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Expert Review of Neurotherapeutics Aug 2021The apolipoprotein E ɛ4-allele (-ɛ4) increases the risk not only for Alzheimer's disease (AD) but also for Parkinson's disease dementia and dementia with Lewy bodies...
The ε4 variant and hippocampal atrophy in Alzheimer's disease and Lewy body dementia: a systematic review of magnetic resonance imaging studies and therapeutic relevance.
The apolipoprotein E ɛ4-allele (-ɛ4) increases the risk not only for Alzheimer's disease (AD) but also for Parkinson's disease dementia and dementia with Lewy bodies (collectively, Lewy body dementia [LBD]). Hippocampal volume is an important neuroimaging biomarker for AD and LBD, although its association with -ɛ4 is inconsistently reported. We investigated the association of -ε4 with hippocampal atrophy quantified using magnetic resonance imaging in AD and LBD. Databases were searched for volumetric and voxel-based morphometric studies published up until December 31, 2020. Thirty-nine studies (25 cross-sectional, 14 longitudinal) were included. We observed that (1) -ε4 was associated with greater rate of hippocampal atrophy in longitudinal studies in AD and in those who progressed from mild cognitive impairment to AD, (2) association of -ε4 with hippocampal atrophy in cross-sectional studies was inconsistent, (3) -ɛ4 may influence hippocampal atrophy in dementia with Lewy bodies, although longitudinal investigations are needed. We comprehensively discussed methodological aspects, -based therapeutic approaches, and the association of -ε4 with hippocampal sub-regions and cognitive performance. The role of -ɛ4 in modulating hippocampal phenotypes may be further clarified through more homogenous, well-powered, and pathology-proven, longitudinal investigations. Understanding the underlying mechanisms will facilitate the development of prevention strategies targeting -ɛ4.
Topics: Alzheimer Disease; Apolipoprotein E4; Atrophy; Cross-Sectional Studies; Dementia; Hippocampus; Humans; Lewy Body Disease; Magnetic Resonance Imaging; Parkinson Disease
PubMed: 34311631
DOI: 10.1080/14737175.2021.1956904 -
Frontiers in Aging Neuroscience 2021Consensus is lacking with regard to whether hearing loss is an independent risk factor for dementia. We therefore conducted a meta-analysis to clarify the relationship...
Consensus is lacking with regard to whether hearing loss is an independent risk factor for dementia. We therefore conducted a meta-analysis to clarify the relationship of hearing loss and dementia. Prospective cohort studies investigating the association between hearing loss and the incidence of dementia in a community-derived population were included by searching electronic databases that included PubMed, Embase, and Cochrane's Library. A random-effects model was adopted to combine the results. Fourteen cohorts including 726,900 participants were analyzed. It was shown that hearing loss was independently associated with dementia [adjusted hazard ratio (HR): 1.59, 95% confidence interval (CI): 1.37 to 1.86, < 0.001; = 86%]. Sensitivity analysis sequentially excluding any of the individual studies included showed similar results. Subgroup analysis according to the diagnostic methods for hearing loss, validation strategy for dementia, follow-up duration, and adjustment of apolipoprotein E genotype also showed consistent results (-values for subgroup differences all > 0.05). Meta-analysis with five studies showed that hearing loss was also connected to higher risk of Alzheimer's disease (adjusted HR: 2.24, 95% CI: 1.32 to 3.79, = 0.003; = 2%). Hearing loss may increase the risk of dementia in the adult population. Whether effective treatment for hearing loss could reduce the incidence of dementia should be explored in the future.
PubMed: 34305572
DOI: 10.3389/fnagi.2021.695117 -
International Journal of Environmental... Jul 2021Physical activity (PA) reduces the risk of cognitive decline (CD) in the general population. However, little is known about whether the presence of the apolipoprotein E... (Review)
Review
Physical activity (PA) reduces the risk of cognitive decline (CD) in the general population. However, little is known about whether the presence of the apolipoprotein E epsilon 4 allele () could modify this beneficial effect. The aim of this systematic review was to analyze and synthetize the scientific evidence related to PA levels and CD risk in cognitively healthy carriers. Four electronic databases were analyzed. Only original articles with longitudinal study design were selected to analyze the relationship between PA and CD in carriers. Five studies were included in the systematic review. All studies except one stated that PA is a protective factor against CD in carriers. Moreover, partial support was found for the hypothesis that a greater amount and intensity of PA are more beneficial in CD prevention. The results support the idea that PA is a protective factor against CD in carriers. Nevertheless, it would be necessary to carry out further studies that would allow these findings to be contrasted.
Topics: Alleles; Apolipoprotein E4; Apolipoproteins E; Cognitive Dysfunction; Exercise; Genotype; Humans; Longitudinal Studies
PubMed: 34299687
DOI: 10.3390/ijerph18147238 -
Chemical Biology & Drug Design Nov 2021Alzheimer's disease (AD) is a progressive neurodegenerative disorder primarily caused by accumulation of amyloid-beta (Aβ) peptide extracellularly and neurofibrillary...
Alzheimer's disease (AD) is a progressive neurodegenerative disorder primarily caused by accumulation of amyloid-beta (Aβ) peptide extracellularly and neurofibrillary tangles intracellularly. Recently, it has been shown that oxidative stress and mitochondrial dysregulation play an important role in pathology of AD. Therefore, modulating various targets such as Aβ aggregation, neuro-inflammation, and oxidative stress, genetic factors such as Apolipoprotein E gene (ApoE) are some of the ways to manage AD. Studying the natural products which can act as multifunctional agents could be key toward discovering new therapeutics. Ferulic acid (FA) represents one such natural product, which has exhibited great potential in this regard. Found in the plant cell walls, FA is an antioxidant, free radical scavenger with anti-inflammatory activity. Taking this into consideration, over the years, various derivatives have been reported as anti-AD molecules based on structure of FA. The present review explores the role of FA and its derivatives as therapeutic agents in AD.
Topics: Alzheimer Disease; Amyloid beta-Peptides; Animals; Antioxidants; Coumaric Acids; Free Radical Scavengers; Humans; Mice; Molecular Structure; Neuroprotective Agents; Oxidative Stress; Plant Extracts; Protein Aggregates; Structure-Activity Relationship
PubMed: 34240555
DOI: 10.1111/cbdd.13922 -
Journal of Exercise Rehabilitation Apr 2021The presence of apolipoprotein (Apo) E4 is a genetic risk factor in cognitive impairment. Physical exercise contributes to slowing cognitive impairment in older adults,... (Review)
Review
The presence of apolipoprotein (Apo) E4 is a genetic risk factor in cognitive impairment. Physical exercise contributes to slowing cognitive impairment in older adults, but little is known about the influence of exercise on ApoE4 carriers and noncarriers. The objective of systematic review is to study the role of physical exercise in older adults' ApoE4 carriers and noncarriers. A systematic literature search was carried out in five international databases: PubMed, Web of Science, PeDro, Scopus, and SPORTDiscus. A total of nine randomized controlled trials were included with a sample size of 2,025 subjects (901 ApoE4 carriers). The exercise reported a significant improvement on cognitive performance in older adults' ApoE4 noncarriers (standardized mean difference [SMD]=0.653; 95% confidence interval [CI], 0.29-1.00; chi=35.36; degrees of freedom [ ]=7; <0.0001; =80%). It was also reported that a total program duration greater than 50 sessions generated different and significant effects on cognitive performance in older adults' ApoE4 noncarriers (SMD=0.878; 95% CI, 0.14-1.61; chi=31.82; =3; <0.0001; =91%). The results reported that high intensity generated a differential effect on cognitive performance in older adults' ApoE4 carriers versus noncarriers (SMD=0.963; 95% CI, 0.25-1.67; chi=18.11; =3; <0.0004; =83%). The effect of physical exercise on cognitive performance in older adults is conditioned by the presence or not of ApoE4.
PubMed: 34012932
DOI: 10.12965/jer.2142130.065 -
European Archives of Psychiatry and... Aug 2021The objective is to understand genetic predisposition to delirium. Following PRISMA guidelines, we undertook a systematic review of studies involving delirium and... (Meta-Analysis)
Meta-Analysis
The objective is to understand genetic predisposition to delirium. Following PRISMA guidelines, we undertook a systematic review of studies involving delirium and genetics in the databases of Pubmed, Scopus, Cochrane Library and PsycINFO, and performed a meta-analysis when appropriate. We evaluated 111 articles, of which 25 were finally included in the analysis. The studies were assessed by two independent researchers for methodological quality using the Downs and Black Tool and for genetic analysis quality. We performed a meta-analysis of 10 studies of the Apolipoprotein E (APOE) gene, obtaining no association with the presence of delirium (LOR 0.18, 95% CI - 0.10-0.47, p = 0.21). Notably, only 5 out of 25 articles met established criteria for genetic studies (good quality) and 6 were of moderate quality. Seven studies found an association with APOE4, the dopamine transporter gene SCL6A3, dopamine receptor 2 gene, glucocorticoid receptor, melatonin receptor and mitochondrial DNA haplotypes. One genome-wide association study found two suggestive long intergenic non-coding RNA genes. Five studies found no association with catechol-o-methyltransferase, melatonin receptor or several interleukins genes. The studies were heterogenous in establishing the presence of delirium. Future studies with large samples should further specify the delirium phenotype and deepen our understanding of interactions between genes and other biological factors.
Topics: Delirium; Genetic Predisposition to Disease; Humans
PubMed: 33779822
DOI: 10.1007/s00406-021-01255-x -
Alzheimer's & Dementia : the Journal of... May 2021Convenient, cost-effective tests for amyloid beta (Aβ) are needed to identify those at higher risk for developing Alzheimer's disease (AD). This systematic review...
INTRODUCTION
Convenient, cost-effective tests for amyloid beta (Aβ) are needed to identify those at higher risk for developing Alzheimer's disease (AD). This systematic review evaluates recent models that predict dichotomous Aβ. (PROSPERO: CRD42020144734).
METHODS
We searched Embase and identified 73 studies from 29,581 for review. We assessed study quality using established tools, extracted information, and reported results narratively.
RESULTS
We identified few high-quality studies due to concerns about Aβ determination and analytical issues. The most promising convenient, inexpensive classifiers consist of age, apolipoprotein E genotype, cognitive measures, and/or plasma Aβ. Plasma Aβ may be sufficient if pre-analytical variables are standardized and scalable assays developed. Some models lowered costs associated with clinical trial recruitment or clinical screening.
DISCUSSION
Conclusions about models are difficult due to study heterogeneity and quality. Promising prediction models used demographic, cognitive/neuropsychological, imaging, and plasma Aβ measures. Further studies using standardized Aβ determination, and improved model validation are required.
Topics: Alzheimer Disease; Amyloid beta-Peptides; Apolipoproteins E; Biomarkers; Brain; Humans; Magnetic Resonance Imaging; Predictive Value of Tests
PubMed: 33583100
DOI: 10.1002/alz.12253 -
Cureus Dec 2020Alzheimer's disease (AD) is caused by several risk factors leading to dementia. It's diagnosis usually depends on clinical presentation and certain biomarkers in the... (Review)
Review
Alzheimer's disease (AD) is caused by several risk factors leading to dementia. It's diagnosis usually depends on clinical presentation and certain biomarkers in the cerebrospinal fluid (CSF). The brain has a high content of cholesterol and the metabolism of cholesterol in the brain can be associated with beta-amyloid plaques formation, which is seen in Alzheimer's disease. Given these implications, we studied if plasma lipid levels can vary in Alzheimer's disease and if these can be used as biomarkers to diagnose and predict the progression of Alzheimer's disease. Certain mutations in the brain cholesterol transport receptors and proteins and their association with Alzheimer's were also studied. This systematic review abides by the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. We searched multiple databases, such as Pubmed, Google Scholar, Pubmed central, ScienceDirect, Web of Science, and Medline with the help of keywords like Alzheimer's disease, cognitive impairment, plasma lipid biomarkers, cholesterol, brain cholesterol metabolism separately and in combination with each other. We collected 49 quality appraised articles on the association between plasma lipids and Alzheimer's disease and the genetic mutations in alleles related to cholesterol metabolism and Alzheimer's disease by applying the inclusion and exclusion criteria. Based on the finding of the studies reviewed, we found an association between plasma lipids, polymorphisms in genes associated with cholesterol transport, and Alzheimer's disease. Increased serum low-density lipoprotein (LDL-C), triglycerides (TG), total cholesterol (TC), sphingolipids, 24S hydroxycholesterol (24S-HC), 27O hydroxycholesterol (27O-HC) was associated with Alzheimer's. Decreased high-density lipoprotein (HDL-C) and phospholipids were noticed. Genetic mutations in apolipoprotein E (ApoE), apolipoprotein B (ApoB), apolipoprotein A (ApoA), ATP binding cassette transporter 1 (ABCA1), ATP binding cassette transporter 7 (ABCA7), amyloid precursor protein (APP), cytochrome P450 family 46 subfamilies A member 1 (CYP46A1), presenilin 1 (PSEN1), presenilin 2 (PSEN2) are also associated with increased risk of Alzheimer's disease. This study found an association between plasma lipids and Alzheimer's, proving that plasma lipids can be used as biomarkers for early diagnosis of Alzheimer's disease. It may also help predict the prognosis and stage the disease severity. Further studies are needed to find out the exact mechanism behind these changes.
PubMed: 33457117
DOI: 10.7759/cureus.12008 -
Cardiology and Therapy Jun 2021Alzheimer's disease (AD) is a progressive neurodegenerative disease for which no effective treatment exists at present. Previous research has found that exercise reduces... (Review)
Review
Alzheimer's disease (AD) is a progressive neurodegenerative disease for which no effective treatment exists at present. Previous research has found that exercise reduces the risk of AD. Since the apolipoprotein E (APOE) ε4 allele increases the risk of AD and is associated with faster disease progression than the other isoforms, we aimed to highlight the impact of exercise on AD pathology in APOE ε4 carriers. This review focuses on the effect of exercise on cognitive function, dementia risk, amyloid-β (Aβ) metabolism, lipid metabolism, neuroinflammation, neurotrophic factors and vascularization in APOE ε4 carriers. We searched the literature in the PubMed electronic database using the following search terms: physical activity, exercise, aerobic fitness, training, sport, APOE4, Alzheimer's disease, AD and dementia. By cross-referencing, additional publications were identified. Selected studies required older adults to take part in an exercise intervention or to make use of self-reported physical activity questionnaires. All included studies were written and published in English between 2000 and 2020. From these studies, we conclude that exercise is a non-pharmacological treatment option for high-risk APOE ε4 carriers to ameliorate the AD pathological processes including reducing Aβ load, protecting against hippocampal atrophy, improving cognitive function, stabilizing cholesterol levels and lowering pro-inflammatory signals. Variation in study design related to age, cognitive outcomes and the type of intervention explained the differences in study outcomes. However, exercise seems to be effective in delaying the onset of AD and may improve the quality of life of AD patients.
PubMed: 33403644
DOI: 10.1007/s40119-020-00209-z -
Geriatrics & Gerontology International Feb 2021Heredity plays an important role in the pathogenesis of Alzheimer's disease (AD) especially for single-nucleotide polymorphism (SNPs) of susceptible genes, which is one... (Meta-Analysis)
Meta-Analysis
AIM
Heredity plays an important role in the pathogenesis of Alzheimer's disease (AD) especially for single-nucleotide polymorphism (SNPs) of susceptible genes, which is one of the significant factors in the pathogenesis of AD. The SNPs of BIN1 rs744373, BIN1 rs7561528 and GAB2 rs2373115 are associated with AD in Asian and white people.
METHODS
We included 34 studies with a total of 38 291 patients with AD and 55 538 controls of diverse races from four main databases. We used meta-analysis to obtain I -values and odds ratios of five genetic models in three SNPs. We carried out analysis of sensitivity, subgroup, publication bias and linkage disequilibrium test.
RESULTS
The forest plots showed the odds ratio value of the three SNPs was >1 in white individuals, but not Asian individuals, in their genetic model. The funnel plot was symmetrical, and the D'-value was 0.986 between rs744373 and rs7561528.
CONCLUSIONS
BIN1 rs744373, BIN1 rs7561528 and GAB2 rs2373115 are pathogenicity sites for AD in white people, and also rs7561528 belongs to a risk site in Asian people. The rs7561528 and rs744373 SNPs have strong linkage disequilibrium in Chinese people. In addition, apolipoprotein E ε4 status promotes them to result in the pathogenesis of AD. Geriatr Gerontol Int 2021; 21: 185-191.
Topics: Adaptor Proteins, Signal Transducing; Alzheimer Disease; Genetic Predisposition to Disease; Humans; Nuclear Proteins; Polymorphism, Single Nucleotide; Tumor Suppressor Proteins; White People
PubMed: 33331110
DOI: 10.1111/ggi.14109