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Journal of Alzheimer's Disease Reports 2024Alzheimer's disease (AD) causes progressive decline of cognition and function. There is a lack of systematic literature reviews on prognostic and predictive factors in...
BACKGROUND
Alzheimer's disease (AD) causes progressive decline of cognition and function. There is a lack of systematic literature reviews on prognostic and predictive factors in its early clinical stages (eAD), i.e., mild cognitive impairment due to AD and mild AD dementia.
OBJECTIVE
To identify prognostic factors affecting eAD progression and predictive factors for treatment efficacy and safety of approved and/or under late-stage development disease-modifying treatments.
METHODS
Databases were searched (August 2022) for studies reporting prognostic factors associated with eAD progression and predictive factors for treatment response. The Quality in Prognostic Factor Studies tool or the Cochrane risk of bias tool were used to assess risk of bias. Two reviewers independently screened the records. A single reviewer performed data extraction and quality assessment. A second performed a 20% check. Content experts reviewed and interpreted the data collected.
RESULTS
Sixty-one studies were included. Self-reporting, diagnosis definition, and missing data led to high risk of bias. Population size ranged from 110 to 11,451. Analyses found data indicating that older age was and depression may be associated with progression. Greater baseline cognitive impairment was associated with progression. may be a prognostic factor, a predictive factor for treatment efficacy and predicts an adverse response (ARIA). Elevated biomarkers (CSF/plasma p-tau, CSF t-tau, and plasma neurofilament light) were associated with disease progression.
CONCLUSIONS
Age was the strongest risk factor for progression. Biomarkers were associated with progression, supporting their use in trial selection and aiding diagnosis. Baseline cognitive impairment was a prognostic factor. predicted ARIA, aligning with emerging evidence and relevant to treatment initiation/monitoring.
PubMed: 38405341
DOI: 10.3233/ADR-230045 -
Ageing Research Reviews Aug 2023The associations between lipocalin-2 (LCN2) with mild cognitive impairment (MCI) and dementia have gained growing interest. However, population-based studies have... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
The associations between lipocalin-2 (LCN2) with mild cognitive impairment (MCI) and dementia have gained growing interest. However, population-based studies have yielded inconsistent findings. Therefore, we conducted this essential systematic review and meta-analysis to analyze and summarize the existing population-based evidence.
METHODS
PubMed, EMBASE, and Web of Science were systematically searched until Mar 18, 2022. Meta-analysis was performed to generate the standard mean difference (SMD) of peripheral blood and cerebrospinal fluid (CSF) LCN2. A qualitative review was performed to summarize the evidence from postmortem brain tissue studies.
RESULTS
In peripheral blood, the overall pooled results showed no significant difference in LCN2 across Alzheimer's disease (AD), MCI and control groups. Further subgroup analysis revealed higher serum LCN2 levels in AD compared to controls (SMD =1.28 [0.44;2.13], p = 0.003), while the difference remained insignificant in plasma (SMD =0.04 [-0.82;0.90], p = 0.931). Besides, peripheral blood LCN2 were higher in AD when age difference between AD and controls ≥ 4 years (SMD =1.21 [0.37;2.06], p = 0.005). In CSF, no differences were found in LCN2 across groups of AD, MCI and controls. However, CSF LCN2 was higher in vascular dementia (VaD) compared to controls (SMD =1.02 [0.17;1.87], p = 0.018), as well as compared to AD (SMD =1.19 [0.58;1.80], p < 0.001). Qualitative analysis supported that LCN2 was increased in the brain tissue of AD-related areas, especially in astrocytes and microglia; while LCN2 increased in infarct-related brain areas and over-expressed in astrocytes and macrophages in mixed dementia (MD).
CONCLUSION
The difference in peripheral blood LCN2 between AD and controls may be affected by the type of biofluid and age. No differences were found in CSF LCN2 across AD, MCI and controls groups. In contrast, CSF LCN2 was elevated in VaD patients. Moreover, LCN2 was increased in AD-related brain areas and cells in AD, while in infarcts-related brain areas and cells in MD.
Topics: Humans; Alzheimer Disease; Biomarkers; Cognitive Dysfunction; Dementia, Vascular; Lipocalin-2; Mixed Dementias
PubMed: 37330019
DOI: 10.1016/j.arr.2023.101984 -
Sleep Medicine Reviews Aug 2023Alzheimer's disease (AD) is the most common type of dementia and is characterized by the aggregation of extracellular amyloid-beta and intracellular hyperphosphorylation... (Meta-Analysis)
Meta-Analysis Review
Alzheimer's disease (AD) is the most common type of dementia and is characterized by the aggregation of extracellular amyloid-beta and intracellular hyperphosphorylation of tau proteins. Obstructive Sleep Apnea (OSA) is associated with increased AD risk. We hypothesize that OSA is associated with higher levels of AD biomarkers. The study aims to conduct a systematic review and meta-analysis of the association between OSA and levels of blood and cerebrospinal fluid biomarkers of AD. Two authors independently searched PubMed, Embase, and Cochrane Library for studies comparing blood and cerebrospinal fluid levels of dementia biomarkers between patients with OSA and healthy controls. Meta-analyses of the standardized mean difference were conducted using random-effects models. From 18 studies with 2804 patients, meta-analysis found that cerebrospinal fluid amyloid beta-40 (SMD:-1.13, 95%CI:-1.65 to -0.60), blood total amyloid beta (SMD:0.68, 95%CI: 0.40 to 0.96), blood amyloid beta-40 (SMD:0.60, 95%CI: 0.35 to 0.85), blood amyloid beta-42 (SMD:0.80, 95%CI: 0.38 to 1.23) and blood total-tau (SMD: 0.664, 95% CI: 0.257 to 1.072, I = 82, p<0.01, 7 studies) were significantly higher in OSA patients compared with healthy controls. These findings suggest that OSA is associated with an elevation of some biomarkers of AD.
Topics: Humans; Alzheimer Disease; Amyloid beta-Peptides; tau Proteins; Sleep Apnea, Obstructive; Biomarkers
PubMed: 37245474
DOI: 10.1016/j.smrv.2023.101790 -
Journal of Neurology, Neurosurgery, and... Dec 2023Biological ageing is one of the principal risk factors for neurodegenerative diseases. It is becoming increasingly clear that acceleration of DNA methylation age, as...
BACKGROUND
Biological ageing is one of the principal risk factors for neurodegenerative diseases. It is becoming increasingly clear that acceleration of DNA methylation age, as measured by the epigenetic clock, is closely associated with many age-related diseases.
METHODS
We searched the PubMed and Web of Science databases to identify eligible studies reporting epigenetic clocks in several neurodegenerative diseases, including Alzheimer's disease (AD), Parkinson's disease (PD), amyotrophic lateral sclerosis (ALS) and Huntington's disease (HD).
RESULTS
Twenty-three studies (12 for AD, 4 for PD, 5 for ALS, and 2 for HD) were included. We systematically summarised the clinical utility of 11 epigenetic clocks (based on blood and brain tissues) in assessing the risk factors, age of onset, diagnosis, progression, prognosis and pathology of AD, PD, ALS and HD. We also critically described our current understandings to these evidences, and further discussed key challenges, potential mechanisms and future perspectives of epigenetic ageing in neurodegenerative diseases.
CONCLUSIONS
Epigenetic clocks hold great potential in neurodegenerative diseases. Further research is encouraged to evaluate the clinical utility and promote the application.
PROSPERO REGISTRATION NUMBER
CRD42022365233.
Topics: Humans; Amyotrophic Lateral Sclerosis; Neurodegenerative Diseases; Alzheimer Disease; Parkinson Disease; Epigenesis, Genetic
PubMed: 36963821
DOI: 10.1136/jnnp-2022-330931 -
Medicine Apr 2024Alzheimer's disease (AD) is a progressive neurodegenerative disorder. Dementia severity was assessed mainly through cognitive function, psychobehavioral symptoms, and... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Alzheimer's disease (AD) is a progressive neurodegenerative disorder. Dementia severity was assessed mainly through cognitive function, psychobehavioral symptoms, and daily living ability. Currently, there are not many drugs that can be selected to treat mild to moderate AD, and the value of drugs remains controversial.
OBJECTIVE
The aim of this study is to quantitatively evaluate the efficacy and safety of cholinesterase inhibitors (ChEIs), memantine, and sodium oligomannate (GV-971) in the treatment of patients with AD. Additionally, molecular docking analysis will be used to investigate the binding affinities of donepezil, galantamine, rivastigmine, and memantine with key receptor proteins associated with AD, including beta-amyloid (Abeta), microtubule-associated protein (MAP), apolipoprotein E4 (APOE4), and Mitofusin-2 (MFN2), to further validate the results of the meta-analysis.
METHODS
We obtained clinical trials characterized by randomization, placebo control, and double-blinded methodologies concerning ChEIs, memantine, and GV-971. Statistical analysis was performed using Review Manager Version 5.4 software. Molecular docking was also conducted to evaluate the results.
RESULTS
All drugs improved the cognitive function, with the effect value ranging from -1.23 (95% CI -2.17 to -0.30) for 20 mg memantine to -3.29 (95% CI -4.14 to -2.45) for 32 mg galantamine. Although 32 mg galanthamine and GV-971 did not improve the clinicians' Global Impression of Change scale, other drugs showed significant results compared with placebo. On NPI, only 10 mg of donepezil and 24 mg of galantamine had improvement effects. On ADCS/ADL, only 20 mg memantine and 900 mg GV-971 had no significant difference from the placebo. Donepezil 5 mg and GV-971 900 mg did not increase the drug withdrawal rates due to various reasons or adverse reactions when compared to the placebo. Donepezil demonstrated superior binding to the protein and exhibited greater efficacy compared to other drugs.
CONCLUSION
ChEIs, memantine, and GV-971 all can slow the progression of AD but have different effects on respective assessments. Donepezil and GV-971 were relatively well tolerated.
Topics: Humans; Alzheimer Disease; Donepezil; Galantamine; Memantine; Molecular Docking Simulation; Cholinesterase Inhibitors; Rivastigmine
PubMed: 38640313
DOI: 10.1097/MD.0000000000037799 -
Therapeutic Advances in Infectious... 2023Fascioliasis is a parasitic zoonosis that can infect humans and be a source of significant morbidity. The World Health Organization lists human fascioliasis as a...
BACKGROUND
Fascioliasis is a parasitic zoonosis that can infect humans and be a source of significant morbidity. The World Health Organization lists human fascioliasis as a neglected tropical disease, but the worldwide prevalence of fascioliasis data is unknown.
OBJECTIVE
We aimed to estimate the global prevalence of human fascioliasis.
DATA SOURCES AND METHODS
We performed a systematic review and prevalence meta-analysis. We used the following inclusion criteria: articles published in the English, Portuguese, or Spanish languages from December 1985 to October 2022 and studies assessing the prevalence of in the general population with an appropriate diagnostic methodology, including longitudinal studies, prospective and retrospective cohorts, case series, and randomized clinical trials (RCTs). We excluded animal studies. Two reviewers independently reviewed the selected studies for methodological quality, performing critical standard measures from JBI SUMARI. A random-effects model was conducted of the summary extracted data on the prevalence proportions. We reported the estimates according to the GATHER statement.
RESULTS
In all, 5617 studies were screened for eligibility. Fifty-five studies from 15 countries were selected, including 154,697 patients and 3987 cases. The meta-analysis revealed a pooled prevalence of 4.5% [95% confidence interval (CI): 3.1-6.1; = 99.4%; = 0.07]. The prevalence in South America, Africa, and Asia was 9.0%, 4.8%, and 2.0%, respectively. The highest prevalence was found in Bolivia (21%), Peru (11%), and Egypt (6%). Subgroup analysis showed higher prevalence estimates in children, in studies from South America, and when Fas2-enzyme-linked immunosorbent assay (ELISA) was used as a diagnostic method. A larger study sample size ( = 0.027) and an increase in female percentage ( = 0.043) correlated with a decrease in prevalence. Multiple meta-regression showed a higher prevalence for hyperendemic than hypoendemic ( = 0.002) or mesoendemic ( = 0.013) regions.
CONCLUSION
The estimated prevalence and projected disease burden of human fascioliasis are high. Study findings support that fascioliasis continues to be a globally neglected tropical disease. Strengthening epidemiological surveillance and implementing measures to control and treat fascioliasis is imperative in the most affected areas.
PubMed: 37434654
DOI: 10.1177/20499361231185413 -
Biomedicine & Pharmacotherapy =... Sep 2023Neurodegenerative diseases (NDDs) encompass a range of conditions that involve progressive deterioration and dysfunction of the nervous system. Some of the common NDDs... (Review)
Review
Neurodegenerative diseases (NDDs) encompass a range of conditions that involve progressive deterioration and dysfunction of the nervous system. Some of the common NDDs include Alzheimer's disease (AD), Parkinson's disease (PD), Huntington's disease (HD), and amyotrophic lateral sclerosis (ALS). Although significant progress has been made in understanding the pathological mechanisms of NDDs in recent years, the development of targeted and effective drugs for their treatment remains challenging. Kaempferol is a flavonoid whose derivatives include kaempferol-O-rhamnoside, 3-O-β-rutinoside/6-hydroxykaempferol 3,6-di-O-β-d-glucoside, and kaempferide. Emerging studies have suggested that kaempferol and its derivatives possess neuroprotective properties and may have potential therapeutic benefits in NDDs. Here, we aimed to provide a theoretical basis for the use of kaempferol and its derivatives in the clinical treatment of NDDs. We systematically reviewed the literature in the PubMed, Web of Science, and Science Direct databases until June 2022 using the search terms "kaempferol," "kaempferol derivatives," "NDDs," "pharmacokinetics," and "biosynthesis" according to the reporting items for systematic review (PRISMA) standard. Based on combined results of in vivo and in vitro studies, we summarize the basic mechanisms and targets of kaempferol and its derivatives in the management of AD, PD, HD, and ALS. Kaempferol and its derivatives exert a neuroprotective role mainly by preventing the deposition of amyloid fibrils (such as Aβ, tau, and α-synuclein), inhibiting microglia activation, reducing the release of inflammatory factors, restoring the mitochondrial membrane to prevent oxidative stress, protecting the blood-brain barrier, and inhibiting specific enzyme activities (such as cholinesterase). Kaempferol and its derivatives are promising natural neuroprotective agents. By determining their pharmacological mechanism, kaempferol and its derivatives may be new candidate drugs for the treatment of NDDs.
Topics: Humans; Neurodegenerative Diseases; Neuroprotective Agents; Amyotrophic Lateral Sclerosis; Kaempferols; Alzheimer Disease; Parkinson Disease; Huntington Disease
PubMed: 37494786
DOI: 10.1016/j.biopha.2023.115215 -
CNS Neuroscience & Therapeutics Nov 2023The aim of this systematic review and meta-analysis was to evaluate the efficacy of noninvasive brain stimulation (NIBS) on cognition using functional magnetic resonance... (Meta-Analysis)
Meta-Analysis Review
The effects of noninvasive brain stimulation on cognitive function in patients with mild cognitive impairment and Alzheimer's disease using resting-state functional magnetic resonance imaging: A systematic review and meta-analysis.
OBJECTIVE
The aim of this systematic review and meta-analysis was to evaluate the efficacy of noninvasive brain stimulation (NIBS) on cognition using functional magnetic resonance imaging (fMRI) in patients with mild cognitive impairment (MCI) and Alzheimer's disease (AD), thus providing the neuroimaging mechanism of cognitive intervention.
METHODS
English articles published up to April 30, 2023 were searched in the PubMed, Web of Science, Embase, and Cochrane Library databases. We included randomized controlled trials where resting-state fMRI was used to observe the effect of NIBS in patients with MCI or AD. RevMan software was used to analyze the continuous variables, and SDM-PSI software was used to perform an fMRI data analysis.
RESULTS
A total of 17 studies comprising 258 patients in the treatment group and 256 in the control group were included. After NIBS, MCI patients in the treatment group showed hyperactivation in the right precuneus and decreased activity in the left cuneus and right supplementary motor area. In contrast, patients in the control group showed decreased activity in the right middle frontal gyrus and no hyperactivation. The clinical cognitive scores in MCI patients were significantly improved by NIBS, while not in AD. Some evidence regarding the modulation of NIBS in resting-state brain activity and functional brain networks in patients with AD was found.
CONCLUSIONS
NIBS could improve cognitive function in patients with MCI and AD. fMRI evaluations could be added to evaluate the contribution of specific NIBS treatment therapeutic effectiveness.
Topics: Humans; Alzheimer Disease; Cognitive Dysfunction; Cognition; Magnetic Resonance Imaging; Brain; Magnetic Resonance Spectroscopy
PubMed: 37349974
DOI: 10.1111/cns.14314 -
Neuroscience and Biobehavioral Reviews Sep 2023Several studies demonstrated that individuals are more likely to remember emotional than neutral information; this phenomenon is known as emotional enhancement of memory... (Meta-Analysis)
Meta-Analysis Review
Several studies demonstrated that individuals are more likely to remember emotional than neutral information; this phenomenon is known as emotional enhancement of memory (EEM). Adults generally tend to remember negative information more efficiently than neutral or positive items. In contrast, healthy elders seem to show an opposite bias for positive information, but results are inconsistent, also because during aging, elaboration of emotional information could change as a consequence of cognitive impairment. In this systematic review and meta-analysis, we conducted literature search of studies investigating emotion memory biases in mild cognitive impairment (MCI) and Alzheimer's disease (AD) on PubMed, Scopus and PsycINFO databases following PRISMA guidelines. The findings showed that emotional memory biases are still present despite the presence of cognitive impairment, both in MCI and at least in early stages of AD. However, the direction of emotion memory biases is not consistent across studies. These results suggest that patients with cognitive impairment might still benefit from EEM and help to define targets of intervention for cognitive rehabilitation in pathological aging.
Topics: Humans; Aged; Alzheimer Disease; Neuropsychological Tests; Cognitive Dysfunction; Mental Recall; Bias
PubMed: 37286118
DOI: 10.1016/j.neubiorev.2023.105277 -
Brain Imaging and Behavior Dec 2023The hippocampus is a complex structure that consists of several subfields with distinct and specialized functions. Although numerous studies have been performed to... (Meta-Analysis)
Meta-Analysis Review
The hippocampus is a complex structure that consists of several subfields with distinct and specialized functions. Although numerous studies have been performed to explore hippocampal atrophy at the sub-regional level in mild cognitive impairment (MCI) and Alzheimer's disease (AD), the results have been inconsistent especially for whether and which subfields can be served as the most potential biomarkers in MCI and AD. Herein, we used a meta-analytic approach to synthesize the extant literatures on hippocampal subfields in MCI and AD through PubMed, Web of Science, and Embase (PROSPERO CRD42021257586). As a result, a total of twenty studies using Freesurfer 5 and Freesurfer 6 were included in this investigation. These studies revealed that at the sub-regional level, hippocampal subfield volume reductions in MCI and AD were not restricted to specific subfields, and subiculum and presubiculum had the largest z-scores across most comparisons. However, none of the subfield performed much better in discriminating MCI and HC, AD and MCI, AD and HC as compared to whole hippocampus volume. These results suggested that we should explore the changes in the hippocampal subfields in subtypes of MCI or even at an earlier stage, that is subjective cognitive impairment.
Topics: Humans; Alzheimer Disease; Magnetic Resonance Imaging; Cognitive Dysfunction; Hippocampus; Atrophy
PubMed: 37768441
DOI: 10.1007/s11682-023-00804-3