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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 -
European Review For Medical and... Apr 2024Dysgeusia is characterized by a loss of taste perception, leading to malnutrition. This situation affects inflammatory conditions such as respiratory and neurological... (Meta-Analysis)
Meta-Analysis
OBJECTIVE
Dysgeusia is characterized by a loss of taste perception, leading to malnutrition. This situation affects inflammatory conditions such as respiratory and neurological conditions, obesity, cancer, chemotherapy, aging, and many others. To date, there is not much information on the prevalence and risk of dysgeusia in an inflammatory condition; also, it is unclear which flavor is altered.
MATERIALS AND METHODS
We systematically searched three databases from January 2018 to January 2023. Participants were children, adults, or elderly persons with an inflammatory condition and evaluated taste loss. A random effects model was used for statistical analysis to calculate the pooled odds ratio with its corresponding 95.0% confidence interval to estimate the probability of taste alteration (dysgeusia) in an inflammatory condition.
RESULTS
The data allowed us to conduct a systematic review, including 63 original articles and 15 studies to perform the meta-analysis. The meta-analysis indicated a heterogenicity of 84.7% with an odds ratio of 3.25 (2.66-3.96), indicating a significant risk of Alzheimer's disease, SARS-CoV-2, chemotherapy, and rhinosinusitis.
CONCLUSIONS
Inflammatory conditions and taste alterations are linked. Dysgeusia is associated with a higher risk of malnutrition and poorer general health status, especially in vulnerable populations.
Topics: Humans; Inflammation; Dysgeusia; Taste Perception; COVID-19; Alzheimer Disease; Taste; Malnutrition; SARS-CoV-2
PubMed: 38708467
DOI: 10.26355/eurrev_202404_36024 -
Frontiers in Aging Neuroscience 2024Vitamin D is a lipid soluble steroid hormone, which plays a critical role in the calcium homeostasis, neuronal development, cellular differentiation, and growth by...
Associations of vitamin D receptor polymorphisms with risk of Alzheimer's disease, Parkinson's disease, and mild cognitive impairment: a systematic review and meta-analysis.
Vitamin D is a lipid soluble steroid hormone, which plays a critical role in the calcium homeostasis, neuronal development, cellular differentiation, and growth by binding to vitamin D receptor (VDR). Associations between VDR gene polymorphism and Alzheimer's disease (AD), Parkinson's disease (PD), and mild cognitive impairment (MCI) risk has been investigated extensively, but the results remain ambiguous. The aim of this study was to comprehensively assess the correlations between four VDR polymorphisms (I, I, I, and I) and susceptibility to AD, PD, and MCI. Crude odds ratios (ORs) and 95% confidence intervals (CIs) were calculated to determine the relationship of interest. Pooled analyses suggested that the I polymorphism decreased the overall AD risk, and the I increased the overall PD susceptibility. In addition, the I and I polymorphisms were significantly correlated with the overall MCI risk. Stratified analysis by ethnicity further showed that the I and I genotypes reduced the AD predisposition among Caucasians, while the I polymorphism enhanced the PD risk among Asians. Intriguingly, carriers with the BB genotype significantly decreased the MCI risk in Asian descents, and the I variant elevated the predisposition to MCI in Caucasians and Asians. Further studies are need to identify the role of VDR polymorphisms in AD, PD, and MCI susceptibility.
PubMed: 38681668
DOI: 10.3389/fnagi.2024.1377058 -
Alzheimer's Research & Therapy Apr 2024Clinical trials in Alzheimer's disease (AD) had high failure rates for several reasons, including the lack of biological endpoints. Fluid-based biomarkers may present a...
BACKGROUND
Clinical trials in Alzheimer's disease (AD) had high failure rates for several reasons, including the lack of biological endpoints. Fluid-based biomarkers may present a solution to measure biologically relevant endpoints. It is currently unclear to what extent fluid-based biomarkers are applied to support drug development.
METHODS
We systematically reviewed 272 trials (clinicaltrials.gov) with disease-modifying therapies starting between 01-01-2017 and 01-01-2024 and identified which CSF and/or blood-based biomarker endpoints were used per purpose and trial type.
RESULTS
We found that 44% (N = 121) of the trials employed fluid-based biomarker endpoints among which the CSF ATN biomarkers (Aβ (42/40), p/tTau) were used most frequently. In blood, inflammatory cytokines, NFL, and pTau were most frequently employed. Blood- and CSF-based biomarkers were used approximately equally. Target engagement biomarkers were used in 26% (N = 72) of the trials, mainly in drugs targeting inflammation and amyloid. Lack of target engagement markers is most prominent in synaptic plasticity/neuroprotection, neurotransmitter receptor, vasculature, epigenetic regulators, proteostasis and, gut-brain axis targeting drugs. Positive biomarker results did not always translate to cognitive effects, most commonly the small significant reductions in CSF tau isoforms that were seen following anti-Tau treatments. On the other hand, the positive anti-amyloid trials results on cognitive function were supported by clear effect in most fluid markers.
CONCLUSIONS
As the field moves towards primary prevention, we expect an increase in the use of fluid-based biomarkers to determine disease modification. Use of blood-based biomarkers will rapidly increase, but CSF markers remain important to determine brain-specific treatment effects. With improving techniques, new biomarkers can be found to diversify the possibilities in measuring treatment effects and target engagement. It remains important to interpret biomarker results in the context of the trial and be aware of the performance of the biomarker. Diversifying biomarkers could aid in the development of surrogacy biomarkers for different drug targets.
Topics: Alzheimer Disease; Humans; Biomarkers; Clinical Trials as Topic; tau Proteins; Amyloid beta-Peptides
PubMed: 38678292
DOI: 10.1186/s13195-024-01456-1