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Brain Sciences Nov 2023Emerging evidence highlights moderate hypoxia as a candidate treatment for brain disorders. This systematic review examines findings and the methodological quality of... (Review)
Review
Emerging evidence highlights moderate hypoxia as a candidate treatment for brain disorders. This systematic review examines findings and the methodological quality of studies investigating hypoxia (10-16% O) for ≥14 days in humans, as well as the neurobiological mechanisms triggered by hypoxia in animals, and suggests optimal treatment protocols to guide future studies. We followed the preferred reporting items for systematic reviews and meta-analysis (PRISMA) 2020. Searches were performed on PubMed/MEDLINE, PsycInfo, EMBASE, and the Cochrane Library, in May-September 2023. Two authors independently reviewed the human studies with the following tools: (1) revised Cochrane collaboration's risk of bias for randomized trials 2.0; (2) the risk of bias in nonrandomized studies of interventions. We identified 58 eligible studies (k = 8 human studies with N = 274 individuals; k = 48 animal studies) reporting the effects of hypoxia on cognition, motor function, neuroimaging, neuronal/synaptic morphology, inflammation, oxidative stress, erythropoietin, neurotrophins, and Alzheimer's disease markers. A total of 75% of human studies indicated cognitive and/or neurological benefits, although all studies were evaluated ashigh risk of bias due to a lack of randomization and assessor blinding. Low-dose intermittent or continuous hypoxia repeated for 30-240 min sessions, preferably in combination with motor-cognitive training, produced beneficial effects, and high-dose hypoxia with longer (≥6 h) durations and chronic exposure produced more adverse effects. Larger and methodologically stronger translational studies are warranted.
PubMed: 38137096
DOI: 10.3390/brainsci13121648 -
Ageing Research Reviews Sep 2023Dementia is prevalent in aged populations and is associated with disability and distress for those affected. Therapeutic benefits of drugs targeting dementia are small.... (Review)
Review
BACKGROUND
Dementia is prevalent in aged populations and is associated with disability and distress for those affected. Therapeutic benefits of drugs targeting dementia are small. Impaired nutrient sensing pathways have been implicated in the pathogenesis of dementia and may offer a novel treatment target.
AIMS
This systematic review collated evidence for novel therapeutic compounds that modify nutrient sensing pathways, particularly the sirtuin pathway, in preventing cognitive decline or improving cognition in normal ageing, mild cognitive impairment (MCI), and dementia.
METHODS
PubMed, Embase and Web of Science databases were searched using key search terms. Articles were screened using Covidence systematic review software. The risk of bias was assessed using the Systematic Review Center for Laboratory animal Experimentation (SYRCLE)'s risk of bias tool for animal studies and Cochrane Risk of Bias tool v 2.0 for human studies.
RESULTS
Out of 3841 articles, 68 were included describing 38 different novel therapeutic compounds that modulate the nutrient sensing pathway via the sirtuin pathway. In animal models (58 studies), all investigated novel therapeutic compounds showed cognitive benefits. Ten studies were human intervention trials targeting normal ageing (1 study) and dementia populations (9 studies). Direct sirtuin (silent mating type information regulation 2 homolog) 1 (SIRT1) activators Resveratrol and Nicotinamide derivatives improved cognitive outcomes among human subjects with normal cognition and MCI.
CONCLUSION
Animal studies support that modulation of the sirtuin pathway has the potential to improve cognitive outcomes. Overall, there is a clear lack of translation from animal models to human populations.
Topics: Humans; Aged; Alzheimer Disease; Sirtuins; Cognitive Dysfunction; Cognition; Nutrients
PubMed: 37549873
DOI: 10.1016/j.arr.2023.102029 -
Frontiers in Public Health 2023Cognitive frailty () is characterized by physical frailty and potentially reversible cognitive impairment without Alzheimer's disease and other dementias. Clarifying the... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
Cognitive frailty () is characterized by physical frailty and potentially reversible cognitive impairment without Alzheimer's disease and other dementias. Clarifying the prevalence and related factors of cognitive frailty can help researchers understand its epidemiological status and formulate intervention measures. This study aims to conduct a systematic review and meta-analysis of the prevalence and related factors of in diabetic patients in Chinas to better understand the current status of in diabetic patients in China and develop effective intervention measures for related factors.
METHODS
PubMed, Web of Science, Embase, Cochrane Library, CNKI, Weipu(VIP), WANFANG, China Biology Medicine (CBM) and DUXIU were searched to collect epidemiological data on Chinese diabetic patients. Articles published through May 29, 2023, were searched. The number of diabetes with and the total number of diabetes in the included studies were extracted to estimate the prevalence of diabetes with For factors related to diabetes with , odds ratios () and 95% confidence intervals () were used for estimation.
RESULTS
A total of 248 records were screened, of which 18 met the inclusion criteria. The results of meta-analysis showed that the prevalence of Chinese diabetic patients with was 25.8% (95% = 19.7 to 31.9%). Subgroup analysis showed that hospital prevalence was higher than in the community and in women than in men. Combined estimates showed that depression, malnutrition, advanced age (≥70, ≥80), combined chronic diseases ≥4 and glycated hemoglobin ≥8.5 were risk factors for in diabetics patients in China, with regular exercise and high education level (≥ college) as protective factors.
CONCLUSION
Cognitive frailty was common in diabetic patients in China. Such populations should be screened early and intervened with relevant factors.: A systematic review of this study evaluated the registered websites as https://www.crd.york.ac.uk/PROSPERO/, CRD42023431396.
Topics: Male; Humans; Female; Frailty; Prevalence; Diabetes Mellitus; China; Cognition
PubMed: 37927856
DOI: 10.3389/fpubh.2023.1249422 -
Journal of Clinical Medicine Aug 2023Music interventions (MIs) have been widely used to relieve anxiety in dementia in clinical settings. However, limited meta-analysis with randomized controlled trials... (Review)
Review
Music interventions (MIs) have been widely used to relieve anxiety in dementia in clinical settings. However, limited meta-analysis with randomized controlled trials (RCTs) on this topic has been conducted so far. A systematic search was conducted in four major databases (PubMed, EMBASE, Web of Science, and Cochrane Library) for data provided by RCTs from the inception to February 2023. The search strategy employed the terms "anxiety AND music AND dementia OR Alzheimer's disease". Thirteen RCTs (827 participants) were included. The results showed MI reduced anxiety significantly (SMD = -0.67, < 0.001), especially for Alzheimer's disease ( = 0.007) and Mixed ( < 0.001)-type dementia. Moreover, significant improvements in agitation ( = 0.021) and depression ( < 0.001) in dementia were observed. Additionally, several psychological mechanisms which may be associated with MI were reviewed comprehensively. In conclusion, our findings support the efficacy of MI in alleviating anxiety symptoms in dementia patients. PROSPERO Registration (ID: CRD42021276646).
PubMed: 37685564
DOI: 10.3390/jcm12175497 -
Maturitas Jul 2024The association between cognitive disorders and orthostatic hypotension (OH) has been empirically explored, but the results have been divergent, casting doubt on the... (Meta-Analysis)
Meta-Analysis Review
The association between cognitive disorders and orthostatic hypotension (OH) has been empirically explored, but the results have been divergent, casting doubt on the presence and direction of the association. The objective of this meta-analysis was to systematically review and quantitatively synthesize the association of OH and cognitive function, specifically mean score on the Mini-Mental State Examination (MMSE), cognitive impairment and incident dementia. A Medline search was conducted in May 2022 with no date limit, using the MeSH terms "orthostatic hypotension" OR "orthostatic intolerance" OR "hypotension" combined with the Mesh terms "cognitive dysfunction" OR "Alzheimer disease" OR "dementia" OR "cognition disorder" OR "neurocognitive disorder" OR "cognition" OR "neuropsychological test". Of the 746 selected studies, 15 longitudinal studies met the selection criteria, of which i) 5 studies were eligible for meta-analysis of mean MMSE score comparison, ii) 5 studies for the association of OH and cognitive impairment, and iii) 6 studies for the association between OH and incident dementia. The pooled effect size in fixed-effects meta-analysis was: i) -0.25 (-0.42; -0.07) for the mean MMSE score, which indicates that the MMSE score was lower for those with OH; ii) OR (95 % CI) = 1.278 (1.162; 1.405), P < 0.0001, indicating a 28 % greater risk of cognitive impairment for those with OH at baseline; and iii) HR (95 % CI) = 1.267 (1.156; 1.388), P < 0.0001, indicating a 27 % greater risk of incident dementia for those with OH at baseline. Patients with OH had a lower MMSE score and higher risk of cognitive impairment and incident dementia in this meta-analysis of longitudinal studies. This study confirmed the presence of an association between OH and cognitive disorders in older adults.
Topics: Humans; Hypotension, Orthostatic; Cognitive Dysfunction; Dementia; Longitudinal Studies; Mental Status and Dementia Tests
PubMed: 38604094
DOI: 10.1016/j.maturitas.2023.107866 -
Alzheimer's Research & Therapy Jun 2024Non-invasive brain stimulation (NIBS) combined with cognitive training (CT) may have shown some prospects on improving cognitive function in patients with Alzheimer's... (Meta-Analysis)
Meta-Analysis Review
The cognitive effect of non-invasive brain stimulation combined with cognitive training in Alzheimer's disease and mild cognitive impairment: a systematic review and meta-analysis.
BACKGROUND
Non-invasive brain stimulation (NIBS) combined with cognitive training (CT) may have shown some prospects on improving cognitive function in patients with Alzheimer's disease (AD) and mild cognitive impairment (MCI). However, data from clinical trials or meta-analysis involving NIBS combined with CT have shown controversial results. The aim of this systematic review and meta-analysis was to evaluate short-term and long-term effects of NIBS combined with CT on improving global cognition and other specific cognitive domains in patients with AD and MCI.
METHODS
This systematic review and meta-analysis was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Five electronic databases including PubMed, Web of Science, EBSCO, Cochrane Library and Embase were searched up from inception to 20 November 2023. The PEDro scale and the Cochrane's risk of bias assessment were used to evaluate risk of bias and methodological quality of included studies. All statistical analyses were conducted with Review Manager 5.3.
RESULTS
We included 15 studies with 685 patients. The PEDro scale was used to assess methodological quality with a mean score of 7.9. The results of meta-analysis showed that NIBS combined with CT was effective on improving global cognition in AD and MCI (SMD = 0.52, 95% CI (0.18, 0.87), p = 0.003), especially for patients accepting repetitive transcranial magnetic stimulation (rTMS) combined with CT (SMD = 0.46, 95% CI (0.14, 0.78), p = 0.005). AD could achieve global cognition improvement from NIBS combined with CT group (SMD = 0.77, 95% CI (0.19, 1.35), p = 0.01). Transcranial direct current stimulation (tDCS) combined with CT could improve language function in AD and MCI (SMD = 0.29, 95% CI (0.03, 0.55), p = 0.03). At evaluation follow-up, rTMS combined with CT exhibited larger therapeutic responses to AD and MCI in global cognition (SMD = 0.55, 95% CI (0.09, 1.02), p = 0.02). AD could achieve global cognition (SMD = 0.40, 95% CI (0.03, 0.77), p = 0.03) and attention/working memory (SMD = 0.72, 95% CI (0.23, 1.20), p = 0.004) improvement after evaluation follow-up from NIBS combined with CT group.
CONCLUSIONS
Overall, NIBS combined with CT, particularly rTMS combined with CT, has both short-term and follow-up effects on improving global cognition, mainly in patients with AD. tDCS combined with CT has advantages on improving language function in AD and MCI. Future more studies need evaluate cognitive effects of NIBS combined with CT on other specific cognitive domain in patients with cognitive deterioration.
Topics: Humans; Cognitive Dysfunction; Alzheimer Disease; Transcranial Magnetic Stimulation; Transcranial Direct Current Stimulation; Cognitive Behavioral Therapy; Cognition; Combined Modality Therapy; Cognitive Training
PubMed: 38937842
DOI: 10.1186/s13195-024-01505-9 -
Diabetes/metabolism Research and Reviews Oct 2023We aimed to summarise current evidence on different antidiabetic drugs to delay cognitive impairment, including mild cognitive impairment, dementia, Alzheimer's disease... (Meta-Analysis)
Meta-Analysis Review
We aimed to summarise current evidence on different antidiabetic drugs to delay cognitive impairment, including mild cognitive impairment, dementia, Alzheimer's disease (AD) and vascular dementia, among subjects with type 2 diabetes mellitus (T2DM). Medline, Cochrane and Embase databases were searched from inception to 31 July 2022. Two investigators independently reviewed and screened trials comparing antidiabetic drugs with no antidiabetic drugs, placebo, or other active antidiabetic drugs on cognitive outcomes in T2DM. Data were analysed using meta-analysis and network meta-analysis. Twenty-seven studies met the inclusion criteria, including 3 randomised controlled trials, 19 cohort studies and 5 case-control studies. Compared with non-user, SGLT-2i (OR 0.41 [95% CI 0.22-0.76]), GLP-1RA (OR 0.34 [95% CI 0.14-0.85]), thiazolidinedione (OR 0.60 [95% CI 0.51-0.69]), and DPP-4i (OR 0.78 [95% CI 0.61-0.99]) users had a decreased risk of dementia, whereas sulfonylurea (OR 1.43 [95% CI 1.11-1.82]) increased dementia risk. Network meta-analysis showed that SGLT-2i was most likely to rank best (SUCRA = 94.4%), GLP-1 RA second best (SUCRA = 92.7%), thiazolidinedione third best (SUCRA = 74.7%) and DPP-4i fourth best (SUCRA = 54.9%), while sulfonylurea second worst (SUCRA = 20.0%) for decreasing dementia outcomes, by synthesising evidence from direct and indirect comparisons of multiple intervention. Evidence suggests the effects of SGLT-2i ≈ GLP-1 RAs > thiazolidinedione > DPP-4i for delaying cognitive impairment, dementia and AD outcomes, whereas sulfonylurea was associated with the highest risk. These findings provide evidence for evaluating the optional treatment for clinical practice. PROSPERO REGISTRATION: Registration no. CRD42022347280.
Topics: Humans; Hypoglycemic Agents; Diabetes Mellitus, Type 2; Network Meta-Analysis; Sulfonylurea Compounds; Glucagon-Like Peptide 1; Dementia; Thiazolidinediones; Cognition; Dipeptidyl-Peptidase IV Inhibitors; Glucagon-Like Peptide-1 Receptor
PubMed: 37302139
DOI: 10.1002/dmrr.3673 -
Alzheimer's Research & Therapy Oct 2023Mild cognitive impairment (MCI) is often considered an early stage of dementia, with estimated rates of progression to dementia up to 80-90% after approximately 6 years... (Review)
Review
Mild cognitive impairment (MCI) is often considered an early stage of dementia, with estimated rates of progression to dementia up to 80-90% after approximately 6 years from the initial diagnosis. Diagnosis of cognitive impairment in dementia is typically based on clinical evaluation, neuropsychological assessments, cerebrospinal fluid (CSF) biomarkers, and neuroimaging. The main goal of diagnosing MCI is to determine its cause, particularly whether it is due to Alzheimer's disease (AD). However, only a limited percentage of the population has access to etiological confirmation, which has led to the emergence of peripheral fluid biomarkers as a diagnostic tool for dementias, including MCI due to AD. Recent advances in biofluid assays have enabled the use of sophisticated statistical models and multimodal machine learning (ML) algorithms for the diagnosis of MCI based on fluid biomarkers from CSF, peripheral blood, and saliva, among others. This approach has shown promise for identifying specific causes of MCI, including AD. After a PRISMA analysis, 29 articles revealed a trend towards using multimodal algorithms that incorporate additional biomarkers such as neuroimaging, neuropsychological tests, and genetic information. Particularly, neuroimaging is commonly used in conjunction with fluid biomarkers for both cross-sectional and longitudinal studies. Our systematic review suggests that cost-effective longitudinal multimodal monitoring data, representative of diverse cultural populations and utilizing white-box ML algorithms, could be a valuable contribution to the development of diagnostic models for AD due to MCI. Clinical assessment and biomarkers, together with ML techniques, could prove pivotal in improving diagnostic tools for MCI due to AD.
Topics: Humans; Alzheimer Disease; Cross-Sectional Studies; Disease Progression; Cognitive Dysfunction; Biomarkers; Machine Learning; Amyloid beta-Peptides; tau Proteins
PubMed: 37838690
DOI: 10.1186/s13195-023-01304-8 -
Journal of Neurology, Neurosurgery, and... Dec 2023Biological ageing is one of the principal risk factors for neurodegenerative diseases. It is becoming increasingly clear that acceleration of DNA methylation age, as...
BACKGROUND
Biological ageing is one of the principal risk factors for neurodegenerative diseases. It is becoming increasingly clear that acceleration of DNA methylation age, as measured by the epigenetic clock, is closely associated with many age-related diseases.
METHODS
We searched the PubMed and Web of Science databases to identify eligible studies reporting epigenetic clocks in several neurodegenerative diseases, including Alzheimer's disease (AD), Parkinson's disease (PD), amyotrophic lateral sclerosis (ALS) and Huntington's disease (HD).
RESULTS
Twenty-three studies (12 for AD, 4 for PD, 5 for ALS, and 2 for HD) were included. We systematically summarised the clinical utility of 11 epigenetic clocks (based on blood and brain tissues) in assessing the risk factors, age of onset, diagnosis, progression, prognosis and pathology of AD, PD, ALS and HD. We also critically described our current understandings to these evidences, and further discussed key challenges, potential mechanisms and future perspectives of epigenetic ageing in neurodegenerative diseases.
CONCLUSIONS
Epigenetic clocks hold great potential in neurodegenerative diseases. Further research is encouraged to evaluate the clinical utility and promote the application.
PROSPERO REGISTRATION NUMBER
CRD42022365233.
Topics: Humans; Amyotrophic Lateral Sclerosis; Neurodegenerative Diseases; Alzheimer Disease; Parkinson Disease; Epigenesis, Genetic
PubMed: 36963821
DOI: 10.1136/jnnp-2022-330931 -
Neurological Sciences : Official... Oct 2023Dementia affects more than 55 million people worldwide. Several technologies have been developed to slow cognitive decline: deep brain stimulation (DBS) of network... (Review)
Review
BACKGROUND
Dementia affects more than 55 million people worldwide. Several technologies have been developed to slow cognitive decline: deep brain stimulation (DBS) of network targets in Alzheimer's disease (AD) and dementia with Lewy bodies (DLB) have been recently investigated.
OBJECTIVE
This study aimed to review the characteristics of the populations, protocols, and outcomes of patients with dementia enrolled in clinical trials investigating the feasibility and efficacy of DBS.
MATERIALS AND METHODS
A systematic search of all registered RCTs was performed on Clinicaltrials.gov and EudraCT, while a systematic literature review was conducted on PubMed, Scopus, Cochrane, and APA PsycInfo to identify published trials.
RESULTS
The literature search yielded 2122 records, and the clinical trial search 15 records. Overall, 17 studies were included. Two of 17 studies were open-label studies reporting no NCT/EUCT code and were analysed separately. Of 12 studies investigating the role of DBS in AD, we included 5 published RCTs, 2 unregistered open-label (OL) studies, 3 recruiting studies, and 2 unpublished trials with no evidence of completion. The overall risk of bias was assessed as moderate-high. Our review showed significant heterogeneity in the recruited populations regarding age, disease severity, informed consent availability, inclusion, and exclusion criteria. Notably, the standard mean of overall severe adverse events was moderately high (SAEs: 9.10 ± 7.10%).
CONCLUSION
The population investigated is small and heterogeneous, published results from clinical trials are under-represented, severe adverse events not negligible, and cognitive outcomes uncertain. Overall, the validity of these studies requires confirmation based on forthcoming higher-quality clinical trials.
Topics: Humans; Deep Brain Stimulation; Alzheimer Disease; Cognitive Dysfunction; Longitudinal Studies
PubMed: 37204563
DOI: 10.1007/s10072-023-06821-w