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JAMA Neurology Sep 2019Neurofilament light protein (NfL) is elevated in cerebrospinal fluid (CSF) of a number of neurological conditions compared with healthy controls (HC) and is a candidate...
IMPORTANCE
Neurofilament light protein (NfL) is elevated in cerebrospinal fluid (CSF) of a number of neurological conditions compared with healthy controls (HC) and is a candidate biomarker for neuroaxonal damage. The influence of age and sex is largely unknown, and levels across neurological disorders have not been compared systematically to date.
OBJECTIVES
To assess the associations of age, sex, and diagnosis with NfL in CSF (cNfL) and to evaluate its potential in discriminating clinically similar conditions.
DATA SOURCES
PubMed was searched for studies published between January 1, 2006, and January 1, 2016, reporting cNfL levels (using the search terms neurofilament light and cerebrospinal fluid) in neurological or psychiatric conditions and/or in HC.
STUDY SELECTION
Studies reporting NfL levels measured in lumbar CSF using a commercially available immunoassay, as well as age and sex.
DATA EXTRACTION AND SYNTHESIS
Individual-level data were requested from study authors. Generalized linear mixed-effects models were used to estimate the fixed effects of age, sex, and diagnosis on log-transformed NfL levels, with cohort of origin modeled as a random intercept.
MAIN OUTCOME AND MEASURE
The cNfL levels adjusted for age and sex across diagnoses.
RESULTS
Data were collected for 10 059 individuals (mean [SD] age, 59.7 [18.8] years; 54.1% female). Thirty-five diagnoses were identified, including inflammatory diseases of the central nervous system (n = 2795), dementias and predementia stages (n = 4284), parkinsonian disorders (n = 984), and HC (n = 1332). The cNfL was elevated compared with HC in a majority of neurological conditions studied. Highest levels were observed in cognitively impaired HIV-positive individuals (iHIV), amyotrophic lateral sclerosis, frontotemporal dementia (FTD), and Huntington disease. In 33.3% of diagnoses, including HC, multiple sclerosis, Alzheimer disease (AD), and Parkinson disease (PD), cNfL was higher in men than women. The cNfL increased with age in HC and a majority of neurological conditions, although the association was strongest in HC. The cNfL overlapped in most clinically similar diagnoses except for FTD and iHIV, which segregated from other dementias, and PD, which segregated from atypical parkinsonian syndromes.
CONCLUSIONS AND RELEVANCE
These data support the use of cNfL as a biomarker of neuroaxonal damage and indicate that age-specific and sex-specific (and in some cases disease-specific) reference values may be needed. The cNfL has potential to assist the differentiation of FTD from AD and PD from atypical parkinsonian syndromes.
PubMed: 31206160
DOI: 10.1001/jamaneurol.2019.1534 -
European Review For Medical and... Sep 2021We aimed this systematic review to analyze and review the currently available published literature related to long COVID, understanding its pattern, and predicting the...
We aimed this systematic review to analyze and review the currently available published literature related to long COVID, understanding its pattern, and predicting the long-term effects on survivors. We thoroughly searched the databases for relevant articles till May 2021. The research articles that met our inclusion and exclusion criteria were assessed and reviewed by two independent researchers. After preliminary screening of the identified articles through title and abstract, 249 were selected. Consequently, 167 full-text articles were assessed and reviewed based on our inclusion criteria and thus 20 articles were regarded as eligible and analyzed in the present analysis. All the studies included adult population aged between 18 and above 60 years. The median length of hospital stay of the COVID-19 patients during the acute infection phase ranged from 8 days to 17 days. The most common prevalent long-term symptoms in COVID-19 patients included persistent fatigue and dyspnea in almost all of the studies. Other reported common symptoms included: shortness of breath, cough, joint pain, chest pain or tightness, headache, loss of smell/taste, sore throat, diarrhea, loss of memory, depression, anxiety. Associated cardiovascular events included arrhythmias, palpitations and hypotension, increased HR, venous thromboembolic diseases, myocarditis, and acute/decompensated heart failure as well. Among neurological manifestations headache, peripheral neuropathy symptoms, memory issues, concentration, and sleep disorders were most commonly observed with varying frequencies. Mental health issues affecting mental abilities, mood fluctuations namely anxiety and depression, and sleep disorders were commonly seen. Further, diarrhea, vomiting, digestive disorders, and Loss of appetite or weight loss are common gastrointestinal manifestations. Therefore, appropriate clinical evaluation is required in long COVID cases which in turn may help us to identify the risk factors, etiology, and to my help, we treat them early with appropriate management strategies.
Topics: COVID-19; Humans; SARS-CoV-2; Post-Acute COVID-19 Syndrome
PubMed: 34533807
DOI: 10.26355/eurrev_202109_26669 -
International Journal of Molecular... Jun 2023Alzheimer's Disease (AD) is a progressive neurodegenerative disorder characterised by cognitive impairment, and amyloid-β plaques and neurofibrillary tau tangles at... (Review)
Review
Alzheimer's Disease (AD) is a progressive neurodegenerative disorder characterised by cognitive impairment, and amyloid-β plaques and neurofibrillary tau tangles at neuropathology. Capsaicin is a spicy-tasting compound found in chili peppers, with anti-inflammatory, antioxidant, and possible neuroprotective properties. Capsaicin intake has been associated with greater cognitive function in humans, and attenuating aberrant tau hyperphosphorylation in a rat model of AD. This systematic review discusses the potential of capsaicin in improving AD pathology and symptoms. A systematic analysis was conducted on the effect of capsaicin on AD-associated molecular changes, cognitive and behaviour resulting in 11 studies employing rodents and/or cell cultures, which were appraised with the Cochrane Risk of Bias tool. Ten studies showed capsaicin attenuated tau deposition, apoptosis, and synaptic dysfunction; was only weakly effective on oxidative stress; and had conflicting effects on amyloid processing. Eight studies demonstrated improved spatial and working memory, learning, and emotional behaviours in rodents following capsaicin treatment. Overall, capsaicin showed promise in improving AD-associated molecular, cognitive, and behavioural changes in cellular and animal models, and further investigations are recommended to test the readily available bioactive, capsaicin, to treat AD.
Topics: Humans; Rats; Animals; Alzheimer Disease; Capsaicin; Amyloid beta-Peptides; Neurofibrillary Tangles; Cognition; tau Proteins; Disease Models, Animal
PubMed: 37373321
DOI: 10.3390/ijms241210176 -
Psychopharmacology Mar 2022±3,4-Methylenedioxymethamphetamine (MDMA) is a recreational drug that shows substantial promise as a psychotherapeutic agent. Still, there is some concern regarding its... (Review)
Review
RATIONALE
±3,4-Methylenedioxymethamphetamine (MDMA) is a recreational drug that shows substantial promise as a psychotherapeutic agent. Still, there is some concern regarding its behavioral toxicity, and its dose-effect relationship is poorly understood. We previously explored the role of dose in the cognitive effects of MDMA in a systematic review of existing literature and found no evidence in animals that MDMA impairs memory at low doses (< 3 mg/kg) but mixed results at high doses (≥ 3 mg/kg). Since this review comprised mostly of single-dose studies and an assortment of methodologies, an empirical dose-ranging study on this topic is warranted.
OBJECTIVES
The current study aims to evaluate the conclusion from our systematic review that 3 mg/kg may be the threshold for MDMA-induced amnesia, and to further understand the dose-effect relationship of MDMA on behavioral assays of memory, addiction, and depression.
METHODS
We systematically examined the effects of 0.01 to 10 mg/kg MDMA on Pavlovian fear conditioning; behavioral sensitization, conditioned place preference, and conditioned responding; and the Porsolt forced swim test in mice.
RESULTS
High doses of MDMA (≥ 3 mg/kg) produced amnesia of fear conditioning memory, some evidence of an addictive potential, and antidepressant effects, while low doses of MDMA (≤ 1 mg/kg) had no effect on these behaviors.
CONCLUSIONS
The present dose-ranging study provides further evidence that 3 mg/kg is the threshold for MDMA-induced amnesia. These findings, in addition to our systematic review, demonstrate that careful selection of MDMA dose is critical. High doses (≥ 3 mg/kg) should likely be avoided due to evidence that they can produce amnesia and addiction. Conversely, there is little evidence to suggest that low doses, which are usually administered in clinical studies (approximately 1-2 mg/kg), will lead to these same adverse effects. Ultra-low doses (< 1 mg/kg) are likely even safer and should be investigated for therapeutic effects in future studies.
Topics: Amnesia; Animals; Conditioning, Classical; Depression; Dose-Response Relationship, Drug; Fear; Mice; N-Methyl-3,4-methylenedioxyamphetamine
PubMed: 35179622
DOI: 10.1007/s00213-022-06086-9 -
Movement Disorders : Official Journal... Mar 2022α-synucleinopathies, encompassing Parkinson's disease, dementia with Lewy bodies, and multiple system atrophy, are devastating neurodegenerative diseases for which... (Review)
Review
α-synucleinopathies, encompassing Parkinson's disease, dementia with Lewy bodies, and multiple system atrophy, are devastating neurodegenerative diseases for which available therapeutic options are scarce, mostly because of our limited understanding of their pathophysiology. Although these pathologies are attributed to an intracellular accumulation of the α-synuclein protein in the nervous system with subsequent neuronal loss, the trigger(s) of this accumulation is/are not clearly identified. Among the existing hypotheses, interest in the hypothesis advocating the involvement of infectious agents in the onset of these diseases is renewed. In this article, we aimed to review the ongoing relevant factors favoring and opposing this hypothesis, focusing on (1) the potential antimicrobial role of α-synuclein, (2) potential entry points of pathogens in regard to early symptoms of diverse α-synucleinopathies, (3) pre-existing literature reviews assessing potential associations between infectious agents and Parkinson's disease, (4) original studies assessing these associations for dementia with Lewy bodies and multiple system atrophy (identified through a systematic literature review), and finally (5) potential susceptibility factors modulating the effects of infectious agents on the nervous system. © 2022 International Parkinson and Movement Disorder Society.
Topics: Humans; Lewy Body Disease; Multiple System Atrophy; Parkinson Disease; Synucleinopathies; alpha-Synuclein
PubMed: 35040520
DOI: 10.1002/mds.28925 -
Clinical Neurophysiology : Official... Nov 2022Although relatively costly and non-scalable, non-invasive neuromodulation interventions are treatment alternatives for neuropsychiatric disorders. The recent...
OBJECTIVE
Although relatively costly and non-scalable, non-invasive neuromodulation interventions are treatment alternatives for neuropsychiatric disorders. The recent developments of highly-deployable transcranial electric stimulation (tES) systems, combined with mobile-Health technologies, could be incorporated in digital trials to overcome methodological barriers and increase equity of access. The study aims are to discuss the implementation of tES digital trials by performing a systematic scoping review and strategic process mapping, evaluate methodological aspects of tES digital trial designs, and provide Delphi-based recommendations for implementing digital trials using tES.
METHODS
We convened 61 highly-productive specialists and contacted 8 tES companies to assess 71 issues related to tES digitalization readiness, and processes, barriers, advantages, and opportunities for implementing tES digital trials. Delphi-based recommendations (>60% agreement) were provided.
RESULTS
The main strengths/opportunities of tES were: (i) non-pharmacological nature (92% of agreement), safety of these techniques (80%), affordability (88%), and potential scalability (78%). As for weaknesses/threats, we listed insufficient supervision (76%) and unclear regulatory status (69%). Many issues related to methodological biases did not reach consensus. Device appraisal showed moderate digitalization readiness, with high safety and potential for trial implementation, but low connectivity.
CONCLUSIONS
Panelists recognized the potential of tES for scalability, generalizability, and leverage of digital trials processes; with no consensus about aspects regarding methodological biases.
SIGNIFICANCE
We further propose and discuss a conceptual framework for exploiting shared aspects between mobile-Health tES technologies with digital trials methodology to drive future efforts for digitizing tES trials.
Topics: Consensus; Electric Stimulation; Humans; Telemedicine; Transcranial Direct Current Stimulation
PubMed: 36115809
DOI: 10.1016/j.clinph.2022.08.018 -
Comprehensive Psychiatry Oct 2023Converging evidence supports that gaming and gambling disorders are associated with executive dysfunction. The involvement of different components of executive functions... (Review)
Review
BACKGROUND
Converging evidence supports that gaming and gambling disorders are associated with executive dysfunction. The involvement of different components of executive functions (EF) in these forms of behavioural addiction is unclear.
AIM
In a systematic review, we aim to uncover the association between working memory (WM), a crucial component of EF, and disordered gaming and gambling. Note that, in the context of this review, gaming has been used synonymously with video gaming.
METHODS
Adhering to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA), we systematically searched for studies published from 2012 onwards.
RESULTS
The search yielded 6081 records after removing duplicates, from which 17 peer-reviewed journal articles were eligible for inclusion. The association between WM and problem or disordered gaming and gambling have been categorized separately to observe possible differences. Essentially, problem gaming or gambling, compared to disorder, presents lesser severity and clinical significance. The results demonstrate reduced auditory-verbal WM in individuals with gambling disorder. Decreased WM capacity was also associated with problem gambling, with a correlation between problem gambling severity and decreased WM capacity. Similarly, gaming disorder was associated with decreased WM. Specifically, gaming disorder patients had lower WM capacity than the healthy controls.
CONCLUSION
Working memory seems to be a significant predictor of gambling and gaming disorders. Therefore, holistic treatment approaches that incorporate cognitive techniques that could enhance working memory may significantly boost gambling and gaming disorders treatment success.
Topics: Humans; Gambling; Memory, Short-Term; Cognition; Disruptive, Impulse Control, and Conduct Disorders; Video Games; Behavior, Addictive
PubMed: 37573802
DOI: 10.1016/j.comppsych.2023.152408 -
The Cochrane Database of Systematic... Aug 2022Autism spectrum disorder (ASD; also known as autism) is a developmental disability that begins in childhood and is typically seen in around 1% to 2% of children. It is... (Review)
Review
BACKGROUND
Autism spectrum disorder (ASD; also known as autism) is a developmental disability that begins in childhood and is typically seen in around 1% to 2% of children. It is characterised by social communication difficulties and repetitive and restricted behaviours and routines that can have a negative impact on a child's quality of life, achievement at school, and social interactions with others. It has been hypothesised that memantine, which is traditionally used to treat dementia, may be effective in reducing the core symptoms of autism as well as some co-occurring symptoms such as hyperactivity and language difficulties. If memantine is being used to treat the core symptoms of autism, it is important to review the evidence of its effectiveness.
OBJECTIVES
To assess the effects of memantine on the core symptoms of autism, including, but not limited to, social communication and stereotypical behaviours.
SEARCH METHODS
We searched CENTRAL, MEDLINE, Embase, nine other databases and three trials registers up to February 2022. We also checked reference lists of key studies and checked with experts in the field for any additional papers. We searched for retractions of the included studies in MEDLINE, Embase, and the Retraction Watch Database. No retractions or corrections were found.
SELECTION CRITERIA
We included randomised controlled trials (RCTs) of any dose of memantine compared with placebo in autistic people. We also included RCTs in which only one group received memantine, but both groups received the same additional therapy (e.g. a behaviour intervention).
DATA COLLECTION AND ANALYSIS
We used standard Cochrane methods. Our primary outcomes were core autism symptoms and adverse effects. Secondary outcomes were language, intelligence, memory, adaptive behaviour, hyperactivity, and irritability. We used GRADE to assess certainty of evidence.
MAIN RESULTS
We included three RCTs (two double-blind and one single-blind) with 204 participants that examined the short-term effect (immediately postintervention) of memantine in autistic people. Two studies took place in the USA and the other in Iran. All three studies focused on children and adolescents, with a mean age of 9.40 (standard deviation (SD) 2.26) years. Most participants were male (range across studies 73% to 87%). The diagnosis of ASD was based on the Diagnostic and Statistical Manual of Mental Disorders (4th edition; 4th edition, text revision; or 5th edition). To confirm the diagnosis, one study used the Autism Diagnostic Observation Schedule (ADOS) and the Autism Diagnostic Interview-Revised (ADI-R); one used ADOS, ADI-R or the Autism Diagnostic Interview Screener; and one used the Gilliam Autism Rating Scale. Dosage of memantine was based on the child's weight and ranged from 3 mg to 15 mg per day. Comparisons Two studies examined memantine compared with placebo; in the other study, both groups had a behavioural intervention while only one group was given memantine. Risk of bias All studies were rated at high risk of bias overall, as they were at high or unclear risk of bias across all but four domains in one study, and all but two domains in the other two studies. One study was funded by Forest Laboratories, LLC, (Jersey City, New Jersey), Allergan. The study sponsor was involved in the study design, data collection (via contracted clinical investigator sites), analysis and interpretation of data, and the decision to present these results. The other two studies reported no financial support or sponsorship; though in one of the two, the study medication was an in-kind contribution from Forest Pharmaceuticals. Primary outcomes There was no clear evidence of a difference between memantine and placebo with respect to severity of core symptoms of autism, although we are very uncertain about the evidence. The standardised mean difference in autism symptoms score in the intervention group versus the control group was -0.74 standard deviations (95% confidence interval (CI) -2.07 to 0.58; 2 studies, 181 participants; very low-certainty evidence; medium effect size); lower scores indicate less severe autistic symptoms. Two studies (144 participants) recorded adverse effects that the authors deemed related to the study and found there may be no difference between memantine and placebo (odds ratio (OR) 0.64, 95% CI 0.17 to 2.39; low-certainty evidence). Secondary outcomes There may be no difference between memantine and placebo on language (2 studies, 144 participants; low-certainty evidence); memory or adaptive behaviour (1 study, 23 participants; both low-certainty evidence); or hyperactivity or irritability (1 study, 121 participants; both low-certainty evidence).
AUTHORS' CONCLUSIONS
It is unclear whether memantine is an effective treatment for autistic children. None of the three included trials reported on the effectiveness of memantine in adults. Further studies using rigorous designs, larger samples, longer follow-up and clinically meaningful outcome measures that are important to autistic people and their families will strengthen our knowledge of the effects of memantine in autism.
Topics: Adolescent; Adult; Autism Spectrum Disorder; Child; Female; Humans; Male; Memantine; Odds Ratio; Outcome Assessment, Health Care; Randomized Controlled Trials as Topic; Treatment Outcome
PubMed: 36006807
DOI: 10.1002/14651858.CD013845.pub2 -
Trends in Psychiatry and Psychotherapy 2023Although post-traumatic stress disorder and obsessive-compulsive disorder have distinct diagnostic criteria, some psychopathological phenomena seem to be shared, which... (Review)
Review
INTRODUCTION
Although post-traumatic stress disorder and obsessive-compulsive disorder have distinct diagnostic criteria, some psychopathological phenomena seem to be shared, which may lead to misdiagnosis and erroneous treatment decisions. This scoping review explores the psychopathological similarities and differences between these two disorders.
METHOD
The review complies with the recommendations of the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) and included articles published in Portuguese, English, or Spanish in the last 50 years indexed in the PubMed database. Case-reports were excluded.
RESULTS
Fifty-three studies with different designs were included (30 [56.5%] were cross-sectional studies; eight [15.1%] were case-control studies; one [1.9%] was a cohort study; three [5.7%] were clinical trials; nine [17%] were reviews/systematic reviews; and two [3.8%] were meta-analyses). The main psychopathological aspects described by the studies included were flashbacks x obsessions; avoidant behavior (AB); depressive, anxious, and somatic symptoms; sexuality, sleep, and appetite; psychiatric comorbidities; and suicidality. The intersection between clinical features seems to occur in the extrinsic psychopathological dimension.
CONCLUSION
The disorders' core psychopathological symptoms (intrinsic characteristics) are distinctly different, since flashbacks and obsessions are consequences of different predominant defective mental functions: the former derives from defective memory, the latter from defective thought. Along the same lines, the ABs observed in the two disorders are products of different purposes and inner necessities.
Topics: Humans; Stress Disorders, Post-Traumatic; Cohort Studies; Obsessive-Compulsive Disorder; Psychopathology; Comorbidity
PubMed: 35244353
DOI: 10.47626/2237-6089-2021-0370 -
Psychological Medicine Jan 2022Antipsychotic treatment resistance affects up to a third of individuals with schizophrenia. Of those affected, 70-84% are reported to be treatment resistant from the... (Meta-Analysis)
Meta-Analysis Review
Antipsychotic treatment resistance affects up to a third of individuals with schizophrenia. Of those affected, 70-84% are reported to be treatment resistant from the outset. This raises the possibility that the neurobiological mechanisms of treatment resistance emerge before the onset of psychosis and have a neurodevelopmental origin. Neuropsychological investigations can offer important insights into the nature, origin and pathophysiology of treatment-resistant schizophrenia (TRS), but methodological limitations in a still emergent field of research have obscured the neuropsychological discriminability of TRS. We report on the first systematic review and meta-analysis to investigate neuropsychological differences between TRS patients and treatment-responsive controls across 17 published studies (1864 participants). Five meta-analyses were performed in relation to (1) executive function, (2) general cognitive function, (3) attention, working memory and processing speed, (4) verbal memory and learning, and (5) visual-spatial memory and learning. Small-to-moderate effect sizes emerged for all domains. Similarly to previous comparisons between unselected, drug-naïve and first-episode schizophrenia samples healthy controls in the literature, the largest effect size was observed in verbal memory and learning [ = -0.53; 95% confidence interval (CI) -0.29 to -0.76; = 4.42; < 0.001]. A sub-analysis of language-related functions, extracted from across the primary domains, yielded a comparable effect size ( = -0.53, 95% CI -0.82 to -0.23; = 3.45; < 0.001). Manipulating our sampling strategy to include or exclude samples selected for clozapine response did not affect the pattern of findings. Our findings are discussed in relation to possible aetiological contributions to TRS.
Topics: Humans; Antipsychotic Agents; Memory, Short-Term; Neuropsychological Tests; Psychotic Disorders; Schizophrenia
PubMed: 36415088
DOI: 10.1017/S0033291721004128