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- Diaz-Galvan, P., et al.
(författare)
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Differential response to donepezil in MRI subtypes of mild cognitive impairment
- 2023
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Ingår i: Alzheimer's Research & Therapy. - 1758-9193. ; 15:1
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Tidskriftsartikel (refereegranskat)abstract
- BackgroundDonepezil is an approved therapy for the treatment of Alzheimer's disease (AD). Results across clinical trials have been inconsistent, which may be explained by design-methodological issues, the pathophysiological heterogeneity of AD, and diversity of included study participants. We investigated whether response to donepezil differs in mild cognitive impaired (MCI) individuals demonstrating different magnetic resonance imaging (MRI) subtypes.MethodsFrom the Hippocampus Study double-blind, randomized clinical trial, we included 173 MCI individuals (donepezil = 83; placebo = 90) with structural MRI data, at baseline and at clinical follow-up assessments (6-12-month). Efficacy outcomes were the annualized percentage change (APC) in hippocampal, ventricular, and total grey matter volumes, as well as in the AD cortical thickness signature. Participants were classified into MRI subtypes as typical AD, limbic-predominant, hippocampal-sparing, or minimal atrophy at baseline. We primarily applied a subtyping approach based on continuous scale of two subtyping dimensions. We also used the conventional categorical subtyping approach for comparison.ResultsDonepezil-treated MCI individuals showed slower atrophy rates compared to the placebo group, but only if they belonged to the minimal atrophy or hippocampal-sparing subtypes. Importantly, only the continuous subtyping approach, but not the conventional categorical approach, captured this differential response.ConclusionsOur data suggest that individuals with MCI, with hippocampal-sparing or minimal atrophy subtype, may have improved benefit from donepezil, as compared with MCI individuals with typical or limbic-predominant patterns of atrophy. The newly proposed continuous subtyping approach may have advantages compared to the conventional categorical approach. Future research is warranted to demonstrate the potential of subtype stratification for disease prognosis and response to treatment.
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- Hampel, H., et al.
(författare)
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The amyloid-beta pathway in Alzheimer's disease: a plain language summary
- 2023
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Ingår i: Neurodegenerative Disease Management. - : Future Medicine Ltd. - 1758-2024 .- 1758-2032. ; 13:3, s. 141-9
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Tidskriftsartikel (refereegranskat)abstract
- What is this summary about? This plain language summary of an article published in Molecular Psychiatry, reviews the evidence supporting the role of the amyloid-b (Ab) pathway and its dysregulation in Alzheimer's disease (AD), and highlights the rationale for drugs targeting the A beta pathway in the early stages of the disease. Why is this important? A beta is a protein fragment (or peptide) that exists in several forms distinguished by their size, shape/structure, degree of solubility and disease relevance. The accumulation of A beta plaques is a hallmark of AD. However, smaller, soluble aggregates of A beta - including Ab protofibrils - also play a role in the disease. Because A beta-related disease mechanisms are complex, the diagnosis, treatment and management of AD should be reflective of and guided by up-to-date scientific knowledge and research findings in this area. This article describes the A beta protein and its role in AD, summarizing the evidence showing that altered A beta clearance from the brain may lead to the imbalance, toxic buildup and misfolding of the protein - triggering a cascade of cellular, molecular and systematic events that ultimately lead to AD. What are the key takeaways? The physiological balance of brain A beta levels in the context of AD is complex. Despite many unanswered questions, mounting evidence indicates that A beta has a central role in driving AD progression. A better understanding of the A beta pathway biology will help identify the best therapeutic targets for AD and inform treatment approaches.
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