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

The Lancet, Год журнала: 2024, Номер 404(10452), С. 572 - 628

Опубликована: Июль 31, 2024

Язык: Английский

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Accelerating Alzheimer’s therapeutic development: The past and future of clinical trials

Cell, Год журнала: 2023, Номер 186(22), С. 4757 - 4772

Опубликована: Окт. 1, 2023

Alzheimer's disease (AD) research has entered a new era with the recent positive phase 3 clinical trials of anti-Aβ antibodies lecanemab and donanemab. Why did it take 30 years to achieve these successes? Developing potent therapies for reducing fibrillar amyloid was key, as selection patients at relatively early stages disease. Biomarkers target pathologies, including tau PET, insights from past were also critical successes. Moving forward, challenge will be develop more efficacious greater efficiency. Novel trial designs, combination umbrella basket protocols, accelerate development. Better diversity inclusivity participants are needed, blood-based biomarkers may help improve access medically underserved groups. Incentivizing innovation in both academia industry through public-private partnerships, collaborative mechanisms, creation career paths build momentum exciting times.

Язык: Английский

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Biomarker-based staging of Alzheimer disease: rationale and clinical applications

Nature Reviews Neurology, Год журнала: 2024, Номер 20(4), С. 232 - 244

Опубликована: Март 1, 2024

Язык: Английский

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Treatment of Alzheimer’s Disease: Beyond Symptomatic Therapies

International Journal of Molecular Sciences, Год журнала: 2023, Номер 24(18), С. 13900 - 13900

Опубликована: Сен. 9, 2023

In an ever-increasing aged world, Alzheimer’s disease (AD) represents the first cause of dementia and one chronic diseases in elderly people. With 55 million people affected, WHO considers AD to be a with public priority. Unfortunately, there are no final cures for this pathology. Treatment strategies aimed mitigate symptoms, i.e., acetylcholinesterase inhibitors (AChEI) N-Methyl-D-aspartate (NMDA) antagonist Memantine. At present, best approaches managing seem combine pharmacological non-pharmacological therapies stimulate cognitive reserve. Over last twenty years, number drugs have been discovered acting on well-established biological hallmarks AD, deposition β-amyloid aggregates accumulation hyperphosphorylated tau protein cells. Although previous efforts disappointed expectations, new era treating has working its way recently. The Food Drug Administration (FDA) gave conditional approval disease-modifying therapy (DMT) treatment aducanumab, monoclonal antibody (mAb) designed against Aβ plaques oligomers 2021, January 2023, FDA granted accelerated second antibody, Lecanemab. This review describes ongoing clinical trials DMTs therapies. We will also present future scenario based biomarkers that can detect preclinical or prodromal stages, identify at risk developing allow early curative treatment.

Язык: Английский

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Clinically Important Benefits and Harms of Monoclonal Antibodies Targeting Amyloid for the Treatment of Alzheimer Disease: A Systematic Review and Meta-Analysis

The Annals of Family Medicine, Год журнала: 2024, Номер 22(1), С. 50 - 62

Опубликована: Янв. 1, 2024

PURPOSE

We conducted a meta-analysis to evaluate clinically meaningful benefits and harms of monoclonal antibodies targeting amyloid in patients with Alzheimer dementia.

METHODS

searched PubMed, Cochrane CENTRAL, 5 trial registries, as well the reference lists identified studies. included randomized controlled trials comparing antibody placebo at dose consistent that used phase 3 or for Food Drug Administration approval. Studies had report least 1 relevant benefit harm. Data were extracted independently by 2 researchers random effects meta-analysis. Changes cognitive functional scales compared between groups, each difference was assessed determine if it met minimal important (MCID).

RESULTS

19 publications 23,202 total participants evaluated 8 anti-amyloid antibodies. There small improvements over Alzheimer's Disease Assessment Scale (ADAS)-Cog-11 -14 score (standardized mean = −0.07; 95% CI, −0.10 −0.04), Mini Mental State Examination (0.32 points; 0.13 0.50), Clinical Dementia Rating-Sum Boxes scale (mean =−0.18 −0.34 −0.03), combined scores 0.09; 0.05 0.13). None changes, including those lecanemab, aducanumab, donanemab, exceeded MCID. Harms significantly increased risks amyloid-related imaging abnormalities (ARIA)-edema (relative risk [RR] 10.29; number needed harm [NNH] 9), ARIA-hemorrhage (RR 1.74; NNH 13), symptomatic ARIA-edema 24.3; 86).

CONCLUSIONS

Although provide on dementia, these are far below MCID outcome accompanied harms.

Язык: Английский

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Data-driven modelling of neurodegenerative disease progression: thinking outside the black box

Nature reviews. Neuroscience, Год журнала: 2024, Номер 25(2), С. 111 - 130

Опубликована: Янв. 8, 2024

Язык: Английский

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Alzheimer's disease pathophysiology in the Retina

Progress in Retinal and Eye Research, Год журнала: 2024, Номер 101, С. 101273 - 101273

Опубликована: Май 15, 2024

The retina is an emerging CNS target for potential noninvasive diagnosis and tracking of Alzheimer's disease (AD). Studies have identified the pathological hallmarks AD, including amyloid β-protein (Aβ) deposits abnormal tau protein isoforms, in retinas AD patients animal models. Moreover, structural functional vascular abnormalities such as reduced blood flow, Aβ deposition, blood-retinal barrier damage, along with inflammation neurodegeneration, been described mild cognitive impairment dementia. Histological, biochemical, clinical studies demonstrated that nature severity pathologies brain correspond. Proteomics analysis revealed a similar pattern dysregulated proteins biological pathways patients, enhanced inflammatory neurodegenerative processes, impaired oxidative-phosphorylation, mitochondrial dysfunction. Notably, investigational imaging technologies can now detect AD-specific deposits, well vasculopathy neurodegeneration living suggesting alterations at different stages links to pathology. Current exploratory ophthalmic modalities, optical coherence tomography (OCT), OCT-angiography, confocal scanning laser ophthalmoscopy, hyperspectral imaging, may offer promise assessment AD. However, further research needed deepen our understanding AD's impact on its progression. To advance this field, future require replication larger diverse cohorts confirmed biomarkers standardized retinal techniques. This will validate aiding early screening monitoring.

Язык: Английский

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Alzheimer’s disease and its treatment–yesterday, today, and tomorrow

Frontiers in Pharmacology, Год журнала: 2024, Номер 15

Опубликована: Май 24, 2024

Alois Alzheimer described the first patient with Alzheimer’s disease (AD) in 1907 and today AD is most frequently diagnosed of dementias. a multi-factorial neurodegenerative disorder familial, life style comorbidity influences impacting global population more than 47 million projected escalation by 2050 to exceed 130 million. In USA demographic encompasses approximately six individuals, expected increase surpass 13 2050, antecedent phase AD, recognized as mild cognitive impairment (MCI), involves nearly 12 individuals. The economic outlay for management AD-related decline estimated at 355 billion USD. addition, intensifying prevalence cases countries modest intermediate income further enhances urgency therapeutically cost-effective treatments improving quality patients their families. This narrative review evaluates pathophysiological basis an initial focus on therapeutic efficacy limitations existing drugs that provide symptomatic relief: acetylcholinesterase inhibitors (AChEI) donepezil, galantamine, rivastigmine, N-methyl-D-aspartate receptor (NMDA) allosteric modulator, memantine. hypothesis amyloid-β (Aβ) tau are appropriate targets have potential halt progress critically analyzed particular clinical trial data anti-Aβ monoclonal antibodies (MABs), namely, aducanumab, lecanemab donanemab. challenges dogma targeting Aβ will benefit majority subjects MABs unlikely be “magic bullet”. A comparison benefits disadvantages different classes forms determining new directions research alternative drug undergoing pre-clinical assessments. we discuss stress importance treatment co-morbidities, including hypertension, diabetes, obesity depression known risk developing AD.

Язык: Английский

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Updated appropriate use criteria for amyloid and tau PET: A report from the Alzheimer's Association and Society for Nuclear Medicine and Molecular Imaging Workgroup

Alzheimer s & Dementia, Год журнала: 2025, Номер unknown

Опубликована: Янв. 8, 2025

Abstract INTRODUCTION The Alzheimer's Association and the Society of Nuclear Medicine Molecular Imaging convened a multidisciplinary workgroup to update appropriate use criteria (AUC) for amyloid positron emission tomography (PET) develop AUC tau PET. METHODS identified key research questions that guided systematic literature review on clinical amyloid/tau Building this review, developed 17 scenarios in which or PET may be considered. A modified Delphi approach was used rate each scenario by consensus as “rarely appropriate,” “uncertain,” “appropriate.” Ratings were performed separately stand‐alone modalities. RESULTS For PET, seven rated appropriate, two uncertain, eight rarely appropriate. five six DISCUSSION provide expert recommendations these technologies evolving landscape diagnostics therapeutics disease. Highlights updated goal is assist clinicians identifying useful guiding diagnosis management patients who have, are at risk for, cognitive decline These intended dementia specialists spend significant proportion their effort caring with complaints, well serve general reference broader audience interested implementation practice.

Язык: Английский

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Amyloid-related imaging abnormalities: manifestations, metrics and mechanisms

Nature Reviews Neurology, Год журнала: 2025, Номер unknown

Опубликована: Янв. 10, 2025

Язык: Английский

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