Longitudinal Change of Biomarkers in Cognitive Decline
Year: 2011
Type: article
Study design: Observational Study
Abstract: OBJECTIVE: To delineate the trajectories of Aβ42 level in cerebrospinal fluid (CSF), fludeoxyglucose F18 (FDG) uptake using positron emission tomography, and hippocampal volume using magnetic resonance imaging and their relative associations with cognitive change at different stages in aging and Alzheimer disease (AD). DESIGN: Cohort study. SETTING: The 59 study sites for the Alzheimer's Disease Neuroimaging Initiative. PARTICIPANTS: A total of 819 participants 55 to 90 years of age with normal cognition, mild cognitive impairment, and AD who were followed up during the period from 2005 to 2007. MAIN OUTCOME MEASURES: Rates of change in level of Aβ42 in CSF, FDG uptake, hippocampal volume, and the Alzheimer Disease's Assessment Scale-cognitive subscale score during up to 36 months of follow-up by diagnostic group as well as prediction of cognitive change by each biomarker. RESULTS: Reductions in the level of Aβ42 in CSF were numerically greater in participants with normal cognition than in participants with mild cognitive impairment or AD; whereas both glucose metabolic decline and hippocampal atrophy were significantly slower in participants with normal cognition than in participants with mild cognitive impairment or AD. Positive APOE4 status accelerated hippocampal atrophic changes in participants with mild cognitive impairment or AD, but did not modify rates of change in level of Aβ42 in CSF or FDG uptake. The Alzheimer Disease's Assessment Scale-cognitive subscale scores were related only to the baseline level of Aβ42 in CSF and the baseline FDG uptake in participants with normal cognition, which were about equally associated with change in FDG uptake and hippocampal volume in participants with mild cognitive impairment and best modeled by change in FDG uptake in participants with AD. CONCLUSION: Trajectories of Aβ42 level in CSF, FDG uptake, and hippocampal volume vary across different cognitive stages. The longitudinal patterns support a hypothetical sequence of AD pathology in which amyloid deposition is an early event before hypometabolism or hippocampal atrophy, suggesting that biomarker prediction for cognitive change is stage dependent.
Source: Archives of Neurology
Language: English
Subfield: Psychiatry and Mental health
Field: Medicine
Domain: Health Sciences
Open Access status: green
Awards: Function BIRN, UC Davis Alzheimer's Disease Core Center, Molecular and Functional Imaging of Age Related Cognitive Decline, G2481881534, A Phase 2 Trial of AAV-NGF Gene Delivery in Alzheimer's Disease, NIA Core Center to Build Neurodegenerative Disease Research Faculty At Penn, Biomarkers in Early Alzheimer's Disease (AD)., Alzheimers Disease Patient Registry, Parkinson's Disease and Dementia, "MR Morphometrics and Cognitive Decline Rate in Large-Scale Aging Studies", Alzheimer's Disease Core Center, Molecular substrates of aging and neuron death, Frontotemporal Dementias: Genotypes and Phenotypes, Alzheimer's Disease Cooperative Study (ADCS), Evaluating and Extending Our Hypothetical Model of Alzheimer's Biomarkers, Resource for MRI of Neurodegenerative Disorders, MRI Progression Markers of Cognitive Decline in the Elderly, Alzheimer's Disease Neuroimaging Initiative, Alzhelmer's Disease Drug Development Program, Amyloid Imaging in Frontotemporal Dementia and Alzheimer's Disease, Kentucky Center for Clinical and Translational Science, VITAMIN E TRIAL IN PERSONS WITH DOWN SYNDROME, High Field Neuroimaging of Epilepsy, Prediction of cognitive decline with structural, diffusion, and perfusion MRI, The Aging Brain: Vasculature, Ischemia, and Behavior, Frontotemporal Dementia: Genes, Images, and Emotions, Alzheimer's Disease Neuroimaging Initiative (ADNI4), Kentucky Center for Clinical and Translational Science, New Approaches to Dementia Heterogeneity, Mayo Alzheimer's Disease Research Center
OpenAlex ID: W1982881439