IMPORTANCE: To understand how a model of Alzheimer disease pathophysiology based on β-amyloidosis and neurodegeneration predicts the regional anatomic expansion of hypometabolism and atrophy in persons with mild cognitive impairment (MCI). OBJECTIVE: To define the role of β-amyloidosis and neurodegeneration in the subsequent progression of topographic cortical structural and metabolic changes in MCI. DESIGN, SETTING, AND PARTICIPANTS: Longitudinal, observational study with serial brain imaging conducted from March 28, 2006, to January6, 2015, using a population-based cohort. A total of 96 participants with MCI (all aged >70 years) with serial imaging biomarkers from the Mayo Clinic Study of Aging or Mayo Alzheimer's Disease Research Center were included. Participants were characterized initially as having elevated or not elevated brain β-amyloidosis (A+ or A-) based on 11C-Pittsburgh compound B positron emission tomography. They were further characterized initially by the presence or absence of neurodegeneration (N+or N-), where the presence of neurodegeneration was defined by abnormally low hippocampal volume or hypometabolism in an Alzheimer disease-like pattern on 18fluorodeoxyglucose (FDG)-positron emission tomography. MAIN OUTCOMES AND MEASURES: Regional FDG standardized uptake value ratio (SUVR) and gray matter volumes in medial temporal, lateral temporal, lateral parietal, and medial parietal regions. RESULTS: In the primary regions of interest (ROI), the A+N+ group (n = 45) had lower FDG SUVR at baseline compared with the A+N-group (n = 17) (all 4 ROIs; P <.001). The A+N+ group also had lower FDG SUVR at baseline (all 4 ROIs;P <.01) compared with the A-N-group (n = 12). The A+N+ group had lower medial temporal gray matter volume at baseline (P <.001) compared with either the A+N-group orA-N-group. The A+N+ group showed large longitudinal declines in FDG SUVR (P <.05 for medial temporal, lateral temporal, and medial parietal regions) and gray matter volumes (P <.05 for medial temporal and lateral temporal regions) compared with the A-N+ group (n = 22). The A+N+ group also showed large longitudinal declines compared with the A-N-groupon FDG SUVR (P <.05 for medial temporal and lateral parietal regions) and gray matter volumes (all 4 ROIs; P <.05) compared with the A+N-group. The A-N+ group did not show declines in FDG SUVR orgray matter volume compared with the A+N-or A-N-groups. CONCLUSIONS AND RELEVANCE: Persons with MCI who were A+N+ demonstrated volumetric and metabolic worsening in temporal and parietal association areas, consistent with the expectation that the MCI stage in the Alzheimer pathway heralds incipient isocortical involvement. The A-N+ group, those with suspected non-Alzheimer pathophysiology, lacked a distinctive longitudinal volumetric or metabolic profile.
ASJC Scopus subject areas
- Clinical Neurology