Speech and language in DDX3X-neurodevelopmental disorder: A call for early augmentative and alternative communication intervention.

Pathogenic variants in DDX3X are associated with neurodevelopmental disorders. Communication impairments are commonly reported, yet specific speech and language diagnoses have not been delineated, preventing prognostic counseling and targeted therapies. Here, we characterized speech and language in 38 female individuals, aged 1.69-24.34 years, with pathogenic and likely pathogenic DDX3X variants (missense, n = 13; nonsense, n = 12; frameshift, n = 7; splice site, n = 3; synonymous, n = 2; deletion, n = 1). Standardized speech, language, motor, social, and adaptive behavior assessments were administered. All participants had gross motor deficits in infancy (34/34), and fine motor deficits were common throughout childhood (94%; 32/34). Intellectual disability was reported in 86% (24/28) of participants over 4 years of age. Expressive, receptive, and social communication skills were, on average, severely impaired. However, receptive language was significantly stronger than expressive language ability. Over half of the assessed participants were minimally verbal (66%; 22/33; range = 2 years 2 months-24 years 4 months; mean = 8 years; SD = 6 years) and augmented speech with sign language, gestures, or digital devices. A quarter of the cohort had childhood apraxia of speech (25%; 9/36). Despite speech and language impairments, social motivation was a relevant strength. Many participants used augmentative and alternative communication (AAC), underscoring the need for early, tailored, and comprehensive AAC intervention.

The impact of caregiving on quality of life in Parkinson's disease: A systematic review.

OBJECTIVE: Parkinson's disease (PD) is a progressive neurodegenerative disease that can reduce quality of life (QOL). Previous research has explored patient specific factors that influence QOL; but understanding external factors that may also affect patient QOL, such as caregiver characteristics, can provide additional intervention targets that may improve QOL for both the person with PD and their caregiver. METHODS: We conducted a systematic review of existing literature on caregiver factors that are related to QOL for the person with PD. We developed a tailored search strategy in six databases and performed a screening procedure according to PRISMA guidelines. We synthesized findings from articles that met inclusion criteria using a narrative approach and identified themes categorizing caregiver factors associated with PD QOL. RESULTS: We found 32 full-text articles that fulfilled the inclusion criteria and passed the quality appraisal. Seven themes were identified, including: (1) burden, (2) strain, (3) QOL and satisfaction, (4) demographic factors, (5) psychological factors, (6) relationship factors, and (7) caregiver input. CONCLUSIONS: Our review presents critical insights into the role of the caregiver in the QOL of a person with PD. Findings reveal several targets for intervention to improve QOL in this population.

Phenomenology of Atypical Anxiety Disorders in Parkinson's Disease: A Systematic Review.

OBJECTIVE: Anxiety is a prominent concern in Parkinson's disease (PD) that negatively impacts quality of life, increases functional disability, and complicates clinical management. Atypical presentations of anxiety are under-recognized and inadequately treated in patients with PD, compromising global PD care. METHODS: This systematic review focuses on the prevalence, symptomology and clinical correlates of atypical presentations of PD-related anxiety following PRISMA guidelines. RESULTS: Of the 60 studies meeting inclusion criteria, 14 focused on 'Anxiety Not Otherwise Specified (NOS)' or equivalent, 31 reported on fluctuating anxiety symptoms, and 22 reported on 'Fear of Falling (FOF)'. Anxiety NOS accounted for a weighted mean prevalence of 14.9%, fluctuating anxiety for 34.19%, and FOF for 51.5%. These latter two exceeded the average reported overall prevalence rate of 31% for anxiety disorders in PD. We identified a diverse array of anxiety symptoms related to motor and non-motor symptoms of PD, to complications of PD medication (such as "on" and "off" fluctuations, or both), and, to a lesser extent, to cognitive symptoms. CONCLUSION: Atypical anxiety is common, clinically relevant, and heterogeneous in nature. A better understanding of the phenomenology, clinical course, and pathophysiology of varied forms of atypical anxiety in PD is needed to improve recognition, advance therapeutic development and ultimately optimize quality of life 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.

Defining Atypical Anxiety in Parkinson's Disease.

BACKGROUND: Anxiety is a major complication in Parkinson's disease (PD). Many PD patients experience clinically significant anxiety not meeting Diagnostic and Statistical Manual of Mental Disorders (DSM-IV) anxiety disorder criteria. This atypical anxiety (anxiety disorder not otherwise specified [NOS]) is often under-recognized and its diagnosis is underdeveloped. OBJECTIVES: This study aimed to identify the demographic, psychiatric, and clinical characteristics of anxiety disorder NOS in PD. METHODS: A cross-sectional design studied a convenience sample of 184 PD patients without dementia recruited from neurology outpatient clinics. A semi-structured interview using DSM-IV criteria categorized PD patients into current anxiety disorder NOS (n = 28), DSM-IV anxiety disorders (n = 42) or no anxiety (n = 86) groups. Logistic regression modeling identified characteristics associated with the anxiety disorder NOS group compared to DSM-IV anxiety and no anxiety groups. RESULTS: The anxiety disorder NOS group was associated with motor complications of PD therapy, episodic, persistent and social anxiety symptoms, depression, non-motor experiences of daily living, poor quality of life, and female sex compared to the no anxiety group. Compared to DSM-IV anxiety, those with anxiety disorder NOS demonstrated greater global cognitive impairment, more severe motor complications of PD therapy, a greater severity and functional impact of dyskinesias, and greater complexity of motor fluctuations. Persistent, episodic, and social anxiety symptoms did not significantly differ between anxiety disorder NOS and DSM-IV anxiety groups. CONCLUSIONS: These findings suggest that PD-specific symptoms characterize anxiety in a subgroup of PD patients who do not fulfill DSM-IV criteria for anxiety disorders.