PT  - JOURNAL ARTICLE
AU  - Kelsey R. Thomas
AU  - Katherine J. Bangen
AU  - Alexandra J. Weigand
AU  - Emily C. Edmonds
AU  - Christina G. Wong
AU  - Shanna Cooper
AU  - Lisa Delano-Wood
AU  - Mark W. Bondi
AU  - for the Alzheimer's Disease Neuroimaging Initiative
TI  - Objective subtle cognitive difficulties predict future amyloid accumulation and neurodegeneration
AID  - 10.1212/WNL.0000000000008838
DP  - 2020 Jan 28
TA  - Neurology
PG  - e397--e406
VI  - 94
IP  - 4
4099  - http://n.neurology.org/content/94/4/e397.short
4100  - http://n.neurology.org/content/94/4/e397.full
SO  - Neurology2020 Jan 28; 94
AB  - 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 18F-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.AD=Alzheimer disease; ADNI=Alzheimer's Disease Neuroimaging Initiative; CN=cognitively normal; LME=linear mixed effects; MCI=mild cognitive impairment; MMSE=Mini-Mental State Examination; MTL=medial temporal lobe; NIA-AA=National Institute on Aging–Alzheimer's Association; Obj-SCD=objectively defined subtle cognitive difficulties; SUVR=standardized uptake value ratio