Dementia prevention, intervention, and care: 2024 report of the Lancet standing Commission

The Lancet, Journal Year: 2024, Volume and Issue: 404(10452), P. 572 - 628

Published: July 31, 2024

Language: Английский

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Revised criteria for diagnosis and staging of Alzheimer's disease: Alzheimer's Association Workgroup

Alzheimer s & Dementia, Journal Year: 2024, Volume and Issue: 20(8), P. 5143 - 5169

Published: June 27, 2024

Abstract The National Institute on Aging and the Alzheimer's Association convened three separate work groups in 2011 single 2012 2018 to create recommendations for diagnosis characterization of disease (AD). present document updates research framework response several recent developments. Defining diseases biologically, rather than based syndromic presentation, has long been standard many areas medicine (e.g., oncology), is becoming a unifying concept common all neurodegenerative diseases, not just AD. consistent with this principle. Our intent objective criteria staging AD, incorporating advances biomarkers, serve as bridge between clinical care. These are intended provide step‐by‐step practice guidelines workflow or specific treatment protocols, but general principles inform AD that reflect current science. Highlights We define (AD) be biological process begins appearance neuropathologic change (ADNPC) while people asymptomatic. Progression burden leads later progression symptoms. Early‐changing Core 1 biomarkers (amyloid positron emission tomography [PET], approved cerebrospinal fluid accurate plasma [especially phosphorylated tau 217]) map onto either amyloid beta tauopathy pathway; however, these presence ADNPC more generally (i.e., both neuritic plaques tangles). An abnormal biomarker result sufficient establish decision making throughout continuum. Later‐changing 2 (biofluid PET) can prognostic information, when abnormal, will increase confidence contributing integrated scheme described accommodates fact copathologies, cognitive reserve, resistance may modify relationships stages.

Language: Английский

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Recent advances in Alzheimer’s disease: Mechanisms, clinical trials and new drug development strategies

Signal Transduction and Targeted Therapy, Journal Year: 2024, Volume and Issue: 9(1)

Published: Aug. 23, 2024

Abstract Alzheimer’s disease (AD) stands as the predominant form of dementia, presenting significant and escalating global challenges. Its etiology is intricate diverse, stemming from a combination factors such aging, genetics, environment. Our current understanding AD pathologies involves various hypotheses, cholinergic, amyloid, tau protein, inflammatory, oxidative stress, metal ion, glutamate excitotoxicity, microbiota-gut-brain axis, abnormal autophagy. Nonetheless, unraveling interplay among these pathological aspects pinpointing primary initiators require further elucidation validation. In past decades, most clinical drugs have been discontinued due to limited effectiveness or adverse effects. Presently, available primarily offer symptomatic relief often accompanied by undesirable side However, recent approvals aducanumab ( 1 ) lecanemab 2 Food Drug Administration (FDA) present potential in disrease-modifying Nevertheless, long-term efficacy safety need Consequently, quest for safer more effective persists formidable pressing task. This review discusses pathogenesis, advances diagnostic biomarkers, latest updates trials, emerging technologies drug development. We highlight progress discovery selective inhibitors, dual-target allosteric modulators, covalent proteolysis-targeting chimeras (PROTACs), protein-protein interaction (PPI) modulators. goal provide insights into prospective development application novel drugs.

Language: Английский

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DCRM 2.0: Multispecialty practice recommendations for the management of diabetes, cardiorenal, and metabolic diseases

Metabolism, Journal Year: 2024, Volume and Issue: 159, P. 155931 - 155931

Published: June 7, 2024

Language: Английский

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Association of rapid eye movement sleep latency with multimodal biomarkers of Alzheimer's disease

Alzheimer s & Dementia, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 27, 2025

Abstract INTRODUCTION Sleep disturbances are associated with Alzheimer's disease (AD) and related dementias (ADRD), but the relationship between sleep architecture, particularly rapid eye movement (REM) sleep, AD/ADRD biomarkers remains unclear. METHODS We enrolled 128 adults (64 disease, 41 mild cognitive impairment [MCI], 23 normal cognition [NC]), mean age 70.8 ± 9.6 years, 56.9% female, from a tertiary hospital in China. Participants underwent overnight polysomnography (PSG), amyloid β (Aβ) positron emission tomography (PET), plasma biomarker analysis: phosphorylated tau at threonine 181 (p‐tau181), neurofilament light (NfL), brain‐derived neurotrophic factor (BDNF). RESULTS After adjusting for demographics, apolipoprotein E ( APOE ) ε4 status, cognition, comorbidities, highest tertile of REM latency was higher Aβ burden = 0.08, 95% confidence interval [CI]: 0.03 to 0.13, p 0.002), elevated p‐tau181 0.19, CI: 0.02 reduced BDNF levels ‐0.47, –0.68 –0.13, 0.013), compared lowest tertile. DISCUSSION Prolonged may serve as novel marker or risk pathogenesis. Highlights Rapid (REML) be potential (AD/ADRD) REML beta burden, tau‐181 lower (BDNF) levels. Intervention trial is needed determine if targeting can modify risk. Slow‐wave not biomarkers.

Language: Английский

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Cutting through the noise: A narrative review of Alzheimer's disease plasma biomarkers for routine clinical use

The Journal of Prevention of Alzheimer s Disease, Journal Year: 2025, Volume and Issue: unknown, P. 100056 - 100056

Published: Jan. 1, 2025

As novel, anti-amyloid therapies have become more widely available, access to timely and accurate diagnosis has integral ensuring optimal treatment of patients with early-stage Alzheimer's disease (AD). Plasma biomarkers are a promising tool for identifying AD pathology; however, several technical clinical factors need be considered prior their implementation in routine use. Given the rapid pace advancements field wide array available tests, this review aims summarize these considerations, evaluate platforms, discuss steps needed bring plasma biomarker testing clinic. We focus on phosphorylated(p)-tau, specifically p-tau217, as robust candidate across both primary secondary care settings. Despite high performance robustness demonstrated research, like all biomarkers, can affected by analytical pre-analytical variability well patient comorbidities, sex, ethnicity, race. This also discusses advantages two-point cut-off approach mitigating factors, challenges raised resulting intermediate range measurements, where guidance is still unclear. Further validation p-tau217 heterogeneous, real-world cohorts will help increase confidence support establishing standardized approach. poised affordable less invasive alternative PET CSF testing. However, understanding that impact measurement interpretation critical

Language: Английский

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Plasma proteomic evidence for increased β-amyloid pathology after SARS-CoV-2 infection

Nature Medicine, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 30, 2025

Abstract Previous studies have suggested that systemic viral infections may increase risks of dementia. Whether this holds true for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus is unknown. Determining important anticipating the potential future incidence To begin to do this, we measured plasma biomarkers linked Alzheimer’s disease pathology in UK Biobank before and after serology-confirmed SARS-CoV-2 infections. infection was associated with β-amyloid pathology: reduced Aβ42:Aβ40 ratio and, more vulnerable participants, lower Aβ42 higher pTau-181. The biomarker changes were greater participants who had been hospitalized COVID-19 or reported hypertension previously. We showed brain structural imaging patterns disease, cognitive test scores poorer overall health evaluations. Our data from post hoc case–control matched study thus provide observational evidence can be older adults. While these results not establish causality, they suggest (and possibly other inflammatory diseases) risk disease.

Language: Английский

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Bridging gap in the treatment of Alzheimer’s disease via postbiotics: Current practices and future prospects

Ageing Research Reviews, Journal Year: 2025, Volume and Issue: unknown, P. 102689 - 102689

Published: Feb. 1, 2025

Language: Английский

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The Brain–Gut Axis, an Important Player in Alzheimer and Parkinson Disease: A Narrative Review

Journal of Clinical Medicine, Journal Year: 2024, Volume and Issue: 13(14), P. 4130 - 4130

Published: July 15, 2024

Neurodegenerative diseases, such as Alzheimer’s disease (AD) and Parkinson’s (PD), are severe age-related disorders with complex multifactorial causes. Recent research suggests a critical link between neurodegeneration the gut microbiome, via gut–brain communication pathway. This review examines role of trimethylamine N-oxide (TMAO), microbiota-derived metabolite, in development AD PD, investigates its interaction microRNAs (miRNAs) along this bidirectional TMAO, which is produced from dietary metabolites like choline carnitine, has been linked to increased neuroinflammation, protein misfolding, cognitive decline. In AD, elevated TMAO levels associated amyloid-beta tau pathologies, blood–brain barrier disruption, neuronal death. can cross promote aggregation amyloid proteins. Similarly, affects alpha-synuclein conformation aggregation, hallmark PD. also activates pro-inflammatory pathways NF-kB signaling, exacerbating neuroinflammation further. Moreover, modulates expression various miRNAs that involved neurodegenerative processes. Thus, microbiome–miRNA–brain axis represents newly discovered mechanistic dysbiosis neurodegeneration. MiRNAs regulate key oxidative stress, death, contributing progression. As direct consequence, specific miRNA signatures may serve potential biomarkers for early detection monitoring PD aims elucidate interrelationships microbiota, trimethylamine-N-oxide (miRNAs), central nervous system, implications these connections diseases. context, an overview current neuroradiology techniques available studying animal models used investigate intricate pathologies will be provided. summary, bulk evidence supports concept modulating pathway through changes, manipulation and/or miRNA-based therapies offer novel approaches implementing treatment debilitating neurological disorders.

Language: Английский

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Multi-target drugs for Alzheimer's disease

Trends in Pharmacological Sciences, Journal Year: 2024, Volume and Issue: 45(7), P. 628 - 638

Published: June 9, 2024

Language: Английский

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