Contribution of Alzheimer's biomarkers and risk factors to cognitive impairment and decline across the Alzheimer's disease continuum
Open Access
- 14 October 2021
- journal article
- research article
- Published by Wiley in Alzheimer's & Dementia
- Vol. 18 (7), 1370-1382
- https://doi.org/10.1002/alz.12480
Abstract
Introduction Amyloid beta (Aβ), tau, and neurodegeneration jointly with the Alzheimer's disease (AD) risk factors affect the severity of clinical symptoms and disease progression. Methods Within 248 Aβ-positive elderly with and without cognitive impairment and dementia, partial least squares structural equation pathway modeling was used to assess the direct and indirect effects of imaging biomarkers (global Aβ-positron emission tomography [PET] uptake, regional tau-PET uptake, and regional magnetic resonance imaging–based atrophy) and risk-factors (age, sex, education, apolipoprotein E [APOE], and white-matter lesions) on cross-sectional cognitive impairment and longitudinal cognitive decline. Results Sixteen percent of variance in cross-sectional cognitive impairment was accounted for by Aβ, 46% to 47% by tau, and 25% to 29% by atrophy, although 53% to 58% of total variance in cognitive impairment was explained by incorporating mediated and direct effects of AD risk factors. The Aβ–tau–atrophy pathway accounted for 50% to 56% of variance in longitudinal cognitive decline while Aβ, tau, and atrophy independently explained 16%, 46% to 47%, and 25% to 29% of the variance, respectively. Discussion These findings emphasize that treatments that remove Aβ and completely stop downstream effects on tau and neurodegeneration would only be partially effective in slowing of cognitive decline or reversing cognitive impairment.Keywords
This publication has 55 references indexed in Scilit:
- Amyloid-β Imaging with Pittsburgh Compound B and Florbetapir: Comparing Radiotracers and Quantification MethodsJournal of Nuclear Medicine, 2012
- Relationship between regional atrophy rates and cognitive decline in mild cognitive impairmentNeurobiology of Aging, 2012
- Neuropathologic features associated with Alzheimer disease diagnosisNeurology, 2011
- Stages of the Pathologic Process in Alzheimer Disease: Age Categories From 1 to 100 YearsJournal of Neuropathology and Experimental Neurology, 2011
- Relationship Between Education and DementiaAlzheimer Disease & Associated Disorders, 2011
- Amyloid Imaging with18F-Florbetaben in Alzheimer Disease and Other DementiasJournal of Nuclear Medicine, 2011
- Use of Florbetapir-PET for Imaging β-Amyloid PathologyJAMA, 2011
- Fibrillar amyloid-β burden in cognitively normal people at 3 levels of genetic risk for Alzheimer's diseaseProceedings of the National Academy of Sciences of the United States of America, 2009
- Adjusting batch effects in microarray expression data using empirical Bayes methodsBiostatistics, 2006
- The Biphasic Relationship between Regional Brain Senile Plaque and Neurofibrillary Tangle Distributions: Modification by Age, Sex, and APOE PolymorphismAnnals of the New York Academy of Sciences, 2004