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Scandinavian Journal of Public Health Dec 2023The association between belonging to a disadvantaged socio-economic status or social class and health outcomes has been consistently documented during recent decades.... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
The association between belonging to a disadvantaged socio-economic status or social class and health outcomes has been consistently documented during recent decades. However, a meta-analysis quantifying the association between belonging to a lower social class and the risk of dementia has yet to be performed. In the present work, we sought to summarise the results of prospective, longitudinal studies on this topic.
METHODS
We conducted a systematic review and meta-analysis of prospective, longitudinal studies measuring the association between indicators of social class and the risk of all-cause/Alzheimer's dementia. The search was conducted in four databases (Medline, Embase, Web of Science and PsychInfo). Inclusion criteria for this systematic review and meta-analysis were: (a) longitudinal prospective study, (b) aged ⩾60 years at baseline, (c) issued from the general population, (d) no dementia at baseline and (e) mention of social class as exposure. Exclusion criteria were: (a) study of rare dementia types (e.g. frontotemporal dementia), (b) abstract-only papers and (c) articles without full text available. The Newcastle-Ottawa scale was used to assess the risk of bias in individual studies. We calculated the overall pooled relative risk of dementia for different social class indicators, both crude and adjusted for sex, age and the year of the cohort start.
RESULTS
Out of 4548 screened abstracts, 15 were included in the final analysis (76,561 participants, mean follow-up 6.7 years (2.4-25 years), mean age at baseline 75.1 years (70.6-82.1 years), mean percentage of women 58%). Social class was operationalised as levels of education, occupational class, income level, neighbourhood disadvantage and wealth. Education (relative risk (RR)=2.48; confidence interval (CI) 1.71-3.59) and occupational class (RR=2.09; CI 1.18-3.69) but not income (RR=1.28; CI 0.81-2.04) were significantly associated with the risk of dementia in the adjusted model. Some of the limitations of this study are the inclusion of studies predominantly conducted in high-income countries and the exclusion of social mobility in our analysis.
CONCLUSIONS
Topics: Humans; Female; Aged; Prospective Studies; Social Class; Educational Status; Social Mobility; Dementia
PubMed: 35815546
DOI: 10.1177/14034948221110019 -
Journal of Clinical Medicine Aug 2023The use of radiomics and artificial intelligence applied for the diagnosis and monitoring of Alzheimer's disease has developed in recent years. However, this approach is... (Review)
Review
The use of radiomics and artificial intelligence applied for the diagnosis and monitoring of Alzheimer's disease has developed in recent years. However, this approach is not yet completely applicable in clinical practice. The aim of this paper is to provide a systematic analysis of the studies that have included the use of radiomics from different imaging techniques and artificial intelligence for the diagnosis and monitoring of Alzheimer's disease in order to improve the clinical outcomes and quality of life of older patients. A systematic review of the literature was conducted in February 2023, analyzing manuscripts and articles of the last 5 years from the PubMed, Scopus and Embase databases. All studies concerning discrimination among Alzheimer's disease, Mild Cognitive Impairment and healthy older people performing radiomics analysis through machine and deep learning were included. A total of 15 papers were included. The results showed a very good performance of this approach in the differentiating Alzheimer's disease patients-both at the dementia and pre-dementia phases of the disease-from healthy older people. In summary, radiomics and AI can be valuable tools for diagnosing and monitoring the progression of Alzheimer's disease, potentially leading to earlier and more accurate diagnosis and treatment. However, the results reported by this review should be read with great caution, keeping in mind that imaging alone is not enough to identify dementia due to Alzheimer's.
PubMed: 37629474
DOI: 10.3390/jcm12165432 -
Ageing Research Reviews Dec 2023In aging, olfactory deficits have been associated with lower cognition and motor function. Olfactory dysfunction is also one of the earliest features of... (Review)
Review
In aging, olfactory deficits have been associated with lower cognition and motor function. Olfactory dysfunction is also one of the earliest features of neurodegenerative disease. A comprehensive review of the neural correlates of olfactive function may reveal mechanisms underlying the associations among olfaction, cognition, motor function, and neurodegenerative diseases. Here, we summarize existing knowledge on the relationship between brain structural and functional measures and olfaction in older adults without and with cognitive impairment, including Alzheimer's disease. We identified 33 eligible studies (30 MRI/DTI,3 fMRI); 31 were cross-sectional, most assessed odor identification, and few examined multiple brain areas. Lower olfactory function was associated with smaller volumes in the temporal lobe (hippocampus,parahippocampal gyrus,fusiform gyrus), olfactory-related regions (piriform cortex,amygdala,entorhinal cortex), pre- and postcentral gyri, and globus pallidus. During aging, olfactory impairment may be associated with pathology in brain areas important for motor function and cognition, especially memory. Future longitudinal studies that include neuroimaging across different brain areas are warranted to determine the neurobiological changes underlying olfactory changes in the aging brain and the progression of neurodegeneration.
Topics: Humans; Aged; Neurodegenerative Diseases; Brain; Entorhinal Cortex; Hippocampus; Temporal Lobe; Magnetic Resonance Imaging; Cognitive Dysfunction
PubMed: 37913831
DOI: 10.1016/j.arr.2023.102095 -
American Journal of Obstetrics and... Jan 2024Hypertensive disorders of pregnancy, including preeclampsia, are associated with an increased risk for maternal cardiovascular disease, stroke, and chronic kidney... (Review)
Review
OBJECTIVE
Hypertensive disorders of pregnancy, including preeclampsia, are associated with an increased risk for maternal cardiovascular disease, stroke, and chronic kidney disease. However, their association with subsequent maternal dementia or cognitive impairment is less well understood. This study aimed to review and synthesize the published literature on hypertensive disorders of pregnancy and the subsequent risk for maternal dementia or cognitive impairment.
DATA SOURCES
PubMed, Web of Science, Pyschinfo, and CINAHL were searched from database inception until July 31, 2022, for observational studies of hypertensive disorders of pregnancy and maternal dementia or cognitive impairment.
STUDY ELIGIBILITY CRITERIA
Selected studies included the following: a population of pregnant women, exposure to a hypertensive disorder of pregnancy of interest, and at least 1 primary outcome (dementia) or secondary outcome (cognitive impairment). Two reviewers were involved in study selection.
METHODS
We followed the Meta-analyses of Observational Studies in Epidemiology guidelines throughout. Random-effects meta-analyses were used to calculate the overall pooled estimates. Bias was assessed using an adapted version of the validated Newcastle-Ottawa Quality Assessment tool.
RESULTS
A total of 25 eligible studies were identified and included 2,501,673 women. Preeclampsia was associated with a significantly increased risk for vascular dementia (adjusted hazard ratio, 1.89; 95% confidence interval, 1.47-2.43), whereas no clear association was noted between preeclampsia and Alzheimer's disease (adjusted hazard ratio, 1.27; 95% confidence interval, 0.95-1.70), nor between preeclampsia and any (undifferentiated) dementia (adjusted hazard ratio, 1.18; 95% confidence interval, 0.95-1.47). However, in an analysis restricted to women aged 65 years and older, preeclampsia was associated with an increased risk for Alzheimer's disease (adjusted hazard ratio, 1.92; 95% confidence interval, 1.35-2.73) and any dementia (adjusted hazard ratio, 1.87; 95% confidence interval, 1.21-2.91).
CONCLUSION
Women whose pregnancies were complicated by preeclampsia seem to be at a substantially increased future risk for vascular dementia. The longer-term risks among these women with regards to Alzheimer's disease and other forms of dementia are less clear.
PubMed: 38278201
DOI: 10.1016/j.ajog.2024.01.013 -
Journal of Sport and Health Science Mar 2024One of the pathological hallmarks distinguishing Alzheimer's disease from other dementias is the accumulation of amyloid beta (Aβ). Higher physical activity is... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
One of the pathological hallmarks distinguishing Alzheimer's disease from other dementias is the accumulation of amyloid beta (Aβ). Higher physical activity is associated with decreased dementia risk, and one potential path could be through Aβ levels modulation. We aimed to explore the relationship between physical activity and Aβ in middle-aged and older adults.
METHODS
A systematic search of PubMed, Web of Science, PsycINFO, Cochrane Central Register of Controlled Trials, and SPORTDiscus was performed from inception to April 28, 2022. Studies were eligible if they included physical activity and Aβ data in adults aged 45 years or older. Multi-level meta-analyses of intervention and observational studies were performed to examine the role of physical activity in modulating Aβ levels.
RESULTS
In total, 37 articles were included (8 randomized controlled trials, 3 non-randomized controlled trials, 4 prospective longitudinal studies, and 22 cross-sectional studies). The overall effect size of physical activity interventions on changes in blood Aβ was medium (pooled standardized mean difference = -0.69, 95% confidence interval (95%CI): -1.41 to 0.03; I = 74.6%). However, these results were not statistically significant, and there were not enough studies to explore the effects of physical activity on cerebrospinal fluid (CSF) and brain Aβ. Data from observational studies were examined based on measurements of Aβ in the brain using positron emission tomography scans, CSF, and blood. Higher physical activity was positively associated with Aβ only in the CSF (Estimate r = 0.12; 95%CI: 0.05-0.18; I = 38.00%).
CONCLUSION
Physical activity might moderately reduce blood Aβ in middle-aged and older adults. However, results were only near statistical significance and might be interpreted with caution given the methodological limitations observed in some of the included studies. In observational studies, higher levels of physical activity were positively associated with Aβ only in CSF. Therefore, further research is needed to understand the modulating role of physical activity in the brain, CSF, and blood Aβ, as well as its implication for cognitive health.
Topics: Middle Aged; Humans; Aged; Amyloid beta-Peptides; Prospective Studies; Cross-Sectional Studies; Alzheimer Disease; Brain
PubMed: 37558161
DOI: 10.1016/j.jshs.2023.08.001 -
Nutrients Oct 2023This systematic review aims to provide a comprehensive understanding of the current literature regarding gut microbiota composition in patients with Parkinson's disease... (Review)
Review
This systematic review aims to provide a comprehensive understanding of the current literature regarding gut microbiota composition in patients with Parkinson's disease (PD) and Alzheimer's disease (AD) compared to healthy controls. To identify the relevant studies, a thorough search of PubMed, Medline, and Embase was conducted following the PRISMA guidelines. Out of 5627 articles, 73 studies were assessed for full-text eligibility, which led to the inclusion of 42 studies (26 PD and 16 AD studies). The risk of bias assessment showed a medium risk in 32 studies (20 PD studies and 12 AD studies), a low risk in 9 studies (5 PD studies and 4 AD studies), and 1 PD study with a high risk. Among the PD studies, 22 out of 26 studies reported a different gut microbiota composition between the PD cases and the healthy controls, and 15 out of 16 AD studies reported differences in gut microbiota composition between the AD cases and the healthy controls. The PD and AD studies consistently identified the phyla Bacteroidetes, Firmicutes, and Proteobacteria as prevalent in the gut microbiota in both the healthy groups and the case groups. Microbial dysbiosis was specifically characterized in the PD studies by a high abundance of , , , and in the cases and a high abundance of , , , and in the controls. Similarly, Bacteroides and Acidobacteriota were abundant in the AD cases, and , Firmicutes, , and were abundant in the AD controls. The microbial signature assessment showed the association of several microbial taxa, including , , , , , and Verrucomicrobia with PD and , , and Actinobacteria with AD. The microbial diversity evaluations in the PD and AD studies indicated comparable alpha diversity in some groups and distinct gut microbiota composition in others, with consistent beta diversity differences between the cases and the controls across multiple studies. The bacterial signatures identified in this study that are associated with PD and AD may offer promising prospects for efficient management and treatment approaches.
Topics: Humans; Gastrointestinal Microbiome; Parkinson Disease; Alzheimer Disease; Feces; Neurodegenerative Diseases; Bacteria
PubMed: 37892440
DOI: 10.3390/nu15204365 -
Obesity Reviews : An Official Journal... Aug 2023Midlife obesity and late-life weight loss confer a greater risk for developing dementia and Alzheimer's disease (AD), but the exact mechanisms behind this phenomenon are... (Meta-Analysis)
Meta-Analysis Review
Midlife obesity and late-life weight loss confer a greater risk for developing dementia and Alzheimer's disease (AD), but the exact mechanisms behind this phenomenon are currently unknown. The answer could lie on the involvement of gastrointestinal factors, such as adipokines (e.g., leptin, adiponectin, and resistin) and ghrelin. In this context, we conducted a pre-registered systematic review and meta-analysis of 42 cross-sectional and 13 longitudinal studies targeting the associations between leptin, adiponectin, resistin, and ghrelin and the prevalence of general dementia, AD, and mild cognitive impairment (MCI). We also examined the relationship between the four gastrointestinal factors and neurocognitive outcomes and AD-related cerebrospinal fluid biomarkers. Patients with AD had lower blood leptin and higher resistin levels than cognitively normal participants. Lower leptin and higher resistin were associated with higher degree of cognitive impairment. Additionally, lower late-life leptin levels might be associated with higher prospective risk of dementia and AD, although more studies are needed to corroborate this. Results in ghrelin and adiponectin were not conclusive, with age, sex distribution, obesity, and severity of dementia seemingly acting as moderators across several analyses. Our work might contribute to the identification of new preclinical blood markers of MCI and AD.
Topics: Humans; Adipokines; Alzheimer Disease; Leptin; Resistin; Adiponectin; Ghrelin; Cross-Sectional Studies; Prospective Studies; Cognitive Dysfunction; Biomarkers; Obesity
PubMed: 37165483
DOI: 10.1111/obr.13573 -
Neuropsychology Review Jun 2024Most people with dementia experience neuropsychiatric symptoms (NPS), including anxiety, depression or disinhibition. There is growing interest in the relationship... (Meta-Analysis)
Meta-Analysis Review
Most people with dementia experience neuropsychiatric symptoms (NPS), including anxiety, depression or disinhibition. There is growing interest in the relationship between NPS and cognitive impairment, but data is still limited. This study aimed to investigate the specific associations between NPS and cognition in people with dementia. MEDLINE, EMBASE and PsycINFO were searched for published, peer-reviewed studies of associations between at least one NPS and one cognitive ability in people with dementia. The quality of the studies was assessed with the NIH National Heart, Lung and Blood Institute's quality assessment tools. A meta-analysis was conducted using Robumeta package for R. Ninety studies were included. We found significant associations between NPS, global cognition and cognitive domains, e.g. apathy was associated with global cognitive and memory impairment; dysphoria was associated with worse attention; delusions with executive dysfunction. Increased NPS in people with dementia are associated with worse cognitive performance. There were few studies looking at associations between some neuropsychiatric clusters and cognitive abilities, and there was little research on causal relationships. Our review was limited by the inclusion of studies that reported associations in specific formats, and most included people with a diagnosis of Alzheimer's disease (AD). However, given the large number of studies, this is unlikely to have biased results. More research is needed that includes diverse people with different dementia syndromes. Registration: PROSPERO 2020 CRD42020165565.
Topics: Humans; Dementia; Cognitive Dysfunction; Cognition; Alzheimer Disease
PubMed: 37477839
DOI: 10.1007/s11065-023-09608-0 -
Neurology and Therapy Dec 2023Alzheimer's disease (AD) is the most common cause of dementia worldwide, making it a major public health issue. Anti-amyloid and anti-tau antibodies are the most... (Review)
Review
Immunotherapies Targeting Amyloid and Tau Protein in Alzheimer's Disease: Should We Move Away from Diseases and Focus on Biological Targets? A Systematic Review and Expert Opinion.
INTRODUCTION
Alzheimer's disease (AD) is the most common cause of dementia worldwide, making it a major public health issue. Anti-amyloid and anti-tau antibodies are the most advanced therapeutic approach at present. Three drugs (lecanemab, donanemab and aducanumab) are on track to be marketed in the coming months. In this systematic review, we review all Phase 2 and Phase 3 clinical trials conducted in this indication and the particularities of the molecules tested.
METHODS
The PubMed and ClinicalTrials.gov databases were searched through February 2023 for Phase 2 and 3 clinical trials involving passive anti-amyloid or anti-tau immunotherapies with published results. This review has been compiled in compliance with the PRISMA checklists.
RESULTS
Of the 165 studies found and after eliminating duplicates, 40 studies had their results published on PubMed and/or ClinicalTrials.gov. Eight anti-amyloid molecules and four anti-tau molecules were the subject of Phase 2 studies, seven anti-amyloids were the subject of Phase 3 trials, and two molecules were granted early marketing approval by the US Food and Drug Administration (FDA). The results were compiled in summary tables showing the primary endpoints used, results, age of the study population and specific adverse events for these molecules.
DISCUSSION
Passive immunotherapy in AD is largely dominated by anti-amyloid antibodies, which are more numerous and more advanced in the pipeline. Lecanemab, donanemab and aducanumab are distinguished by their relative efficacy in terms of cognitive and functional evaluation but also by a decrease in amyloid and tau proteins in the brain. These three molecules have in common that they bind to N-terminal ends of amyloid fibrils and plaques. The findings of their studies raise the question of which criteria to apply when choosing which patient will receive them when marketed, such as the apoliprotein E gene's fourth allele (APOE4) genetic status of patients. The large number of negative studies may also raise the question of the criteria for defining the disease and the possible interest in redefining it on biological grounds to offer a more personalized medicine to patients suffering from neurodegenerative diseases.
PubMed: 37812325
DOI: 10.1007/s40120-023-00541-1 -
Brain Sciences Nov 2023Emerging evidence highlights moderate hypoxia as a candidate treatment for brain disorders. This systematic review examines findings and the methodological quality of... (Review)
Review
Emerging evidence highlights moderate hypoxia as a candidate treatment for brain disorders. This systematic review examines findings and the methodological quality of studies investigating hypoxia (10-16% O) for ≥14 days in humans, as well as the neurobiological mechanisms triggered by hypoxia in animals, and suggests optimal treatment protocols to guide future studies. We followed the preferred reporting items for systematic reviews and meta-analysis (PRISMA) 2020. Searches were performed on PubMed/MEDLINE, PsycInfo, EMBASE, and the Cochrane Library, in May-September 2023. Two authors independently reviewed the human studies with the following tools: (1) revised Cochrane collaboration's risk of bias for randomized trials 2.0; (2) the risk of bias in nonrandomized studies of interventions. We identified 58 eligible studies (k = 8 human studies with N = 274 individuals; k = 48 animal studies) reporting the effects of hypoxia on cognition, motor function, neuroimaging, neuronal/synaptic morphology, inflammation, oxidative stress, erythropoietin, neurotrophins, and Alzheimer's disease markers. A total of 75% of human studies indicated cognitive and/or neurological benefits, although all studies were evaluated ashigh risk of bias due to a lack of randomization and assessor blinding. Low-dose intermittent or continuous hypoxia repeated for 30-240 min sessions, preferably in combination with motor-cognitive training, produced beneficial effects, and high-dose hypoxia with longer (≥6 h) durations and chronic exposure produced more adverse effects. Larger and methodologically stronger translational studies are warranted.
PubMed: 38137096
DOI: 10.3390/brainsci13121648