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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databases (Pubmed, Scopus and Web of Science) as well as through searching cited literature and contacting authors for unpublished data. 122 studies involving 32,547 participants were included in a meta-analysis, and the remaining studies are included in a descriptive review.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 -
GeroScience Jun 2024Aging is a multifactorial biological process that may be associated with cognitive decline. Photobiomodulation (PBM) is a non-pharmacological therapy that shows... (Review)
Review
Aging is a multifactorial biological process that may be associated with cognitive decline. Photobiomodulation (PBM) is a non-pharmacological therapy that shows promising results in the treatment or prevention of age-related cognitive impairments. The aim of this review is to compile the preclinical and clinical evidence of the effect of PBM during aging in healthy and pathological conditions, including behavioral analysis and neuropsychological assessment, as well as brain-related modifications. 37 studies were identified by searching in PubMed, Scopus, and PsycInfo databases. Most studies use wavelengths of 800, 810, or 1064 nm but intensity and days of application were highly variable. In animal studies, it has been shown improvements in spatial memory, episodic-like memory, social memory, while different results have been found in recognition memory. Locomotor activity improved in Parkinson disease models. In healthy aged humans, it has been outlined improvements in working memory, cognitive inhibition, and lexical/semantic access, while general cognition was mainly enhanced on Alzheimer disease or mild cognitive impairment. Anxiety assessment is scarce and shows mixed results. As for brain activity, results outline promising effects of PBM in reversing metabolic alterations and enhancing mitochondrial function, as evidenced by restored CCO activity and ATP levels. Additionally, PBM demonstrated neuroprotective, anti-inflammatory, immunomodulatory and hemodynamic effects. The findings suggest that PBM holds promise as a non-invasive intervention for enhancing cognitive function, and in the modulation of brain functional reorganization. It is necessary to develop standardized protocols for the correct, beneficial, and homogeneous use of PBM.
PubMed: 38861125
DOI: 10.1007/s11357-024-01231-y -
Journal of Alzheimer's Disease : JAD 2024To date, the magnitude of association and the quality of evidence for cognitive decline (mild cognitive impairment, Alzheimer's disease, and dementia) in couples and... (Meta-Analysis)
Meta-Analysis
BACKGROUND
To date, the magnitude of association and the quality of evidence for cognitive decline (mild cognitive impairment, Alzheimer's disease, and dementia) in couples and risk factors for outcomes have not been reviewed and analyzed systematically.
OBJECTIVE
The aim of this study was to investigate the concordance of cognitive impairment in unrelated spouses and to qualitatively describe potential risk factors.
METHODS
Eight databases were searched from inception to October 20, 2023. Eligible studies were independently screened and assessed for quality. Statistical analysis was conducted using Stata 15.1 software. The study was preregistered with PROSPERO (CRD42023488024).
RESULTS
Eleven studies involving couples were included, with moderate to high evidence quality. Compared to controls, spouses of individuals with cognitive impairment had lower cognitive scores (Cohen's d: 0.18-0.62) and higher risk of cognitive decline (OR = 1.42, 95% CI: 1.15-1.76). The consistency of cognitive impairment between spouses was attributed to three theories: 1) the impact of caregiving stress experienced by the spouse; 2) assortative mating, which suggests that individuals select partners with similar characteristics; and 3) the influence of shared living environments and lifestyles.
CONCLUSIONS
The cognitive status of one spouse can affect the cognitive function of the other spouse. It is important to consider shared lifestyle, environmental, and psychobehavioral factors, as they may contribute to the risk of cognitive decline by couples. Identifying these factors can inform the development of targeted recommendations for interventions and preventive measures.
Topics: Humans; Cognitive Dysfunction; Spouses; Risk Factors; Male; Alzheimer Disease
PubMed: 38848191
DOI: 10.3233/JAD-240325 -
Journal of Alzheimer's Disease : JAD 2024Dementia is a general term for several progressive neurodegenerative disorders including Alzheimer's disease. Timely and accurate detection is crucial for early...
BACKGROUND
Dementia is a general term for several progressive neurodegenerative disorders including Alzheimer's disease. Timely and accurate detection is crucial for early intervention. Advancements in artificial intelligence present significant potential for using machine learning to aid in early detection.
OBJECTIVE
Summarize the state-of-the-art machine learning-based approaches for dementia prediction, focusing on non-invasive methods, as the burden on the patients is lower. Specifically, the analysis of gait and speech performance can offer insights into cognitive health through clinically cost-effective screening methods.
METHODS
A systematic literature review was conducted following the PRISMA protocol (Preferred Reporting Items for Systematic Reviews and Meta-Analyses). The search was performed on three electronic databases (Scopus, Web of Science, and PubMed) to identify the relevant studies published between 2017 to 2022. A total of 40 papers were selected for review.
RESULTS
The most common machine learning methods employed were support vector machine followed by deep learning. Studies suggested the use of multimodal approaches as they can provide comprehensive and better prediction performance. Deep learning application in gait studies is still in the early stages as few studies have applied it. Moreover, including features of whole body movement contribute to better classification accuracy. Regarding speech studies, the combination of different parameters (acoustic, linguistic, cognitive testing) produced better results.
CONCLUSIONS
The review highlights the potential of machine learning, particularly non-invasive approaches, in the early prediction of dementia. The comparable prediction accuracies of manual and automatic speech analysis indicate an imminent fully automated approach for dementia detection.
Topics: Humans; Machine Learning; Dementia; Speech; Gait Analysis
PubMed: 38848181
DOI: 10.3233/JAD-231459 -
European Journal of Pharmacology Aug 2024Astaxanthin is a potent lipid-soluble carotenoid produced by several different freshwater and marine microorganisms, including microalgae, bacteria, fungi, and yeast.... (Review)
Review
Astaxanthin is a potent lipid-soluble carotenoid produced by several different freshwater and marine microorganisms, including microalgae, bacteria, fungi, and yeast. The proven therapeutic effects of astaxanthin against different diseases have made this carotenoid popular in the nutraceutical market and among consumers. Recently, astaxanthin is also receiving attention for its effects in the co-adjuvant treatment or prevention of neurological pathologies. In this systematic review, studies evaluating the efficacy of astaxanthin against different neurodegenerative diseases such as Alzheimer's disease, Parkinson's disease, multiple sclerosis, cerebrovascular diseases, and spinal cord injury are analyzed. Based on the current literature, astaxanthin shows potential biological activity in both in vitro and in vivo models. In addition, its preventive and therapeutic activities against the above-mentioned diseases have been emphasized in studies with different experimental designs. In contrast, none of the 59 studies reviewed reported any safety concerns or adverse health effects as a result of astaxanthin supplementation. The preventive or therapeutic role of astaxanthin may vary depending on the dosage and route of administration. Although there is a consensus in the literature regarding its effectiveness against the specified diseases, it is important to determine the safe intake levels of synthetic and natural forms and to determine the most effective forms for oral intake.
Topics: Xanthophylls; Neuroprotective Agents; Humans; Animals; Neurodegenerative Diseases; Antioxidants; Aquatic Organisms
PubMed: 38843946
DOI: 10.1016/j.ejphar.2024.176706 -
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