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MedRxiv : the Preprint Server For... Jun 2024Plasma p-tau217 and Tau-PET are strong prognostic biomarkers in Alzheimer's disease (AD), but their relative performance in predicting future cognitive decline among...
Plasma p-tau217 and Tau-PET are strong prognostic biomarkers in Alzheimer's disease (AD), but their relative performance in predicting future cognitive decline among cognitively unimpaired (CU) individuals is unclear. In this head-to-head comparison study including 9 cohorts and 1534 individuals, we found that plasma p-tau217 and medial temporal lobe Tau-PET signal showed similar associations with cognitive decline on a global cognitive composite test (R =0.32 vs R =0.32, p =0.812) and with progression to mild cognitive impairment (Hazard ratio[HR] =1.56[1.43-1.70] vs HR =1.63[1.50-1.77], p =0.627). Combined plasma and PET models were superior to the single biomarker models (R =0.36, p<0.01). Furthermore, sequential selection using plasma p-tau217 and then Tau-PET reduced the number of participants required for a clinical trial by 94%, compared to a 75% reduction when using plasma p-tau217 alone. We conclude that plasma p-tau217 and Tau-PET showed similar performance for predicting future cognitive decline in CU individuals, and their sequential use (i.e., plasma p-tau217 followed by Tau-PET in a subset with high plasma p-tau217) is useful for screening in clinical trials in preclinical AD.
PubMed: 38947004
DOI: 10.1101/2024.06.12.24308824 -
MedRxiv : the Preprint Server For... Jun 2024Blood tests have the potential to improve the accuracy of Alzheimer disease (AD) clinical diagnosis, which will enable greater access to AD-specific treatments. This...
INTRODUCTION
Blood tests have the potential to improve the accuracy of Alzheimer disease (AD) clinical diagnosis, which will enable greater access to AD-specific treatments. This study compared leading commercial blood tests for amyloid pathology and other AD-related outcomes.
METHODS
Plasma samples from the Alzheimers Disease Neuroimaging Initiative were assayed with AD blood tests from C2N Diagnostics, Fujirebio Diagnostics, ALZPath, Janssen, Roche Diagnostics, and Quanterix. Outcomes measures were amyloid positron emission tomography (PET), tau PET, cortical thickness, and dementia severity. Logistic regression models assessed the classification accuracies of individual or combined plasma biomarkers for binarized outcomes, and Spearman correlations evaluated continuous relationships between individual plasma biomarkers and continuous outcomes.
RESULTS
Measures of plasma p-tau217, either individually or in combination with other plasma biomarkers, had the strongest relationships with all AD outcomes.
DISCUSSION
This study identified the plasma biomarker analytes and assays that most accurately classified amyloid pathology and other AD-related outcomes.
PubMed: 38946970
DOI: 10.1101/2024.06.12.24308839 -
Research Square Jun 2024Tauopathies, including Alzheimer's disease (AD) and Frontotemporal Dementia (FTD), are histopathologically defined by the aggregation of hyperphosphorylated pathological...
Virus-like particle (VLP)-based vaccine targeting tau phosphorylated at Ser396/Ser404 (PHF1) site outperforms phosphorylated S199/S202 (AT8) site in reducing tau pathology and restoring cognitive deficits in the rTg4510 mouse model of tauopathy.
Tauopathies, including Alzheimer's disease (AD) and Frontotemporal Dementia (FTD), are histopathologically defined by the aggregation of hyperphosphorylated pathological tau (pTau) as neurofibrillary tangles in the brain. Site-specific phosphorylation of tau occurs early in the disease process and correlates with progressive cognitive decline, thus serving as targetable pathological epitopes for immunotherapeutic development. Previously, we developed a vaccine (Qβ-pT181) displaying phosphorylated Thr181 tau peptides on the surface of a Qβ bacteriophage virus-like particle (VLP) that induced robust antibody responses, cleared pathological tau, and rescued memory deficits in a transgenic mouse model of tauopathy. Here we report the characterization and comparison of two additional Qβ VLP-based vaccines targeting the dual phosphorylation sites Ser199/Ser202 (Qβ-AT8) and Ser396/Ser404 (Qβ-PHF1). Both Qβ-AT8 and Qβ-PHF1 vaccines elicited high-titer antibody responses against their pTau epitopes. However, only Qβ-PHF1 rescued cognitive deficits, reduced soluble and insoluble pathological tau, and reactive microgliosis in a 4-month rTg4510 model of FTD. Both sera from Qβ-AT8 and Qβ-PHF1 vaccinated mice were specifically reactive to tau pathology in human AD post-mortem brain sections. These studies further support the use of VLP-based immunotherapies to target pTau in AD and related tauopathies and provide potential insight into the clinical efficacy of various pTau epitopes in the development of immunotherapeutics.
PubMed: 38946961
DOI: 10.21203/rs.3.rs-4390998/v1 -
MedRxiv : the Preprint Server For... Jun 2024Older adults with mild cognitive impairment (MCI) exhibit deficits in cerebrovascular reactivity (CVR), suggesting CVR is a biomarker for vascular contributions to MCI....
BACKGROUND
Older adults with mild cognitive impairment (MCI) exhibit deficits in cerebrovascular reactivity (CVR), suggesting CVR is a biomarker for vascular contributions to MCI. This study examined if spontaneous CVR is associated with MCI and memory impairment.
METHODS
161 older adults free of dementia or major neurological/psychiatric disorders were recruited. Participants underwent clinical interviews, cognitive testing, venipuncture for Alzheimer's biomarkers, and brain MRI. Spontaneous CVR was quantified during 5 minutes of rest.
RESULTS
Whole brain CVR was negatively associated with age, but not MCI. Lower CVR in the parahippocampal gyrus (PHG) was found in participants with MCI and was linked to worse memory performance on memory tests. Results remained significant after adjusting for Alzheimer's biomarkers and vascular risk factors.
CONCLUSION
Spontaneous CVR deficits in the PHG are observed in older adults with MCI and memory impairment, indicating medial temporal microvascular dysfunction's role in cognitive decline.
PubMed: 38946941
DOI: 10.1101/2024.06.18.24309109 -
Saudi Journal of Biological Sciences Aug 2024Plant phenolics have been known for various biological activities. This study aims to extract and examine the presence of phenolics in Bao mango (Mangifera indica L....
Plant phenolics have been known for various biological activities. This study aims to extract and examine the presence of phenolics in Bao mango (Mangifera indica L. var.) peel ethanolic extract (MPE). Further, antioxidant, anti-diabetic (α-amylase, and α-glucosidase inhibitory activity), and anti- Alzheimer's disease (AD) (acetylcholinesterase (AChE), butyrylcholinesterase (BChE), and β-secretase (BACE-1) inhibitory activity) efficacy of MPE were determined. The results indicated that mangiferin (8755.89 mg/ 100 g extract) was the major phenolic compound in MPE. An antioxidant mechanism revealed that MPE had a higher radical scavenging ability (4266.70 µmol TE/g extract) compared to reducing power (FRAP) or oxygen radical absorption capacity (ORAC). Further enzyme inhibitory assay against diabetic and AD involved enzymes showed that MPE had stronger inhibitory action against an enzyme involved in diabetes compared to their standard drug (Acarbose) (P < 0.05). While a lower IC value was observed against AD-involved enzymes compared to their standard drug (donepezil) (P < 0.05). The results show that Thai Bao mango peel byproduct can be a potential source of nutraceuticals to lower diabetes and improve cognitive health.
PubMed: 38946846
DOI: 10.1016/j.sjbs.2024.104033 -
Frontiers in Nutrition 2024The MIND diet is a healthy dietary pattern that has some benefits for many health outcomes. Our study aims to conduct a bibliometric analysis of the MIND diet,...
The MIND diet is a healthy dietary pattern that has some benefits for many health outcomes. Our study aims to conduct a bibliometric analysis of the MIND diet, identifying leading edges and hotspots to provide a reference for future research. The research on the MIND diet was gathered from the Web of Science Core Collection (WOSCC) database. For bibliometric analysis, VOSviewer 1.6.16 and the WOSCC Online Analysis Platform were utilized. In total, this comprehensive investigation encompassed 171 documents in the field of the MIND diet. The publications are globally distributed, with contributions from 953 authors across 362 institutions in 37 countries/regions, and published in 94 journals. The United States leads with 72 publications, and Iran and the People's Republic of China also show notable engagement with 28 and 19 publications, respectively. Rush University stands out with 21 publications, followed by Harvard University and Tehran University of Medical Sciences, demonstrating their substantial contributions to this field. Martha Clare Morris is a key figure with 10 publications, alongside Klodian Dhana and Puja Agarwal, each contributing 9 publications, highlighting their influence in the MIND diet research. The journal "Nutrients" is a major publication venue with 20 related articles, followed by "Frontiers in Nutrition" and "Journal of Nutrition Health Aging," reflecting their crucial roles in advancing knowledge about the MIND diet. The first high-cited publication was published in and conducted by Martha Clare Morris, which focuses on the MIND diet's relationship with Alzheimer's disease prevention and cognitive decline and emphasizes the diet's neuroprotective potential, highlighting how even moderate adherence can substantially reduce Alzheimer's risk and slow cognitive decline. In conclusion, this is the first comprehensive bibliometric study that quantitatively and qualitatively analyzed the publications in the field of the MIND diet. The MIND diet may be a promising dietary pattern for dementia. However, the current evidence is restricted and highlights the urgency and necessity of further research to investigate the efficacy of this diet for cognitive function. In addition, the MIND diet may have some benefits for other health outcomes, including CVDs, cancer, and diabetes. The number of studies in the field of the MIND diet is limited. More studies are needed, and will give us more knowledge about the MIND diet to improve human health, especially for dementia.
PubMed: 38946791
DOI: 10.3389/fnut.2024.1348808 -
Frontiers in Aging Neuroscience 2024Alzheimer's disease (AD) is a prevalent neurodegenerative disorder characterized by abnormal protein deposition. With an alarming 30 million people affected worldwide,... (Review)
Review
Alzheimer's disease (AD) is a prevalent neurodegenerative disorder characterized by abnormal protein deposition. With an alarming 30 million people affected worldwide, AD poses a significant public health concern. While inhibiting key enzymes such as -site amyloid precursor protein-cleaving enzyme 1 and -secretase or enhancing amyloid- clearance, has been considered the reasonable strategy for AD treatment, their efficacy has been compromised by ineffectiveness. Furthermore, our understanding of AD pathogenesis remains incomplete. Normal aging is associated with a decline in glucose uptake in the brain, a process exacerbated in patients with AD, leading to significant impairment of a critical post-translational modification: glycosylation. Glycosylation, a finely regulated mechanism of intracellular secondary protein processing, plays a pivotal role in regulating essential functions such as synaptogenesis, neurogenesis, axon guidance, as well as learning and memory within the central nervous system. Advanced glycomic analysis has unveiled that abnormal glycosylation of key AD-related proteins closely correlates with the onset and progression of the disease. In this context, we aimed to delve into the intricate role and underlying mechanisms of glycosylation in the etiopathology and pathogenesis of AD. By highlighting the potential of targeting glycosylation as a promising and alternative therapeutic avenue for managing AD, we strive to contribute to the advancement of treatment strategies for this debilitating condition.
PubMed: 38946780
DOI: 10.3389/fnagi.2024.1398641 -
Alzheimer's & Dementia : the Journal of... Jul 2024The study aimed to investigate the associations of changes in social isolation, loneliness, or both, with cognitive function.
INTRODUCTION
The study aimed to investigate the associations of changes in social isolation, loneliness, or both, with cognitive function.
METHODS
Data were from 7299 older adults in the Chinese Longitudinal Healthy Longevity Survey. We defined four change patterns (no, incident, transient, and persistent) for social isolation and loneliness, and created nine-category variable to represent the joint changes. Tobit regression models and Cox models were performed.
RESULTS
Incident, transient, and persistent social isolation or loneliness may accelerate cognitive decline (p < 0.05). Incident, transient, and persistent social isolation were associated with higher cognitive impairment risk, while only persistent loneliness was associated with higher cognitive impairment risk (p < 0.001). Notably, short-term or persistent social isolation was associated with accelerated cognitive decline and incident cognitive impairment, regardless of different loneliness change status (p < 0.05).
DISCUSSION
Short-term or persistent social isolation and persistent loneliness may be a salient risk factor for cognitive decline and cognitive impairment.
HIGHLIGHTS
Incident, transient, and persistent social isolation were associated with accelerated cognitive decline and higher cognitive impairment risk. Persistent loneliness was associated with accelerated cognitive decline and higher cognitive impairment risk. Short-term or persistent social isolation with concurrent different loneliness change status accelerated cognitive decline and higher cognitive impairment risk.
PubMed: 38946708
DOI: 10.1002/alz.14080 -
Alzheimer's & Dementia : the Journal of... Jul 2024We assessed the relationship of liver fibrosis score with incident dementia in a large, national sample.
BACKGROUND
We assessed the relationship of liver fibrosis score with incident dementia in a large, national sample.
METHODS
For this retrospective cohort study, data of dementia-free individuals aged 40-69 years were derived from electronic records of the largest healthcare provider in Israel. The association between liver fibrosis score (FIB-4), assessed from routine laboratory measurements, and incident dementia was explored through multivariate cox regression models.
RESULTS
Of the total sample (N = 826,578, mean age 55 ± 8 years at baseline), 636,967 (77%) had no fibrosis, 180,114 (21.8%) had inconclusive fibrosis status and 9497 (1.2%) had high risk for advanced fibrosis. Over a median follow-up of 17 years, 41,089 dementia cases were recorded. Inconclusive liver fibrosis and advanced fibrosis were associated with increased dementia risk (HR = 1.09, 95%CI: 1.07-1.11 and HR = 1.18, 95%CI: 1.10-1.27, respectively). This association remained robust through seven sensitivity analyses.
CONCLUSIONS
Liver fibrosis assessed through a serum-based algorithm may serve as a risk factor for dementia in the general population.
HIGHLIGHTS
Liver fibrosis may predict dementia diagnosis in the general population. Inconclusive liver fibrosis was associated with 9% increased dementia risk. Advanced liver fibrosis was associated with 18% increased dementia risk. Findings remained robust in sensitivity analyses and after adjustments.
PubMed: 38946688
DOI: 10.1002/alz.14033 -
Alzheimer's & Dementia : the Journal of... Jul 2024Evidence for the effect of early menopause on cognition among older women is not consistent and is scant among the Indian population.
BACKGROUND
Evidence for the effect of early menopause on cognition among older women is not consistent and is scant among the Indian population.
METHODS
We aimed to examine the effect of early menopause (≤45 years) on cognitive performance and brain morphology among older dementia-free females of the TLSA cohort using a multiple linear regression analysis.
RESULTS
In a sample of 528 women, 144 (27%) had early menopause. The linear regression analysis showed that women with early menopause performed poorly in cognition and had lesser total gray matter volume [β = -11973.94, p = 0.033], left middle frontal [β = -353.14, p = 0.033], and left superior frontal [β = -460.97, p < 0.026] volume.
CONCLUSION
Dementia-free women with early menopause had poorer cognition, lower total gray matter, and frontal lobe. More research is needed to explore the link between earlier menopause and cognitive decline and develop ways to address it.
HIGHLIGHTS
Evidence on the effect of early menopause on brain morphology is inconsistent and scant in low and middle-income countries, such as India. In a cohort of dementia-free individuals in urban Bangalore, we observed that participants with early menopause had significantly lower cognitive performance and lower total gray matter and frontal lobe volume. We recommend increasing awareness of this fact among the medical community and the general public. There is an urgent need to explore the underlying biological mechanism and to discover effective interventions to mitigate the effect.
PubMed: 38946683
DOI: 10.1002/alz.14069