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CNS Neuroscience & Therapeutics Dec 2023Parkinsonian disorders, such as Parkinson's disease (PD), multiple system atrophy (MSA), dementia with Lewy bodies (DLB), progressive supranuclear palsy (PSP) and... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND & AIMS
Parkinsonian disorders, such as Parkinson's disease (PD), multiple system atrophy (MSA), dementia with Lewy bodies (DLB), progressive supranuclear palsy (PSP) and corticobasal syndrome (CBS), share early motor symptoms but have distinct pathophysiology. As a result, accurate premortem diagnosis is challenging for neurologists, hindering efforts for disease-modifying therapeutic discovery. Extracellular vesicles (EVs) contain cell-state-specific biomolecules and can cross the blood-brain barrier to the peripheral circulation, providing a unique central nervous system (CNS) insight. This meta-analysis evaluated blood-isolated neuronal and oligodendroglial EVs (nEVs and oEVs) α-synuclein levels in Parkinsonian disorders.
METHODS
Following PRISMA guidelines, the meta-analysis included 13 studies. An inverse-variance random-effects model quantified effect size (SMD), QUADAS-2 assessed risk of bias and publication bias was evaluated. Demographic and clinical variables were collected for meta-regression.
RESULTS
The meta-analysis included 1,565 patients with PD, 206 with MSA, 21 with DLB, 172 with PSP, 152 with CBS and 967 healthy controls (HCs). Findings suggest that combined concentrations of nEVs and oEVs α-syn is higher in patients with PD compared to HCs (SMD = 0.21, p = 0.021), while nEVs α-syn is lower in patients with PSP and CBS compared to patients with PD (SMD = -1.04, p = 0.0017) or HCs (SMD = -0.41, p < 0.001). Additionally, α-syn in nEVs and/or oEVs did not significantly differ in patients with PD vs. MSA, contradicting the literature. Meta-regressions show that demographic and clinical factors were not significant predictors of nEVs or oEVs α-syn concentrations.
CONCLUSION
The results highlight the need for standardized procedures and independent validations in biomarker studies and the development of improved biomarkers for distinguishing Parkinsonian disorders.
Topics: Humans; alpha-Synuclein; Biomarkers; Central Nervous System; Extracellular Vesicles; Multiple System Atrophy; Parkinson Disease; Parkinsonian Disorders
PubMed: 37416941
DOI: 10.1111/cns.14341 -
Neurological Sciences : Official... Feb 2024Tics and stereotypies are childhood-onset repetitive behaviours that can pose significant diagnostic challenges in clinical practice. Both tics and stereotypies are... (Review)
Review
BACKGROUND
Tics and stereotypies are childhood-onset repetitive behaviours that can pose significant diagnostic challenges in clinical practice. Both tics and stereotypies are characterised by a complex co-morbidity profile, however little is known about the co-occurrence of these hyperkinetic disorders in the same patient population.
OBJECTIVE
This review aimed to assess the relationship between tics and stereotypies when these conditions present in co-morbidity.
METHODS
We conducted a systematic literature review of original studies on co-morbid tics and stereotypies, according to the standards outlined in the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines.
RESULTS
Our literature search identified six studies of suitable sample size (n ≥ 40) presenting data on the association between tics and stereotypies in otherwise typically developing patients. A considerable proportion (23%) of patients diagnosed with stereotypic movement disorder present with co-morbid tics (range 18-43%). Likewise, the prevalence of primary stereotypies is increased in patients with tic disorders such as Tourette syndrome (8%, range 6-12%).
DISCUSSION
Tics and stereotypies can often develop in co-morbidity. The association of tics and stereotypies in the same patient has practical implications, in consideration of the different treatment approaches. Future research should focus on the assessment and management of both conditions, particularly in special populations (e.g. patients with pervasive developmental disorders).
Topics: Child; Humans; Comorbidity; Stereotypic Movement Disorder; Tic Disorders; Tics; Tourette Syndrome
PubMed: 37775616
DOI: 10.1007/s10072-023-07095-y -
Neurology Jul 2023Functional neurologic disorder (FND) represents genuine involuntary neurologic symptoms and signs including seizures, weakness, and sensory disturbance, which have...
BACKGROUND AND OBJECTIVES
Functional neurologic disorder (FND) represents genuine involuntary neurologic symptoms and signs including seizures, weakness, and sensory disturbance, which have characteristic clinical features, and represent a problem of voluntary control and perception despite normal basic structure of the nervous system. The historical view of FND as a diagnosis of exclusion can lead to unnecessary health care resource utilization and high direct and indirect economic costs. A systematic review was performed using Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines to assess these economic costs and to assess for any cost-effective treatments.
METHODS
We searched electronic databases (PubMed, PsycInfo, MEDLINE, EMBASE, and the National Health Service Economic Evaluations Database of the University of York) for original, primary research publications between inception of the databases and April 8, 2022. A hand search of conference abstracts was also conducted. Key search terms included "functional neurologic disorder," "conversion disorder," and "functional seizures." Reviews, case reports, case series, and qualitative studies were excluded. We performed a descriptive and qualitative thematic analysis of the resulting studies.
RESULTS
The search resulted in a total of 3,244 studies. Sixteen studies were included after screening and exclusion of duplicates. These included the following: cost-of-illness (COI) studies that were conducted alongside cohort studies without intervention and those that included a comparator group, for example, another neurologic disorder (n = 4); COI studies that were conducted alongside cohort studies without intervention and those that did not include a comparator group (n = 4); economic evaluations of interventions that were either pre-post cohort studies (n = 6) or randomized controlled trials (n = 2). Of these, 5 studies assessed active interventions, and 3 studies assessed costs before and after a definitive diagnosis of FND. Studies showed an excess annual cost associated with FND (range $4,964-$86,722 2021 US dollars), which consisted of both direct and large indirect costs. Studies showed promise that interventions, including provision of a definitive diagnosis, could reduce this cost (range 9%-90.7%). No cost-effective treatments were identified. Study comparison was limited by study design and location heterogeneity.
DISCUSSION
FND is associated with a significant use of health care resources, resulting in economic costs to both the patient and the taxpayer and intangible losses. Interventions, including accurate diagnosis, seem to offer an avenue toward reducing these costs.
Topics: Nervous System Diseases; Humans; Conversion Disorder; Seizures; Health Care Costs; Cost-Benefit Analysis
PubMed: 37339887
DOI: 10.1212/WNL.0000000000207388 -
Psychopharmacology Feb 2024Dopamine antagonists induce dopamine receptor supersensitivity. This may manifest in late-appearing movement disorders (tardive dyskinesia (TD). VMAT-2 inhibitors reduce... (Meta-Analysis)
Meta-Analysis Review
RATIONALE
Dopamine antagonists induce dopamine receptor supersensitivity. This may manifest in late-appearing movement disorders (tardive dyskinesia (TD). VMAT-2 inhibitors reduce dopaminergic transmission but have limited activity at postsynaptic receptors and so may have antipsychotic activity with lower risk of tardive dyskinesia.
METHODS
We conducted a systematic database search from inception to September 2022 for articles describing the use of VMAT-2 inhibitors in psychosis. Inclusion criteria were as follows: Population: adults diagnosed with psychosis or schizophrenia; Intervention: treatment with tetrabenazine, deutetrabenazine or valbenazine; Comparison: comparison with placebo or/and antipsychotic drug; Outcomes: with efficacy outcomes (e.g. Brief Psychiatric Rating Scale (BPRS) change or clinician assessment) and adverse effects ratings (e.g. rating scale or clinician assessment or dropouts); and Studies: in randomised controlled trials and non-randomised studies.
RESULTS
We identified 4892 records relating to VMAT-2 inhibitor use of which 5 (173 participants) met our a priori meta-analysis inclusion criteria. VMAT-2 inhibitors were more effective than placebo for the outcome 'slight improvement' (risk ratio (RR) = 1.77 (95% CI 1.03, 3.04)) but not for 'moderate improvement' (RR 2.81 (95% CI 0.27, 29.17). VMAT-2 inhibitors were as effective as active comparators on both measures for-'slight improvement' (RR 1.05 (95% CI 0.6, 1.81)) and 'moderate improvement' (RR 1.11 (95% CI 0.51, 2.42). Antipsychotic efficacy was also suggested by a narrative review of 37 studies excluded from the meta-analysis.
CONCLUSIONS
VMAT-2 inhibitors may have antipsychotic activity and may offer promise for treatment of psychosis with the potential for a reduced risk of TD.
Topics: Adult; Humans; Antipsychotic Agents; Psychotic Disorders; Schizophrenia; Tardive Dyskinesia; Tetrabenazine; Vesicular Monoamine Transport Proteins
PubMed: 38238580
DOI: 10.1007/s00213-023-06488-3 -
Journal of Medical Internet Research Aug 2023The prevalence of Parkinson disease (PD) is becoming an increasing concern owing to the aging population in the United Kingdom. Wearable devices have the potential to... (Review)
Review
BACKGROUND
The prevalence of Parkinson disease (PD) is becoming an increasing concern owing to the aging population in the United Kingdom. Wearable devices have the potential to improve the clinical care of patients with PD while reducing health care costs. Consequently, exploring the features of these wearable devices is important to identify the limitations and further areas of investigation of how wearable devices are currently used in clinical care in the United Kingdom.
OBJECTIVE
In this scoping review, we aimed to explore the features of wearable devices used for PD in hospitals in the United Kingdom.
METHODS
A scoping review of the current research was undertaken and reported according to the PRISMA-ScR (Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews) guidelines. The literature search was undertaken on June 6, 2022, and publications were obtained from MEDLINE or PubMed, Embase, and the Cochrane Library. Eligible publications were initially screened by their titles and abstracts. Publications that passed the initial screening underwent a full review. The study characteristics were extracted from the final publications, and the evidence was synthesized using a narrative approach. Any queries were reviewed by the first and second authors.
RESULTS
Of the 4543 publications identified, 39 (0.86%) publications underwent a full review, and 20 (0.44%) publications were included in the scoping review. Most studies (11/20, 55%) were conducted at the Newcastle upon Tyne Hospitals NHS Foundation Trust, with sample sizes ranging from 10 to 418. Most study participants were male individuals with a mean age ranging from 57.7 to 78.0 years. The AX3 was the most popular device brand used, and it was commercially manufactured by Axivity. Common wearable device types included body-worn sensors, inertial measurement units, and smartwatches that used accelerometers and gyroscopes to measure the clinical features of PD. Most wearable device primary measures involved the measured gait, bradykinesia, and dyskinesia. The most common wearable device placements were the lumbar region, head, and wrist. Furthermore, 65% (13/20) of the studies used artificial intelligence or machine learning to support PD data analysis.
CONCLUSIONS
This study demonstrated that wearable devices could help provide a more detailed analysis of PD symptoms during the assessment phase and personalize treatment. Using machine learning, wearable devices could differentiate PD from other neurodegenerative diseases. The identified evidence gaps include the lack of analysis of wearable device cybersecurity and data management. The lack of cost-effectiveness analysis and large-scale participation in studies resulted in uncertainty regarding the feasibility of the widespread use of wearable devices. The uncertainty around the identified research gaps was further exacerbated by the lack of medical regulation of wearable devices for PD, particularly in the United Kingdom where regulations were changing due to the political landscape.
Topics: Humans; Male; Aged; Middle Aged; Female; Parkinson Disease; Artificial Intelligence; Aging; Commerce; Hospitals
PubMed: 37594791
DOI: 10.2196/42950 -
BMC Geriatrics Dec 2023Faced with the lack of physical activity caused by mandatory home isolation during special periods and patients' inconvenience in carrying out professionally supervised... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Faced with the lack of physical activity caused by mandatory home isolation during special periods and patients' inconvenience in carrying out professionally supervised exercise, many home-based exercise programs have been developed. This systematic review and meta-analysis aimed to examine the effects of home-based exercise on measures of motor symptoms, quality of life and functional performance in Parkinson's disease (PD) patients.
METHODS
We performed a systematic review and meta-analysis, and searched PubMed, MEDLINE, Embase, Cochrane library, and Web of Science from their inception date to April 1, 2023. The quality of the literature was assessed using PEDro's quality scale. The data was pooled using R software. Results are presented as pooled standardized mean difference (SMD) with 95% confidence interval (CI).
RESULTS
A total of 20 studies involving 1885 PD patients were included. Meta-analysis results showed that home-based exercise had a small effect in relieving overall motor symptoms in PD patients (SMD = -0.29 [-0.45, -0.13]; P < 0.0001), improving quality of life (SMD = 0.20 [0.08, 0.32]; P < 0.0001), walking speed (SMD = 0.26 [0.05, 0.48]; P = 0.005), balance ability (SMD = 0.23 [0.10, 0.36]; P < 0.0001), finger dexterity (SMD = 0.28 [0.10, 0.46]; P = 0.003) and decreasing fear of falling (SMD = -0.29 [-0.49, -0.08]; P = 0.001). However, home-based exercise did not significantly relieve the overall motor symptoms of PD patients when the training period was less than 8 weeks and the total number of sessions was less than 30.
CONCLUSION
During times of limited physical activity due to pandemics such as COVID-19, home-based exercise is an alternative to maintain and improve motor symptoms in PD patients. In addition, for the minimum dose of home-based exercise, we recommend that the exercise period is no less than 8 weeks and the total number of sessions is no less than 30 times.
TRIAL REGISTRATION
PROSPERO registration number: CRD42022329780.
Topics: Humans; Quality of Life; Parkinson Disease; Accidental Falls; Fingers; Fear; Motor Skills; Exercise; Exercise Therapy; Physical Functional Performance
PubMed: 38114897
DOI: 10.1186/s12877-023-04595-6 -
Psychiatry Research Nov 2023Assessing and managing suicide behaviors is highly relevant to individuals with schizophrenia spectrum disorders. Our study aims to assess the association between... (Meta-Analysis)
Meta-Analysis Review
Assessing and managing suicide behaviors is highly relevant to individuals with schizophrenia spectrum disorders. Our study aims to assess the association between adverse childhood experiences and suicidal behaviors in individuals with schizophrenia spectrum disorders. We included observational studies comparing the probability of suicide behaviors in adults with schizophrenia spectrum disorders exposed and unexposed to adverse childhood experiences. Odds ratio estimates were obtained by pooling data using a random-effects pairwise meta-analysis. Standardized criteria were used to assess the strength of the association of the pooled estimate. We found 21 eligible studies reporting outcomes for 6257 individuals from 11 countries. The primary outcome revealed an association between any suicidal behavior and adverse childhood experiences, which resulted "highly suggestive" according to validated Umbrella Criteria. Similarly, a positive association was confirmed for suicidal ideation and suicide attempt and for any subtype of adverse childhood experience. This meta-analysis showed that exposure to adverse childhood experiences strongly increases the probability of suicide behaviors in people with schizophrenia spectrum disorders.
Topics: Adult; Humans; Suicidal Ideation; Schizophrenia; Adverse Childhood Experiences; Suicide, Attempted; Probability
PubMed: 37769371
DOI: 10.1016/j.psychres.2023.115488 -
Drugs & Aging Nov 2023The acetylcholinesterase inhibitors (AChEIs) donepezil, galantamine, and rivastigmine are commonly used in the management of various forms of dementia. (Meta-Analysis)
Meta-Analysis
BACKGROUND
The acetylcholinesterase inhibitors (AChEIs) donepezil, galantamine, and rivastigmine are commonly used in the management of various forms of dementia.
OBJECTIVES
While these drugs are known to induce classic cholinergic adverse events such as diarrhea, their potential to cause psychiatric adverse events has yet to be thoroughly examined.
METHODS
We sought to determine the risk of psychiatric adverse events associated with the use of AChEIs through a systematic review and meta-analysis of double-blind randomized controlled trials involving patients with Alzheimer's dementia and Parkinson's dementia.
RESULTS
A total of 48 trials encompassing 22,845 patients were included in our analysis. Anorexia was the most commonly reported psychiatric adverse event, followed by agitation, insomnia, and depression. Individuals exposed to AChEIs had a greater risk of experiencing appetite disorders, insomnia, or depression compared with those who received placebo (anorexia: odds ratio [OR] 2.93, 95% confidence interval [CI] 2.29-3.75; p < 0.00001; decreased appetite: OR 1.93, 95% CI 1.33-2.82; p = 0.0006; insomnia: OR 1.55, 95% CI 1.25-1.93; p < 0.0001; and depression: OR 1.59, 95% CI 1.23-2.06, p = 0.0004). Appetite disorders were also more frequent with high-dose versus low-dose therapy. A subgroup analysis revealed that the risk of insomnia was higher for donepezil than for galantamine.
CONCLUSIONS
Our findings suggest that AChEI therapy may negatively impact psychological health, and careful monitoring of new psychiatric symptoms is warranted. Lowering the dose may resolve some psychiatric adverse events, as may switching to galantamine in the case of insomnia.
CLINICAL TRIAL REGISTRATION
The study was pre-registered on PROSPERO (CRD42021258376).
Topics: Humans; Acetylcholinesterase; Alzheimer Disease; Anorexia; Cholinesterase Inhibitors; Donepezil; Galantamine; Parkinson Disease; Phenylcarbamates; Randomized Controlled Trials as Topic; Rivastigmine; Sleep Initiation and Maintenance Disorders
PubMed: 37682445
DOI: 10.1007/s40266-023-01065-x -
Ageing Research Reviews Jan 2024Previous studies suggest that there may be important links between functional connectivity, disease mechanisms underpinning the Dementia with Lewy Body (DLB) and the key... (Review)
Review
A systematic literature review of fMRI and EEG resting-state functional connectivity in Dementia with Lewy Bodies: Underlying mechanisms, clinical manifestation, and methodological considerations.
Previous studies suggest that there may be important links between functional connectivity, disease mechanisms underpinning the Dementia with Lewy Body (DLB) and the key clinical symptoms, but the exact relationship remains unclear. We performed a systematic literature review to address this gap by summarising the research findings while critically considering the impact of methodological differences on findings. The main methodological choices of fMRI articles included data-driven, seed-based or regions of interest approaches, or their combinations. Most studies focused on examining large-scale resting-state networks, which revealed a consistent decrease in connectivity and some associations with non-cognitive symptoms. Although the inter-network connectivity showed mixed results, the main finding is consistent with theories positing disconnection between visual and attentional areas of the brain implicated in the aetiology of psychotic symptoms in the DLB. The primary methodological choice of EEG studies was implementing the phase lag index and using graph theory. The EEG studies revealed a consistent decrease in connectivity on alpha and beta frequency bands. While the overall trend of findings showed decreased connectivity, more subtle changes in the directionality of connectivity were observed when using a hypothesis-driven approach. Problems with cognition were also linked with greater functional connectivity disturbances. In summary, connectivity measures can capture brain disturbances in the DLB and remain crucial in uncovering the causal relationship between the networks' disorganisation and underlying mechanisms resulting in psychotic, motor, and cognitive symptoms of the DLB.
Topics: Humans; Lewy Body Disease; Magnetic Resonance Imaging; Brain; Cognition; Electroencephalography; Alzheimer Disease
PubMed: 38056505
DOI: 10.1016/j.arr.2023.102159 -
Journal of Alzheimer's Disease Reports 2024Alzheimer's disease (AD) causes progressive decline of cognition and function. There is a lack of systematic literature reviews on prognostic and predictive factors in...
BACKGROUND
Alzheimer's disease (AD) causes progressive decline of cognition and function. There is a lack of systematic literature reviews on prognostic and predictive factors in its early clinical stages (eAD), i.e., mild cognitive impairment due to AD and mild AD dementia.
OBJECTIVE
To identify prognostic factors affecting eAD progression and predictive factors for treatment efficacy and safety of approved and/or under late-stage development disease-modifying treatments.
METHODS
Databases were searched (August 2022) for studies reporting prognostic factors associated with eAD progression and predictive factors for treatment response. The Quality in Prognostic Factor Studies tool or the Cochrane risk of bias tool were used to assess risk of bias. Two reviewers independently screened the records. A single reviewer performed data extraction and quality assessment. A second performed a 20% check. Content experts reviewed and interpreted the data collected.
RESULTS
Sixty-one studies were included. Self-reporting, diagnosis definition, and missing data led to high risk of bias. Population size ranged from 110 to 11,451. Analyses found data indicating that older age was and depression may be associated with progression. Greater baseline cognitive impairment was associated with progression. may be a prognostic factor, a predictive factor for treatment efficacy and predicts an adverse response (ARIA). Elevated biomarkers (CSF/plasma p-tau, CSF t-tau, and plasma neurofilament light) were associated with disease progression.
CONCLUSIONS
Age was the strongest risk factor for progression. Biomarkers were associated with progression, supporting their use in trial selection and aiding diagnosis. Baseline cognitive impairment was a prognostic factor. predicted ARIA, aligning with emerging evidence and relevant to treatment initiation/monitoring.
PubMed: 38405341
DOI: 10.3233/ADR-230045