Telehealth Cognitive Behavior Therapy to Reduce Anxiety in People Living with Cognitive Impairment: A Randomized Feasibility Pilot Study.

OBJECTIVES: To evaluate the feasibility of telehealth-based cognitive behavior therapy for people living with cognitive impairment experiencing anxiety (Tele-CBT), and to assess whether this leads to improvements in anxiety, depression, and quality of life post-intervention. METHODS: This was a single-blind randomized feasibility pilot trial of the Tele-CBT versus usual care. People living with mild cognitive impairment or dementia experiencing anxiety were recruited and randomized to receive Tele-CBT (n = 5) or continue usual care (n = 5). Feasibility data comprised recruitment uptake and retention, adherence, and ease of use. Outcomes of anxiety (primary outcome - Rating Anxiety in Dementia; RAID), depression, stress, and quality of life were measured pre- and post-intervention. RESULTS: Intervention feasibility was demonstrated through minimal attrition, acceptability, and ease of use via videoconferencing. Both groups showed a decrease of anxiety symptoms (RAID) from baseline to post-assessment. CONCLUSIONS: The Tele-CBT program was acceptable to use via videoconferencing. Reduced anxiety symptoms were observed in both groups at post-. An RCT with a larger sample is required to determine the efficacy and implementation of the intervention. CLINICAL IMPLICATIONS: This study indicates the feasibility of videoconference CBT to address anxiety experienced by people living with cognitive impairment with minimal assistance from support persons.

Hippocampal resting-state connectivity is associated with posterior-cortical cognitive impairment in Parkinson's disease.

AIM: Frontal and posterior-cortical cognitive subtypes in Parkinson's disease (PD) present with executive/attention and memory/visuospatial deficits, respectively. As the posterior-cortical subtype is predicted to progress rapidly toward dementia, the present study aimed to explore biological markers of this group using resting-state functional magnetic resonance imaging (rs-fMRI). METHODS: K-means cluster analysis delineated subtypes (cognitively intact, frontal, posterior-cortical, and globally impaired) among 85 people with PD. A subset of PD participants (N = 42) and 20 healthy controls (HCs) underwent rs-fMRI. Connectivity of bilateral hippocampi with regions of interest was compared between posterior-cortical, cognitively intact, and HC participants using seed-based analysis, controlling for age. Exploratory correlations were performed between areas of interest from the group analysis and a series of cognitive tests. RESULTS: The posterior-cortical subtype (N = 19) showed weaker connectivity between the left hippocampus and right anterior temporal fusiform cortex compared to the cognitively intact (N = 11) group, p-false discovery rate (FDR) = .01, and weaker connectivity between bilateral hippocampi and most fusiform regions compared to HCs (N = 20). No differences were found between HCs and cognitively intact PD. Exploratory analyses revealed strongest associations between connectivity of the right anterior temporal fusiform cortex and left hippocampus with category fluency (p-FDR = .01). CONCLUSION: Results suggest that weakened connectivity between the hippocampus and fusiform region is a unique characteristic of posterior-cortical cognitive deficits in PD. Further exploration of hippocampal and fusiform functional integrity as a marker of cognitive decline in PD is warranted.

Predictors of the placebo response in a nutraceutical randomized controlled trial for depression.

OBJECTIVE: The placebo response in depression studies is the change in symptoms amongst those who receive an inactive treatment. Many well-designed randomized controlled trials (RCTs) of depression have a high proportion of placebo responders, with little understanding as to why. The present study assesses characteristics associated with the placebo response in a nutraceutical trial with a large proportion of placebo responders. METHODS: This is a secondary analysis of a nutraceutical depression RCT which identified no overall treatment benefit relative to placebo (n = 69 in placebo group). We investigated participant characteristics such as socio-demographics, clinical features, and recruitment methods, and their association with the placebo response. Monoaminergic genetic polymorphisms were also assessed. Placebo response was measured based on change in Montgomery-Asberg Depression Rating Scale score. The association of these hypothesis-driven variables of interest and the placebo response was examined using linear mixed effects models. RESULTS: Greater levels of education, particularly pursuing post-high school education, better self-reported general health, marriage/de facto, greater improvement in the first trial week, and more failed antidepressant therapies in the current depressive episode were associated with greater placebo response. An increased placebo response was not found in those recruited via social media nor in those with concomitant antidepressant therapy. Single nucleotide polymorphisms from the tryptophan hydroxylase 1 (TPH1) gene (A779C and A218C) were weakly associated with greater placebo response, although the evidence was attenuated after accounting for multiple comparisons. CONCLUSION: This is, to our knowledge, the first study within nutraceutical research for depression to assess the association between participant characteristics and variation in the placebo response. Several variables appeared to predict the placebo response. Such findings may encourage future trial designs which could dampen placebo response, improve assay sensitivity, and allow for treatment effects to be potentially more detectable. Please cite this article as: Arnold R, Murphy-Smith J, Ng CH, Mischoulon D, Byrne GJ, Bousman CA, Stough C, Berk M, Sarris J. Predictors of the placebo response in a nutraceutical randomized controlled trial for depression. J Integr Med. 2024; 22(1): 46-53.

Feasibility and Acceptability of a Videoconferencing CBT Intervention for Anxiety in People with Parkinson's Disease.

OBJECTIVES: In people with Parkinson's disease (PwPD), non-motor symptoms such as anxiety are common and have negative impacts on their quality of life. There are currently few interventions that address anxiety in PwPD, and access to diagnosis and treatment is often limited for those living in rural areas. The aim of this study was to evaluate the feasibility and acceptability of a telehealth videoconferencing CBT intervention for anxiety in PwPD. METHODS: A pre- and post-test feasibility study (N = 10) was conducted and evaluated utilizing the RE-AIM framework (Reach, Effectiveness, Adoption, Implementation, and Maintenance). RESULTS: Lack of access to the internet and videoconferencing technology were identified as barriers to participation. Physical health issues also impacted recruitment and retention. Non-completers were significantly older and less likely to have a carer involved in the intervention. Clinician adoption of the intervention was low while participant acceptability of videoconferencing technology varied and required carer support. CONCLUSIONS: Providing access to technology and support to overcome technological issues, as well as telehealth training for clinicians, are recommended in future studies to improve recruitment, retention, and implementation. CLINICAL IMPLICATIONS: Identification of barriers and facilitators provides future studies with the knowledge to tailorize their program to better suit PwPD.

Levetiracetam for the treatment of mild cognitive impairment in Parkinson's disease: a double-blind controlled proof-of-concept trial protocol.

BACKGROUND: Mild memory impairment, termed amnestic mild cognitive impairment (aMCI), is associated with rapid progression towards dementia in Parkinson's disease (PD). Studies have shown hyperactivation of hippocampal DG/CA3 subfields during an episodic memory task as a biomarker of aMCI related to Alzheimer's disease. This project investigates the feasibility of a trial to establish the efficacy of a repurposed antiepileptic drug, levetiracetam, in low doses as a putative treatment to target DG/CA3 hyperactivation and improve episodic memory deficits in aMCI in PD. Based on previous work, it is hypothesized that levetiracetam will normalize DG/CA3 overactivation in PD-aMCI participants and improve memory performance. METHODS: Twenty-eight PD-aMCI participants, 28 PD participants without memory impairment (PD-nMI), and 28 healthy controls will be recruited. PD-aMCI participants will undertake a 12-week randomized, placebo-controlled, double-blind cross-over trial with a 14-day treatment of 125 mg levetiracetam or placebo twice daily, separated by a 4-week washout period. After each treatment period, participants will complete an episodic memory task designed to tax hippocampal subregion-specific function during high-resolution functional magnetic resonance imaging (fMRI). PD-nMI and healthy controls will undergo the fMRI protocol only, to compare baseline DG/CA3 subfield activity. RESULTS: Episodic memory task performance and functional activation in the DG/CA3 subfield during the fMRI task will be primary outcome measures. Global cognition, PD severity, and adverse events will be measured as secondary outcomes. Recruitment, eligibility, and study completion rates will be explored as feasibility outcomes. CONCLUSIONS: This study, the first of its kind, will establish hippocampal subregion functional impairment and proof of concept of levetiracetam as an early therapeutic option to reduce dementia risk in PD. TRIAL REGISTRATION: ClinicalTrials.gov, NCT04643327 . Registered on 25 November 2020.

Effect of kava (Piper methysticum) on peripheral gene expression among individuals with generalized anxiety disorder: A post hoc analysis of a randomized controlled trial.

Kava is a South Pacific plant-based medicine with anxiolytic properties, but little is known about the impact kava has on gene expression or whether gene expression can serve as a marker of kava response. This study aimed to determine whether kava treatment alters the expression of genes with physiological relevance to anxiety pathophysiology and whether the baseline expression of these physiologically relevant genes modifies the efficacy of kava treatment. In this post hoc analysis, we examined the expression of 48 genes relevant to the pathophysiology of anxiety collected from a double-blind randomized controlled trial that assessed the efficacy of kava treatment in generalized anxiety disorder. Peripheral blood gene expression was measured in 71 (34 kava, 37 placebo) adults at baseline and in 40 (19 kava, 21 placebo) after 8 weeks of treatment by reverse transcription polymerase chain reaction (PCR). Results revealed that kava decreased the expression of a subunit of the GABAA -rho receptor gene (GABRR2) and catechol-O-methyltransferase (COMT), a gene related to catecholamine metabolism. Kava efficacy was not found to be modified by baseline (pretreatment) expression of relevant genes. Although these results did not withstand statistical correction for multiple comparisons and require external validation, they support the notion that kava's mechanism of action includes interaction with GABAergic and catecholaminergic systems.

Longitudinal follow up of data-driven cognitive subtypes in Parkinson's disease.

AIM: The dual syndrome hypothesis proposes that there are two cognitive subtypes in Parkinson's disease (PD): a frontal subtype with executive/attention impairment and gradual cognitive decline, and a posterior-cortical subtype with memory/visuospatial deficits and rapid cognitive decline. We aimed to compare the rate of global cognitive decline between subtypes derived using data-driven methods and explore their longitudinal performance within specific cognitive domains to better understand the prognosis of each subtype. METHOD: Frontal, posterior-cortical, globally impaired, and cognitively intact PD subtypes were identified at baseline using k-means clustering (N = 85), and 29 participants (34%) returned for follow-up assessments on average 4.87 years from baseline. Linear mixed effects models compared progression of subtypes on global cognition; psychological symptoms; parkinsonism; and the memory, attention, executive, language, and visuospatial cognitive domains. RESULTS: The frontal subtype was lost to attrition. While rate of change in parkinsonism, anxiety, and apathy differed between subtypes, there was no difference in the rate of global cognitive decline. However, the posterior-cortical subtype declined most rapidly in verbal memory, card sorting, trail making, and judgement of line orientation (JLO), while the cognitively intact group declined most rapidly on verbal memory and semantic fluency. The globally impaired subtype declined most rapidly in JLO, although this should be interpreted with caution due to high attrition. CONCLUSION: Despite limited sample size, the present study supports the differential progression of the posterior-cortical subtype compared to cognitively intact and globally impaired PD. These results encourage further, large-scale longitudinal investigations of cognitive subtypes in PD.

Global assessment, cognitive profile, and characteristics of mild cognitive impairment in Parkinson's disease.

BACKGROUND: Cognitive deficits are evident throughout the course of Parkinson's disease (PD), with 24% of patients experiencing subtle cognitive disturbances at the time of diagnosis, and with up to 80% of patients developing PD dementia (PDD) at advanced stages of the disease PD patients with mild cognitive impairment (MCI), an at-risk phenotype of PDD, present with heterogeneous clinical characteristics that complicate the management of PD. OBJECTIVES: This study aims to examine the characteristics of PD-MCI by using the Movement Disorder Society (MDS) diagnostic criteria and evaluate the validity of global cognitive scales in identifying PD-MCI. METHODS: Seventy-nine (79) PD patients completed neuropsychological assessments and a comprehensive cognitive battery. PD-MCI was classified according to the level 2 MDS task force criteria. Mini-Mental State Examination (sMMSE), Montreal Cognitive Assessment (MoCA) and Parkinson's Disease Cognitive Rating Scale (PDCRS) were examined against a level 2 dichotomised PD-MCI diagnosis. Characteristics of PD-MCI were evaluated using logistic regression analysis. RESULTS: Twenty-seven patients met criteria for PD-MCI (34%). The MoCA and PDCRS demonstrated high validity to screen for PD-MCI. Impairments in multiple cognitive domains were observed in 77.8% of PD-MCI patients. There were significantly more males in the PD-MCI group compared to PD patients without MCI (p < 0.01). CONCLUSIONS: PD patients with MCI exhibited impairments in the attention/working memory, executive function and memory domains. Heterogeneous cognitive characteristics in PD warrant further investigation into specific cognitive subtypes to advance understanding and effective evaluation of PD-MCI.

Interventions for generalized anxiety disorder.

PURPOSE OF REVIEW: To provide an overview of recently published work on anxiety, focusing on generalized anxiety disorder (GAD) and its treatment. RECENT FINDINGS: Self-reported anxiety symptoms were highly prevalent during the COVID-19 global pandemic in both the general population and in selected groups. There remains divided opinion about whether internet-based cognitive behavioural therapy (CBT) is noninferior to face-to-face CBT for GAD. A systematic review of drug treatment for GAD showed efficacy for selective serotonin reuptake inhibitors (SNRIs), agomelatine, and quetiapine. There may be a place for repetitive transcranial magnetic stimulation in the treatment of GAD. There was some evidence of efficacy for complementary therapies, including physical exercise, yoga, acupuncture, and Withania somnifera (ashwagandha). However, a systematic review of cannabidiol and tetrahydrocannabinol found insufficient evidence of efficacy in anxiety disorders. SUMMARY: Antidepressants and quetiapine show efficacy in the treatment of GAD. Internet-based psychological interventions have a place in the treatment of GAD when face-to-face treatment is inaccessible. There is increasing evidence for the use of physical exercise in the management of GAD. Some other complementary therapies, including cannabinoids, require further, methodologically sound, research.

Phenomenology of anxiety in people living with mild to moderate dementia: A conceptual meta-ethnographic review.

OBJECTIVES: This conceptual review aims to integrate findings from published qualitative studies focusing on individual experiences of people living with dementia to generate a better understanding and conceptualisation of anxiety in dementia, including its subclinical manifestations. The review aims to inform the clinical practice to facilitate the development of targeted psychological interventions and provision of holistic support to people living with dementia. DESIGN: The review was conducted according to the guide for reporting meta-ethnographic qualitative syntheses eMERGe and the PRISMA guidelines. RESULTS: The search yielded a total of 2947 studies, out of which 13 were included in the final qualitative synthesis. The interpretive synthesis identified common experiences of people living with mild to moderate dementia, characterised by clusters of themes around worry, emotional experiences, and behavioural reactions in response to the diagnosis of dementia and its symptoms. These represent the components of a conceptual framework of anxiety in mild to moderate dementia, where anxiety is triggered by negative appraisals of living with an irreversible neurodegenerative disease. Stemming from these appraisals of dementia progression and its impact on the person's overall future, the content of worrisome thoughts and concerns include the loss of self and identity, losing independence and the ability to perform previous activities, concerns about being a burden to loved ones, and worry about the impact on interpersonal relationships. CONCLUSION: This conceptualisation of anxiety in dementia, including its subclinical manifestations facilitates the development of psychological interventions and provision of holistic support to people living with dementia.

Systematic review of data-driven cognitive subtypes in Parkinson disease.

BACKGROUND AND PURPOSE: Recent application of the mild cognitive impairment concept to Parkinson disease (PD) has proven valuable in identifying patients at risk of dementia. However, it has sparked controversy regarding the existence of cognitive subtypes. The present review evaluates the current literature pertaining to data-driven subtypes of cognition in PD. METHODS: Following PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines, systematic literature searches for peer-reviewed articles on the topic of cognitive subtyping in PD were performed. RESULTS: Twenty-two relevant articles were identified in the systematic search. Subtype structures showed either a spectrum of severity or specific domains of impairment. Domain-specific subtypes included amnestic/nonamnestic, memory/executive, and frontal/posterior dichotomies, as well as more complex structures with less definitive groupings. Preliminary longitudinal evidence showed some differences in cognitive progression among subtypes. Neuroimaging evidence provided insight into distinct patterns of brain alterations among subtypes. CONCLUSIONS: Recurring phenotypes in the literature suggest strong clinical relevance of certain cognitive subtypes in PD. Although the current literature is limited, it raises critical questions about the utility of data-driven methods in cognitive research. The results encourage further integration of neuroimaging research to define the latent neural mechanisms behind divergent subtypes. Although there is no consensus, there appears to be growing consistency and inherent value in identifying cognitive subtypes in PD.

Semantic fluency deficits and associated brain activity in Parkinson's disease with mild cognitive impairment.

People living with Parkinson's disease (PD) with poor verbal fluency have an increased risk of developing dementia. This study examines the neural mechanisms underpinning semantic fluency deficits in patients with PD with mild cognitive impairment (PD-MCI) compared to those without MCI (PD-NC) and control participants without PD (non-PD). Thirty-seven (37) participants with PD completed a cognitive assessment battery to identify MCI (13 PD-MCI). Twenty sex- and age-matched non-PD patients also participated. Participants were scanned (3T Siemens PRISMA) while performing semantic fluency, semantic switching, and automatic speech tasks. The number of responses and fMRI data for semantic generation and semantic switching were analyzed. Participants also completed a series of verbal fluency tests outside the scanner, including letter fluency. Participants with PD-MCI performed significantly worse than PD-NC and non-PD participants during semantic fluency and semantic switching tasks. PD-MCI patients showed greater activity in the right angular gyrus than PD-NC and non-PD patients during semantic switching. Increased right angular activity correlated with worse verbal fluency performance outside the scanner. Our study showed that the PD-MCI group performed worse on semantic fluency than either the PD-NC or non-PD groups. Increased right angular gyrus activity in participants with PD-MCI during semantic switching suggests early compensatory mechanisms, predicting the risk of future dementia in PD.

Relationships Between Aging Attitudes and Successful Aging Outcomes in Middle-age and Older Women.

OBJECTIVES: This study aimed to explore the relationships between aging attitudes and the outcomes of successful aging, including whether aging attitudinal types moderate psychological adjustment in the context of medical and mental health diagnoses. METHODS: In total, 409 community-dwelling women aged 40-79 years in Australia completed the Reactions to Aging Questionnaire (RAQ), Geriatric Depression Scale, Center of Epidemiological Studies Depression Scale, and Geriatric Anxiety Inventory. Information about medical and mental health diagnoses were collected. RESULTS: Overall, aging attitudes and all three RAQ subscales were negatively correlated with scores on measures of depression and anxiety, and number of medical diagnoses. Attitudinal types toward aging were found to moderate the relationship between the number of mental health diagnoses and scores on the psychological measures of depression but not anxiety. Unique RAQ domain-specific relationships were found with the number of mental health diagnoses. CONCLUSIONS: The findings support the link between aging attitudes and psychological outcomes, the potential clinical value of RAQ attitudinal typologies classification as well as a multidimensional conceptualization of aging attitudes. CLINICAL IMPLICATIONS: The findings reinforce the need for efforts to reduce ageism on a societal level, as well as informing clinical decision-making with older clients.

The prevalence of subthreshold psychiatric symptoms and associations with alcohol and substance use disorders: from a nationally representative survey of 36,309 adults.

BACKGROUND: Our aim was to describe a broad number of subthreshold psychiatric symptoms (SPS) in a nationally representative population and evaluate associations with substance use. SPS describe groups of symptoms with significant pathology, but that do not quite meet full psychiatric diagnostic criteria. They have been associated with significant impairment and cost. METHODS: The National Epidemiologic Survey on Alcohol and Related Conditions-III was a multistage, weighted, cross-sectional survey completed in the United States in 2013 comprising 36,309 noninstitutionalized adults. We report lifetime prevalence rates of 14 SPS related to mood, anxiety, trauma, eating, and personality disorders. We then evaluate associations with lifetime alcohol use disorders (AUD) and all substance use disorders (SUD) using logistic regression and adjusted odds ratios. SPS and psychiatric diagnoses were mutually exclusive (could not co-occur). RESULTS: Lifetime prevalence of having at least one of 14 SPS was 57% compared with 37% for the related psychiatric disorders. This was similar for males and females, in contrast to psychiatric disorders in which prevalence was 42% in females and 31% in males. Otherwise, overall SPS and disorders had similar prevalence patterns across sociodemographic characteristics. Subthreshold personality symptoms had the highest prevalence rates (schizotypal 21.3%, antisocial 18.3%, and borderline 17.6%), followed by posttraumatic stress (13.1%). Subthreshold bipolar and depression had lifetime prevalence rates of 2.7 and 8.5%, respectively. Prevalence rates of subthreshold anxiety symptoms ranged from 2.2% (agoraphobia) to 9.8% (specific phobia). Subthreshold eating disorder related symptoms had the lowest prevalence rates (anorexia 1.5% and bulimia 1.7%). Half (seven) of the SPS had significantly increased odds of lifetime AUD. This number increased to 12 for all SUD. Subthreshold antisocial personality symptoms had the highest odds of AUD (2.2; 95% CI 2.00-2.37) and SUD (3.5; 95% CI 3.22-3.81). CONCLUSIONS: We found high lifetime SPS prevalence rates and significant associations with AUD and SUD. To our knowledge, this is the first published study evaluating a broad number of SPS. This indicates possible opportunities for early intervention and prevention but requires additional research and development of infrastructure and guidelines to better understand and manage patients who experience SPS.

The Attention Network Test in Parkinson and Lewy Body Disease: A Systematic Review.

BACKGROUND: The Attention Network Test (ANT) is a well-established measure of efficiency for the alerting, orienting, and executive attentional networks. However, its novel application in Parkinson disease (PD) and Lewy body dementia (LBD) research more broadly has yet to be evaluated systematically. OBJECTIVE: To compare and consolidate the outcomes of studies reporting use of the ANT in PD and LBD groups and to identify the methodological considerations for the conduct of such studies. METHOD: We performed a systematic literature search for articles exploring attention in PD and LBD groups using the ANT. We excluded articles on the basis of irrelevant scope, non-English, and groups other than PD and LBD. Once the full text articles were identified, we extracted the data and assessed the studies' quality. RESULTS: The final sample included 16 articles ranging from low to moderate quality. Behavioral findings suggested a general slowing of responses yet preserved accuracy from the PD group compared with controls. Overall, the evidence was inconclusive regarding the state of the alerting network in the PD and LBD groups, mostly supportive of an intact orienting network, and strongly suggestive of an impaired executive network. Differences in sample stratification, patient symptomatology, and dopaminergic medication levels were identified as influential factors in the attentional results across studies. CONCLUSION: Although sparse, the existing evidence indicates that the ANT is a viable option for measuring attention in PD; it can also be harnessed to explore the impact of symptoms and medications on attentional networks in PD and LBD groups.

Caring for a loved one with Parkinson's disease: the role of coping styles and relationship quality.

OBJECTIVE: Informal carers play an essential role in the care of individuals with Parkinson's disease (PD). This role, however, is often fraught with difficulties, including emotional, physical, and financial. Coping styles and relationship quality have been hypothesized to influence the impact of stressors. The aim of this study is to examine the relationship between carers' coping style, relationship quality, and carer burden. DESIGN: Cross-sectional. PARTICIPANTS: Thirty-nine PD patient carer dyads were included in the study. MEASUREMENTS: Participants completed self-rated questionnaires including the Dyadic Adjustment Scale, Zarit Burden Interview, and Brief Coping Orientation to Problems Experienced Inventory. RESULTS: Correlational analyses found significant and positive correlation between carer burden and all three coping styles (problem-focused, emotion-focused, and dysfunctional). There was also a moderate association between carers' perceived relationship quality and satisfaction and carer burden. Regression analyses found that carer's gender, severity of PD, relationship quality, emotion-focused, and dysfunctional coping styles did not predict carer burden. Conversely, problem-focused coping style predicted carer burden. CONCLUSION: The results highlight that there is no perfect way to react and care for a loved one and serves as important information for practitioners who design and implement interventions.

Designing Virtual Reality Assisted Psychotherapy for Anxiety in Older Adults Living with Parkinson's Disease: Integrating Literature for Scoping.

Objective: This review integrates literature to discuss the potential use of virtual reality (VR) in treatment of anxiety in Parkinson's disease (PD) and inform next steps.Methods: A systematic search was performed to identify studies of VR use in PD, using four databases. Data were reported in accordance to the Preferred Reporting Items for Systematic reviews and Meta-Analyzes extension for Scoping Reviews (PRISMA-ScR).Results: Thirty-two studies met the inclusion criteria with four VR studies from the same study group directly assessing the effects of anxiety on motor symptoms in PD. Primary studies implementing a VR protocol in PD identified focus areas of understanding and alleviating freezing of gait (FOG), balance training, and cognitive and motor rehabilitation, and informed design considerations.Conclusion: VR in PD studies suggested established feasibility. With appropriate design considerations, a VR based protocol could improve anxiety outcomes in PD.Clinical implications: VR in PD provides control of a patient's field of view, which can be exploited to induce specific responses, provide visual feedback, analysis of patient actions, and introduce safe challenges in the context of training. VR assisted Cognitive Behavioral Therapy (CBT) tailored to suit subtypes of anxiety disorders in PD have the potential to improve the efficacy and effectiveness of psychotherapy in PD.

Anxiety disorders are associated with verbal memory impairment in patients with Parkinson's disease without dementia.

INTRODUCTION: Preliminary evidence has demonstrated a link between anxiety and memory impairment in Parkinson's disease (PD). This study further investigated this association using the Diagnostic and Statistical Manual of Mental Disorders (DSM-5) criteria for anxiety disorders and a standardized cognitive test battery. METHODS: A convenience sample of 89 PD patients without dementia was recruited from neurology outpatient clinics. A cross-sectional design was applied. Participants completed two semi-structured interviews. The first interview diagnosed DSM-5 anxiety disorders, unspecified anxiety disorder, and no anxiety. The second interview applied a neurocognitive test battery comprising two tests for each domain. Logistic regression models compared cognitive characteristics associated with anxiety disorders to no anxiety. RESULTS: Clinically significant anxiety was associated with immediate verbal memory impairment compared to the no anxiety group (OR, 95% CI 0.52, 0.30-0.89; p = 0.018), controlling for sex and age. The anxiety disorders group demonstrated immediate (OR, 95% CI 0.46, 0.26-0.83; p = 0.010) and delayed (OR, 95% CI 0.63, 0.40-0.99; p = 0.047) verbal memory impairments compared to those without anxiety, controlling for sex and age. This association remained for immediate (OR, 95% CI 0.43, 0.22-0.84; p = 0.013), but not delayed verbal memory impairment (OR, 95% CI 0.65, 0.39-1.06; p = 0.081) when additionally controlling for disease severity, education and levodopa dose. CONCLUSION: These findings present first evidence that anxiety disorders are associated with verbal memory impairment in PD and have implications for the management and treatment of anxiety in PD.