1. Objective subtle cognitive difficulties predict future amyloid accumulation and neurodegeneration.
- Author
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Thomas KR, Bangen KJ, Weigand AJ, Edmonds EC, Wong CG, Cooper S, Delano-Wood L, and Bondi MW
- Subjects
- Aged, Aged, 80 and over, Cognitive Dysfunction diagnosis, Female, Humans, Magnetic Resonance Imaging, Male, Middle Aged, Nerve Degeneration pathology, Neuropsychological Tests, Positron-Emission Tomography, Amyloid beta-Peptides analysis, Brain pathology, Cognitive Dysfunction etiology, Early Diagnosis, Nerve Degeneration diagnosis
- Abstract
Objective: To determine the temporal sequence of objectively defined subtle cognitive difficulties (Obj-SCD) in relation to amyloidosis and neurodegeneration, the current study examined the trajectories of amyloid PET and medial temporal neurodegeneration in participants with Obj-SCD relative to cognitively normal (CN) and mild cognitive impairment (MCI) groups., Method: A total of 747 Alzheimer's Disease Neuroimaging Initiative participants (305 CN, 153 Obj-SCD, 289 MCI) underwent neuropsychological testing and serial amyloid PET and structural MRI examinations. Linear mixed effects models examined 4-year rate of change in cortical
18 F-florbetapir PET, entorhinal cortex thickness, and hippocampal volume in those classified as Obj-SCD and MCI relative to CN., Result: Amyloid accumulation was faster in the Obj-SCD group than in the CN group; the MCI and CN groups did not significantly differ from each other. The Obj-SCD and MCI groups both demonstrated faster entorhinal cortical thinning relative to the CN group; only the MCI group exhibited faster hippocampal atrophy than CN participants., Conclusion: Relative to CN participants, Obj-SCD was associated with faster amyloid accumulation and selective vulnerability of entorhinal cortical thinning, whereas MCI was associated with faster entorhinal and hippocampal atrophy. Findings suggest that Obj-SCD, operationally defined using sensitive neuropsychological measures, can be identified prior to or during the preclinical stage of amyloid deposition. Further, consistent with the Braak neurofibrillary staging scheme, Obj-SCD status may track with early entorhinal pathologic changes, whereas MCI may track with more widespread medial temporal change. Thus, Obj-SCD may be a sensitive and noninvasive predictor of encroaching amyloidosis and neurodegeneration, prior to frank cognitive impairment associated with MCI., (© 2019 American Academy of Neurology.)- Published
- 2020
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