Information Recognition and Recall in Older Adults Bearing Vascular Risk Factors with or without Diagnosis of Mild Cognitive Impairment DOI Open Access
Glykeria Tsentidou, Despina Μoraitou, Elvira Masoura

et al.

Journal of dementia and Alzheimer's disease, Journal Year: 2024, Volume and Issue: 1(1), P. 72 - 86

Published: Sept. 23, 2024

Episodic memory is affected early and a basic indication of neurodegeneration especially for Alzheimer’s disease. The aim this study was to examine whether adults with vascular risk factors are differentiated in their episodic performance from individuals mild cognitive impairment (MCI). diagnosed MCI, (VRF; blood pressure, diabetes mellitus, or hypercholesterolemia), healthy controls assessed using the Doors People test. Statistical processing included mediation analyses which were performed separately VRF control groups, MCI groups. ANOVA used groups matched age education. showed that had significantly lower than verbal recall only, F (1, 83) = 9.541, p 0.003, ηp2 0.10. A direct effect diagnosis on found via analysis as concerns controls, b 0.506, SE 0.128, < 0.001, 95%CI: 0.221–0.771, favor controls. Concerning tendency directly affect shown (α 0.005) 0.388, 0.150, 0.010, 0.043–0.720. In conclusion, it supported patients present deficit recall; addition, diagnostic category affects all groups’ same condition. These results indicated aspect can be sensitive indicator differentiate factors, well two pathological each other.

Language: Английский

CpGPT: a Foundation Model for DNA Methylation DOI Creative Commons
Lucas Paulo de Lima Camillo, Raghav Sehgal, Judith Armstrong

et al.

Published: Oct. 29, 2024

Abstract DNA methylation is a critical epigenetic modification that regulates gene expression and plays significant role in development disease processes. Here, we present the Cytosine-phosphate-Guanine Pretrained Transformer (CpGPT), novel foundation model pretrained on over 1,500 datasets encompassing 100,000 samples from diverse tissues conditions. CpGPT leverages an improved transformer architecture to learn comprehensive representations of patterns, allowing it impute reconstruct genome-wide profiles limited input data. By capturing sequence, positional, contexts, outperforms specialized models when finetuned for aging-related tasks, including chronological age prediction, mortality risk, morbidity assessments. The highly adaptable across different platforms tissue types. Furthermore, analysis sample-specific attention weights enables identification most influential CpG sites individual predictions. As model, sets new benchmark analysis, achieving strong performance Biomarkers Aging Challenge, where placed second overall estimation first public leaderboard methylation-based prediction. Highlights 100,000+ samples. demonstrates zero-shot tasks imputation, array conversion, reference mapping. achieves state-of-the-art results prediction estimation. Sample-specific interpretability enabled through weights.

Language: Английский

Citations

5
Evaluation of Exploratory Fluid Biomarker Results from a Phase 1 Senolytic Trial in Mild Alzheimer’s Disease DOI Creative Commons
Miranda E. Orr, Valentina R. Garbarino, Juan Pablo Palavicini

et al.

Research Square (Research Square), Journal Year: 2024, Volume and Issue: unknown

Published: March 8, 2024

Abstract Senescent cell accumulation contributes to the progression of age-related disorders including Alzheimer’s disease (AD). Clinical trials evaluating senolytics, drugs that clear senescent cells, are underway, but lack standardized outcome measures. Our team recently published data from first open-label trial evaluate senolytics (dasatinib plus quercetin) in AD. After 12-weeks intermittent treatment, we reported brain exposure dasatinib, favorable safety and tolerability, modest post-treatment changes cerebrospinal fluid (CSF) inflammatory AD biomarkers using commercially available assays. Herein, present more comprehensive exploratory analyses senolytic associated relevant proteins, metabolites, lipids, transcripts measured across blood, CSF, urine. These included mass spectrometry for precise quantification amyloid beta (Aß) tau CSF; immunoassays assess senescence secretory factors plasma, urine; analysis urinary metabolites lipids blood transcriptomic chronic stress peripheral cells. Levels Aß species remained stable. Targeted cytokine chemokine revealed treatment-associated increases plasma fractalkine MMP-7 CSF IL-6. Urinary unchanged. Modest lipid profile suggestive decreased inflammation were observed both peripherally centrally. Blood indicated downregulation genes FOS, FOSB, IL1β, IL8, JUN, JUNB, PTGS2. provide a foundation developing measures studies indicate distinct biofluid-specific signatures will require validation future studies. ClinicalTrials.gov: NCT04063124.

Language: Английский

Citations

4
Protocol for a pilot clinical trial of the senolytic drug combination Dasatinib Plus Quercetin to mitigate age-related health and cognitive decline in mental disorders DOI Creative Commons
Abigail Schweiger, Breno S. Diniz, Ginger E. Nicol

et al.

F1000Research, Journal Year: 2025, Volume and Issue: 13, P. 1072 - 1072

Published: March 5, 2025

Background Major depressive disorder (MDD) and schizophrenia are linked to accelerated aging leading reduced lifespan, health span cognitive decline. Cellular senescence, in which cells lose proliferative capacity develop a senescence-associated secretory phenotype (SASP), plays role this process. Emerging research suggests that the senolytic regimen of dasatinib+quercetin (D+Q) reduces senescent cells, potentially mitigating age-related This pilot study aims assess feasibility safety D+Q older adults with schizophrenia, schizoaffective disorder, treatment-resistant depression (TRD). Methods single-center will recruit 30 participants total aged 50 years or schizophrenia/schizoaffective 60 TRD; difference age limits is because individuals biologically about 10 than general population owing metabolic burden. Each participant receive two consecutive days 100 mg oral dasatinib plus 1250 quercetin at baseline weeks one through three, (i.e., on, five off ) along lifestyle risk management education. Questionnaires assessments measure function as well psychiatric baseline, week 10, year. Magnetic Resonance Imaging (MRI) structural functional brain weeks. Blood sampling for SASP testing occur seven time points: four, Conclusion evaluate D+Q’s potential counteract TRD. Trial registration Dasatinib Plus Quercetin Accelerated Aging Mental Disorders registered on ClinicalTrials.gov: NCT05838560; posted May 1, 2023.

Language: Английский

Citations

0
The Effects of Time‐Restricted Feeding on Handgrip Strength, Vigilance, and Perceived Anxiety and Depression in Older Adults: A Comparative Study Between Active and Sedentary Populations DOI Creative Commons
Mohamed Ali Boujelbane, Khaled Trabelsi, Haitham Jahrami

et al.

Health Science Reports, Journal Year: 2025, Volume and Issue: 8(4)

Published: April 1, 2025

ABSTRACT Background and Aims Ramadan intermittent fasting (RIF), a form of time‐restricted feeding, influences various physiological psychological functions. However, its effects on older adults remain insufficiently understood. This study examined the impact RIF physical mental health parameters, comparing active sedentary individuals. Specifically, we assessed handgrip strength (HGS), vigilance performance, anxiety, depression levels to determine whether regular activity mitigates potential adverse RIF. Methods Fifty‐eight (mean age 62.93 ± 3.99 years; 50% female) participated in this study. They were classified into an group ( n = 26) 32) based self‐reported levels. Assessments conducted before during included HGS measurement using handheld dynamometer, digital psychomotor test, validated questionnaires (General Anxiety Disorder‐7, Geriatric Depression Scale, Physical Activity Scale for Elderly). Results During RIF, both groups showed significant improvements vigilance, scores, with more pronounced benefits group. participants experienced decline HGS, whereas individuals maintained stable muscle strength. Conclusion Regular appears enhance while preventing adults. These findings highlight importance maintaining lifestyle support aging populations.

Language: Английский

Citations

0
Evaluation of exploratory fluid biomarkers from a phase 1 senolytic trial in mild Alzheimer’s disease DOI Creative Commons
Valentina R. Garbarino, Juan Pablo Palavicini, Justin Melendez

et al.

Neurotherapeutics, Journal Year: 2025, Volume and Issue: unknown, P. e00591 - e00591

Published: April 1, 2025

Language: Английский

Citations

0
Elevated senescence-associated secretory phenotype index in late-life bipolar disorder DOI

Tselot Tessema,

Breno S. Diniz, Érica Leandro Marciano Vieira

et al.

Journal of Affective Disorders, Journal Year: 2024, Volume and Issue: 360, P. 163 - 168

Published: May 23, 2024

Language: Английский

Citations

3
Novel Insights into Psychosis and Antipsychotic Interventions: From Managing Symptoms to Improving Outcomes DOI Open Access
Adonis Sfera,

Hassan Imran,

Dan O. Sfera

et al.

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(11), P. 5904 - 5904

Published: May 28, 2024

For the past 70 years, dopamine hypothesis has been key working model in schizophrenia. This contributed to development of numerous inhibitors dopaminergic signaling and antipsychotic drugs, which led rapid symptom resolution but only marginal outcome improvement. Over decades, there limited research on quantifiable pathological changes schizophrenia, including premature cellular/neuronal senescence, brain volume loss, attenuation gamma oscillations electroencephalograms, oxidation lipids plasma mitochondrial membranes. We surmise that aberrant activation aryl hydrocarbon receptor by toxins derived from gut microbes or environment drives cellular neuronal a hallmark Early aging promotes secondary changes, impairment loss mitochondria, gray matter depletion, decreased oscillations, compensatory metabolic shift lactate lactylation. The aim this narrative review is twofold: (1) summarize what known about senescence schizophrenia schizophrenia-like disorders, (2) discuss novel strategies for improving long-term outcomes severe mental illness with natural senotherapeutics, membrane lipid replacement, transplantation, microbial phenazines, antioxidant phenothiazines, glycogen synthase kinase-3 beta, antagonists.

Language: Английский

Citations

2
Chronic constipation and diarrhea are associated with depression in the elderly: Insights from a large cross-sectional study DOI

明骏 陈,

Hengheng Dai,

Zhanqi Tong

et al.

Research Square (Research Square), Journal Year: 2024, Volume and Issue: unknown

Published: Feb. 21, 2024

Abstract Background: This study was to investigate the relationship between chronic constipation, diarrhea, and depression among elderly, as extent of their association remains elusive despite well-established impact gastrointestinal symptoms on depression. Methods: Cross-sectional analyses were conducted using data from 2005-2010 U.S. National Health Nutrition Examination Surveys (NHANES), focusing adults aged 60 above with a sample size 4878. Depressive measured Patient Questionnaire 9 (PHQ-9) scale. Information about diarrhea or constipation retrieved bowel health questionnaire. Multivariable weighted logistic regression analysis models employed estimate gut status, adjusting for potential confounders (e.g., age, gender, race, education, marital education level, smoking drinking habits, medical history). Results: Probable (PHQ-9≥10) depressive (PHQ-9≥5) more prevalent elderly individuals than those without them (P <0.05). After all-cause, likely have significant increases in scores several subtypes <0.05, six out nine symptoms). We observed significantly positive correlation patients low mood/despair, appetite, lack concentration Conclusion: The (PHQ-9 ≥5) may be associated based nationally representative 2005 2010. These findings suggest that experiencing higher prevalence psychological symptoms.

Language: Английский

Citations

0
Information Recognition and Recall in Older Adults Bearing Vascular Risk Factors with or without Diagnosis of Mild Cognitive Impairment DOI Open Access
Glykeria Tsentidou, Despina Μoraitou, Elvira Masoura

et al.

Journal of dementia and Alzheimer's disease, Journal Year: 2024, Volume and Issue: 1(1), P. 72 - 86

Published: Sept. 23, 2024

Episodic memory is affected early and a basic indication of neurodegeneration especially for Alzheimer’s disease. The aim this study was to examine whether adults with vascular risk factors are differentiated in their episodic performance from individuals mild cognitive impairment (MCI). diagnosed MCI, (VRF; blood pressure, diabetes mellitus, or hypercholesterolemia), healthy controls assessed using the Doors People test. Statistical processing included mediation analyses which were performed separately VRF control groups, MCI groups. ANOVA used groups matched age education. showed that had significantly lower than verbal recall only, F (1, 83) = 9.541, p 0.003, ηp2 0.10. A direct effect diagnosis on found via analysis as concerns controls, b 0.506, SE 0.128, < 0.001, 95%CI: 0.221–0.771, favor controls. Concerning tendency directly affect shown (α 0.005) 0.388, 0.150, 0.010, 0.043–0.720. In conclusion, it supported patients present deficit recall; addition, diagnostic category affects all groups’ same condition. These results indicated aspect can be sensitive indicator differentiate factors, well two pathological each other.

Language: Английский

Citations

0