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.

Acquired Stuttering in Parkinson's Disease.

Background: Parkinson's disease frequently causes communication impairments, but knowledge about the occurrence of new-onset stuttering is limited. Objectives: To determine the presence of acquired neurogenic stuttering and its relationship with cognitive and motor functioning in individuals with Parkinson's disease. Method: Conversation, picture description, and reading samples were collected from 100 people with Parkinson's disease and 25 controls to identify the presence of stuttered disfluencies (SD) and their association with neuropsychological test performance and motor function. Results: Participants with Parkinson's disease presented with twice as many stuttered disfluencies during conversation (2.2% ± 1.8%SD) compared to control participants (1.2% ± 1.2%SD; P < 0.01). 21% of people with Parkinson's disease (n = 20/94) met the diagnostic criterion for stuttering, compared with 1/25 controls. Stuttered disfluencies also differed significantly across speech tasks, with more disfluencies during conversation compared to reading (P < 0.01). Stuttered disfluencies in those with Parkinson's disease were associated with longer time since disease onset (P < 0.01), higher levodopa equivalent dosage (P < 0.01), and lower cognitive (P < 0.01) and motor scores (P < 0.01). Conclusion: One in five participants with Parkinson's disease presented with acquired neurogenic stuttering, suggesting that speech disfluency assessment, monitoring and intervention should be part of standard care. Conversation was the most informative task for identifying stuttered disfluencies. The frequency of stuttered disfluencies was higher in participants with worse motor functioning, and lower cognitive functioning. This challenges previous suggestions that the development of stuttered disfluencies in Parkinson's disease has purely a motoric basis.

Dimensions of apathy in Parkinson's disease.

INTRODUCTION: Apathy is one of the most common neuropsychiatric manifestations in Parkinson's disease (PD). Recent proposals consider apathy as a multidimensional construct, which can manifest in behavioral, cognitive, emotional, and/or social dimensions. Apathy also overlaps conceptually and clinically with other non-motor comorbidities, particularly depression. Whether all of these dimensions are applicable to the apathetic syndrome experienced by people with PD is unclear. In the present study, we investigated the multidimensional pattern of apathy associated with PD, using the recently developed Apathy Motivation Index (AMI) which probes behavioral, emotional, and social apathy dimensions. We then examined the relationship between these dimensions and other features of PD commonly associated with apathy, including depression, anxiety, cognition, and motor state. METHODS: A total of 211 participants were identified from the New Zealand Brain Research Institute (NZBRI) longitudinal PD cohort. One hundred eight patients and 45 controls completed the AMI, administered as an online questionnaire, and additional assessments including neuropsychiatric, neuropsychological, and motor scores. The pattern of dimensional apathy in PD was assessed using a repeated-measured analysis of variance, while simple linear regressions were performed to evaluate relationships between these dimensions and other variables. RESULTS: We found a significant interaction between group (PD versus control) and apathy subscale, driven mainly by higher levels of social and behavioral-but not emotional-apathy in those with PD. This result was strikingly similar to a previous study investigating social apathy in PD. Distinct patterns of dimensional apathy were associated with depression and anxiety, with social and behavioral apathy positively associated with depression, and emotional apathy negatively associated with anxiety. CONCLUSION: This work provides further evidence for a distinct pattern of apathy in people with PD in which deficits manifest in some-but not all-dimensions of motivated behavior. It emphasizes the importance of considering apathy as a multidimensional construct in clinical and research settings.

Altered nucleus accumbens functional connectivity precedes apathy in Parkinson's disease.

Work in animal and human neuroscience has identified neural regions forming a network involved in the production of motivated, goal-directed behaviour. In particular, the nucleus accumbens and anterior cingulate cortex are recognized as key network nodes underlying decisions of whether to exert effort for reward, to drive behaviour. Previous work has convincingly shown that this cognitive mechanism, known as effort-based decision making, is altered in people with Parkinson's disease with a syndrome of reduced goal-directed behaviour-apathy. Building on this work, we investigated whether the neural regions implementing effort-based decision-making were associated with apathy in Parkinson's disease, and more importantly, whether changes to these regions were evident prior to apathy development. We performed a large, multimodal neuroimaging analysis in a cohort of people with Parkinson's disease (n = 199) with and without apathy at baseline. All participants had ∼2-year follow-up apathy scores, enabling examination of brain structure and function specifically in those with normal motivation who converted to apathy by ∼2-year follow-up. In addition, of the people with normal motivation, a subset (n = 56) had follow-up neuroimaging data, allowing for examination of the 'rate of change' in key nodes over time in those who did, and did not, convert to apathy. Healthy control (n = 54) data were also included to aid interpretation of findings. Functional connectivity between the nucleus accumbens and dorsal anterior cingulate cortex was higher in people with normal motivation who later converted to apathy compared to those who did not, whereas no structural differences were evident between these groups. In contrast, grey matter volume in these regions was reduced in the group with existing apathy. Furthermore, of those with normal motivation who had undergone longitudinal neuroimaging, converters to apathy showed a higher rate of change in grey matter volume within the nucleus accumbens. Overall, we show that changes in functional connectivity between nucleus accumbens and anterior cingulate cortex precedes apathy in people with Parkinson's disease, with conversion to apathy associated with higher rate of grey matter volume loss in nucleus accumbens, despite no baseline differences. These findings significantly add to an accumulating body of transdiagnostic evidence that apathy arises from disruption to key nodes within a network in which normal goal-directed behaviour is instantiated, and raise the possibility of identifying those at risk for developing apathy before overt motivational deficits have arisen.

Multiple sclerosis mortality in New Zealand: a nationwide prospective study.

BACKGROUND: Mortality data from Europe and North America show a shorter life expectancy for people with multiple sclerosis (MS). It is not known if a similar mortality risk exists in the southern hemisphere. We analysed the mortality outcomes of a comprehensive New Zealand (NZ) MS cohort, 15 years postrecruitment. METHODS: All participants of the nationwide 2006 NZ MS prevalence study were included and mortality outcomes were compared with life table data from the NZ population using classic survival analyses, standardised mortality ratios (SMRs) and excess death rates (EDRs). RESULTS: Of 2909 MS participants, 844 (29%) were deceased at the end of the 15-year study period. Median survival age for the MS cohort was 79.4 years (78.5, 80.3), compared with 86.6 years (85.5, 87.7) for the age-matched and sex-matched NZ population. The overall SMR was 1.9 (1.8, 2.1)). Symptom onset between 21 and 30 years corresponded to an SMR of 2.8 and a median survival age 9.8 years lower than the NZ population. Progressive-onset disease was associated with a survival gap of 9 years compared with 5.7 years for relapsing onset. The EDR for those diagnosed in 1997-2006 was 3.2 (2.6, 3.9) compared with 7.8 (5.8, 10.3) for those diagnosed between 1967 and 1976. CONCLUSIONS: New Zealanders with MS have a median survival age 7.2 years lower than the general population and twice the mortality risk. The survival gap was greater for progressive-onset disease and for those with an early age of onset.

Non-Contact Hand Movement Analysis for Optimal Configuration of Smart Sensors to Capture Parkinson's Disease Hand Tremor.

Parkinson's disease affects millions worldwide with a large rise in expected burden over the coming decades. More easily accessible tools and techniques to diagnose and monitor Parkinson's disease can improve the quality of life of patients. With the advent of new wearable technologies such as smart rings and watches, this is within reach. However, it is unclear what method for these new technologies may provide the best opportunity to capture the patient-specific severity. This study investigates which locations on the hand can be used to capture and monitor maximal movement/tremor severity. Using a Leap Motion device and custom-made software the volume, velocity, acceleration, and frequency of Parkinson's (n = 55, all right-handed, majority right-sided onset) patients' hand locations (25 joints inclusive of all fingers/thumb and the wrist) were captured simultaneously. Distal locations of the right hand, i.e., the ends of fingers and the wrist showed significant trends (p < 0.05) towards having the largest movement velocities and accelerations. The right hand, compared with the left hand, showed significantly greater volumes, velocities, and accelerations (p < 0.01). Supplementary analysis showed that the volumes, acceleration, and velocities had significant correlations (p < 0.001) with clinical MDS-UPDRS scores, indicating the potential suitability of using these metrics for monitoring disease progression. Maximal movements at the distal hand and wrist area indicate that these locations are best suited to capture hand tremor movements and monitor Parkinson's disease.

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.

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.

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.

The timing mega-study: comparing a range of experiment generators, both lab-based and online.

Many researchers in the behavioral sciences depend on research software that presents stimuli, and records response times, with sub-millisecond precision. There are a large number of software packages with which to conduct these behavioral experiments and measure response times and performance of participants. Very little information is available, however, on what timing performance they achieve in practice. Here we report a wide-ranging study looking at the precision and accuracy of visual and auditory stimulus timing and response times, measured with a Black Box Toolkit. We compared a range of popular packages: PsychoPy, E-Prime®, NBS Presentation®, Psychophysics Toolbox, OpenSesame, Expyriment, Gorilla, jsPsych, Lab.js and Testable. Where possible, the packages were tested on Windows, macOS, and Ubuntu, and in a range of browsers for the online studies, to try to identify common patterns in performance. Among the lab-based experiments, Psychtoolbox, PsychoPy, Presentation and E-Prime provided the best timing, all with mean precision under 1 millisecond across the visual, audio and response measures. OpenSesame had slightly less precision across the board, but most notably in audio stimuli and Expyriment had rather poor precision. Across operating systems, the pattern was that precision was generally very slightly better under Ubuntu than Windows, and that macOS was the worst, at least for visual stimuli, for all packages. Online studies did not deliver the same level of precision as lab-based systems, with slightly more variability in all measurements. That said, PsychoPy and Gorilla, broadly the best performers, were achieving very close to millisecond precision on several browser/operating system combinations. For response times (measured using a high-performance button box), most of the packages achieved precision at least under 10 ms in all browsers, with PsychoPy achieving a precision under 3.5 ms in all. There was considerable variability between OS/browser combinations, especially in audio-visual synchrony which is the least precise aspect of the browser-based experiments. Nonetheless, the data indicate that online methods can be suitable for a wide range of studies, with due thought about the sources of variability that result. The results, from over 110,000 trials, highlight the wide range of timing qualities that can occur even in these dedicated software packages for the task. We stress the importance of scientists making their own timing validation measurements for their own stimuli and computer configuration.

Positive Association of Ascorbate and Inverse Association of Urate with Cognitive Function in People with Parkinson's Disease.

Oxidative stress is thought to contribute to the aetiology of neurological disorders such as Parkinson's disease. Ascorbate (vitamin C) is a potent antioxidant and is associated with neurological and cognitive function. In this study we assessed the ascorbate status of a cohort of people with Parkinson's disease (n = 215), aged 50-90 years, compared with a cohort of age matched healthy controls (n = 48). The study sample's cognitive status ranged from normal to mild cognitive impairment and dementia. There was no difference between the Parkinson's disease and healthy control groups with respect to mean ascorbate status, however, a higher proportion of participants with Parkinson's disease had hypovitaminosis C (i.e., <23 µmol/L) compared with healthy controls (20% vs. 8%, respectively). Within the Parkinson's disease group, Montreal Cognitive Assessment (MoCA) scores correlated positively with ascorbate concentrations, with higher ascorbate status associated with better cognitive function (r = 0.14, p = 0.045). Participants with hypovitaminosis C had significantly lower MoCA scores relative to participants with ascorbate concentrations >23 µmol/L (p = 0.014). Ascorbate concentrations were significantly lower in the cognitively impaired subgroup compared with the normal cognition subgroup in the Parkinson's disease cohort (p = 0.03). In contrast, urate showed an inverse correlation with cognitive function (r = -0.19, p = 0.007), with higher urate concentrations observed in the cognitively impaired subgroup compared with the normal cognition subgroup (p = 0.015). There was an inverse association between ascorbate status and urate concentrations (r = -0.15, p = 0.017). Plasma protein carbonyls, a measure of systemic oxidative stress, were not significantly different between the Parkinson's disease cohort and healthy controls, and there was no association with cognitive function (r = 0.09, p = 0.19) or with ascorbate status (r = -0.05, p = 0.45). Overall, our study showed ascorbate status was positively associated with cognitive function in Parkinson's disease, suggesting that longitudinal studies investigating the temporal sequence of cognitive decline and ascorbate status are warranted.

Changes of plasma cGP/IGF-1 molar ratio with age is associated with cognitive status of Parkinson disease.

OBJECTIVE: Cognitive impairment is a common feature of Parkinson disease (PD), for which age is a major contributing factor. Insulin-like growth factor-1 (IGF-1) declines with age and contributes to age-related cognitive impairment in PD. Cyclic glycine-proline (cGP) is a metabolite of IGF-1 and normalizes bioavailable IGF-1. Plasma cGP/IGF-1 molar ratio that represents bioactive IGF-1 in circulation, may associate with the cognitive status in PD. METHODS: We examined the association of plasma cGP/IGF-1 molar ratio with the cognitive scores or age in PD patients with normal cognition (PD-N, n = 74), mild cognitive impairment (PD-MCI, n = 71), or dementia (PD-D, n = 33), and with the cognitive scores in 23 age-matched healthy controls. Plasma concentrations of IGF-1, IGF binding protein-3, and cGP were evaluated using enzyme-linked immunosorbent assay (ELISA) and high-performance liquid chromatography-mass spectrometry (HPLC-MS), respectively. RESULTS: The cGP/IGF-1 molar ratio was positively correlated with the age of PD-N group, negatively correlated with the age of PD-D group, and not associated with the age of PD-MCI group. Independent of age, the cGP/IGF-1 molar ratio was positively correlated with the cognitive scores of healthy controls, but not in PD groups. CONCLUSION: Old healthy people with a higher cGP/IGF-1 molar ratio showed better preserved cognition, possibly due to improved IGF-1 function. Increased cGP/IGF-1 molar ratio with age may contribute to cognitive retention in the PD-N group. The absence or reversal of such association with age in the PD-MCI and PD-D groups may indicate the conversion of cognitive status in PD, if confirmed through longitudinal investigations within the individuals with advancing cognitive impairment.

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.

Exploring eye movements of Parkinson's disease patients performing the Judgement of line orientation test.

INTRODUCTION: Parkinson's disease (PD) patients are reported to score significantly lower on the Judgement of Line Orientation (JLO) test compared with controls. The traditional method of scoring JLO ignores potentially interesting information on the mechanism of errors made. AIM: The aim of the current study was to analyse the performance of PD patients on the JLO while monitoring eye movements. Employing eye tracking methods while PD participants attempt JLO items may prove valuable in further characterising error-patterns. METHODS: We recruited three groups, each comprising 16 participants: PD participants with normal cognition (PD-N), PD participants with mild cognitive impairment (PD-MCI) and matched controls. RESULTS: The mean correct response rates were high: 93% (±6) for controls, 88% (±12) for PD-N and 87% (±11) for PD-MCI; the difference did not reach statistical significance (p = 0.21). Participants made more errors as they progressed from easy to harder item (r = 0.7; p = 0.02). Using the Ska classification, error types QO1 and QO3 were by far and away the most common. The mean amplitudes of saccadic eye movements were 5.9° (±0.9) for controls, 5.7° (±1.1) for PD-N, and 5.5° (±1.0) for PD-MCI. The differences among the three groups did not reach statistical significance (p = 0.64). As a whole, participant fixation patterns were similar throughout the JLO task. For the reference lines, most fixations were made on the distal ends. Fixations on the test lines, on the other hand, appeared to vary among trials, dependent on whether the response was correct or incorrect. CONCLUSIONS: There were few differences among the study groups in test performance-eye movement associations. However, we gained important insights into oculomotor behaviour during JLO test completion in both healthy controls and PD patients which could reflect the underlying disease state as we hypothesised.

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.

Ocular drift reflects volitional action preparation.

Human cognitive behavior is predictive rather than reflexive because of volitional action preparation. Recent studies have shown that the covert process of volitional action preparation can be decoded from overt fixational eye movements of fixational/microsaccades and pupil dilation. Ocular drift, the slowest fixational eye movements, is also under the active neural control, but its relationship with cognitive behavior is unknown. Here, we examined whether ocular drift also reflects volitional action preparation. We analyzed ocular drift while adult humans maintained fixation on a central visual stimulus as they prepared to generate a volitional saccade. We adopted the antisaccade paradigm in which subjects generate a targeting saccade toward the opposite direction of a peripheral visual stimulus. Our findings are the following five points. First, ocular drift was slower when subjects prepared for targeting saccade initiation than when such preparation was unnecessary. Second, ocular drift was slowed down with elapsed time from fixation initiation, which was associated with the facilitation of targeting saccade initiation. Third, ocular drift was further slowed on correct antisaccade trials than when subjects failed to suppress targeting saccades toward peripheral stimuli. Fourth, such correlation with antisaccade performance was observed immediately after fixation initiation in ocular drift, but it emerged more slowly in the other fixational eye movements. Fifth, subjects with unstable fixation because of faster ocular drift had poorer antisaccade performance. We suggest that fixation stability measured by ocular drift can be used to decode the covert process of volitional action preparation along with the other fixational eye movements.

PsychoPy2: Experiments in behavior made easy.

PsychoPy is an application for the creation of experiments in behavioral science (psychology, neuroscience, linguistics, etc.) with precise spatial control and timing of stimuli. It now provides a choice of interface; users can write scripts in Python if they choose, while those who prefer to construct experiments graphically can use the new Builder interface. Here we describe the features that have been added over the last 10 years of its development. The most notable addition has been that Builder interface, allowing users to create studies with minimal or no programming, while also allowing the insertion of Python code for maximal flexibility. We also present some of the other new features, including further stimulus options, asynchronous time-stamped hardware polling, and better support for open science and reproducibility. Tens of thousands of users now launch PsychoPy every month, and more than 90 people have contributed to the code. We discuss the current state of the project, as well as plans for the future.