Cognition, Brain Atrophy, and Cerebrospinal Fluid Biomarkers Changes from Preclinical to Dementia Stage of Alzheimer's Disease and the Influence of Apolipoprotein E
Affiliations: Center for Cognitive Neuroscience, Neuroscience and Behavioral Disorders Program, Duke-National University of Singapore Graduate Medical School, Singapore
Correspondence:
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Correspondence to: Juan Zhou, PhD, Center for Cognitive Neuroscience, Neuroscience and Behavioral Disorders Program, Duke-National University of Singapore Graduate Medical School, 8 College Road, #06-33, 169857 Singapore. Tel.: +65 66012392; Fax: +65 62218625; E-mail: helen.zhou@duke-nus.edu.sg.
Note: [1] Data used in preparation of this article were obtained from the Alzheimer's Disease Neuroimaging Initiative (ADNI) database (http://adni.loni.usc.edu/). As such, the investigators within the ADNI contributed to the design and implementation of ADNI and/or provided data but did not participate in analysis or writing of this report. A complete listing of ADNI investigators can be found at: http://adni.loni.usc.edu/wp-content/uploads/how_to_apply/ADNI_Acknowledgement_List.pdf
Abstract: Background:Knowledge of Alzheimer’s disease (AD) manifestation in the pre-dementia stage facilitates the selection of appropriate measures for early detection and disease progression. Objective:To examine the trajectories of cognitive performance, gray matter volume (GMV), and cerebrospinal fluid (CSF) biomarkers, together with the influence of apolipoprotein E (APOE) in subjects with amyloid-β (Aβ) deposits across the pre-clinical to dementia stages of AD. Methods:356 subjects were dichotomized into Aβ+ and Aβ− groups based on their CSF Aβ1-42 level. We derived AD-related atrophic regions (AD-ROIs) using the voxel-based morphometry approach. We characterized the trajectories of cognitive scores, GMV at AD-ROIs, and CSF biomarkers from preclinical to disease stages in Aβ+ subjects. The effect of APOE ε4 genotype on these trajectories was examined. Results:Impairments in executive functioning/processing speed (EF/PS) and atrophy at the right supramarginal/inferior parietal gyrus were detected in cognitively normal Aβ+ subjects. Together with the APOE ε4 carrier status, these measures showed potential to identify cognitively normal elderly with abnormal CSF Aβ1-42 level in another independent cohort. Subsequently, impairment in memory, visuospatial, language, and attention as well as atrophy in the temporal lobe, thalamus, and mid-cingulate cortex were detectable in Aβ+ mild cognitive impairment (MCI) subjects. In MCI and dementia Aβ+ subjects, ε4 carriers had more severe atrophy of the medial temporal lobe and memory impairment but higher EF/PS compared to non-carriers. Conclusions:EF/PS decline and right parietal atrophy might act as non-invasive screening tests for abnormal amyloid deposition in cognitively normal elderly. APOE modulation on subsequent trajectories in cognition and atrophy should be taken into account when analyzing disease progression.
