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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 -
Expert Review of Neurotherapeutics Jun 2024Gantenerumab is a monoclonal antibody targeting amyloid β protein (Aβ) in early Alzheimer's disease (AD). The authors sought to evaluate gantenerumab safety and... (Review)
Review
INTRODUCTION
Gantenerumab is a monoclonal antibody targeting amyloid β protein (Aβ) in early Alzheimer's disease (AD). The authors sought to evaluate gantenerumab safety and efficacy in early AD patients.
METHODS
MEDLINE, Embase, and Cochrane databases were systematically searched until 2 December 2023. Data were examined using the Mantel-Haenszel method and 95% confidence intervals (CIs). Meta-regression analysis was conducted to evaluate a possible link between baseline Clinical Dementia Rating Scale - Sum of Boxes (CDR-SB) and amyloid-related imaging abnormalities (ARIA) at follow-up. R, version 4.2.3, was used for statistical analysis.
RESULTS
A total of 4 RCTs and 2848 patients were included, of whom 1580 (55%) received subcutaneous gantenerumab. Concerning clinical scores, the placebo group achieved better rates of change in the Disease Assessment Scale (ADAS-Cog13) (SMD -0.11; 95% CI -0.19- -0.03; = 0.008569; I = 0%). Gantenerumab was strongly associated with the occurrence of ARIA-E and ARIA-H: (19.67% vs. 2.31%; RR 9.46; 95% CI 5.55-16.11; = <0.000001; I = 10%) and (21.95% vs. 12.38%; RR 1.79; 95% CI 1.50-2.13; = <0.000001; I = 0%), respectively.
DISCUSSION
In this meta-analysis, consistent results suggest that gantenerumab is not safe and efficient for early AD, showing no improvement in clinical scores for AD and being associated with the occurrence of ARIA-E and ARIA-H.
PubMed: 38879828
DOI: 10.1080/14737175.2024.2367016 -
Archives of Gerontology and Geriatrics Jun 2024A growing body of research examining effects of exercise on brain-derived neurotrophic factor (BDNF) in Alzheimer's disease (AD) models, while due to differences in... (Review)
Review
A growing body of research examining effects of exercise on brain-derived neurotrophic factor (BDNF) in Alzheimer's disease (AD) models, while due to differences in gender, age, disease severity, brain regions examined, and type of exercise intervention, findings of available studies were conflicting. In this study, we aimed to evaluate current evidence regarding effects of exercise on BDNF in AD models. Searches were performed in PubMed, Web of Science, Cochrane, and EBSCO electronic databases, through July 20, 2023. We included studies that satisfied the following criteria: eligible studies should (1) report evidence on experimental work with AD models; (2) include an exercise group and a control group (sedentary); (3) use BDNF as the outcome indicator; and (4) be randomized controlled trials (RCTs). From 1196 search records initially identified, 36 studies met the inclusion criteria. There was a significant effect of exercise on increasing BDNF levels in AD models [standardized mean differences (SMD) = 0.98, P < 0.00001]. Subgroup analysis showed that treadmill exercise (SMD = 0.92, P< 0.0001), swimming (SMD = 1.79, P< 0.0001), and voluntary wheel running (SMD = 0.51, P= 0.04) were all effective in increasing BDNF levels in AD models. In addition, exercise significantly increased BDNF levels in the hippocampus (SMD = 0.92, P< 0.00001) and cortex (SMD = 1.56, P= 0.02) of AD models. Exercise, especially treadmill exercise, swimming, and voluntary wheel running, significantly increased BDNF levels in hippocampus and cortex of AD models, with swimming being the most effective intervention type.
PubMed: 38878598
DOI: 10.1016/j.archger.2024.105538 -
Clinical Nutrition (Edinburgh, Scotland) Jul 2024Microbiota plays an essential role in maintaining body health, through positive influences on metabolic, defensive, and trophic processes and on intercellular... (Review)
Review
BACKGROUND AND AIMS
Microbiota plays an essential role in maintaining body health, through positive influences on metabolic, defensive, and trophic processes and on intercellular communication. Imbalance in intestinal flora, with the proliferation of harmful bacterial species (dysbiosis) is consistently reported in chronic illnesses, including neurodegenerative diseases (ND). Correcting dysbiosis can have a beneficial impact on the symptoms and evolution of ND. This review examines the effects of microbiota modulation through administration of probiotics, prebiotics, symbiotics, or prebiotics' metabolites (postbiotics) in patients with ND like multiple sclerosis (MS), Alzheimer's disease (AD), Parkinson's disease (PD) and amyotrophic lateral sclerosis (ALS).
METHODS
PubMed, Web of Science, Medline databases and ClinicalTrials.gov registry searches were performed using pre-/pro-/postbiotics and ND-related terms. Further references were obtained by checking relevant articles.
RESULTS
Although few compared to animal studies, the human studies generally show positive effects on disease-specific symptoms, overall health, metabolic parameters, on oxidative stress and immunological markers. Therapy with probiotics in various forms (mixtures of bacterial strains, fecal microbiota transplant, diets rich in fermented foods) exert favorable effects on patients' mental health, cognition, and quality of life, targeting pathogenetic ND mechanisms and inducing reparatory mechanisms at the cellular level. More encouraging results have been observed in prebiotic/postbiotic therapy in some ND.
CONCLUSIONS
The effects of probiotic-related interventions depend on the patients' ND stage and pre-existing allopathic medication. Further studies on larger cohorts and long term comprehensive neuropsychiatric, metabolic, biochemical testing, and neuroimaging monitoring are necessary to optimize therapeutic protocols in ND.
Topics: Humans; Gastrointestinal Microbiome; Neurodegenerative Diseases; Probiotics; Prebiotics; Dysbiosis; Animals; Fecal Microbiota Transplantation
PubMed: 38878554
DOI: 10.1016/j.clnu.2024.05.036 -
Cortex; a Journal Devoted To the Study... May 2024The ε4 allele of the apolipoprotein E (APOE4) gene is an established risk factor for Alzheimer's disease but its impact on cognition in healthy adults across the... (Review)
Review
The ε4 allele of the apolipoprotein E (APOE4) gene is an established risk factor for Alzheimer's disease but its impact on cognition in healthy adults across the lifespan is unclear. One cognitive domain that is affected early in the course of Alzheimer's disease is spatial cognition, yet the evidence for APOE-related changes in spatial cognition is mixed. In this meta-analysis we assessed the impact of carrying the APOE4 allele on five subdomains of spatial cognition across the lifespan. We included studies of healthy human participants where an APOE4-carrier group (heterozygous or homozygous) could be compared to a homozygous group of APOE3-carriers. We identified 156 studies in total from three databases (Pubmed, Scopus and Web of Science) as well as through searching cited literature and contacting authors for unpublished data. 122 studies involving 32,547 participants were included in a meta-analysis, and the remaining studies are included in a descriptive review. APOE4 carriers scored significantly lower than APOE3 carriers (θˆ = -.08 [-.14, -.02]) on tests of spatial long-term memory; this effect was very small and was not modulated by age. On other subdomains of spatial cognition (spatial construction, spatial working memory, spatial reasoning, navigation) there were no effects of genotype. Overall, our results demonstrate that the APOE4 allele exerts little influence on spatial cognitive abilities in healthy adults.
PubMed: 38878339
DOI: 10.1016/j.cortex.2024.05.006 -
Journal of Alzheimer's Disease : JAD Jun 2024Aging is a complex and natural process. The physiological decline related to aging is accompanied by a slowdown in cognitive processes, which begins shortly after...
BACKGROUND
Aging is a complex and natural process. The physiological decline related to aging is accompanied by a slowdown in cognitive processes, which begins shortly after individuals reach maturity. These changes have been sometimes interpreted as a compensatory sign and others as a fingerprint of deterioration.
OBJECTIVE
In this context, our aim is to uncover the mechanisms that underlie and support normal cognitive functioning in the brain during the later stages of life.
METHODS
With this purpose, a systematic literature search was conducted using PubMed, Scopus, and Web of Science databases, which identified 781 potential articles. After applying inclusion and exclusion criteria, we selected 12 studies that examined the brain oscillations patterns in resting-state conditions associated with cognitive performance in cognitively unimpaired older adults.
RESULTS
Although cognitive healthy aging was characterized differently across studies, and various approaches to analyzing brain activity were employed, our review indicates a relationship between alpha peak frequency (APF) and improved performance in neuropsychological scores among cognitively unimpaired older adults.
CONCLUSIONS
A higher APF is linked with a higher score in intelligence, executive function, and general cognitive performance, and could be considered an optimal, and easy-to-assess, electrophysiological marker of cognitive health in older adults.
PubMed: 38875030
DOI: 10.3233/JAD-231009 -
Neuropsychology Review Jun 2024Social cognition-the complex mental ability to perceive social stimuli and negotiate the social environment-has emerged as an important cognitive ability needed for... (Review)
Review
Social cognition-the complex mental ability to perceive social stimuli and negotiate the social environment-has emerged as an important cognitive ability needed for social functioning, everyday functioning, and quality of life. Deficits in social cognition have been well documented in those with severe mental illness including schizophrenia and depression, those along the autism spectrum, and those with other brain disorders where such deficits profoundly impact everyday life. Moreover, subtle deficits in social cognition have been observed in other clinical populations, especially those that may have compromised non-social cognition (i.e., fluid intelligence such as memory). Among people living with HIV (PLHIV), 44% experience cognitive impairment; likewise, social cognitive deficits in theory of mind, prosody, empathy, and emotional face recognition/perception are gradually being recognized. This systematic review and meta-analysis aim to summarize the current knowledge of social cognitive ability among PLHIV, identified by 14 studies focused on social cognition among PLHIV, and provides an objective consensus of the findings. In general, the literature suggests that PLHIV may be at-risk of developing subtle social cognitive deficits that may impact their everyday social functioning and quality of life. The causes of such social cognitive deficits remain unclear, but perhaps develop due to (1) HIV-related sequelae that are damaging the same neurological systems in which social cognition and non-social cognition are processed; (2) stress related to coping with HIV disease itself that overwhelms one's social cognitive resources; or (3) may have been present pre-morbidly, possibly contributing to an HIV infection. From this, a theoretical framework is proposed highlighting the relationships between social cognition, non-social cognition, and social everyday functioning.
PubMed: 38869661
DOI: 10.1007/s11065-024-09643-5 -
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