Abstract
BackgroundAs investigations of disease modifying drugs aim to slow down progression of Alzheimer’ disease (AD) biomarkers to reliably track disease progression gain more importance. This is especially important as clinical symptoms, including psychometric measures, are only modestly associated with the underlying disease pathology, in particular at the pre-dementia stages. The decision which biomarkers to choose in clinical trials is crucial and depends on effect size. However, longitudinal studies of multiple biomarkers in parallel that allow direct comparison on effect size are scarce.MethodsWe calculated effect size and minimal sample size for three common imaging biomarkers of AD, namely amyloid deposition measured with PiB-PET, neuronal dysfunction measured with FDG-PET and cortical thickness measured with MRI in a prospective 24-month follow-up study in a monocentric cohort of early AD.ResultsPost hoc power calculation revealed large effect sizes of Cohen’s d for PiB-PET and cortical thickness and a small effect size for FDG-PET (1.315, 0.914, and 0.341, respectively). Accordingly, sample sizes for PiB-PET and cortical thickness required significantly smaller sample sizes than FDG-PET to reliably detect statistically significant changes after 24 months in early AD (n = 7, n = 12, and n = 70, respectively).ConclusionAmyloid imaging with PET and measuring cortical thickness with MRI are suitable biomarkers to detect disease progression in early AD within a small sample.
Highlights
As investigations of disease modifying drugs aim to slow down progression of Alzheimer’ disease (AD) biomarkers to reliably track disease progression gain more importance
No previous study investigated effect sizes and minimal samples sizes to detect changes of these biomarkers within one monocentric cohort over time. In this long-term predefined 24-month follow-up study we set out to determine effect sizes and minimal sample sizes for three imaging biomarkers in the same monocentric Alzheimer’s disease cohort: Amyloid beta (Aβ) deposition measured with Pittsburgh compound B (PiB)-positron emission tomography (PET), neuronal dysfunction measured with FDG-PET, and neuronal loss measured by cortical thickness on magnetic resonance imaging (MRI)
The severity of cognitive impairment was rated on the Clinical Dementia Rating scale sum of boxes (CDR-SOB) [26]
Summary
As investigations of disease modifying drugs aim to slow down progression of Alzheimer’ disease (AD) biomarkers to reliably track disease progression gain more importance This is especially important as clinical symptoms, including psychometric measures, are only modestly associated with the underlying disease pathology, in particular at the pre-dementia stages. While there is still no definite treatment for the cause of Alzheimer’s disease (AD), modifying therapies that aim to slow down disease progression are under investigation Primary endpoints in these trials are usually measures of cognitive functions such as the Alzheimer’s Disease Assessment Scale - Cognitive Subscale (ADAScog) [1] or the Clinical Dementia Rating Scale (CDR) [2,3,4,5]. No previous study investigated effect sizes and minimal samples sizes to detect changes of these biomarkers within one monocentric cohort over time
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