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Ageing Research Reviews Mar 2024The role of lithium as a possible therapeutic strategy for neurodegenerative diseases has generated scientific interest. We systematically reviewed and meta-analyzed... (Meta-Analysis)
Meta-Analysis Review
The role of lithium as a possible therapeutic strategy for neurodegenerative diseases has generated scientific interest. We systematically reviewed and meta-analyzed pre-clinical and clinical studies that evidenced the neuroprotective effects of lithium in Alzheimer's (AD) and Parkinson's disease (PD). We followed the PRISMA guidelines and performed the systematic literature search using PubMed, EMBASE, Web of Science, and Cochrane Library. A total of 32 articles were identified. Twenty-nine studies were performed in animal models and 3 studies were performed on human samples of AD. A total of 17 preclinical studies were included in the meta-analysis. Our analysis showed that lithium treatment has neuroprotective effects in diseases. Lithium treatment reduced amyloid-β and tau levels and significantly improved cognitive behavior in animal models of AD. Lithium increased the tyrosine hydroxylase levels and improved motor behavior in the PD model. Despite fewer clinical studies on these aspects, we evidenced the positive effects of lithium in AD patients. This study lends further support to the idea of lithium's therapeutic potential in neurodegenerative diseases.
Topics: Animals; Humans; Parkinson Disease; Lithium; Alzheimer Disease; Neuroprotective Agents; Neurodegenerative Diseases; Lithium Compounds
PubMed: 38364914
DOI: 10.1016/j.arr.2024.102231 -
American Journal of Epidemiology Jul 2023Metal exposure has been suggested as a possible environmental risk factor for Parkinson disease (PD). We searched the PubMed, EMBASE, and Cochrane databases to... (Meta-Analysis)
Meta-Analysis
Metal exposure has been suggested as a possible environmental risk factor for Parkinson disease (PD). We searched the PubMed, EMBASE, and Cochrane databases to systematically review the literature on the relationship between metal exposure and PD risk and to examine the overall quality of each study and the exposure assessment method. A total of 83 case-control studies and 5 cohort studies published during the period 1963-July 2021 were included, of which 73 were graded as being of low or moderate overall quality. Investigators in 69 studies adopted self-reported exposure and biomonitoring after disease diagnosis for exposure assessment approaches. The meta-analyses showed that concentrations of copper and iron in serum and concentrations of zinc in either serum or plasma were lower, while concentrations of magnesium in CSF and zinc in hair were higher, among PD cases as compared with controls. Cumulative lead levels in bone were found to be associated with increased risk of PD. We did not find associations between other metals and PD. The current level of evidence for associations between metals and PD risk is limited, as biases from methodological limitations cannot be ruled out. High-quality studies assessing metal levels before disease onset are needed to improve our understanding of the role of metals in the etiology of PD.
Topics: Humans; Cohort Studies; Copper; Lead; Parkinson Disease; Zinc; Metals
PubMed: 37022311
DOI: 10.1093/aje/kwad082 -
Frontiers in Neurology 2023Past research indicates a higher prevalence, incidence, and severe clinical manifestations of alpha-synucleinopathies in men, leading to a suggestion of neuroprotective...
BACKGROUND
Past research indicates a higher prevalence, incidence, and severe clinical manifestations of alpha-synucleinopathies in men, leading to a suggestion of neuroprotective properties of female sex hormones (especially estrogen). The potential pathomechanisms of any such effect on alpha-synucleinopathies, however, are far from understood. With that aim, we undertook to systematically review, and to critically assess, contemporary evidence on sex and gender differences in alpha-synucleinopathies using a bench-to-bedside approach.
METHODS
In this systematic review, studies investigating sex and gender differences in alpha-synucleinopathies (Rapid Eye Movement (REM) Behavior Disorder (RBD), Parkinson's Disease (PD), Dementia with Lewy Bodies (DLB), Multiple System Atrophy (MSA)) from 2012 to 2022 were identified using electronic database searches of PubMed, Embase and Ovid.
RESULTS
One hundred sixty-two studies were included; 5 RBD, 6 MSA, 20 DLB and 131 PD studies. Overall, there is conclusive evidence to suggest sex-and gender-specific manifestation in demographics, biomarkers, genetics, clinical features, interventions, and quality of life in alpha-synucleinopathies. Only limited data exists on the effects of distinct sex hormones, with majority of studies concentrating on estrogen and its speculated neuroprotective effects.
CONCLUSION
Future studies disentangling the underlying sex-specific mechanisms of alpha-synucleinopathies are urgently needed in order to enable novel sex-specific therapeutics.
PubMed: 37545736
DOI: 10.3389/fneur.2023.1204104 -
Epilepsy & Behavior : E&B Mar 2024Epilepsy and dementia are bidirectional. The purpose of this review was to investigate the epidemiological characteristics of and to identify the risk factors for... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Epilepsy and dementia are bidirectional. The purpose of this review was to investigate the epidemiological characteristics of and to identify the risk factors for epilepsy in patients with dementia and dementia in patients with epilepsy.
METHODS
We retrieved the PubMed, Embase, Cochrane and Web of Science databases through January 2023. Two individuals screened the articles, extracted the data, and used a random effects model to pool the estimates and 95% confidence intervals (CIs).
RESULTS
From 3475 citations, 25 articles were included. The prevalence of seizures/epilepsy was 4% among dementia patients and 3% among Alzheimer's disease (AD) patients. For vascular dementia, Lewy body dementia, and frontotemporal dementia, the pooled period prevalence of seizures/epilepsy was 6%, 3%, and 2%, respectively. Baseline early-onset AD was associated with the highest risk of 5-year epilepsy (pooled hazard ratios: 4.06; 95% CI: 3.25-5.08). Dementia patients had a 2.29-fold greater risk of seizures/epilepsy than non-dementia patients (95% CI: 1.37-3.83). Moreover, for baseline epilepsy, the pooled prevalence of dementia was 17% (95% CI: 10-25%), and that of AD was 15% (95% CI: 9-21%). The pooled results suggested that epilepsy is associated with a greater risk of dementia (risk ratio: 2.83, 95% CI: 1.64-4.88).
CONCLUSIONS
There are still gaps in epidemiology regarding the correlation between dementia types and epilepsy, vascular risk factors, and the impact of antiseizure medication or cognitive improvement drugs on epilepsy and AD comorbidity.
Topics: Humans; Epilepsy; Alzheimer Disease; Lewy Body Disease; Comorbidity; Seizures
PubMed: 38301455
DOI: 10.1016/j.yebeh.2024.109640 -
Evidence-based Dentistry Sep 2023To summarize the data on association between periodontal diseases and cognitive impairment in adults this systematic review scrutinized various observational studies...
DESIGN
To summarize the data on association between periodontal diseases and cognitive impairment in adults this systematic review scrutinized various observational studies till September 2021. This review was carried out in accordance with the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA 2020) guidelines. The authors used PECO framework question,: population-Adults (18 years or older), exposure-adults suffering from periodontitis, comparator-adult group without periodontitis, outcome-adults at high risk for cognitive impairment.
CASE/CONTROL SELECTION
Search for the literature was conducted on PubMed, Web of Science, and Cumulative Index to Nursing and Allied Health Literature (CINAHL). Search was limited to human studies with no limitation to year of publication prior to September 2021. Search terms used were related to gingiva, oral bacteria like Porphyromonas gingivalis, gum inflammation, periodontitis, dementia, neuroinflammation, cognitive impairment, Alzheimer's disease, Parkinson disease. Following research, all the studies providing association between periodontal diseases and neurodegenerative diseases with quantitative measures were included in the study. Non-human studies, studies on patients below 18 year old, studies related to influence of treatment and in subjects already suffering from neurological disease were excluded. After removing duplicates, eligible studies were identified and data extracted by two reviewers to make ensure inter examiner reliability and to prevent data entry errors. Data from the studies were tabulated as study design, sample characteristics, diagnosis, exposure biomarkers/measures, outcomes and results.
DATA ANALYSIS
Methodological quality of studies was assessed by adapted Newcastle-Ottawa scale. Selection of study groups, comparability and exposure/outcome were used as parameters. Case-control and cohort studies were considered as high-quality studies if six or more stars were awarded out of nine maximum stars and four or more stars for cross-sectional studies out of six stars. Comparability among the groups was studied by taking into account primary factors for Alzheimer's disease such as age and sex and secondary factors like hypertension, osteoarthritis, depression, diabetes mellitus, and cerebrovascular disease. For cohort studies, 10 year follow up and dropout of <10% was considered to be successful.
RESULTS
A total of 3693 studies were identified by two independent reviewers and finally 11 studies were included in the final analysis. Six cohort studies, three cross-sectional and two case-control studies were included after excluding remaining studies. Bias in studies was assessed by adapted Newcastle-Ottawa Scale. All included studies were of high methodological quality. Association between periodontitis and cognitive impairment was determined by using different criteria like International classification of disease, clinical measurement of periodontitis subjects, inflammatory biomarkers, microbes and antibodies. It was suggested that subjects with chronic periodontitis since 8 years or more, are at a higher risk of having dementia. Clinical measures of periodontal disease like probing depth, clinical attachment loss, alveolar bone loss were found to be positively associated with cognitive impairment. Inflammatory biomarkers and pre-existing elevated levels of serum IgG specific to periodontopathogens was reported to be associated with cognitive impairment. Within the limitations of the study, the authors concluded that though the patients with long-standing periodontitis are at greater risk for developing cognitive impairment by neurodegenerative diseases, the mechanism by which periodontitis can lead to cognitive impairment is still vague.
CONCLUSIONS
Evidence suggests a strong association between periodontitis and cognitive impairment. Still further studies should be done to explore the mechanism involved.
Topics: Adult; Humans; Alzheimer Disease; Cross-Sectional Studies; Reproducibility of Results; Chronic Periodontitis; Cognitive Dysfunction; Biomarkers
PubMed: 37433922
DOI: 10.1038/s41432-023-00915-2 -
International Journal of Molecular... Sep 2023Aging is a complex process influenced by genetics and the environment, leading to physiological decline and increased susceptibility to diseases. Cognitive decline is a... (Review)
Review
Aging is a complex process influenced by genetics and the environment, leading to physiological decline and increased susceptibility to diseases. Cognitive decline is a prominent feature of aging, with implications for different neurodegenerative disorders. The gut microbiome has gained attention for its potential impact on health and disease, including cognitive function. This systematic review and meta-analysis aimed to investigate the relationship between the gut microbiome and cognitive function in the context of aging. Following PRISMA guidelines, a comprehensive search strategy was employed in PubMed, Scopus, and Web of Science databases. Studies exploring the role of the microbiome in cognition and neurodegenerative disorders, published between 2013 and 2023, were included. Data extraction and quality assessment were performed. Quantitative synthesis using statistical analyses was performed to examine microbial diversity and relative abundance in various cognitive conditions. Sixteen studies involving a total of 1303 participants were included in the analysis. The gut microbiota's relative abundance was different in individuals with cognitive impairments such as Alzheimer's disease, Parkinson's disease, and dementia, compared to the healthy controls. The most prevalent phyla affected were Firmicutes, Bacteroidetes, Actinobacteria, and Proteobacteria. Meta-analyses indicated substantial heterogeneity among studies focusing on Alzheimer's disease. The overall quality of evidence related to microbial analysis was moderate. The gut microbiome's role in cognitive decline and neurodegenerative disorders warrants investigation. Altered microbial abundance, particularly in specific phyla, is associated with cognitive impairments. However, variations in study findings and methodologies highlight the complexity of the relationship between the gut microbiome and cognitive function. Further studies are needed to better understand the mechanisms underlying this connection and its potential implications for aging and cognitive health.
PubMed: 37761988
DOI: 10.3390/ijms241813680 -
Movement Disorders Clinical Practice Dec 2023Individuals with multiple system atrophy (MSA) often complain about pain, nonetheless this remains a poorly investigated non-motor feature of MSA. (Review)
Review
BACKGROUND
Individuals with multiple system atrophy (MSA) often complain about pain, nonetheless this remains a poorly investigated non-motor feature of MSA.
OBJECTIVES
Here, we aimed at assessing the prevalence, characteristics, and risk factors for pain in individuals with MSA.
METHODS
Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyzes (PRISMA) guidelines, we systematically screened the PubMED, Cochrane, and Web of Science databases for papers published in English until September 30, 2022, combining the following keywords: "pain," "multiple system atrophy," "MSA," "olivopontocerebellar atrophy," "OPCA," "striatonigral degeneration," "SND," "Shy Drager," and "atypical parkinsonism."
RESULTS
The search identified 700 records. Sixteen studies provided information on pain prevalence in cohorts of MSA individuals and were included in a qualitative assessment based on the Quality Assessment of Diagnostic Accuracy Studies (QUADAS) tool. Thirteen studies (11 cross-sectional, two longitudinal) scored ≥14 points on QUADAS assessment and were included in a quantitative analysis, pooling data from 1236 MSA individuals. The resulting pooled prevalence of pain in MSA was 67% (95% confidence intervals [CI] = 57%-75%), and significantly higher in individuals with MSA of parkinsonian rather than cerebellar type (76% [95% CI = 63%-87%] vs. 45% [95% CI = 33%-57%], = 0.001). Pain assessment tools and collected information were highly heterogeneous across studies. Two studies reported pain treatment strategies and found that only every second person with MSA complaining about pain had received targeted treatment.
CONCLUSIONS
We found that pain is a frequent, but still under-recognized and undertreated feature of MSA. Further research is needed to improve pain detection and treatment in MSA.
PubMed: 38094640
DOI: 10.1002/mdc3.13897 -
Age and Ageing Nov 2023Cholinesterase inhibitors are commonly used to treat patients with neurocognitive disorders, who often have an elevated risk of falling. Effective use of these... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Cholinesterase inhibitors are commonly used to treat patients with neurocognitive disorders, who often have an elevated risk of falling. Effective use of these medications requires a thoughtful assessment of risks and benefits.
OBJECTIVE
To provide an update on previous reviews and determine the association between cholinesterase inhibitors and falls, syncope, fracture and accidental injuries in patients with neurocognitive disorders.
METHODS
Embase, MEDLINE, Cochrane Central Register of Controlled Trials, Cumulative Index of Nursing and Allied Health Literature and AgeLine were systematically searched through March 2023 to identify all randomised controlled trials of cholinesterase inhibitors (donepezil, galantamine, rivastigmine) in patients with cognitive impairment. Corresponding authors were contacted for additional data necessary for meta-analysis. Inclusion criteria consisted of adults ≥19 years, with a diagnosis of dementia, Parkinson's disease, mild cognitive impairment or traumatic brain injury. Data were extracted in duplicate for the aforementioned primary outcomes and all outcomes were analysed using random-effects meta-analysis.
RESULTS
Fifty three studies (30 donepezil, 14 galantamine, 9 rivastigmine) were included providing data on 25, 399 patients. Cholinesterase inhibitors, compared to placebo, were associated with reduced risk of falls (risk ratio [RR] 0.84 [95% confidence interval [CI] = 0.73-0.96, P = 0.009]) and increased risk of syncope (RR 1.50 [95% CI = 1.02-2.21, P = 0.04]). There was no association with accidental injuries or fractures.
CONCLUSION
In patients with neurocognitive disorders, cholinesterase inhibitors were associated with decreased risk of falls, increased risk of syncope and no association with accidental trauma or fractures. These findings will help clinicians better evaluate risks and benefits of cholinesterase inhibitors.
Topics: Humans; Cholinesterase Inhibitors; Donepezil; Rivastigmine; Accidental Falls; Galantamine; Accidental Injuries; Cognitive Dysfunction; Fractures, Bone; Syncope
PubMed: 37993407
DOI: 10.1093/ageing/afad205 -
Brain and Behavior Sep 2023To identify and synthesize existing research on the effectiveness and feasibility of multiform humor therapy on people suffering from depression or anxiety, with the... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVES
To identify and synthesize existing research on the effectiveness and feasibility of multiform humor therapy on people suffering from depression or anxiety, with the hope of benefiting future research.
METHODS
An integrative literature review of quantitative, qualitative, and mixed studies was performed. The PubMed, Cochrane Library, Web of Science, Embase, and CINAHL databases were searched up to March 2022. Two independent reviewers conducted each stage of the review process, by assessing eligibility using preferred reporting items for systematic review and meta-analyses (PRISMA) and quality appraisal using the Mixed Methods Appraisal Tool, and data extraction.
RESULTS
In this integrative review, 29 papers were included, containing 2964 participants across a diverse range of studies, including quantitative, qualitative, and mixed methods. The articles were from the United States, Australia, Italy, Turkey, South Korea, Iran, Israel, China, and Germany. The findings indicated that most of the subjects thought humor therapy was effective in improving depression and anxiety while a few participants considered the effect insignificant. However, more high-quality studies will be needed to confirm these conclusions.
DISCUSSION
This review collated and summarized findings from studies examining the impact of humor therapy (medical clowns, laughter therapy/yoga) on people with depression or anxiety, including children undergoing surgery or anesthesia, older people in nursing homes, patients with Parkinson's disease, cancer, mental illness, and undergoing dialysis, retired women, and college students. The results from this review may help inform future research, policy, and practice in humor therapy to improve people's symptoms of depression and anxiety.
IMPACT
This systematic review objectively evaluated the effect of humor therapy on depression and anxiety. As a simple and feasible complementary alternative therapy, humor therapy may provide a favorable alternative for clinicians, nurses, and patients in the future.
Topics: Child; Humans; Female; Aged; Depression; Anxiety; Anxiety Disorders; Renal Dialysis; Australia
PubMed: 37340873
DOI: 10.1002/brb3.3108 -
Sleep Medicine Reviews Oct 2023Although rapid eye movement (REM) sleep behavior disorder (RBD) has been widely considered as a male-predominant parasomnia, the existing evidence for the sex difference... (Meta-Analysis)
Meta-Analysis Review
Although rapid eye movement (REM) sleep behavior disorder (RBD) has been widely considered as a male-predominant parasomnia, the existing evidence for the sex difference in the risk of RBD in the general population was conflicting. The present study conducted a systematic review to explore the sex differences in the prevalence, comorbidities, clinical characteristics, and phenoconversion of RBD. One hundred thirty-five eligible studies were identified for the systematic review, and 133 were finally included in the meta-analysis. Males in the general population showed a trend for a higher risk of probable/possible RBD (pRBD), especially among the male older adults (aged ≥60). In the clinical populations, males showed a significantly higher risk of confirmed RBD, but not of pRBD. Among idiopathic RBD (iRBD) patients, males had a significantly earlier age onset of RBD compared with females. Male patients with Parkinson's disease (PD) had a higher risk of comorbid RBD. There was no significant sex difference in the risk of developing neurodegenerative diseases in iRBD patients. Large scale and prospective studies utilizing stringent diagnostic criteria for RBD are recommended to further verify the sex differences in RBD and to investigate the mechanism underlying the sex difference.
Topics: Humans; Male; Female; Aged; Sex Characteristics; Prospective Studies; REM Sleep Behavior Disorder; Polysomnography; Parkinson Disease
PubMed: 37422999
DOI: 10.1016/j.smrv.2023.101810