI (n = 467). Risk for developing PDD was examined using a Cox model. Global cognitive tests were compared to neuropsychological test batteries (Level I&II) in determining risk for PDD.ResultsPD-MCI based on a global cognitive test (MMSE or MoCA) increases the hazard for developing PDD (respectively HR = 2.57, P = 0.001; HR = 4.14, P =

INTRODUCTION: Recent work suggests that amyloid beta (Aβ) 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 Aβ 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 (Aβ) 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 Aβ burden.Thus, eFBB may serve as a surrogate measure for brain metabolism/perfusion. [ABSTRACT FROM AUTHOR]

We describe the New Zealand Parkinson's Progression Programme (NZP3), its goals, findings, and future plans. To date, 354 people with Parkinson's disease and 89 healthy older controls have participated over a 14-year period. A major focus of the programme has been the characterisation of current cognitive impairment, and the identification of biomarkers for its future emergence in people with Parkinson's. The programme has made significant contributions to the concept of mild cognitive impairment (MCI) in Parkinson's and the development and validation of standardised criteria for it. Brain imaging, both MRI and PET, has also been a focus, showing associations between increasing brain pathology and declining cognitive function. Additional biomarkers such as genetics, fluid biomarkers, eye movement, speech, and quantitative electroencephalography (EEG) are also under investigation. The programme has become a platform supporting many other avenues of research, from investigating the personal impacts of caregiver burden through to national-level epidemiology. To date, the programme has led to multiple journal publications and 17 completed and 9 ongoing PhDs, and many other postgraduate theses. It has led to the development of a skilled core of early-career through to senior researchers and clinicians. We discuss the future directions for the programme. [ABSTRACT FROM AUTHOR]

Cognitive impairment is a well‐recognized and debilitating symptom of Parkinson's disease (PD). Degradation in the cortical cholinergic system is thought to be a key contributor. Both postmortem and in vivo cholinergic positron emission tomography (PET) studies have provided valuable evidence of cholinergic system changes in PD, which are pronounced in PD dementia (PDD). A growing body of literature has employed magnetic resonance imaging (MRI), a noninvasive, more cost‐effective alternative to PET, to examine cholinergic system structural changes in PD. This review provides a comprehensive discussion of the methodologies and findings of studies that have focused on the relationship between cholinergic basal forebrain (cBF) integrity, based on T1‐ and diffusion‐weighted MRI, and cognitive function in PD. Nucleus basalis of Meynert (Ch4) volume has been consistently reduced in cognitively impaired PD samples and has shown potential utility as a prognostic indicator for future cognitive decline. However, the extent of structural changes in Ch4, especially in early stages of cognitive decline in PD, remains unclear. In addition, evidence for structural change in anterior cBF regions in PD has not been well established. This review underscores the importance of continued cross‐sectional and longitudinal research to elucidate the role of cholinergic dysfunction in the cognitive manifestations of PD. © 2024 The Author(s). Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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 Māori. The 2006-2013 age-standardized incidence (per 100,000 population per year) was European, 33; Asian, 28; Pasifika, 27; Māori, 20. The 2013 age-standardized prevalence (per 100,000 population) was European, 223; Asian, 174; Pasifika, 160; Māori, 114.Conclusions: There is a differential occurrence of Parkinson's disease across the major ethnic groups within the New Zealand population, with indigenous Māori 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. [ABSTRACT FROM AUTHOR]

Background & Objectives: Cross-sectional magnetic resonance imaging (MRI) suggests that Parkinson’s disease (PD) is associated with changes in cerebral tissue volume, diffusion tensor imaging metrics, and perfusion values. Here, we performed a longitudinal multimodal MRI study—including structural, diffusion tensor imaging (DTI), and perfusion MRI—to investigate progressive brain changes over one year in a group of older PD patients at a moderate stage of disease. Methods: Twenty-three non-demented PD (mean age (SD) = 69.5 (6.4) years, disease duration (SD) = 5.6 (4.3) years) and 23 matched control participants (mean age: 70.6 (6.8)) completed extensive neuropsychological and clinical assessment, and multimodal 3T MRI scanning at baseline and one year later. We used a voxel-based approach to assess change over time and group-by-time interactions for cerebral structural and perfusion metrics. Results: Compared to controls, in PD participants there was localized grey matter atrophy over time in bilateral inferior and right middle temporal, and left orbito-frontal cortices. Using a voxel-based approach that focused on the centers of principal white matter tracts, the PD and control cohorts exhibited similar levels of change in DTI metrics. There was no significant change in perfusion, cognitive, or motor severity measures. Conclusions: In a cohort of older, non-demented PD participants, macrostructural MRI detected atrophy in the PD group compared with the control group in temporal and orbito-frontal cortices. Changes in diffusion MRI along principal white matter tracts over one year were found, but this was not differentially affected by PD. [ABSTRACT FROM AUTHOR]

Emerging evidence suggests that Alzheimer's disease (AD) and Parkinson's disease dementia (PDD) share neurodegenerative mechanisms. We sought to directly compare cerebral perfusion in these two conditions using arterial spin labeling magnetic resonance imaging (ASL-MRI). In total, 17 AD, 20 PDD, and 37 matched healthy controls completed ASL and structural MRI, and comprehensive neuropsychological testing. Alzheimer's disease and PDD perfusion was analyzed by whole-brain voxel-based analysis (to assess absolute blood flow), a priori specified region of interest analysis, and principal component analysis (to generate a network differentiating the two groups). Corrections were made for cerebral atrophy, age, sex, education, and MRI scanner software version. Analysis of absolute blood flow showed no significant differences between AD and PDD. Comparing each group with controls revealed an overlapping, posterior pattern of hypoperfusion, including posterior cingulate gyrus, precuneus, and occipital regions. The perfusion network that differentiated AD and PDD groups identified relative differences in medial temporal lobes (AD

We have developed a modular virtual environment platform for movement research and rehabilitation. The system uses several networked computers running Linux to share computation. An electromagnetic tracker is the primary position tracker and both a head-mounted display and stereo goggles are used for visual display. System software is written in a combination of C++, JAVA, and Python and makes considerable use of the open-source toolkits VR Juggler and OpenSceneGraph. These are integrated with additional toolkits and custom modules written specifically for the study of motor control and rehabilitation. The system performs well with low latency, accurate calibration, and a consistently high graphics update rate. Preliminary applications have confirmed that the system is a powerful tool for sensory-motor investigation and has considerable potential as a tool for neurorehabilitation. Its primary advantage over other systems is its ability to utilize different display and input devices, and run a range of experiments simply by changing XML configuration files. Additionally, the use of powerful open-source libraries provides a feature-rich foundation for advanced features and low-cost duplication. Further work and experiments are needed to extend, further validate, and fully utilize this platform. [ABSTRACT FROM AUTHOR]

Abstract: Studies of saccades in Parkinson''s disease (PD) have seldom examined the influence of cognitive status, ranging from normal cognition, through mild cognitive impairment, to dementia. In a large and heterogeneous sample, we examined how motor and cognitive impairment was reflected in the performance of reflexive, visually-guided saccades. We examined 163 people with PD and 47 similar-aged controls. Ninety three of the PD group had normal cognition (PDN), 48 had mild cognitive impairment (PD-MCI), and 22 had dementia (PDD). Pseudo-random targets (amplitudes of 5, 10, 15 and 20deg and inter-stimulus-intervals ranging from 550 to 1800ms) were shown in 108 mixed randomised trials, incorporating gap, step, and overlap onset conditions. Analyses were conducted using multi-level regression modeling. Participants were first assessed by continuous measures (Unified PD Rating Scale motor score and the Montreal Cognitive Assessment). Prolonged latency was significantly related to both motor and cognitive impairment, with the cognitive effect being compounded by increasing age. Decreased saccade amplitude, meanwhile, was primarily related to motor impairment. When assessed by discrete cognitive categories, all of the PD groups showed reduced saccadic amplitude relative to controls. Saccadic latencies, meanwhile, were abnormally prolonged only in the PD-MCI and PDD groups (the control and PDN groups were similar to each other). Latency in the overlap task was particularly sensitive to increasing motor and cognitive impairment. We conclude that reflexive saccades in PD are subtly decreased in amplitude even early in the disease process. Prolonged saccade latency, meanwhile, tends to occur later in the disease process, in the presence of more substantial motor and cognitive impairment, and greater age. The progressive impairment of reflexive saccades, and the differential onset of amplitude and latency impairments, may make them a useful objective tool for assessing disease status. [Copyright &y& Elsevier]

• A new algorithm for substantia nigra and red nucleus segmentation from QSM images. • Contrast enhancement technique using local and global mean. • High correlation of QSM values extracted from manual and proposed segmentations. • Increased iron content observed in substantia nigra of Parkinsonʼs disease patients. • Substantia nigra QSM values showed association with cognitive and motor impairments. Accurate segmentation of substantia nigra (SN) and red nucleus (RN) is challenging, yet important for understanding health problems like Parkinson's disease (PD). This paper proposes an algorithm to segment SN and RN from quantitative susceptibility mapping (QSM) MRI and use the results to investigate PD. Algorithm-derived segments (based on level set and watershed transform) are compared to expert manually-derived segmentations in 40 participants. Using Bayesian regression models, we compare QSM values between PD and control groups, and investigate relationships with global cognitive ability and motor severity in PD. The proposed algorithm produces high quality segmentations, validated against expert manual segmentation. We show moderate evidence of increased QSM values in SN in PD relative to controls, with moderate evidence for association between QSM, global cognitive ability, and motor impairment in the SN in PD. We suggest an improved midbrain segmentation algorithm may be useful for monitoring iron-related disease severity in Parkinson's. [Display omitted] [ABSTRACT FROM AUTHOR]