Neuroimaging and clinical characteristics of cognitive migration in community-dwelling older adults

Abstract

Background: Multiple neuroimaging and clinical biomarkers have been identified to predict cognitive decline and clinical progression to mild cognitive impairment (MCI) or dementia. However, early biomarkers associated with transition to and reversion from cognitive impairment (cognitive migration) require further understanding. We investigated the impacts of baseline neuroimaging and clinical biomarkers on cognitive migration in a community-dwelling older cohort.

Methods: We studied 391 participants from the Wake Forest Alzheimer's Disease Research Center Clinical Core cohort who underwent neuropsychological assessment and magnetic resonance imaging (MRI). At baseline, each participant was categorized to a functional/cognitive state using global Clinical Dementia Rating (CDR) score: CDR = 0 indicates normal cognitive function; CDR = 0.5 is minimal cognitive impairment. The primary outcome was cognitive migration status determined by CDR change between baseline and follow-up (mean difference = 13.9 months): CDR-0 Stables (no migration; maintained CDR = 0), CDR-0.5 Stables (no migration; maintained CDR = 0.5), Migrants^- (negative migration; CDR 0 to CDR 0.5), and Reverters⁺ (positive migration; CDR 0.5 to CDR 0). Baseline T1-weighted MRI was analyzed for gray matter (GM) volume using voxel-based morphometry (VBM). For VBM, we used a two-sample t-test controlling for age, sex, education years and intracranial volume for group comparisons: CDR-0 Stables vs CDR-0.5 Stables, CDR-0 Stables vs Migrants^-, CDR-0.5 Stables vs Reverters⁺ and Migrants^- vs Reverters⁺ (thresholded at k = 30 voxels, p <.01 uncorrected). Oral Glucose Tolerance Testing (OGTT-2h) assessed blood glucose 120-minute post challenge. Multinomial logistic regression estimated average predicted probabilities of cognitive migration status using OGTT-2h and age range (55-65, 65-75 and 75+) as predictors.

Results: VBM analyses revealed lower GM volume in inferior and middle temporal gyri, hippocampus, parahippocampal gyrus, and superior and inferior frontal regions in Migrants^- and CDR-0.5 Stables. Predicted probabilities indicated that individuals aged 55-65 with normal OGTT-2h levels were more likely to have better cognitive migration status (e.g., CDR-0 Stables or Reverters⁺) than those aged 75+ with high OGTT-2h.

Conclusions: Lower GM volumes and high OGTT-2h glucose levels may predict worse cognitive migration status in early stages of disease. The opposite is true for better cognitive migration. Validating these biomarkers may guide clinical diagnosis and treatments.

Keywords: Biomarkers; Cognition; Dementia; MRI; OGTT.