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Frontiers in Neurology 2023People with Alzheimer's disease (AD) have difficulties in performing activities of daily living (ADLs) as the disease progresses, commonly experience neuropsychiatric... (Review)
Review
Exploring the relationship between patient-relevant outcomes and Alzheimer's disease progression assessed using the clinical dementia rating scale: a systematic literature review.
BACKGROUND
People with Alzheimer's disease (AD) have difficulties in performing activities of daily living (ADLs) as the disease progresses, commonly experience neuropsychiatric symptoms (NPS), and often have comorbidities such as cardiovascular disease. These factors all contribute to a requirement for care and considerable healthcare costs in AD. The Clinical Dementia Rating (CDR) scale is a widely used measure of dementia staging, but the correlations between scores on this scale and patient-/care partner-relevant outcomes have not been characterized fully. We conducted a systematic literature review to address this evidence gap.
METHODS
Embase, MEDLINE, and the Cochrane Library were searched September 13, 2022, to identify published studies (no restriction by date or country) in populations with mild cognitive impairment due to AD or AD dementia. Studies of interest reported data on the relationships between CDR Global or CDR-Sum of Boxes (CDR-SB) scores and outcomes including NPS, comorbidities, ADLs, nursing home placement, healthcare costs, and resource use.
RESULTS
Overall, 58 studies met the inclusion criteria (42 focusing on comorbidities, 14 on ADLs or dependence, five on nursing home placement, and six on economic outcomes). CDR/CDR-SB scores were correlated with the frequency of multiple NPS and with total scores on the Neuropsychiatric Inventory. For cardiovascular comorbidities, no single risk factor was consistently linked to AD progression. Increasing CDR/CDR-SB scores were correlated with decline in multiple different measures of ADLs and were also associated with nursing home placement and increasing costs of care.
CONCLUSION
NPS, ADLs, and costs of care are clearly linked to AD progression, as measured using CDR Global or CDR-SB scores, from the earliest stages of disease. This indicates that scores derived from the CDR are a meaningful way to describe the severity and burden of AD for patients and care partners across disease stages.
PubMed: 37669257
DOI: 10.3389/fneur.2023.1208802 -
Frontiers in Psychiatry 2023Several psychiatric disorders have been associated with an increased risk of developing a neurodegenerative disease and/or dementia. Attention-deficit/hyperactivity...
PURPOSE OF REVIEW
Several psychiatric disorders have been associated with an increased risk of developing a neurodegenerative disease and/or dementia. Attention-deficit/hyperactivity disorder (ADHD), a neurodevelopmental disorder, has been understudied in relation to dementia risk. We summarized existing literature investigating the risk of incident neurodegenerative disease or dementia associated with ADHD.
RECENT FINDINGS
We searched five databases for cohort, case-control, and clinical trial studies investigating associations between ADHD and neurodegenerative diseases/dementia in May 2023. Study characteristics were extracted by two independent raters, and risk of bias was assessed using the Newcastle Ottawa Scale. Search terms yielded 2,137 articles, and seven studies (five cohort and two case-control studies) ultimately met inclusion criteria. Studies examined the following types of neurodegeneration: all-cause dementia, Alzheimer's disease, Parkinson's and Lewy body diseases, vascular dementia, and mild cognitive impairment. Heterogeneity in study methodology, particularly covariates used in analyses and types of ratios for risk reported, prevented a meta-analysis and data were therefore summarized as a narrative synthesis. The majority of studies (4/7) demonstrated an overall low risk of bias.
SUMMARY
The current literature on risk of developing a neurodegenerative disease in ADHD is limited. Although the studies identified present evidence for a link between ADHD and subsequent development of dementia, the magnitude of the direct effect of ADHD on neurodegeneration is yet to be determined and better empirically designed studies are first needed. Furthermore, the mechanism of how or why ADHD is associated with an increased risk of developing a neurocognitive disorder is still unclear and should be explored in future studies.
SYSTEMATIC REVIEW REGISTRATION
https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42022348976, the PROSPERO number is CRD42022348976.
PubMed: 37663597
DOI: 10.3389/fpsyt.2023.1158546 -
Journal of Neurology Jan 2024Poor cardiometabolic health is associated with dementia. Considering previous meta-analyses have confirmed associations between ultra-processed foods (UPFs) and... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND AND AIMS
Poor cardiometabolic health is associated with dementia. Considering previous meta-analyses have confirmed associations between ultra-processed foods (UPFs) and cardiometabolic disease, we were interested in the contribution of UPF consumption to the risk of developing dementia.
METHODS
We performed a systematic review and meta-analysis of all records registered on Ovid Medline and Web of Science from inception until December 2022 [PROSPERO (CRD42023388363)]. Studies that assessed UPF consumption in adults, determined according to NOVA, and that reported dementia (Alzheimer's disease, vascular dementia and mild cognitive impairment) determined by clearly stated diagnostic criteria (including formal assessment of dementia or use of diagnostic codes) were included. The association between UPF consumption and dementia was assessed using random-effects meta-analysis, controlling for confounding variables. Study quality was assessed using the Newcastle Ottawa Scale and evidence credibility evaluated using the NutriGrade system.
RESULTS
Seven thousand ten records were screened, and 122 records underwent full text review. From these, 10 observational (8 longitudinal) studies, analysing 867,316 individuals, were included. Included studies adjusted for age, socioeconomic status and co-morbidity, alongside other confounders. High (vs. low) intake of UPF was associated with increased risk of dementia (pooled relative risk 1.44 (95% confidence interval 1.09-1.90) (p = 0.02)) (I = 97.0%), although moderate (vs. low) intake of UPF was not (1.12 (0.96-1.31) (0.13)) (85.0%). Funnel plots demonstrate low risk of publication bias.
CONCLUSION
High UPF consumption is associated with dementia. Public health measures to reduce overconsumption of UPFs are imperative to reduce the burden of dementia.
Topics: Adult; Humans; Diet; Food, Processed; Public Health; Dementia; Observational Studies as Topic
PubMed: 37831127
DOI: 10.1007/s00415-023-12033-1 -
Cureus Oct 2023The aim of this review was to evaluate the relationship between periodontal disease (PD) and the onset and progression of Alzheimer's disease (AD) and to determine... (Review)
Review
The aim of this review was to evaluate the relationship between periodontal disease (PD) and the onset and progression of Alzheimer's disease (AD) and to determine whether patients with PD would be at greater risk of developing AD compared to periodontally healthy subjects. This systematic review was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. An electronic search for cross-sectional, cohort, or case-control studies was conducted on five databases (PubMed, ScienceDirect, EBSCO, Web of Science, and Scopus). No restrictions were applied to the language and year of publication. Exposure was PD, and the outcome of interest was the onset and/or progression of AD. The risk of bias of the included studies was assessed using the Newcastle-Ottawa Scale (NOS) designed for non-randomized studies. Six studies fulfilling the selection criteria were included in this systematic review. Four of the studies were of cohort design and two were of case-control design. All except one showed a significant association between PD and the risk of AD onset and progression. According to the NOS bias risk assessment, three studies were found to be of good quality, and three other cohort studies were of low quality. Data from this systematic review indicate that patients with PD present a significantly higher risk of AD compared to individuals with healthy periodontium. However, results should be interpreted with caution given the methodological limitations found. For future research, powerful and comparable epidemiological studies are needed to evaluate the relationship between PD and AD.
PubMed: 37916259
DOI: 10.7759/cureus.46311 -
Brain Sciences Aug 2023Social cognition has a broad theoretical definition, which includes the ability to mentalise, i.e., recognise and infer mental states to explain and predict another's... (Review)
Review
Social cognition has a broad theoretical definition, which includes the ability to mentalise, i.e., recognise and infer mental states to explain and predict another's behaviour. There is growing recognition of the clinical, diagnostic, and prognostic value of assessing a person's ability to perform social cognitive tasks, particularly aspects of theory of mind, such as mentalising. One such measure of mentalising is the 'Reading the Mind in the Eyes' test (RMET). This systematic review and meta-analysis consider performance on the RMET, applied to people with neurodegenerative conditions in matched control studies, since its publication in 2001. Overall, this review includes 22 papers with data from N = 800 participants with neurodegenerative conditions: Alzheimer's disease, = 31; Parkinson's disease, = 221; Lewy body dementia, = 33; motor neuron disease, = 218; Huntington's disease = 80; multiple sclerosis, = 217; and N = 601 matched typical controls. Our meta-analyses show that deficits in mentalising, as measured by the RMET, are consistently reported across neurodegenerative conditions, with participants in both early and late disease stages being affected. Social cognition is an emerging field of cognitive neuroscience requiring specific and sensitive measurement across each subdomain. Adult-based meta-normative data feature, for which future groups or individuals could be compared against, and hypotheses relating to the source of these mentalising deficits are further discussed. This review was registered with PROSPERO (CRD42020182874).
PubMed: 37759869
DOI: 10.3390/brainsci13091268 -
Frontiers in Medicine 2023Glaucoma, the leading cause of irreversible blindness, is a common disorder that contributes to gradual optic nerve degeneration. The beneficial impacts of uric acid...
BACKGROUND
Glaucoma, the leading cause of irreversible blindness, is a common disorder that contributes to gradual optic nerve degeneration. The beneficial impacts of uric acid (UA) have been reported in some neurodegenerative conditions such as Parkinson's disease, Alzheimer's disease, and amyotrophic lateral sclerosis. But the results of current studies about the association between serum UA level and glaucoma are conflicting. The present meta-analysis was conducted to provide a better understanding of the association between serum UA level and glaucoma.
METHODS
We searched the databases of PubMed, Scopus, Web of Science, and Google Scholar systematically until November 20, 2022 to identify case-control studies, comparing the serum UA concentrations of the patients with glaucoma and controls. The mean ± standard division difference was used to assess the difference in serum UA concentrations between the glaucoma patients and controls.
RESULTS
Six studies involving 1,221 glaucoma patients and 1,342 control group were included in the present meta-analysis. This meta-analysis using a random effect model indicated that the mean UA level in glaucoma patients was 0.13 ( = 91.92%, 95% CI = -0.42 to 0.68) higher than the controls; however, it was not statistically significant.
CONCLUSIONS
Our findings provide evidence that glaucoma patients have a higher serum UA level compared to the controls, but this difference is not statistically significant. Prospective studies are needed to determine the possible association between increased UA and glaucoma pathogenesis.
SYSTEMATIC REVIEW REGISTRATION
https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42022364055, identifier: CRD42022364055.
PubMed: 37575992
DOI: 10.3389/fmed.2023.1159316 -
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 -
Frontiers in Endocrinology 2023Alzheimer's disease (AD) is a neurodegenerative disorder that is the major cause of dementia in the aged population. Recent researches indicate that patients with AD... (Review)
Review
BACKGROUND
Alzheimer's disease (AD) is a neurodegenerative disorder that is the major cause of dementia in the aged population. Recent researches indicate that patients with AD have a significantly increased fracture risk, but the pathological mechanisms are still unclear.
OBJECTIVE
We systematically reviewed studies regarding bone fracture risk in AD to uncover links between the pathologies of osteoporosis and AD.
METHODS
We searched the literature using the databases of PubMed, Web of Science, Embase and Cochrane Library. Studies were included if they evaluated bone fracture risk in AD patients and if they explored the pathogenesis and prevention of bone fractures in these patients.
RESULTS
AD patients had a significantly higher risk of bone fractures than age-matched controls. Multiple factors contributed to the increased risk of bone fractures in AD patients, including the direct effects of amyloid pathology on bone cells, abnormal brain-bone interconnection, Wnt/β-catenin signalling deficits, reduced activity, high risk of falls and frailty, and chronic immune activity. Exercise, prevention of falls and fortified nutrition were beneficial for reducing the fracture risk in AD patients. However, the efficacy of anti-osteoporotic agents in preventing bone fractures should be further evaluated in AD patients as corresponding clinical studies are very scarce.
CONCLUSION
Alzheimer's disease patients have increased bone fracture risk and decreased bone mineral density owing to multiple factors. Assessment of anti-osteoporotic agents' efficacy in preventing bone fractures of AD patients is urgently needed.
Topics: Humans; Aged; Alzheimer Disease; Fractures, Bone; Osteoporosis; Amyloidogenic Proteins; Brain
PubMed: 37635980
DOI: 10.3389/fendo.2023.1190762 -
Scientific Reports Apr 2024Neurodegenerative diseases (NDDs) are characterized by neuronal damage and progressive loss of neuron function. Microbiome-based interventions, such as dietary... (Meta-Analysis)
Meta-Analysis
Neurodegenerative diseases (NDDs) are characterized by neuronal damage and progressive loss of neuron function. Microbiome-based interventions, such as dietary interventions, biotics, and fecal microbiome transplant, have been proposed as a novel approach to managing symptoms and modulating disease progression. Emerging clinical trials have investigated the efficacy of interventions modulating the GM in alleviating or reversing disease progression, yet no comprehensive synthesis have been done. A systematic review of the literature was therefore conducted to investigate the efficacy of microbiome-modulating methods. The search yielded 4051 articles, with 15 clinical trials included. The overall risk of bias was moderate in most studies. Most microbiome-modulating interventions changed the GM composition. Despite inconsistent changes in GM composition, the meta-analysis showed that microbiome-modulating interventions improved disease burden (SMD, - 0.57; 95% CI - 0.93 to - 0.21; I = 42%; P = 0.002) with a qualitative trend of improvement in constipation. However, current studies have high methodological heterogeneity and small sample sizes, requiring more well-designed and controlled studies to elucidate the complex linkage between microbiome, microbiome-modulating interventions, and NDDs.
Topics: Humans; Fecal Microbiota Transplantation; Gastrointestinal Microbiome; Microbiota; Neurodegenerative Diseases; Probiotics
PubMed: 38664425
DOI: 10.1038/s41598-024-59250-w -
Dementia and Neurocognitive Disorders Jan 2024Dementia subtypes, including Alzheimer's dementia (AD), dementia with Lewy bodies (DLB), and frontotemporal dementia (FTD), pose diagnostic challenges. This review...
BACKGROUND AND PURPOSE
Dementia subtypes, including Alzheimer's dementia (AD), dementia with Lewy bodies (DLB), and frontotemporal dementia (FTD), pose diagnostic challenges. This review examines the effectiveness of F-Fluorodeoxyglucose Positron Emission Tomography (F-FDG PET) in differentiating these subtypes for precise treatment and management.
METHODS
A systematic review following Preferred Reporting Items for Systematic reviews and Meta-Analyses guidelines was conducted using databases like PubMed and Embase to identify studies on the diagnostic utility of F-FDG PET in dementia. The search included studies up to November 16, 2022, focusing on peer-reviewed journals and applying the gold-standard clinical diagnosis for dementia subtypes.
RESULTS
From 12,815 articles, 14 were selected for final analysis. For AD versus FTD, the sensitivity was 0.96 (95% confidence interval [CI], 0.88-0.98) and specificity was 0.84 (95% CI, 0.70-0.92). In the case of AD versus DLB, 18F-FDG PET showed a sensitivity of 0.93 (95% CI 0.88-0.98) and specificity of 0.92 (95% CI, 0.70-0.92). Lastly, when differentiating AD from non-AD dementias, the sensitivity was 0.86 (95% CI, 0.80-0.91) and the specificity was 0.88 (95% CI, 0.80-0.91). The studies mostly used case-control designs with visual and quantitative assessments.
CONCLUSIONS
F-FDG PET exhibits high sensitivity and specificity in differentiating dementia subtypes, particularly AD, FTD, and DLB. This method, while not a standalone diagnostic tool, significantly enhances diagnostic accuracy in uncertain cases, complementing clinical assessments and structural imaging.
PubMed: 38362056
DOI: 10.12779/dnd.2024.23.1.54