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Brain Sciences Jul 2023Apathy, a frequent neuropsychiatric symptom in aging neurocognitive disorders, has been associated with cognitive decline and functional disability. Therefore, timely... (Review)
Review
OBJECTIVE
Apathy, a frequent neuropsychiatric symptom in aging neurocognitive disorders, has been associated with cognitive decline and functional disability. Therefore, timely provision of pharmacological interventions for apathy is greatly needed.
DESIGN
A systematical literature review of existing studies was conducted up to 30 May 2023 in several databases (PubMed, PsychInfo, Cochrane, Google Scholar, etc.) that included randomized controlled trials (RCTs) and meta-analyses assessing pharmacological treatments for apathy in aging neurocognitive disorders. The quality of the studies was appraised.
RESULTS
In patients with Alzheimer's Disease (AD), donepezil, galantamine, rivastigmine, methylphenidate, and gingko biloba were proven efficacious for apathy, while rivastigmine, cognitive enhancer IRL752 and piribedil were found to be beneficial in patients with Parkinson's Disease (PD) and agomelatine in patients with Frontotemporal Dementia (FD). The extensive proportion of RCTs in which apathy was used as a secondary outcome measure, along with the considerable methodological heterogeneity, did not allow the evaluation of group effects.
CONCLUSIONS
Pharmacological interventions for apathy in aging neurocognitive disorders are complex and under-investigated. The continuation of systematic research efforts and the provision of individualized treatment for patients suffering from these disorders is vital.
PubMed: 37508993
DOI: 10.3390/brainsci13071061 -
European Stroke Journal Mar 2024A quarter of ischaemic strokes are lacunar subtype, typically neurologically mild, usually resulting from intrinsic cerebral small vessel pathology, with risk factor...
A quarter of ischaemic strokes are lacunar subtype, typically neurologically mild, usually resulting from intrinsic cerebral small vessel pathology, with risk factor profiles and outcome rates differing from other stroke subtypes. This European Stroke Organisation (ESO) guideline provides evidence-based recommendations to assist with clinical decisions about management of lacunar ischaemic stroke to prevent adverse clinical outcomes. The guideline was developed according to ESO standard operating procedures and Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) methodology. We addressed acute treatment (including progressive lacunar stroke) and secondary prevention in lacunar ischaemic stroke, and prioritised the interventions of thrombolysis, antiplatelet drugs, blood pressure lowering, lipid lowering, lifestyle, and other interventions and their potential effects on the clinical outcomes recurrent stroke, dependency, major adverse cardiovascular events, death, cognitive decline, mobility, gait, or mood disorders. We systematically reviewed the literature, assessed the evidence and where feasible formulated evidence-based recommendations, and expert concensus statements. We found little direct evidence, mostly of low quality. We recommend that patients with suspected acute lacunar ischaemic stroke receive intravenous alteplase, antiplatelet drugs and avoid blood pressure lowering according to current acute ischaemic stroke guidelines. For secondary prevention, we recommend single antiplatelet treatment long-term, blood pressure control, and lipid lowering according to current guidelines. We recommend smoking cessation, regular exercise, other healthy lifestyle modifications, and avoid obesity for general health benefits. We cannot make any recommendation concerning progressive stroke or other drugs. Large randomised controlled trials with clinically important endpoints, including cognitive endpoints, are a priority for lacunar ischaemic stroke.
Topics: Humans; Brain Ischemia; Cerebral Small Vessel Diseases; Lipids; Platelet Aggregation Inhibitors; Stroke; Stroke, Lacunar
PubMed: 38380638
DOI: 10.1177/23969873231219416 -
Ageing Research Reviews Dec 2023Alterations in nitric oxide (NO) synthesis have been reported in Alzheimer's disease and vascular dementia. However, as the measurement of NO in biological samples is... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Alterations in nitric oxide (NO) synthesis have been reported in Alzheimer's disease and vascular dementia. However, as the measurement of NO in biological samples is analytically challenging, alternative, stable circulatory biomarkers of NO synthesis may be useful to unravel new pathophysiological mechanisms and treatment targets in dementia.
METHODS
We conducted a systematic review and meta-analysis of the circulating concentrations of arginine metabolites linked to NO synthesis, arginine, citrulline, asymmetric (ADMA) and symmetric (SDMA) dimethylarginine, and ornithine, in Alzheimer's disease and vascular dementia. We searched for relevant studies in PubMed, Scopus, and Web of Science from inception to the 31st of May 2023. The JBI checklist and GRADE were used to assess the risk of bias and the certainty of evidence, respectively.
RESULTS
In 14 selected studies, there were no significant between-group differences in arginine and ornithine concentrations. By contrast, compared to controls, patients with dementia had significantly higher ADMA (standard mean difference, SMD=0.62, 95% CI 0.06-1.19, p = 0.029), SDMA (SMD=0.70, 95% CI 0.34-1.35, p<0.001), and citrulline concentrations (SMD=0.50, 95% CI 0.08-0.91, p = 0.018). In subgroup analysis, the effect size was significantly associated with treatment with cholinesterase inhibitors and/or antipsychotics for ADMA, and underlying disorder (Alzheimer's disease), study continent, and analytical method for citrulline.
CONCLUSION
Alterations in ADMA, SDMA, and citrulline, biomarkers of NO synthesis, may be useful to investigate the pathophysiology of different forms of dementia and identify novel therapeutic strategies. (PROSPERO registration number: CRD42023439528).
Topics: Humans; Alzheimer Disease; Dementia, Vascular; Citrulline; Arginine; Biomarkers; Ornithine
PubMed: 38007048
DOI: 10.1016/j.arr.2023.102139 -
Aging Clinical and Experimental Research Mar 2024Dementia affects 5-8% of the population aged over 65 years (~50 million worldwide). Several factors are associated with increased risk, including diet. The... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Dementia affects 5-8% of the population aged over 65 years (~50 million worldwide). Several factors are associated with increased risk, including diet. The Mediterranean diet (MedDiet) has shown potential protective effects against several chronic diseases.
AIMS
This systematic review with meta-analysis aim was to assess the association between adherence to the MedDiet and the risk of dementia in the elderly.
METHODS
PRISMA-2020 guidelines were followed. PubMed/MEDLINE and Scopus were searched on 17 July 2023. The Newcastle-Ottawa Scale tool was used to assess the risk of bias. The protocol was pre-registered in PROSPERO (registration number: CRD 42023444368). Heterogeneity was assessed using the I test. Publication bias was assessed by visual inspection of the funnel plot and by Egger's regression asymmetry test. The final effect size was reported as OR or HR, depending on the study design of the included studies.
RESULTS
Out of 682 records, 21 were included in the analysis. The pooled OR was 0.89 (95% CI = 0.84-0.94) based on 65,955 participants (I = 69.94). When only cohort studies were included, HR was 0.84 (95% CI = 0.76-0.94) based on 55,205 participants (I = 89.70). When only Alzheimer Disease was considered OR was 0.73 (95% CI = 0.62-0.85) based on 38,292 participants (I = 63.85).
DISCUSSION
Despite the relatively low risk reduction associated with higher adherence to MedDiet among elderly, it should be considered that this population is the most affected.
CONCLUSIONS
Adherence to MedDiet could be an effective non-pharmacological measure to reduce the burden of dementia, even among elderly.
Topics: Aged; Humans; Alzheimer Disease; Diet, Mediterranean; Cohort Studies; Risk; Research Design
PubMed: 38519775
DOI: 10.1007/s40520-024-02718-6 -
BMC Infectious Diseases Oct 2023Approximately 10% of patients experience prolonged symptoms after Lyme disease. PTLDS (post treatment Lyme disease syndrome) is a controversial topic. It has been...
BACKGROUND
Approximately 10% of patients experience prolonged symptoms after Lyme disease. PTLDS (post treatment Lyme disease syndrome) is a controversial topic. It has been described as a source of overdiagnosis and off-label treatment. This review aims to describe the diagnostic errors and adverse events associated with the diagnosis and treatment of PTLDS.
METHODS
systematic review of the literature in the Medline and Cochrane Library databases, according to PRISMA criteria, including randomized clinical trials (RCT), observational studies, and case reports addressing diagnostic errors and adverse events published between January 2010 and November 2020 in English or French. Selection used a quadruple reading process on the basis of the titles and abstracts of the different articles, followed by a full reading.
RESULTS
17 studies were included: 1 RCT, 6 observational studies and 10 case reports. In the 6 observational studies, overdiagnosis rates were very high, ranging from 80 to 100%. The new diagnoses were often psychiatric, rheumatological and neurological. Disorders with somatic symptoms were often cited. Diagnostic delays were identified for cancers and frontoparietal dementia. In the RCT and observational studies, prolonged anti-infective treatments were also responsible for adverse events, with emergency room visits and/or hospitalization. The most common adverse events were diarrhea, sometimes with Clostridium difficile colitis, electrolyte abnormalities, sepsis, bacterial and fungal infections, and anaphylactic reactions.
CONCLUSION
This review highlights the risks of prolonged anti-infective treatments that have not been proven to be beneficial in PTLDS. It emphasizes the ethical imperative of the "primum non nocere" principle, which underscores the importance of not causing harm to patients. Physicians should exercise caution in diagnosing PTLDS and consider the potential risks associated with off-label treatments.
Topics: Humans; Enterocolitis, Pseudomembranous; Lyme Disease; Anti-Bacterial Agents; Sepsis
PubMed: 37784031
DOI: 10.1186/s12879-023-08618-w -
Frontiers in Neurology 2023The recognition of Auditory Processing Disorder (APD) as a distinct clinical condition that impacts hearing capacity and mental health has gained attention. Although... (Review)
Review
The recognition of Auditory Processing Disorder (APD) as a distinct clinical condition that impacts hearing capacity and mental health has gained attention. Although pure tone audiometry is the gold standard for assessing hearing, it inadequately reflects everyday hearing abilities, especially in challenging acoustic environments. Deficits in speech perception in noise, a key aspect of APD, have been linked to an increased risk of dementia. The World Health Organization emphasizes the need for evaluating central auditory function in cases of mild hearing loss and normal audiometry results. Specific questionnaires play a crucial role in documenting and quantifying the difficulties faced by individuals with APD. Validated questionnaires such as the Children's Auditory Processing Performance Scale, the Fisher's Auditory Problems Checklist, and the Auditory Processing Domains Questionnaire are available for children, while questionnaires for adults include items related to auditory functions associated with APD. This systematic review and meta-analysis identified six questionnaires used for screening and evaluating APD with a total of 783 participants across 12 studies. The questionnaires exhibited differences in domains evaluated, scoring methods, and evaluation of listening in quiet and noise. Meta-analysis results demonstrated that individuals with APD consistently exhibited worse scores compared to healthy controls across all questionnaires. Additionally, comparisons with clinical control groups showed varying results. The study highlights (i) the importance of standardized questionnaires in identifying and assessing APD, aiding in its diagnosis and management, and (ii) the need to use sub-scores as well as overall scores of questionnaires to elaborate on specific hearing and listening situations. There is a need to develop more APD specific questionnaires for the adult population as well as for more focused research on APD diagnosed individuals to further establish the validity and reliability of these questionnaires.
PubMed: 37621857
DOI: 10.3389/fneur.2023.1243170 -
Cells Dec 2023The greatest risk factor for neurodegeneration is the aging of the multiple cell types of human CNS, among which microglia are important because they are the "sentinels"... (Review)
Review
The greatest risk factor for neurodegeneration is the aging of the multiple cell types of human CNS, among which microglia are important because they are the "sentinels" of internal and external perturbations and have long lifespans. We aim to emphasize microglial signatures in physiologic brain aging and Alzheimer's disease (AD). A systematic literature search of all published articles about microglial senescence in human healthy aging and AD was performed, searching for PubMed and Scopus online databases. Among 1947 articles screened, a total of 289 articles were assessed for full-text eligibility. Microglial transcriptomic, phenotypic, and neuropathological profiles were analyzed comprising healthy aging and AD. Our review highlights that studies on animal models only partially clarify what happens in humans. Human and mice microglia are hugely heterogeneous. Like a two-sided coin, microglia can be protective or harmful, depending on the context. Brain health depends upon a balance between the actions and reactions of microglia maintaining brain homeostasis in cooperation with other cell types (especially astrocytes and oligodendrocytes). During aging, accumulating oxidative stress and mitochondrial dysfunction weaken microglia leading to dystrophic/senescent, otherwise over-reactive, phenotype-enhancing neurodegenerative phenomena. Microglia are crucial for managing Aβ, pTAU, and damaged synapses, being pivotal in AD pathogenesis.
Topics: Humans; Mice; Animals; Alzheimer Disease; Microglia; Healthy Aging; Aging; Brain
PubMed: 38132144
DOI: 10.3390/cells12242824 -
European Stroke Journal Dec 2023The pathogenesis of cerebral small vessel disease (cSVD) remains elusive despite evidence of an association between white matter hyperintensities (WMH) and endothelial... (Meta-Analysis)
Meta-Analysis Review
PURPOSE
The pathogenesis of cerebral small vessel disease (cSVD) remains elusive despite evidence of an association between white matter hyperintensities (WMH) and endothelial cerebrovascular dysfunction. Neurovascular coupling (NVC) may be a practical alternative measure of endothelial function. We performed a systematic review of reported associations between NVC and cSVD.
METHODS
EMBASE and PubMed were searched for studies reporting an association between any STRIVE-defined marker of cSVD and a measure of NVC during functional magnetic resonance imaging, transcranial Doppler, positron emission tomography, near-infrared spectroscopy or single-photon emission computed tomography, from inception to November 3rd, 2022. Where quantitative data was available from studies using consistent tests and analyses, results were combined by inverse-variance weighted random effects meta-analysis.
FINDINGS
Of 29 studies (19 case-controls; 10 cohorts), 26 reported decreased NVC with increasing severity of cSVD, of which 18 were individually significant. In 28 studies reporting associations with increasing WMH, 25 reported reduced NVC. Other markers of cSVD were associated with reduced NVC in: eight of nine studies with cerebral microbleeds (six showing a significant effect); three of five studies with lacunar stroke; no studies reported an association with enlarged perivascular spaces. Specific SVD diseases were particularly associated with reduced NVC, including six out of seven studies in cerebral amyloid angiopathy and all four studies in CADASIL. In limited meta-analyses, %BOLD occipital change to a visual stimulus was consistently reduced with more severe WMH (seven studies, SMD -1.51, < 0.01) and increasing microbleeds (seven studies, SMD -1.31, < 0.01).
DISCUSSION AND CONCLUSION
In multiple, small studies, neurovascular coupling was reduced in patients with increasing severity of all markers of cSVD in sporadic disease, CAA and CADASIL. Cerebrovascular endothelial dysfunction, manifest as impaired NVC, may be a common marker of physiological dysfunction due to small vessel injury that can be easily measured in large studies and clinical practice.
Topics: Humans; CADASIL; Neurovascular Coupling; Tomography, X-Ray Computed; Cerebral Small Vessel Diseases; Cerebral Hemorrhage
PubMed: 37697725
DOI: 10.1177/23969873231196981 -
Clinical Journal of Sport Medicine :... Nov 2023Although physical trauma has been reported in boxing since its inception, boxing still appeals to athletes and spectators. This systematic review and meta-analysis... (Meta-Analysis)
Meta-Analysis
OBJECTIVES
Although physical trauma has been reported in boxing since its inception, boxing still appeals to athletes and spectators. This systematic review and meta-analysis assess both acute and chronic neurological and neuropsychological effects that boxing has on the brain. Further assessments in terms of comparisons of the concussion ratio in boxing to other combat sports, as well as the efficiency of wearing headguards, are also performed.
DATA SOURCES
This systematic review and meta-analysis used the Preferred Reporting Items for Systematic reviews and Meta-Analyses guidelines. The outcomes incorporated included physical chronic abnormalities of the brain, neuropsychiatric, and neurological disorders sustained in amateur or professional boxing, in addition to the safety benefits of boxing headguards. Odds ratios, descriptive statistics, and inferential statistics are also reported.
MAIN RESULTS
From the 84 articles reviewed, the 35 included articles suggested that boxers have a significantly elevated risk of sustaining a concussion compared with other combat sports (risk ratio [RR]: 0.253 vs RR: 0.065, P < 0.001). From the 631 amateur and professional boxers analyzed, 147 (23.30%) had cavum septum pellucidum, whereas 125 of 411 amateur and professional boxers (30.41%) presented with some form of brain atrophy. Dementia or amnesia was observed in 46 of 71 boxers (61.79%), 36 of 70 (51.43%) had various forms and severities of cognitive disorders, and 57 of 109 (52.29%) displayed abnormal computed tomography or electroencephalogram scan results. Utilization of headguards significantly increased the risk for stoppages in amateur bouts, compared with boxers not wearing a headguard (OR: 1.75 vs 0.53, P < 0.050).
CONCLUSIONS
Boxing is a hazardous sport that has the potential to have fatal and negative life-changing results. Because of the limited reliable data regarding the efficiency of boxing headguards, future research should focus on the overall significance that headguards may have for reducing head trauma.
Topics: Humans; Boxing; Craniocerebral Trauma; Brain Concussion; Brain; Sports
PubMed: 37862081
DOI: 10.1097/JSM.0000000000001195 -
Healthcare (Basel, Switzerland) Jan 2024Dementia has become one of the leading causes of death across the world. (Review)
Review
BACKGROUND
Dementia has become one of the leading causes of death across the world.
AIMS
The aim of this study was to investigate the incidence, prevalence, and mortality of dementia in China between 2010 and 2020, and to investigate any geographical, age, and sex differences in the prevalence and incidence of dementia.
METHODS
Five databases were searched. The Joanna Briggs Institute (JBI) critical appraisal tool was used to assess the quality of the included studies. A random-effects meta-analysis was performed to estimate the pooled prevalence of dementia. Subgroup analysis was based on the type of dementia. The incidence and mortality of dementia were synthesized qualitatively.
RESULTS
A total of 19 studies were included. The meta-analysis showed that the prevalence of dementia was 6% (95%CI 5%, 8%), the prevalence of Alzheimer's disease (AD) was 5% (95%CI 4%, 6%), and the prevalence of vascular dementia (VaD) was 1% (95%CI 0%, 2%). The subgroup analysis showed that the prevalence rates of dementia in rural (6%, 95%CI 4%, 8%) and urban areas were similar (6%, 95%CI 4%, 8%). Deaths due to dementia increased over time.
CONCLUSION
The prevalence, incidence, and mortality of dementia increased with age and over time. Applying consistent criteria to the diagnosis of cognitive impairment and dementia is necessary to help with disease monitoring. Promoting dementia knowledge and awareness at the community level is necessary.
PubMed: 38338219
DOI: 10.3390/healthcare12030334