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PloS One 2024The Neutrophil-to-Lymphocyte Ratio (NLR) is a clinical indicator of peripheral inflammation that is easily accessible. It is worth noting that the formation of... (Meta-Analysis)
Meta-Analysis
BACKGROUND
The Neutrophil-to-Lymphocyte Ratio (NLR) is a clinical indicator of peripheral inflammation that is easily accessible. It is worth noting that the formation of amyloid-β (Aβ) plaques and neurofibrillary tangles has been linked to inflammation and immune dysregulation. The main objective of this systematic review and meta-analysis is to comprehensively evaluate the existing body of research concerning the NLR in the context of Alzheimer's disease (AD) and mild cognitive impairment (MCI).
METHOD
We conducted a comprehensive online search and included studies that evaluated the NLR in 1) patients with AD or MCI and 2) healthy control (HC) participants. We also pooled mean and standard deviation (SD) data for each group.
RESULTS
Ultimately, 12 studies encompassed 1,309 individuals diagnosed with AD with mean NLR levels of 2.68, 1,929 individuals with MCI with mean NLR levels of 2.42, and 2,064 HC with mean NLR levels of 2.06 were included in this systematic review and meta-analysis. The mean NLR was 0.59 higher in AD patients compared to HC participants (mean difference (MD) = 0.59 [0.38; 0.80]). Similarly, the mean NLR was higher in AD than MCI patients (MD = 0.23 [0.13; 0.33]). Additionally, the mean NLR was higher in individuals with MCI compared to HC participants (MD = 0.37 [0.22; 0.52]). In the subgroup meta-analysis based on the Mini-Mental State Examination (MMSE), AD patients with lower MMSE scores (using a cut-off of 20) exhibited significantly higher mean NLR (3.10 vs. 2.70, with a p-value for subgroup differences < 0.01).
CONCLUSION
The NLR, which serves as a marker of peripheral inflammation, shows increased levels in individuals with AD and MCI compared to HC participants. Furthermore, our study indicates that NLR levels are significantly higher in AD than MCI. Additionally, our novel finding suggests significantly higher NLR levels among AD patients with more severe cognitive decline compared to AD patients with less severe cognitive decline. So, it can be concluded that the higher cognitive decline in humans is accompanied by higher NLR levels. Further longitudinal researches are needed to explore more details about the relationship between inflammation and dementia.
Topics: Alzheimer Disease; Humans; Neutrophils; Lymphocytes; Cognitive Dysfunction; Lymphocyte Count
PubMed: 38917167
DOI: 10.1371/journal.pone.0305322 -
BMC Geriatrics Jun 2024Mild cognitive impairment has received widespread attention as a high-risk population for Alzheimer's disease, and many studies have developed or validated predictive...
BACKGROUND
Mild cognitive impairment has received widespread attention as a high-risk population for Alzheimer's disease, and many studies have developed or validated predictive models to assess it. However, the performance of the model development remains unknown.
OBJECTIVE
The objective of this review was to provide an overview of prediction models for the risk of Alzheimer's disease dementia in older adults with mild cognitive impairment.
METHOD
PubMed, EMBASE, Web of Science, and MEDLINE were systematically searched up to October 19, 2023. We included cohort studies in which risk prediction models for Alzheimer's disease dementia in older adults with mild cognitive impairment were developed or validated. The Predictive Model Risk of Bias Assessment Tool (PROBAST) was employed to assess model bias and applicability. Random-effects models combined model AUCs and calculated (approximate) 95% prediction intervals for estimations. Heterogeneity across studies was evaluated using the I statistic, and subgroup analyses were conducted to investigate sources of heterogeneity. Additionally, funnel plot analysis was utilized to identify publication bias.
RESULTS
The analysis included 16 studies involving 9290 participants. Frequency analysis of predictors showed that 14 appeared at least twice and more, with age, functional activities questionnaire, and Mini-mental State Examination scores of cognitive functioning being the most common predictors. From the studies, only two models were externally validated. Eleven studies ultimately used machine learning, and four used traditional modelling methods. However, we found that in many of the studies, there were problems with insufficient sample sizes, missing important methodological information, lack of model presentation, and all of the models were rated as having a high or unclear risk of bias. The average AUC of the 15 best-developed predictive models was 0.87 (95% CI: 0.83, 0.90).
DISCUSSION
Most published predictive modelling studies are deficient in rigour, resulting in a high risk of bias. Upcoming research should concentrate on enhancing methodological rigour and conducting external validation of models predicting Alzheimer's disease dementia. We also emphasize the importance of following the scientific method and transparent reporting to improve the accuracy, generalizability and reproducibility of study results.
REGISTRATION
This systematic review was registered in PROSPERO (Registration ID: CRD42023468780).
Topics: Humans; Cognitive Dysfunction; Alzheimer Disease; Aged; Risk Assessment
PubMed: 38898411
DOI: 10.1186/s12877-024-05044-8 -
PCN Reports : Psychiatry and Clinical... Jun 2024The behavioral variant of frontotemporal dementia (bvFTD) is thought to be the commonest clinical presentation of frontotemporal lobar degeneration and is predominantly... (Review)
Review
The behavioral variant of frontotemporal dementia (bvFTD) is thought to be the commonest clinical presentation of frontotemporal lobar degeneration and is predominantly characterized by changes in behavior. In patients lacking unequivocal biomarker evidence of frontotemporal neurodegeneration, the clinical diagnosis of bvFTD is often unstable. In response, we conducted a systematic review and critical appraisal of cognitive and behavioral tools that have sought to differentiate bvFTD from other conditions. A systematic literature review of PubMed, Scopus, and Web of Science was conducted on December 31, 2023 for cognitive and behavioral tools that differentiated bvFTD from other cohorts. Ninety-six studies were included. The quality appraisal of almost all studies was low and introduced a high risk of bias. The few studies that were of high quality had a prospective study design and recruited patients suspected (but not yet confirmed) to have bvFTD. These studies reported that behavioral tools (e.g., the Frontal Behavioral Inventory) and social cognition tests (e.g., the Ekman's Faces Test) had good test performance in differentiating bvFTD from a broad range of psychiatric and neurological conditions. Importantly, the review highlighted the extreme paucity of studies that have evaluated methods where, in Bayesian terms, there is genuine clinical uncertainty regarding a diagnosis of bvFTD. Most studies used healthy controls of typical Alzheimer's disease as comparators-groups that often have negligible pretest probability of bvFTD. In response, we propose a study design checklist for studies seeking to develop diagnostic algorithms in bvFTD research.
PubMed: 38887313
DOI: 10.1002/pcn5.210 -
European Stroke Journal Jun 2024There are limited data regarding cerebrospinal fluid (CSF) and plasma biomarkers among patients with Cerebral Amyloid Angiopathy (CAA). We sought to investigate the...
INTRODUCTION
There are limited data regarding cerebrospinal fluid (CSF) and plasma biomarkers among patients with Cerebral Amyloid Angiopathy (CAA). We sought to investigate the levels of four biomarkers [β-amyloids (Aβ42 and Aβ40), total tau (tau) and phosphorylated tau (p-tau)] in CAA patients compared to healthy controls (HC) and patients with Alzheimer Disease (AD).
PATIENTS AND METHODS
A systematic review and meta-analysis of published studies, including also a 5 year single-center cohort study, with available data on CSF and plasma biomarkers in symptomatic sporadic CAA versus HC and AD was conducted. Biomarkers' comparisons were investigated using random-effects models based on the ratio of mean (RoM) biomarker concentrations. RoM < 1 and RoM > 1 indicate lower and higher biomarker concentration in CAA compared to another population, respectively.
RESULTS
We identified nine cohorts, comprising 327 CAA patients (mean age: 71 ± 5 years; women: 45%) versus 336 HC (mean age: 65 ± 5 years; women: 45%) and 384 AD patients (mean age: 68 ± 3 years; women: 53%) with available data on CSF biomarkers. CSF Aβ42 levels [RoM: 0.47; 95% CI: 0.36-0.62; < 0.0001], Aβ40 levels [RoM: 0.70; 95% CI: 0.63-0.79; < 0.0001] and the ratio Aβ42/Aβ40 [RoM: 0.62; 95% CI: 0.39-0.98; = 0.0438] differentiated CAA from HC. CSF Aβ40 levels [RoM: 0.73; 95% CI: 0.64-0.83; = 0.0003] differentiated CAA from AD. CSF tau and p-tau levels differentiated CAA from HC [RoM: 1.71; 95% CI: 1.41-2.09; = 0.0002 and RoM: 1.44; 95% CI: 1.20-1.73; = 0.0014, respectively] and from AD [RoM: 0.65; 95% CI: 0.58-0.72; < 0.0001 and RoM: 0.64; 95% CI: 0.57-0.71; < 0.0001, respectively]. Plasma Aβ42 [RoM: 1.14; 95% CI: 0.89-1.45; = 0.2079] and Aβ40 [RoM: 1.07; 95% CI: 0.91-1.25; = 0.3306] levels were comparable between CAA and HC.
CONCLUSIONS
CAA is characterized by a distinct CSF biomarker pattern compared to HC and AD. CSF Aβ40 levels are lower in CAA compared to HC and AD, while tau and p-tau levels are higher in CAA compared to HC, but lower in comparison to AD patients.
PubMed: 38869035
DOI: 10.1177/23969873241260538 -
Brain and Behavior Jun 2024The US Food and Drug Administration authorized lecanemab for the therapeutic use of Alzheimer's disease (AD) in January 2023. To assess the effectiveness and safety of...
PURPOSE
The US Food and Drug Administration authorized lecanemab for the therapeutic use of Alzheimer's disease (AD) in January 2023. To assess the effectiveness and safety of lecanemab in treating AD, we thoroughly examined the studies that are currently accessible.
METHOD
Preferred Reporting Items for Systematic Reviews and Meta-Analysis recommendations were followed. In order to find relevant studies on lecanemab, we carried out a thorough literature search utilizing the electronic databases MEDLINE via PubMed, Cochrane, Web of Science, EBSCOhost, and Scopus. Excluding any research using experimental animals, we looked at lecanemab's effectiveness and side effects in treating AD in human clinical trials. Three randomized controlled studies were included.
FINDINGS
According to studies, lecanemab lessens clinical deterioration and reduces brain amyloid-beta plaques (difference,.45; 95% confidence interval,.67 to.23; p < .001). Participants who received lecanemab saw a greater frequency of amyloid-related imaging abnormalities (ARIA)-H (17.3% vs. 9.0%) and ARIA-E (12.6% vs. 1.7%), which is a significant adverse outcome.
CONCLUSION
Lecanemab has been shown to have an impact on the two primary pathophysiologic indicators of AD (Aβ and tau). There are still a lot of unresolved issues related to lecanemab. Future research on the effectiveness and safety of lecanemab is advised in order to determine that the advantages of this medication exceed the disadvantages.
Topics: Humans; Alzheimer Disease; Amyloid beta-Peptides; Brain; Plaque, Amyloid; Antibodies, Monoclonal, Humanized
PubMed: 38867460
DOI: 10.1002/brb3.3592 -
Frontiers in Aging Neuroscience 2024Soluble triggering receptor expressed on myeloid cells 2 (sTREM2) is a potential neuroinflammatory biomarker linked to the pathogenesis of Alzheimer's disease (AD) and...
OBJECTIVE
Soluble triggering receptor expressed on myeloid cells 2 (sTREM2) is a potential neuroinflammatory biomarker linked to the pathogenesis of Alzheimer's disease (AD) and mild cognitive impairment (MCI). Previous studies have produced inconsistent results regarding sTREM2 levels in various clinical stages of AD. This study aims to establish the correlation between sTREM2 levels and AD progression through a meta-analysis of sTREM2 levels in cerebrospinal fluid (CSF) and blood.
METHODS
Comprehensive searches were conducted in PubMed, Embase, Web of Science, and the Cochrane Library to identify observational studies reporting CSF and blood sTREM2 levels in AD patients, MCI patients, and healthy controls. A random effects meta-analysis was used to calculate the standardized mean difference (SMD) and 95% confidence intervals (CIs).
RESULTS
Thirty-six observational studies involving 3,016 AD patients, 3,533 MCI patients, and 4,510 healthy controls were included. CSF sTREM2 levels were significantly higher in both the AD [SMD = 0.28, 95% CI (0.15, 0.41)] and MCI groups [SMD = 0.30, 95% CI (0.13, 0.47)] compared to the healthy control group. However, no significant differences in expression were detected between the AD and MCI groups [SMD = 0.09, 95% CI (-0.09, 0.26)]. Furthermore, increased plasma sTREM2 levels were associated with a higher risk of AD [SMD = 0.42, 95% CI (0.01, 0.83)].
CONCLUSION
CSF sTREM2 levels are positively associated with an increased risk of AD and MCI. Plasma sTREM2 levels were notably higher in the AD group than in the control group and may serve as a promising biomarker for diagnosing AD. However, sTREM2 levels are not effective for distinguishing between different disease stages of AD. Further investigations are needed to explore the longitudinal changes in sTREM2 levels, particularly plasma sTREM2 levels, during AD progression.
SYSTEMATIC REVIEW REGISTRATION
https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42024514593.
PubMed: 38841103
DOI: 10.3389/fnagi.2024.1407980 -
Journal of Stroke May 2024Possible differences in the prevalence of cerebral amyloid angiopathy (CAA) in East-Asian compared to Western populations have received little attention, and results so... (Review)
Review
BACKGROUND AND PURPOSE
Possible differences in the prevalence of cerebral amyloid angiopathy (CAA) in East-Asian compared to Western populations have received little attention, and results so far have been ambiguous. Our aim is to compare the prevalence of CAA neuropathology and magnetic resonance imaging markers of CAA in East-Asian and Western cohorts reflecting the general population, cognitively normal elderly, patients with Alzheimer's disease (AD), and patients with (lobar) intracerebral hemorrhage (ICH).
METHODS
We performed a systematic literature search in PubMed and Embase for original research papers on the prevalence of CAA and imaging markers of CAA published up until February 17th 2022. Records were screened by two independent reviewers. Pooled estimates were determined using random-effects models. We compared studies from Japan, China, Taiwan, South Korea (East-Asian cohorts) to studies from Europe or North America (Western cohorts) by meta-regression models.
RESULTS
We identified 12,257 unique records, and we included 143 studies on Western study populations and 53 studies on East-Asian study populations. Prevalence of CAA neuropathology did not differ between East-Asian and Western cohorts in any of the investigated patient domains. The prevalence of strictly lobar microbleeds was lower in East-Asian cohorts of population-based individuals (5.6% vs. 11.4%, P=0.020), cognitively normal elderly (2.6% vs. 11.4%, P=0.001), and patients with ICH (10.2% vs. 24.6%, P<0.0001). However, age was in general lower in the East-Asian cohorts.
CONCLUSION
The prevalence of CAA neuropathology in the general population, cognitively normal elderly, patients with AD, and patients with (lobar) ICH is similar in East-Asian and Western countries. In East-Asian cohorts reflecting the general population, cognitively normal elderly, and patients with ICH, strictly lobar microbleeds were less prevalent, likely due to their younger age. Consideration of potential presence of CAA is warranted in decisions regarding antithrombotic treatment and potential new anti-amyloid-β immunotherapy as treatment for AD in East-Asian and Western countries alike.
PubMed: 38836267
DOI: 10.5853/jos.2023.04287 -
Cognitive Neurodynamics Jun 2024In recent years, Alzheimer's disease (AD) has been a serious threat to human health. Researchers and clinicians alike encounter a significant obstacle when trying to... (Review)
Review
In recent years, Alzheimer's disease (AD) has been a serious threat to human health. Researchers and clinicians alike encounter a significant obstacle when trying to accurately identify and classify AD stages. Several studies have shown that multimodal neuroimaging input can assist in providing valuable insights into the structural and functional changes in the brain related to AD. Machine learning (ML) algorithms can accurately categorize AD phases by identifying patterns and linkages in multimodal neuroimaging data using powerful computational methods. This study aims to assess the contribution of ML methods to the accurate classification of the stages of AD using multimodal neuroimaging data. A systematic search is carried out in IEEE Xplore, Science Direct/Elsevier, ACM DigitalLibrary, and PubMed databases with forward snowballing performed on Google Scholar. The quantitative analysis used 47 studies. The explainable analysis was performed on the classification algorithm and fusion methods used in the selected studies. The pooled sensitivity and specificity, including diagnostic efficiency, were evaluated by conducting a meta-analysis based on a bivariate model with the hierarchical summary receiver operating characteristics (ROC) curve of multimodal neuroimaging data and ML methods in the classification of AD stages. Wilcoxon signed-rank test is further used to statistically compare the accuracy scores of the existing models. With a 95% confidence interval of 78.87-87.71%, the combined sensitivity for separating participants with mild cognitive impairment (MCI) from healthy control (NC) participants was 83.77%; for separating participants with AD from NC, it was 94.60% (90.76%, 96.89%); for separating participants with progressive MCI (pMCI) from stable MCI (sMCI), it was 80.41% (74.73%, 85.06%). With a 95% confidence interval (78.87%, 87.71%), the Pooled sensitivity for distinguishing mild cognitive impairment (MCI) from healthy control (NC) participants was 83.77%, with a 95% confidence interval (90.76%, 96.89%), the Pooled sensitivity for distinguishing AD from NC was 94.60%, likewise (MCI) from healthy control (NC) participants was 83.77% progressive MCI (pMCI) from stable MCI (sMCI) was 80.41% (74.73%, 85.06%), and early MCI (EMCI) from NC was 86.63% (82.43%, 89.95%). Pooled specificity for differentiating MCI from NC was 79.16% (70.97%, 87.71%), AD from NC was 93.49% (91.60%, 94.90%), pMCI from sMCI was 81.44% (76.32%, 85.66%), and EMCI from NC was 85.68% (81.62%, 88.96%). The Wilcoxon signed rank test showed a low P-value across all the classification tasks. Multimodal neuroimaging data with ML is a promising future in classifying the stages of AD but more research is required to increase the validity of its application in clinical practice.
PubMed: 38826669
DOI: 10.1007/s11571-023-09993-5 -
BMC Geriatrics Jun 2024Research the dose-response relationship between overall and certain types of exercise and cognitive function in older adults with Alzheimer's disease and dementia. (Meta-Analysis)
Meta-Analysis
Effective dosage and mode of exercise for enhancing cognitive function in Alzheimer's disease and dementia: a systematic review and Bayesian Model-Based Network Meta-analysis of RCTs.
OBJECTIVE
Research the dose-response relationship between overall and certain types of exercise and cognitive function in older adults with Alzheimer's disease and dementia.
DESIGN
Systemic and Bayesian Model-Based Network Meta-Analysis.
METHODS
In our study, we analyzed data from randomized controlled trials investigating the effects of different exercises on cognitive outcomes in older adults with AD. We searched the Web of Science, PubMed, Cochrane Central Register of Controlled Trials, and Embase up to November 2023. Using the Cochrane Risk of Bias tool (Rob2) for quality assessment and R software with the MBNMA package for data analysis, we determined standard mean differences (SMDs) and 95% confidence intervals (95%CrI) to evaluate exercise's impact on cognitive function in AD.
RESULTS
Twenty-seven studies with 2,242 AD patients revealed a nonlinear relationship between exercise and cognitive improvement in AD patients. We observed significant cognitive enhancements at an effective exercise dose of up to 1000 METs-min/week (SMDs: 0.535, SD: 0.269, 95% CrI: 0.023 to 1.092). The optimal dose was found to be 650 METs-min/week (SMDs: 0.691, SD: 0.169, 95% CrI: 0.373 to 1.039), with AE (Aerobic exercise) being particularly effective. For AE, the optimal cognitive enhancement dose was determined to be 660 METs-min/week (SMDs: 0.909, SD: 0.219, 95% CrI: 0.495 to 1.362).
CONCLUSION
Nonlinear dose-response relationship between exercise and cognitive improvement in Alzheimer's disease, with the optimal AE dose identified at 660 METs-min/week for enhancing cognitive function in AD.
Topics: Humans; Alzheimer Disease; Bayes Theorem; Randomized Controlled Trials as Topic; Cognition; Network Meta-Analysis; Exercise Therapy; Dementia; Aged
PubMed: 38824515
DOI: 10.1186/s12877-024-05060-8 -
BMJ Mental Health May 2024Does neurodegenerative disease underlie the increased rate of dementia observed in older people with schizophrenia? Several studies have reported a higher prevalence of... (Meta-Analysis)
Meta-Analysis Review
QUESTION
Does neurodegenerative disease underlie the increased rate of dementia observed in older people with schizophrenia? Several studies have reported a higher prevalence of dementia in people with schizophrenia compared with the general population. This may reflect a higher risk of developing neurodegenerative diseases such as vascular dementia or Alzheimer's disease (AD). Alternatively, this may reflect non-pathological, age-related cognitive decline in a population with low cognitive reserve.
STUDY SELECTION AND ANALYSIS
We reviewed papers that compared postmortem findings, hippocampal MRI volume or cerebrospinal fluid (CSF) markers of AD, between patients with schizophrenia with evidence of cognitive impairment (age ≥45 years) with controls. We subsequently performed a meta-analysis of postmortem studies that compared amyloid-β plaques (APs) or neurofibrillary tangles (NFTs) in cognitively impaired patients with schizophrenia to normal controls or an AD group.
FINDINGS
No studies found a significant increase of APs or NFTs in cognitively impaired patients with schizophrenia compared with controls. All postmortem studies that compared APs or NFTs in patients with schizophrenia to an AD group found significantly more APs or NFTs in AD. No studies found a significant differences in CSF total tau or phosphorylated tau between patients with schizophrenia and controls. The two studies which compared CSF Aβ42 between patients with schizophrenia and controls found significantly decreased CSF Aβ42 in schizophrenia compared with controls. Hippocampal volume findings were mixed.
CONCLUSIONS
Studies have not found higher rates of AD-related pathology in cognitively impaired individuals with schizophrenia compared with controls. Higher rates of dementia identified in population studies may reflect a lack of specificity in clinical diagnostic tools used to diagnose dementia.
Topics: Humans; Schizophrenia; Biomarkers; Neurodegenerative Diseases; Alzheimer Disease; Amyloid beta-Peptides; Neurofibrillary Tangles; Plaque, Amyloid
PubMed: 38796179
DOI: 10.1136/bmjment-2024-301017