Sleep structure of short-term insomnia disorder with mild cognitive impairment in older adults and their correlation with cognitive function: a case-control study

Frontiers in Aging Neuroscience, Journal Year: 2025, Volume and Issue: 16

Published: Jan. 3, 2025

This study seeks to delineate the sleep architecture characteristics in older adults with short-term insomnia and mild cognitive impairment (MCI) explore their association performance. Ninety elderly individuals were enrolled stratified into two cohorts based on Montreal Cognitive Assessment (MoCA) scores: Short-Term Insomnia Group (STID) comprising 35 participants Impairment (STID-MCI) 55 participants. Demographic data, Pittsburgh Sleep Quality Index (PSQI), MoCA, Hamilton Depression Rating Scale (HAMD-17), Anxiety (HAMA), polysomnography (PSG) parameters compared between groups. Correlations MoCA scores PSG metrics also analyzed. No significant disparities noted groups terms of HAMD-17, HAMA, PSQI (p > 0.05). However, marked differences identified its subdomains < Significant variations observed duration proportion slow-wave (N3) In STID-MCI patients, memory correlated positively N3 percentage 0.05), while verbal functions attention associated rapid eye movement (REM) duration. highlights potential clinical assessment function underscores need for targeted interventions improve quality this vulnerable population.

Language: Английский

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Bis(7)-harmine derivatives as potential multi-target anti-Alzheimer agents

Frontiers in Chemistry, Journal Year: 2025, Volume and Issue: 13

Published: Jan. 29, 2025

Introduction The multi-targeted ligands (MTDL) strategy has been recognized as a promising Approach for the development of effective treatments against Alzheimer’s disease (AD), due to presence multiple pathological mechanisms in AD. In this study, series bis(7)-harmine derivatives were designed and synthesized multifunctional drugs treatment Methods by chemical methods their structure was confirmed nuclear magnetic resonance (NMR). Ellman’s assay utilized assess inhibitory potential h AChE BuChE. activity these on both MAO-A MAO-B assessed using fluorescence-based method. thioflavin T (Th-T) fluorescence used inhibition A β 1−42 self-aggregation. cytotoxicity evaluated MTT assay. Surflex-Dock program Sybyl-X2.0 Software employed molecular docking. Results vitro studies revealed that numerous compounds exhibited potent AChE, (IC 50 &lt; 1 μM), well aggregation 20 μM). Importantly, multitarget 6d , 8c 8d remarkable efficacy simultaneously mitigating -induced toxicity SH−SY5Y cells while demonstrating minimal cytotoxicity. Furthermore, predicted ADMET results suggested possessed favorable pharmacokinetic properties demonstrated low levels. Additionally, docking within activesites MAO-B, elucidated mechanism. Discussion conclusion Based findings, it is evident hold multi-functional AD treatment.

Language: Английский

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Immune cells: Mediators in the metabolites and Alzheimer’s disease

Journal of Alzheimer s Disease, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 29, 2025

Background Alzheimer’s disease (AD) is a progressive neurodegenerative disorder that predominantly affects elderly individuals across the globe. While genetic, environmental, and lifestyle factors are known to influence onset of AD, underlying mechanisms remain unclear. Objective To elucidate intricate interplay between metabolites immune cell activation in ethology determine their collective impact on AD risk. Methods We conducted comprehensive analysis genome-wide association studies data examine relationships metabolites, phenotypes, risk AD. Our study encompassed examination involving 731 distinct types, 1400 large cohort comprising10,520 cases with 401,661 controls. employed univariate Mendelian randomization assess bidirectional cells, as well cells Subsequently, multivariate was then applied evaluate potential mediating role relationship Results Specific histidine/pyruvate ratio homoarginine, were positively associated mediated by cells. Conversely, 4-hydroxycoumarin glycolithocholate sulfate showed protective associations against Immune markers, CD64 monocytes HLA DR CD14 + CD16 − linked higher risk, while CD33 dim CD11b myeloid CD8 T protective. Conclusions This highlights critical pathogenesis demonstrating how interaction specific influences

Language: Английский

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Effects of a Loosening Meditation Practice on Older Adults With Mild Cognitive Impairment: A Pilot Study

Cureus, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 9, 2025

Background Holistic medical practices, including meditation and mindfulness, are increasingly recognized for their benefits in mental health stress reduction, with applications clinical settings. However, effects on older adults mild cognitive impairment (MCI) remain underexplored. This study aimed to evaluate the impact of loosening meditation, a brief accessible practice we developed, this population. Methods Nine MCI, defined by Mini-Mental State Examination (MMSE) scores 21-28 during screening period, participated pilot study. The sessions our were conducted weekly over four weeks. Cognitive function was assessed using MMSE Revised Hasegawa's Dementia Scale (HDS-R), while psychological well-being evaluated 30-item General Health Questionnaire (GHQ-30) Japanese version University Wales Institute Science Technology Mood Adjective Checklist (JUMACL). Serum levels representative biomarkers measured before after first session. Results Participants had mean age 78.1 years (± 4.8 years) score 25.1 points 2.5). These participants could complete all safely. No significant differences observed MMSE, HDS-R, GHQ-30, or JUMACL (tension arousal) intervention. (emotion significantly improved fourth session (pre-first, 25.3 ± 6.2; post-fourth, 28.7 7.3; p = 0.004). Among these biomarkers, serum cortisol decreased following (before versus after, 10.8 5.8 7.4 2.3 μg/dl; 0.04). Additionally, although not statistically significant, there trend towards lower level adrenaline 0.057 0.026 0.050 0.027 ng/ml; 0.06). Conclusions Our feasible, acceptable, safe, might enhance mood reduce even MCI. preliminary findings suggest its potential as supportive intervention

Language: Английский

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Targeting Amyloid Pathology in Early Alzheimer’s: The Promise of Donanemab-Azbt

Pharmacy, Journal Year: 2025, Volume and Issue: 13(1), P. 23 - 23

Published: Feb. 8, 2025

Objective: The purpose of this review is to examine the potential role donanemab-azbt in treatment and management early-stage Alzheimer’s disease (AD), with a focus on its efficacy, safety, clinical relevance based data from key trials. Data Sources: A comprehensive literature search PubMed was conducted using relevant keywords such as “donanemab”, “Alzheimer’s disease”, “Kisunla”, “TRAILBLAZER trials”, “amyloid-related imaging abnormalities (ARIA)”. Additional were extracted trial records (clinicaltrials.gov), conference abstracts, product monographs. Study Selection Extraction: Only English-language studies human populations included. Clinical trials peer-reviewed detailing mechanistic insights prioritized. Synthesis: Key findings TRAILBLAZER series highlighted slowing cognitive functional decline AD: (1) TRAILBLAZER-ALZ (Phase 2): This focused participants intermediate levels tau protein. Results demonstrated statistically significant decline. (2) 2 3): large-scale, randomized, double-blind, placebo-controlled study confirmed efficacy reducing amyloid plaque accumulation results included 35% Integrated Disease Rating Scale (iADRS) 36% Dementia Rating-Sum Boxes (CDR-SB). secondary outcomes showed improvements activities daily living reduced risk progression. (3) 3: ongoing evaluating donanemab’s delaying or preventing Alois Alzheimer cognitively normal individuals plaques, broadening scope early intervention strategies. (4) 4: head-to-head comparison aducanumab revealed superior clearance donanemab. (5) 5: Currently recruiting, aims evaluate safety across diverse varying comorbidities. (6) 6 3b): investigates modified dosing regimens reduce ARIA while maintaining particularly genetic factors like ApoE ε4 homozygotes. Relevance Patient Care Practice: Donanemab-azbt represents promising option for patients AD. It specifically targets reduces beta hallmark disease, potentially progression preserving function. However, administration requires careful patient selection, including testing status, mitigate risks ARIA. Furthermore, emphasize importance close monitoring during treatment. Conclusions: offers new avenue managing AD, showing promise burden While have been trials, further research essential validate long-term outcomes, assess effectiveness populations, refine strategies minimize side effects. With continued investigation, could significantly impact landscape AD

Language: Английский

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Subjective and functional cognitive impairment: diagnostics using biological markers of Alzheimer's disease

Neurology neuropsychiatry Psychosomatics, Journal Year: 2025, Volume and Issue: 17(1), P. 4 - 9

Published: Feb. 15, 2025

Cognitive impairment (CI) is one of the most common disorders in elderly. The development dementia usually preceded by subjective (SCI) and mild cognitive (MCI) over several years. Patients with SCI are at increased risk developing MCI dementia, but may not progress for a long time many cases functional nature (functional CI – FCI). article discusses manifestations diagnostic issues FCI possibilities diagnosing Alzheimer's disease (AD) stage using biological markers AD cerebrospinal fluid (CSF). presents results long-term follow-up (more than 4 years) two patients who showed no significant disturbances repeated neuropsychological examinations. In patient SCI, positive were found CSF, indicating an early (second) AD, while other absence these indicated CI. treatment anti-amyloid therapy when detected.

Language: Английский

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TaiChi-MSS protocol: enhancing cognitive and brain function in MCI patients through Tai Chi exercise combined with multisensory stimulation

Frontiers in Aging Neuroscience, Journal Year: 2025, Volume and Issue: 17

Published: Feb. 25, 2025

The aging population in China is confronted with considerable challenges, 14.71% of elderly individuals affected by mild cognitive impairment (MCI). practice Tai Chi has been demonstrated to enhance function, while sensory stimulation shown facilitate neural activity. Nevertheless, the combined impact and on cognitive, functions, brain activation older adults MCI remains uncertain. This study aims ascertain whether integration can more efficacious interventions for these outcomes. TaiChi-MSS (Tai Multisensory Stimulation Cognitive Function) a multi-center, randomized controlled trial (RCT) conducted Suzhou Shanghai, enrolling 88 participants aged 60 years or MCI. Participants will be randomly assigned one four groups: Chi, multisensory stimulation, control. intervention last 6 months, follow-up assessments at 3, 6, 9 months. Primary outcomes include assessments, assessed using Montreal Assessment (MoCA), Mini-Mental State Examination (MMSE), domain-specific tests, Pure Tone Audiometry (PTA), Sniffin' Sticks Odor Identification Test. Secondary involve activation, measured through functional Magnetic Resonance Imaging (fMRI) scans. fMRI used assess structure connectivity changes, focusing neuroplasticity. Data analyzed mixed-effects models. False Discovery Rate (FDR) correction method multiple comparisons control expected proportion false positives. was approved ethics committee Shanghai University Sport (No. 102772023RT200). results this disseminated peer-reviewed journals presented academic conferences.

Language: Английский

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Age-Related Differences in Lipopolysaccharide-Induced Delirium-like Behavior Implicate the Distinct Microglial Composition in the Hippocampus

International Journal of Molecular Sciences, Journal Year: 2025, Volume and Issue: 26(5), P. 2055 - 2055

Published: Feb. 26, 2025

As the global population ages, mechanisms underlying age-related susceptibility to delirium have attracted attention. Given central role of microglia in pathogenesis inflammation-related delirium, we investigated temporal dynamics neurobehavioral changes and microglial responses, following lipopolysaccharide (LPS, 200 μg/kg) administration young old male C57BL/6 mice. Although a similar illness trajectory across 48 h post-treatment (HPT) was observed both age groups, old-LPS mice exhibited worsened delirium-like behavior. At HPT, but not mice, significantly decreased hippocampal neuronal activity coincided with overactivation. Widespread activation present at 3 HPT subsided by 12 indicating generally retarded prolonged response LPS challenge However, for p16INK4a-negative (with low abundance aged brain) comparable morphological activation, which p16INK4a-positive (highly abundant brain). These results suggest that LPS-induced behavior accompanied different patterns might implicate composition shifts optimizing represents promising approach reduce vulnerability inflammatory challenge.

Language: Английский

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Discovery of novel theophylline derivatives bearing tetrazole scaffold for the treatment of Alzheimer's disease

RSC Advances, Journal Year: 2025, Volume and Issue: 15(9), P. 6994 - 7003

Published: Jan. 1, 2025

Alzheimer's disease (AD) is associated with AChE and BACE1 enzymes. Designing inhibitors for preventing these enzymes can be benefit AD treatment. In this context, theophylline derivatives were generated to prevent the biological activity of BACE1. particular, potential inhibitory compounds was rapidly accurately estimated via knowledge-methods. The in vitro tests then performed validate artificial intelligent approach. Among these, compound 12 exhibited most potent inhibition an IC50 15.68 μM, while showing limited against addition, six indicated that are able inhibit AChE, however, play poor performance over target. Atomistic simulations finally applied clarify ligand-binding mechanism outcomes disclose rigidly form van der Waals interactions π-stacking SC contacts. Overall, may offer a scaffold novel anti-AD agents.

Language: Английский

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HDAC3 as an Emerging Therapeutic Target for Alzheimer's Disease and other Neurological Disorders

Molecular Neurobiology, Journal Year: 2025, Volume and Issue: unknown

Published: March 24, 2025

Language: Английский

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