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BACKGROUND: Cognitive impairment is common in Parkinson's disease (PD) and often leads to dementia, with no effective treatment. Aging studies suggest that physical activity (PA) intensity has a positive impact on cognition and enhanced functional connectivity may underlie these benefits. However, less is known in PD. This cross-sectional study examined the relationship between PA intensity, cognitive performance, and resting state functional connectivity in PD and whether PA intensity influences the relationship between functional connectivity and cognitive performance. METHODS: 96 individuals with mild-moderate PD completed a comprehensive neuropsychological battery. Intensity of PA was objectively captured over a seven-day period using a wearable device (ActiGraph). Time spent in light and moderate intensity PA was determined based on standardized actigraphy cut points. Resting-state fMRI was assessed in a subset of 50 individuals to examine brain-wide functional connectivity. RESULTS: Moderate intensityPA (MIPA), but not light PA, was associated with better global cognition, visuospatial function, memory, and executive function. Individuals who met the WHO recommendation of ≥150 min/week of MIPA demonstrated better global cognition, executive function, and visuospatial function. Resting-state functional connectivity associated with MIPA included a combination of brainstem, hippocampus, and regions in the frontal, cingulate, and parietal cortices, which showed higher connectivity across the brain in those achieving the WHO MIPA recommendation. Meeting this recommendation positively moderated the associations between identified functional connectivity and global cognition, visuospatial function, and language. CONCLUSION: Encouraging MIPA, particularly the WHO recommendation of ≥150 min of MIPA/week, may represent an important prescription for PD cognition.

Background and Purpose: Resting-state functional MRI (rs-fMRI) studies in Parkinson’s disease (PD) patients with freezing of gait (FOG) have implicated dysfunctional connectivity over multiple resting-state networks. While these findings provided network-specific insights and information related to the aberrant or altered regional functional connectivity, whether these alterations have any effect on topological reorganization in PD-FOG patients is incompletely understood. Understanding the higher-order functional organization, which could be derived from the ‘hub’ and the ‘rich-club’ organization of the functional networks could be crucial to identifying the distinct and unique pattern of the network connectivity associated with PD-FOG. Methods: In this study, we use rs-fMRI data and graph theoretical approaches to explore the reorganization of resting-state network topology in PD-FOG when compared to those without FOG (PD-nFOG). We also compared the higher-order functional organization derived using the hub and rich-club measures in the functional connectivity networks of these PD-FOG patients to understand whether there is a topological reorganization of these hubs in PD-FOG. Results: We found that the PD-FOG patients showed a noticeable reorganization of hub regions. Regions that are part of the prefrontal cortex, primary somatosensory, motor, and visuomotor coordination areas showed were some of the regions exhibiting altered hub measures in PD-FOG patients. We also found a significantly altered feeder and local connectivity in PD-FOG. Conclusions: Overall our findings demonstrate a widespread topological reorganization and disrupted higher-order functional network topology in PD-FOG which may further assist in improving our understanding of functional network disturbances associated with PD-FOG.

Objectives People who identify as lesbian, gay, bisexual, transgender, queer/questioning, intersex, asexual, other non-cisgender, and non-heterosexual identities (LGBTQIA+) experience discrimination when accessing health care. We investigated specific experiences of LGBTQIA+ people with Parkinson’s disease (PwP) as they are less known. Methods Data were obtained from Fox Insight for PwP identifying as LGBTQIA+ (n = 210), cisgender, heterosexual women (n = 2,373) or cisgender, heterosexual men (n = 2,453). Discrimination in Medical Settings Scale responses and reports of whether gender identity or sexual orientation played a role in the perceived discrimination were compared across the groups. Results Parkinson’s diagnosis age was the youngest for LGBTQIA+ PwP. Despite similar levels of education with cisgender, heterosexual men, LGBTQIA+ people had lower levels of income and were more likely to be unemployed. Cisgender, heterosexual women and LGBTQIA+ PwP reported greater discrimination than cisgender, heterosexual men. Compared to cisgender, heterosexual men; LGBTQIA+ people (25%) and cisgender, heterosexual women (20%) were more likely to report their gender affected how they were treated; LGBTQIA+ PwP (19%) were more likely to report their sexual orientation affected how they were treated. Discussion Women and LGBTQIA+ PwP may be at a higher risk for discrimination in medical settings. Facing disparities while receiving health care based on gender or sexual orientation can affect the health care utilization of PwP. Health care providers should consider their behaviors and interactions with PwP to ensure inclusive and welcoming health care environments.

BackgroundLewy body (LB) dementias have limited clinical diagnostic accuracy because of frequent copathologies contributing to clinical heterogeneity. Although sex differences in clinical prevalence and frequency of pure LB pathology were shown, differences for clinicopathological correlations are less known.ObjectiveThe aim of this study was to determine sex differences for clinical associations of Alzheimer's disease (AD) copathology in those with LB pathology.MethodsData were from National Alzheimer's Coordinating Center for 223 women and 468 men with limbic or neocortical LB, separated into two groups as those with high likelihood and low/intermediate likelihood for LB clinical phenotype based on pathology. Clinical associations of sex and interaction of sex and pathology for the clinical phenotype were analyzed.ResultsMore severe AD copathology was associated with worse cognitive decline and lower likelihood of LB disease clinical phenotype. Women with more severe AD copathology and tau had worse cognitive decline and higher likelihood of AD clinical phenotype than men. Men with more severe AD copathology had lower likelihood of LB clinical phenotype than women. Interaction of sex and pathology was more pronounced in those aged between 70 and 80 years.ConclusionsAD copathology reduces the likelihood of LB clinical phenotype for both women and men; however, men may be at higher risk for LB disease underdiagnosis and women at higher risk for dementia. The use of both LB and AD biomarkers, even when LB or AD pathology is not clinically expected, is necessary for the accurate clinical diagnosis of both LB diseases and AD. © 2022 International Parkinson and Movement Disorder Society.

Background and Purpose: Resting-state functional MRI (rs-fMRI) studies in Parkinson’s disease (PD) patients with freezing of gait (FOG) have implicated dysfunctional connectivity over multiple resting-state networks. While these findings provided network-specific insights and information related to the aberrant or altered regional functional connectivity, whether these alterations have any effect on topological reorganization in PD-FOG patients is incompletely understood. Understanding the higher-order functional organization, which could be derived from the ‘hub’ and the ‘rich-club’ organization of the functional networks could be crucial to identifying the distinct and unique pattern of the network connectivity associated with PD-FOG. Methods: In this study, we use rs-fMRI data and graph theoretical approaches to explore the reorganization of resting-state network topology in PD-FOG when compared to those without FOG (PD-nFOG). We also compared the higher-order functional organization derived using the hub and rich-club measures in the functional connectivity networks of these PD-FOG patients to understand whether there is a topological reorganization of these hubs in PD-FOG. Results: We found that the PD-FOG patients showed a noticeable reorganization of hub regions. Regions that are part of the prefrontal cortex, primary somatosensory, motor, and visuomotor coordination areas showed were some of the regions exhibiting altered hub measures in PD-FOG patients. We also found a significantly altered feeder and local connectivity in PD-FOG. Conclusions: Overall our findings demonstrate a widespread topological reorganization and disrupted higher-order functional network topology in PD-FOG which may further assist in improving our understanding of functional network disturbances associated with PD-FOG.

Visuospatial working memory (WM) impairments in Parkinson's disease (PD) are more prominent and evolve earlier than verbal WM deficits, suggesting some differences in underlying pathology. WM is regulated by dopaminergic neurotransmission in the prefrontal cortex, but the effect of dopamine on specific processes supporting visuospatial WM are not well understood. Dopamine therapeutic effects on different WM processes may also differ given the heterogeneity of cognitive changes in PD. The present study examined the effect of dopamine therapy on memory load and distraction during visuospatial WM. Exploratory analyses evaluated whether individual differences in medication effects were associated with a gene, catechol-O-methyltransferase (COMT), which regulates prefrontal cortex dopamine levels. Cognitively normal PD participants (n=28) and controls (n=25) performed a visuospatial WM task, which manipulated memory load and the presence/absence of distractors. PD participants performed the task on and off medication. PD COMT groups were comprised of Met homozygote (lower COMT activity) and heterozygote and Val homozygote carriers (higher COMT activity, Het/Val). The results showed that handling higher memory loads and suppressing distraction were impaired in PD off, but not on medication. Medication improved distraction resistance in Met, but not Het/Val group. COMT did not modulate medication effects on memory load. These findings demonstrate that dopaminergic therapy restores visuospatial WM processes in patients without cognitive impairment and suggest that COMT variants may partly explain the mixed effects of medication on specific processes governed by distinct brain systems. Future investigations into gene-modulated effects of medication could lead to individualized strategies for treating cognitive decline.

Repeated data are increasingly collected in studies to investigate the trajectory of change in measurements over time. Determining a link between one repeated measurement with another that is considered as the biomarker for disease progression, may provide a new target for drug development. When a third variable is associated with one of the two measurements, partial correlation after eliminating the effect of that variable is able to provide reliable estimate for association as compared to the existing raw correlation for repeated data. We propose using linear regression models to compute residuals by modeling a relationship between each measurement and a third variable. The computed residuals are then used in a linear mixed model (implemented by SAS Proc Mixed) to compute partial correlation for repeated data. Alternatively, the partial correlation may be computed as the average of partial correlations at each visit. We provide two real examples to illustrate the application of the proposed partial correlation, and conduct extensive numerical studies to compare the proposed partial correlation coefficients.

Objective:To evaluate the sex differences in cognitive course over 4 years in Parkinson’s disease (PD) patients with and without mild cognitive impairment (MCI) compared to controls.Methods:Four-year longitudinal cognitive scores of 257 cognitively intact PD, 167 PD-MCI, and 140 controls from the Parkinson’s Progression Markers Initiative were included. Longitudinal scores of men and women, and PD with and without MCI were compared.Results:Women had better verbal memory, men had better visuospatial function. There was no interaction between sex, diagnostic group, and/or time (4-year follow-up period).Conclusions:Sex differences in cognitive course in de novo PD are similar to healthy aging. Cognitive decline rates in PD with and without MCI are similar for the first 4 years of PD.

Parkinson's disease (PD) is associated with verb deficits detected with tasks including picture naming and verbal fluency. However, these deficits are not frequently reported by the patients themselves. Levodopa, the gold standard for motor symptoms in PD, has been previously implicated to improve these verb deficits. We evaluated the effect of levodopa by using a spontaneous speech task which is more naturalistic than the previously used tasks to detect verb deficits. Thirty PD patients, and 30 age-, gender-, years of education-matched healthy controls were included. Patients were tested while motor ‘on’ and ‘off’. Levodopa did not affect spontaneous speech, although it improved the motor symptoms. Compared to controls, PD patients produced shorter and a lower number of sentences. The verb deficit was independent of cognitive or motor performance. The pathophysiology of motor symptoms and verb deficits most likely differ, and levodopa does not improve verb deficits during spontaneous speech.

More than half of the patients with Alzheimer’s disease (AD) have comorbidities including TDP-43 and Lewy bodies, which are also associated with frontotemporal lobar degeneration and dementia with Lewy bodies, respectively. These comorbidities may help explain the overlapping neuropsychiatric symptoms between AD and other dementias. Data on 221 AD patients with Neuropsychiatric Inventory-Questionnaire were obtained from the National Alzheimer’s Coordinating Center. TDP-43 was associated with aberrant motor activity, whereas Lewy bodies were associated with anxiety, irritability, sleep behavior, and appetite problems. The associations between these comorbidities and neuropsychiatric symptoms were more significant for patients with sparse diffuse plaques.

Background The etiology of freezing of gait in Parkinson’s disease (PD) is yet to be clarified. Non-motor risk factors including cognitive impairment, sleep disturbance and mood disorders have been shown in freezing of gait. Research question We aimed to determine the predictive value of non-motor features in freezing of gait development. Methods Data were obtained from the Parkinson’s Progression Markers Initiative. Fifty PD patients with self-reported freezing of gait, and 50 PD patients without freezing of gait at the fourth year visit were included. Groups were matched for Movement Disorders Society-Unified Parkinson’s Disease Rating Scale Part III scores. Several cognitive and non-cognitive tests were used for non-motor features at baseline and over time. Executive function, visuospatial function, processing speed, learning and memory tests were used for cognition. Non-cognitive tests included sleepiness, REM sleep behavior disorder, depression and anxiety scales. Results Patients with freezing of gait had higher scores on sleepiness, REM sleep behavior disorder, depression and anxiety scales. However, predictor model analysis revealed that baseline processing speed, learning and sleepiness scores were predictive of self-reported freezing of gait development over time. Significance Our findings suggest that specific cognitive deficits and sleep disorders are predictive of future freezing of gait. These features may be helpful in identifying underlying networks in freezing of gait and should be further investigated with neuroimaging studies.

Dystonia refers to an involuntary, repetitive, sustained, painful and twisting movements of the affected body part. This movement disorder was first described in 1911 by Hermain Oppenheim, and many studies have been conducted to understand the mechanism, the diagnosis and the treatment of dystonia ever since. However, there are still many unexplained aspects of this phenomenon. Dystonia is diagnosed by clinical manifestations, and various classifications are recommended for the diagnosis and the treatment. Anatomic classification, which is based on the muscle groups involved, is the most helpful classification model to plan the course of the treatment. Dystonias can also be classified based on the age of onset and the cause. These dystonic syndromes can be present without an identified etiology or they can be clinical manifestations of a neurodegenerative or neurometabolic disease. In this review we summarized the differential diagnosis, definition, classifications, possible mechanisms and treatment choices of dystonia.

Author(s): Damron, Lisa; Litvan, Irene; Bayram, Ece; Berk, Sarah; Siddiqi, Bernadette; Shill, Holly | Abstract: Background: Hispanics are under-represented in Parkinson’s disease (PD) research despite the importance of diversity for results to apply to a wide range of patients. Objective: To investigate the perspective of Hispanic persons with Parkinson disease (PWP) regarding awareness, interest, and barriers to participation in research. Methods: We developed and administered a survey and qualitative interview in English and Spanish. For the survey, 62 Hispanic and 38 non-Hispanic PWP linked to a tertiary center were recruited in Arizona. For interviews, 20 Hispanic PWP, 20 caregivers, and six physicians providing service to Hispanic PWP in the community were recruited in California. Survey responses of Hispanic and non-Hispanic PWP were compared. Major survey themes were identified by applying grounded theory and open coding. Results: The survey found roughly half (Q1 54%, Q2 55%) of Hispanic PWP linked to a tertiary center knew about research; there was unawareness among community Hispanic PWP. Most preferred having physician recommendations for research participation and were willing to participate. Hispanics preferred teams who speak their native language and include family. Research engagement, PD knowledge, role of family, living with PD, PD care, pre-diagnosis/diagnosis emerged as themes from the interview. Conclusion: Barriers exist for participation of Hispanic PWP in research, primarily lack of awareness of PD research opportunities. Educating physicians of the need to encourage research participation of Hispanic PWP can address this. Physicians need to be aware of ongoing research and should not assume PWP disinterest. Including family members and providing research opportunities in their native language can increase research recruitment.

Cognitive impairment is a common non-motor symptom in Parkinson’s Disease (PD) and an important source of patient disability and caregiver burden. The timing, profile and rate of cognitive decline varies widely among individuals with PD and can range from normal cognition to mild cognitive impairment (PD-MCI) and dementia (PDD). Beta-amyloid and tau brain accumulation, oxidative stress and neuroinflammation are reported risk factors for cognitive impairment. Traumatic brain injury and pesticide and tobacco exposure have also been described. Genetic risk factors including genes such as COMT, APOE, MAPT and BDNF may also play a role. Less is known about protective factors, although the Mediterranean diet and exercise may fall in this category. Nonetheless, there is conflicting evidence for most of the factors that have been studied. The use of inconsistent criteria and lack of comprehensive assessment in many studies are important methodological issues. Timing of exposure also plays a crucial role, although identification of the correct time window has been historically difficult in PD. Our understanding of the mechanism behind these factors, as well as the interactions between gene and environment as determinants of disease phenotype and the identification of modifiable risk factors will be paramount, as this will allow for potential interventions even in established PD.

IntroductionSex differences in dementia with Lewy bodies (DLB) have been reported in clinically defined cohorts; however, clinical diagnostic accuracy in DLB is suboptimal and phenotypic differences have not been assessed in pathologically confirmed participants.MethodsCore DLB features were compared across 55 women and 156 men with pathologically defined DLB in the National Alzheimer’s Coordinating Center. These analyses were repeated for 55 women and 55 men matched for age, education and tau burden.ResultsIn the total sample, women died older, had fewer years of education, had higher tau burden but were less likely to be diagnosed with dementia and clinical DLB. In the matched sample, visual hallucinations continued to be less common in women, and fewer women met clinical DLB criteria.DiscussionSex impacts clinical manifestations of underlying pathologies in DLB. Despite similar underlying Lewy body pathology, women are less likely to manifest core DLB features and may be clinically underdiagnosed.

Author(s): Wu, Melanie; Ceponiene, Rita; Bayram, Ece; Litvan, Irene | Abstract: BackgroundNiemann-Pick disease type C (NPC) is a rare, autosomal recessive lysosomal lipid storage disorder. It may present with cerebellar ataxia, vertical supranuclear gaze palsy, and cognitive impairment, and the age of symptom onset in adult-onset NPC is usually earlier than the fourth decade.CasesWe present 2 patients with adult-onset NPC diagnosed in the seventh decade of life. The slow motor progression and subtle findings of supranuclear vertical gaze palsy and ataxia can lead to a delayed diagnosis and misdiagnosis with parkinsonian disorders, particularly progressive supranuclear palsy.ConclusionThis report highlights and differentiates key clinical characteristics between NPC and parkinsonian disorders. It is important to consider NPC in the differential diagnosis when patients present with slowed vertical saccades, vertical supranuclear gaze palsy, ataxia, and cognitive impairment present at any age. This will allow appropriate and prompt treatment with miglustat and novel experimental therapies.

Author(s): Bayram, Ece; Litvan, Irene | Abstract: This scientific commentary refers to ‘Diabetes medications and risk of Parkinson’s disease: a cohort study of patients with diabetes’, by Brauer etal. (doi:10.1093/brain/awaa262).

Introduction Statins were proposed to be neuroprotective; however, the effects are unknown in progressive supranuclear palsy (PSP), a pure tauopathy. Methods Data of 284 PSP cases and 284 age-matched, sex-matched, and race-matched controls were obtained from the environmental and genetic PSP (ENGENE-PSP) study. Cases were evaluated with the PSP Rating Scale, Unified Parkinson's Disease Rating Scale, Mattis Dementia Rating Scale, and Neuropsychiatric Inventory. Statin associations with PSP risk, onset age, and disease features were analyzed. Results Univariate models showed lower PSP risk for type 1 statin users (simvastatin, lovastatin, pravastatin). After adjusting for confounding variables, statin use and lower PSP risk association remained only at a trend level. For PSP cases, type 1 statins were associated with 1-year older onset age; type 2 statins (atorvastatin, rosuvastatin) were associated with the lower PSP Rating Scale and Unified Parkinson's Disease Rating Scale. Conclusion Statins may have inverse associations with PSP risk and motor impairment. Randomized prospective studies are required to confirm this effect. © 2020 International Parkinson and Movement Disorder Society.

INTRODUCTION: Cognitive decline and mood symptoms are common in Parkinson’s disease (PD). Reductions in striatal dopaminergic binding have been associated with worse cognition and mood. We investigated whether this association persists throughout the disease progression in newly diagnosed PD. METHODS: Four-year data from Parkinson Progression Markers Initiative (PPMI) were used. Groups consisted of left and right limb dominantly affected PD patients, and controls. Longitudinal relationships between cognition, mood and striatal binding ratios were assessed by repeated measures correlations. RESULTS: Reduced binding was associated with general cognitive decline in controls; reduced processing speed and increased mood symptoms in PD. Anxiety was associated with striatum only in left limb dominantly affected PD. Dominantly affected limb side did not impact striatum and cognition association. CONCLUSION: There are longitudinal associations between striatum, processing speed and anxiety. Dopamine transporter availability imaging may have some prognostic value for cognition and mood in PD.

Visuospatial working memory impairments are common in Parkinson's disease (PD), yet the underlying neural mechanisms are poorly understood. The present study investigated abnormalities in context-dependent functional connectivity of working memory hubs in PD. Cognitively normal PD and control participants underwent fMRI while performing a visuospatial working memory task. To identify sources of dysfunction, distraction, and load-modulated connectivity were disentangled for encoding and retrieval phases of the task. Despite normal working memory performance in PD, two features of abnormal connectivity were observed, one due to a loss in normal context-related connectivity and another related to upregulated connectivity of hubs for which the controls did not exhibit context-dependent connectivity. During encoding, striatal-prefrontal coupling was lost in PD, both during distraction and high memory loads. However, long-range connectivity of prefrontal, medial temporal and occipital hubs was upregulated in a context-specific manner. Memory retrieval was characterized by different aberrant connectivity patterns, wherein precuneus connectivity was upregulated during distraction, whereas prefrontal couplings were lost as memory load approached capacity limits. Features of abnormal functional connectivity in PD had pathological and compensatory influences as they correlated with poorer working memory or better visuospatial skills. The results offer new insights into working memory-related signatures of aberrant cortico-cortical and corticostriatal functional connections, which may portend future declines in different facets of working memory.

Lateralization of default mode network (DMN) functioning has been shown to change with age. Similarly, lateralization of frontal lobe function has been shown to decline in age. The impact of amyloid pathology and the progression of Alzheimer's disease (AD) on resting state lateralization has not been investigated. Due to the preferential involvement of the left hemisphere in verbal tasks, there may be a benefit to higher levels of left-lateralization in the performance of verbal memory tasks. Here we compared functional lateralization of the anterior and posterior DMN between four groups of participants: amyloid negative (Aβ-) and amyloid positive (Aβ+) groups with normal cognition (NC), and Aβ+ groups with mild cognitive impairment (Aβ+MCI) or dementia (Aβ+AD). Differences were evident between groups in posterior DMN; the Aβ-NC group was more left-lateralized than both cognitively impaired Aβ+ groups. There was no difference in anterior DMN. No differences in overall network connectivity between groups were observed, suggesting that the functional lateralization finding is not secondary to general changes in connectivity. Left-lateralization of both networks was associated with better verbal recall performance. Older subjects, overall, had less left functional lateralization of the anterior DMN.

Alzheimer's disease (AD) is caused by a cascade of changes to brain integrity. Neuroimaging biomarkers are important in diagnosis and monitoring the effects of interventions. As memory impairments are among the first symptoms of AD, the relationship between imaging findings and memory deficits is important in biomarker research. The most established magnetic resonance imaging (MRI) finding is hippocampal atrophy, which is related to memory decline and currently used as a diagnostic criterion for AD. While the medial temporal lobes are impacted early by the spread of neurofibrillary tangles, other networks and regional changes can be found quite early in the progression. Atrophy in several frontal and parietal regions, cortical thinning, and white matter alterations correlate with memory deficits in early AD. Changes in activation and connectivity have been detected by functional MRI (fMRI). Task-based fMRI studies have revealed medial temporal lobe hypoactivation, parietal hyperactivation, and frontal hyperactivation in AD during memory tasks, and activation patterns of these regions are also altered in preclinical and prodromal AD. Resting state fMRI has revealed alterations in default mode network activity related to memory in early AD. These studies are limited in part due to the historic inclusion of patients who had suspected AD but likely did not have the disorder. Modern biomarkers allow for more diagnostic certainty, allowing better understanding of neuroimaging markers in true AD, even in the preclinical stage. Larger patient cohorts, comparison of candidate imaging biomarkers to more established biomarkers, and inclusion of more detailed neuropsychological batteries to assess multiple aspects of memory are needed to better understand the memory deficit in AD and help develop new biomarkers. This article reviews MRI findings related to episodic memory impairments in AD and introduces a new study with multimodal imaging and comprehensive neuropsychiatric evaluation to overcome current limitations.

Introduction Freezing of gait is an episodic inability to move the feet forward despite the intention to walk. It is a common cause of falls and subsequent morbidity and mortality in Parkinson's disease. Virtual reality paradigms provide an opportunity to safely evaluate freezing of gait, in order to better understand the underlying pathophysiology. This article focuses on the methodology, threshold used to define freezing of gait, results, limitations of studies using virtual reality paradigms, and proposes future directions of research. Summarizing these articles improves our understanding of freezing of gait in Parkinson's disease, and critical evaluation provides an opportunity for future studies to improve upon these efforts. Methods We performed a systematic review following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement guidelines, of studies using VR paradigms to elucidate the underlying pathophysiology of PD-FOG. Results This review initially identified 57 articles, but after exclusion of duplicates, abstracts, and studies not focused on the underlying pathophysiology of this disorder, 12 peer-reviewed articles using virtual reality paradigms to evaluate freezing of gait in Parkinson's disease were found. Conclusion Virtual reality paradigms are able to reproduce freezing of gait. Studies using MRI compatible virtual reality to evaluate freezing of gait found dysfunctional connectivity between cortical and subcortical structures during episodes. However, several important limitations of these studies should caution our interpretation of these results. Future studies which improve the design and methodology are needed to ultimately identify the cause and subsequent treatments for freezing of gait in Parkinson's disease.

Introduction Freezing of gait (FOG) is a disabling phenomenon characterized by a brief, episodic absence or reduction of forward progression of the feet despite the intention to walk. It is a common cause of falls and mortality in cases with Parkinson's disease (PD). This article reviews neuropsychological and neuroimaging studies to date and introduces a new study of multimodal imaging and cognition in PD-FOG. Methods A comprehensive literature search identified studies using neuropsychological evaluation and/or neuroimaging to evaluate PD-FOG. Results Several studies have evaluated PD-FOG, but few have combined neuropsychological and comprehensive neuroimaging and none longitudinally. Discussion A study using a combined approach longitudinally evaluating cognitive dysfunction and underlying neural networks in FOG is needed. We introduce the framework of a study which demonstrates the use of establishing an infrastructure for studying neurodegenerative disorders using the National Institutes of Health/National Institute of General Medical Science Center of Biomedical Research Excellence grant mechanism.

WOS: 000424114000007, PubMed ID: 30363359, Background: Movement Disorders Society Unified Parkinson's Disease Rating Scale (MDS-UPDRS) and Unified Dyskinesia Rating Scale (UDysRS) were developed as standard tools to rate Parkinson's disease (PD) and drug-induced dyskinesias of PD. As these scales have become widely used, there is a need for translation to non-English languages. Here we present the standardization for the Turkish translations. Methods: The scales were translated into Turkish and then back-translated to English. These back-translations were reviewed by the MDS team. After cognitive pretesting, movement disorder specialists from nine centers tested 352 patients for MDS-UPDRS, and 250 patients for UDysRS. Confirmatory factor analyses (CFAs) were used to determine if the factor structures for the reference standards could be confirmed in the Turkish data. The comparative fit indexes (CFIs) for the scales were required to be 0.90 or higher. Exploratory factor analyses (EFAs) were conducted to explore the underlying factor structure without the constraint of a pre-specified factor structure. Results: For both scales, the CFIs were 0.94 or greater as compared to the reference standard factor structures. The factor structures were consistent with that of reference standards, although there were some differences in some areas as compared to the EFA of the reference standard dataset. This may be due to the inclusion of patients with different stages of PD and different cultural properties of raters and patients. Conclusions: These results demonstrate that the Turkish translations of MDS-UPDRS and UDysRS have adequate clinimetric properties. They are established as the official translations and can be reliably used in Turkish speaking populations., International Parkinson and Movement Disorder Society, All authors received financial support provided by the International Parkinson and Movement Disorder Society for this study.

In this study we present a picture database of 160 nouns and 160 verbs. All verbs and nouns are divided into two groups as action and non-action words. Age of acquisition, familiarity, imageability, name agreement and complexity norms are reported alongside frequency, word length and morpheme count for each word. Data were collected from 600 native Turkish adults in total. The results show that although several measures have weak correlations with each other, only age of acquisition had moderate downhill relationships with familiarity and frequency with familiarity and frequency having a rather strong positive correlation with each other. The norms and the picture database are available as supplemental materials for use in psycholinguistic studies in Turkish.

Intracranial hypotension is usually seen in middle-aged adults and appears with orthostatic headache. It is characterized by low cerebrospinal fluid (CSF) pressure and pachymeningeal-dural thickening on magnetic resonance imaging (MRI). Lumbar puncture, dural rupture with CSF leakage secondary to spinal anesthesia or spinal traumas, and under-production or over-absorption of CSF due to some metabolic events such as dehydration, uremia and diabetic coma are the main etiologic factors. It is sometimes considered as idiopathic when no etiologic factor is present. In addition, some connective tissue disorders have risk of CSF leakage due to spontaneous dural rupture. Neck pain, tinnitus, nausea and vomiting, and diplopia may accompany headache. CSF leakage can be identified by computerized tomography (CT) myelography, CSF-flow MRI, and radionuclide cisternography. Bed rest, fluid resuscitation, caffeine, theophylline, and non-steroidal antiinflammatory drugs (NSAIDs) are important treatment options. In patients resistant to therapy, interventional measures such as epidural saline or blood patch can be applied. In this case report, we evaluated the results of pain treatment options in a patient having headache due to intracranial hypotension who was hospitalized in the Neurology Department of Ege University Hospital.