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Journal of Alzheimer's Disease : JAD 2024Although Lumipulse assays and conventional ELISA are strongly correlated, the precise relationship between their measured values remains undetermined.
Relationship Between Cerebrospinal Fluid Alzheimer's Disease Biomarker Values Measured via Lumipulse Assays and Conventional ELISA: Single-Center Experience and Systematic Review.
BACKGROUND
Although Lumipulse assays and conventional ELISA are strongly correlated, the precise relationship between their measured values remains undetermined.
OBJECTIVE
To determine the relationship between Lumipulse and ELISA measurement values.
METHODS
Patients who underwent cerebrospinal fluid (CSF) Alzheimer's disease (AD) biomarker measurements and consented to biobanking between December 2021 and June 2023 were included. The relationship between values measured via Lumipulse assays and conventional ELISA were evaluated by Passing-Bablok analyses for amyloid-β 1-42 (Aβ42), total tau (t-tau), and phospho-tau 181 (p-tau 181). Studies using both assays were systematically searched for in PubMed and summarized after quality assessment.
RESULTS
Regression line slopes and intercepts were 1.41 (1.23 to 1.60) and -77.8 (-198.4 to 44.5) for Aβ42, 0.94 (0.88 to 1.01) and 98.2 (76.9 to 114.4) for t-tau, and 1.60 (1.43 to 1.75) and -21.1 (-26.9 to -15.6) for p-tau181. Spearman's correlation coefficients were 0.90, 0.95, and 0.95 for Aβ42, t-tau, and p-tau181, respectively. We identified 13 other studies that included 2,117 patients in total. Aβ42 slope varied among studies, suggesting inter-lab difference of ELISA. The slope and intercept of t-tau were approximately 1 and 0, respectively, suggesting small proportional and systematic differences. Conversely, the p-tau181 slope was significantly higher than 1, distributed between 1.5-2 in most studies, with intercepts significantly lower than 0, suggesting proportional and systematic differences.
CONCLUSIONS
We characterized different relationship between measurement values for each biomarker, which may be useful for understanding the differences in CSF biomarker measurement values on different platforms and for future global harmonization.
Topics: Alzheimer Disease; Humans; Biomarkers; Amyloid beta-Peptides; Enzyme-Linked Immunosorbent Assay; tau Proteins; Peptide Fragments
PubMed: 38759016
DOI: 10.3233/JAD-240185 -
Journal of Alzheimer's Disease : JAD 2024Early intervention is essential for meaningful disease modification in Alzheimer's disease (AD). (Meta-Analysis)
Meta-Analysis
BACKGROUND
Early intervention is essential for meaningful disease modification in Alzheimer's disease (AD).
OBJECTIVE
We aimed to determine the efficacy and safety of pharmacologic and nutritional interventions for early AD.
METHODS
PubMed, Embase, the Cochrane Library, and ClinicalTrials.gov were searched from database inception until 1 September 2023. We included randomized controlled trials that evaluated the efficacy of interventions in early AD. Only interventions that demonstrated efficacy compared to placebo were included in the network meta-analysis (NMA). Then we performed frequentist fixed-effects NMA to rank the interventions. GRADE criteria were used to evaluate the level of evidence.
RESULTS
Fifty-eight trials including a total of 33,864 participants and 48 interventions were eligible for inclusion. Among the 48 interventions analyzed, only 6 (12.5%) treatments- ranging from low to high certainty- showed significant improvement in cognitive decline compared to placebo. High certainty evidence indicated that donanemab (standardized mean difference [SMD] -0.239, 95% confidence interval [CI] -0.343 to -0.134) and lecanemab (SMD -0.194, 95% CI -0.279 to -0.108) moderately slowed the clinical progression in patients with amyloid pathology. Additionally, methylphenidate, donepezil, LipiDiDiet, and aducanumab with low certainty showed significant improvement in cognitive decline compared to placebo. However, there was no significant difference in serious adverse events as reported between the six interventions and placebo.
CONCLUSIONS
Only 12.5% of interventions studied demonstrated efficacy in reducing cognitive impairment in early AD. Donanemab and lecanemab have the potential to moderately slow the clinical progression in patients with amyloid pathology. Further evidence is required for early intervention in AD.
Topics: Alzheimer Disease; Humans; Randomized Controlled Trials as Topic; Network Meta-Analysis
PubMed: 38759015
DOI: 10.3233/JAD-240161 -
Frontiers in Aging Neuroscience 2024Abnormal cerebrospinal fluid (CSF)/serum albumin ratio (Qalb) levels have been observed in patients with cognitive impairment. Few studies have specifically focused on... (Review)
Review
BACKGROUND
Abnormal cerebrospinal fluid (CSF)/serum albumin ratio (Qalb) levels have been observed in patients with cognitive impairment. Few studies have specifically focused on Lewy Body Disease (LBD), and the results were controversial. Thus, we conducted this systematic review and meta-analysis to investigate Qalb levels in patients with LBD by including data from different studies.
METHOD
We systematically searched PubMed, Embase, Cochrane Library, and Web of Science databases for a collection of studies containing studies comparing Qalb levels in patients with LBD and healthy controls (including healthy controls and other dementia subtypes). In the initial search, 86 relevant papers were retrieved. Standardized mean differences (SMD) in Qalb levels were calculated using a random effects model.
RESULTS
A total of 13 eligible studies were included. Mean Qalb levels were significantly higher in patients with LBD compared to healthy older adults [standardized mean difference (SMD): 2.95, 95% confidence interval (CI): 0.89-5.00, = 2.81, = 0.005]; and were significantly higher in patients with LBD than in patients with Alzheimer's disease (AD) (SMD: 1.13, 95% CI: 0.42-1.83, = 3.15, = 0.002);whereas mean Qalb levels were significantly higher in patients with frontotemporal lobar degeneration (FTLD) compared to those with AD (SMD: 1.13, 95% CI,0.14-2.13, = 2.24, = 0.03).
CONCLUSION
Qalb levels were significantly elevated in LBD patients compared with normal older adults and were higher than those in AD patients and FTLD patients, which helped in the differential diagnosis of LBD from other neurodegenerative diseases.
SYSTEMATIC REVIEW REGISTRATION
https://www.crd.york.ac.uk/prospero/, identifier CRD42024496616.
PubMed: 38756533
DOI: 10.3389/fnagi.2024.1390036 -
Journal of Alzheimer's Disease Reports 2024Alzheimer's disease (AD) is the most common cause of dementia. While preclinical studies have shown benefits of glucagon-like peptide 1 receptor agonists (GLP-1 RA) in...
BACKGROUND
Alzheimer's disease (AD) is the most common cause of dementia. While preclinical studies have shown benefits of glucagon-like peptide 1 receptor agonists (GLP-1 RA) in targeting core AD pathology, clinical studies are limited.
OBJECTIVE
A systematic review was performed to evaluate GLP-1 RAs in AD for their potential to target core AD pathology and improve cognition.
METHODS
Searches were conducted via three different databases (PubMed, Embase, and Cochrane Library). Search terms included Medical Subject Headings (MeSH) terms: 'glucagon-like peptide 1 receptor agonist' and 'Alzheimer's disease', as well as entry terms 'GLP-1 RA', 'AD', and three types of GLP-1 RA: 'liraglutide', 'exenatide', and 'lixisenatide'.
RESULTS
A total of 1,444 studies were screened. Six articles that met criteria were included (four randomized control trials [RCTs] and two protocol studies). Two RCTs with amyloid-β and tau biomarker endpoints did not observe an end of treatment difference between the placebo and treated groups. In three RCTs with cognitive endpoints, there was no end of treatment difference between placebo and treated groups. GLP-1 RA showed metabolic benefits, such as lower body mass index and improved glucose levels on oral glucose tolerance tests in treated groups. GLP-1 RA may mitigate the decline in cerebral glucose metabolism and show enhanced blood-brain glucose transport capacity using F-FDG PET, however, more data is needed.
CONCLUSIONS
GLP-1 RA therapy did not alter amyloid-β and tau biomarkers nor show improvements in cognition but showed potential metabolic and neuroprotective benefits.
PubMed: 38746639
DOI: 10.3233/ADR-230181 -
Journal of Alzheimer's Disease Reports 2024The current cognitive tests have been developed based on and standardized against Western constructs and normative data. With older people of minority ethnic background...
BACKGROUND
The current cognitive tests have been developed based on and standardized against Western constructs and normative data. With older people of minority ethnic background increasing across Western countries, there is a need for cognitive screening tests to address factors which influence performance bias and timely diagnostic dementia accuracy. The diagnostic accuracy in translated and culturally adapted cognitive screening tests and their impact on test performance in diverse populations have not been well addressed to date.
OBJECTIVE
This review aims to highlight considerations relating to the adaptation processes, language, cultural influences, impact of immigration, and level of education to assess for dementia in non-Western and/or non-English speaking populations.
METHODS
We conducted a systematic search for studies addressing the effects of translation and cultural adaptations of cognitive screening tests (developed in a Western context) upon their diagnostic accuracy and test performance across diverse populations. Four electronic databases and manual searches were conducted, using a predefined search strategy. A narrative synthesis of findings was conducted.
RESULTS
Search strategy yielded 2,890 articles, and seventeen studies (4,463 participants) met the inclusion criteria. There was variability in the sensitivity and specificity of cognitive tests, irrespective of whether they were translated only, culturally adapted only, or both. Cognitive test performance was affected by education, linguistic ability, and aspects of acculturation.
CONCLUSIONS
We highlight the importance of translating and culturally adapting tests that have been developed in the Western context. However, these findings should be interpreted with caution as results varied due to the broad selection of included cognitive tests.
PubMed: 38746627
DOI: 10.3233/ADR-230198 -
Heliyon May 2024Magnetic resonance spectroscopy (MRS) is an imaging technique used to measure metabolic changes in the tissue. Due to the lack of evidence, MRS is not a priority in...
BACKGROUND
Magnetic resonance spectroscopy (MRS) is an imaging technique used to measure metabolic changes in the tissue. Due to the lack of evidence, MRS is not a priority in diagnosing neurodegenerative diseases because it is a relatively specialized technique that requires specialized equipment and expertise to perform and interpret. This systematic review aimed to present a comprehensive collection of MRS results in the most common neurodegenerative diseases.
METHODS
A systematic search of four electronic databases (PubMed, Scopus, Web of Science, and ScienceDirect) was conducted for studies published from 2017 to 2022. Articles that provided specific biomarker levels were selected, and studies that assessed the diseases via treatment, featured MRS applying nuclei other than 1H, or compared different animal models were excluded.
RESULTS
A total of 25 articles, plus 3 articles for extra information in the introduction, were included in this review. Six of the most common neurodegenerative diseases, i.e., Alzheimer's and Parkinson's disease, Huntington chorea, ataxia, multiple sclerosis (MS), multiple system atrophy (MSA), and progressive supranuclear palsy (PSP) were examined via MRS. The changes and ratios of N-acetylaspartate (NAA) could be seen in all of these disorders, which could lead to early diagnosis. However, there are other biomarkers, such as Cr and Chon, which can give convincing results.
DISCUSSION
This observational study is the first synthesis of the latest evidence proving metabolic changes during neurodegenerative diseases using MRS as a diagnosis method. The findings indicate decreased N-acetylaspartate (NAA) and NAA/Cr ratios in Alzheimer's disease (AD), Parkinson's disease (PD), ataxias, and MS, reflecting neuronal loss or dysfunction. Increased choline and myo-inositol were noted in some studies, suggesting cell membrane turnover and neuroinflammation. Findings were less consistent for other metabolites like glutamate and gamma-aminobutyric acid. However, there were limitations due to the lack of studies on the same volumes of interest (VOIs) and the small number of participants.
PubMed: 38726104
DOI: 10.1016/j.heliyon.2024.e30521 -
Frontiers in Immunology 2024Previous studies reported possible connections between inflammatory bowel disease (IBD) and several neurodegenerative disorders. However, the comprehensive relationships... (Meta-Analysis)
Meta-Analysis
The two-directional prospective association between inflammatory bowel disease and neurodegenerative disorders: a systematic review and meta-analysis based on longitudinal studies.
OBJECTIVE
Previous studies reported possible connections between inflammatory bowel disease (IBD) and several neurodegenerative disorders. However, the comprehensive relationships between IBD and various neurodegenerative disorders were not summarized. We executed a meta-analysis of longitudinal studies to provide an estimate of the strength of the two-directional prospective association between IBD and neurodegenerative disorders.
METHODS
We accomplished a thorough bibliographic search of PubMed, Web of Science, Embase, PsycINFO, and Cochrane Library databases until June 2023 to locate relevant longitudinal studies. The extracted data were then analyzed via meta-analysis using either a fixed or random effects model.
RESULTS
The final analysis encompassed 27 studies. Individuals with IBD faced an increased risk of developing four neurodegenerative disorders than the general public, namely, Alzheimer's disease (hazard ratio[HR] = 1.35, 95% confidence interval [CI]: 1.03-1.77, P=0.031), dementia (HR =1.24, 95% CI: 1.13-1.36, P<0.001), multiple sclerosis (HR =2.07, 95% CI:1.42-3.02, P<0.001) and Parkinson's disease (HR =1.23, 95% CI:1.10-1.38, P<0.001). Two articles reported an increased incidence of amyotrophic lateral sclerosis or multiple system atrophy in IBD patients. Three studies investigated the prospective association between multiple sclerosis and IBD, revealing an elevated risk of the latter in patients with the former. (HR=1.87, 95% CI:1.66-2.10, P<0.001).
INTERPRETATION
These findings verified the two-directional relationship between the brain-gut axis, specifically demonstrating a heightened risk of various neurodegenerative diseases among IBD patients. It may be profitable to prepare screening strategies for IBD patients to find neurodegenerative diseases during the long-term course of treatment for IBD with a view to potential earlier diagnosis and treatment of neurodegenerative diseases, reducing public health and social burden.
SYSTEMATIC REVIEW REGISTRATION
PROSPERO (CRD42023437553).
Topics: Humans; Inflammatory Bowel Diseases; Neurodegenerative Diseases; Longitudinal Studies; Risk Factors; Prospective Studies
PubMed: 38720896
DOI: 10.3389/fimmu.2024.1325908 -
Journal of Nutrition and Metabolism 2024Pathomechanisms of dementias involve increasing damage to neuronal energy metabolism, resulting in degeneration-related insulin resistance and glucose hypometabolism. In... (Review)
Review
Pathomechanisms of dementias involve increasing damage to neuronal energy metabolism, resulting in degeneration-related insulin resistance and glucose hypometabolism. In this case, ketone bodies can provide an alternative energy source. Supplementation with medium-chain triglycerides (MCTs), which can induce ketogenesis, may alleviate brain energy deficits and improve neuronal function. This review aims to determine the effectiveness of MCT as a symptomatic treatment approach. The systematic literature search was conducted in April 2023 following the Cochrane Handbook and PRISMA guidelines. A total of 21 studies were included, comprising eight uncontrolled trials and 13 RCTs investigating the effects of MCT on Alzheimer's disease (AD) and mild cognitive impairment (MCI). A substantial increase in plasma ketone levels and brain metabolic rates was observed. Cognitive assessments showed only occasional or domain-specific performance improvements. The effects on functional abilities or psychological outcomes have been inadequately studied. Besides gastrointestinal side effects, no harmful effects were observed. However, the evidence was severely weakened by heterogeneous and poorly designed study protocols, bias, and conflicts of interest. In conclusion, the ketogenic properties of MCTs may have beneficial effects on brain metabolism in AD and MCI but do not always result in measurable clinical improvement. Current evidence is insufficient to recommend MCT as a comparable symptomatic treatment option.
PubMed: 38715705
DOI: 10.1155/2024/9672969 -
BMC Geriatrics May 2024Abnormal amyloid β (Aβ) deposits in the brain are a hallmark of Alzheimer's disease (AD). Insufficient sleep duration and poor sleep quality are risk factors for... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Abnormal amyloid β (Aβ) deposits in the brain are a hallmark of Alzheimer's disease (AD). Insufficient sleep duration and poor sleep quality are risk factors for developing AD. Sleep may play a role in Aβ regulation, but the magnitude of the relationship between sleep and Aβ deposition remains unclear. This systematic review examines the relationship between sleep (i.e., duration and efficiency) with Aβ deposition in later-life adults.
METHODS
A search of PubMed, CINAHL, Embase, and PsycINFO generated 5,005 published articles. Fifteen studies met the inclusion criteria for qualitative syntheses; thirteen studies for quantitative syntheses related to sleep duration and Aβ; and nine studies for quantitative syntheses related to sleep efficiency and Aβ.
RESULTS
Mean ages of the samples ranged from 63 to 76 years. Studies measured Aβ using cerebrospinal fluid, serum, and positron emission tomography scans with two tracers: Carbone 11-labeled Pittsburgh compound B or fluorine 18-labeled. Sleep duration was measured subjectively using interviews or questionnaires, or objectively using polysomnography or actigraphy. Study analyses accounted for demographic and lifestyle factors. Based on 13 eligible articles, our synthesis demonstrated that the average association between sleep duration and Aβ was not statistically significant (Fisher's Z = -0.055, 95% CI = -0.117 ~ 0.008). We found that longer self-report sleep duration is associated with lower Aβ (Fisher's Z = -0.062, 95% CI = -0.119 ~ -0.005), whereas the objectively measured sleep duration was not associated with Aβ (Fisher's Z = 0.002, 95% CI = -0.108 ~ 0.113). Based on 9 eligible articles for sleep efficiency, our synthesis also demonstrated that the average association between sleep efficiency and Aβ was not statistically significant (Fisher's Z = 0.048, 95% CI = -0.066 ~ 0.161).
CONCLUSION
The findings from this review suggest that shorter self-reported sleep duration is associated with higher Aβ levels. Given the heterogeneous nature of the sleep measures and outcomes, it is still difficult to determine the exact relationship between sleep and Aβ. Future studies with larger sample sizes should focus on comprehensive sleep characteristics and use longitudinal designs to better understand the relationship between sleep and AD.
Topics: Humans; Amyloid beta-Peptides; Sleep; Aged; Sleep Quality; Time Factors; Cognition; Alzheimer Disease; Middle Aged; Sleep Duration
PubMed: 38714912
DOI: 10.1186/s12877-024-05010-4 -
Alzheimer's & Dementia : the Journal of... Jun 2024We investigate Alzheimer's disease and related dementia (ADRD) prevalence, incidence rate, and risk factors in individuals racialized as Asian and/or Asian-American and... (Meta-Analysis)
Meta-Analysis Review
A systematic review/meta-analysis of prevalence and incidence rates illustrates systemic underrepresentation of individuals racialized as Asian and/or Asian-American in ADRD research.
We investigate Alzheimer's disease and related dementia (ADRD) prevalence, incidence rate, and risk factors in individuals racialized as Asian and/or Asian-American and assess sample representation. Prevalence, incidence rate, risk factors, and heterogeneity of samples were assessed. Random-effects meta-analysis was conducted, generating pooled estimates. Of 920 records across 14 databases, 45 studies were included. Individuals racialized as Asian and/or Asian-American were mainly from Eastern and Southern Asia, had higher education, and constituted a smaller sample relative to non-Hispanic white cohorts. The average prevalence was 10.9%, ranging from 0.4% to 46%. The average incidence rate was 20.03 (12.01-33.8) per 1000 person-years with a range of 75.19-13.59 (12.89-14.33). Risk factors included physiological, genetic, psychological, behavioral, and social factors. This review underscores the systemic underrepresentation of individuals racialized as Asian and/or Asian-American in ADRD research and the need for inclusive approaches accounting for culture, language, and immigration status. HIGHLIGHTS: There is considerable heterogeneity in the prevalence of ADRD among studies of Asian-Americans. There is limited data on group-specific risk factors for ADRD among Asian-Americans. The average prevalence of (ADRD) among Asian-Americans was found to be 7.4%, with a wide range from 0.5% to 46%.
Topics: Humans; Prevalence; Asian; Incidence; Alzheimer Disease; Risk Factors; Dementia
PubMed: 38708587
DOI: 10.1002/alz.13820