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

Abstract

AbstractBackgroundLongitudinal studies in cognitively unimpaired older adults have identified a wide range of neuroimaging and clinical biomarkers that predict cognitive decline and clinical progression to mild cognitive impairment (MCI) or dementia. However, early biomarkers associated with progression from normal to impaired brain functioning and cognition (cognitive migration) in ADRD require further validation. We investigated the impacts of baseline neuroimaging and clinical biomarkers on functional and cognitive migration in a community‐dwelling cohort of older adults.MethodParticipants from the Wake Forest Alzheimer’s Disease Research Center (ADRC) Clinical Core cohort who completed their baseline and 1‐year follow‐up clinical visits with available neuropsychological and MRI data were evaluated. Each participant was categorized to a functional/cognitive state based on baseline global CDR (Clinical Dementia Rating); CDR=0 (n=120) indicates normal function and CDR=0.5 (n=57) corresponds to MCI. Cognitive measures included MoCA (Montreal Cognitive Assessment) and preclinical Alzheimer's cognitive composite (PACC5) scores. Oral Glucose Tolerance Testing (OGTT) assessed blood glucose 120‐minute post‐challenge; OGTT >140 mg/dl indicates impaired glucose tolerance. The primary outcome measure was cognitive migration determined by CDR increase/decrease between baseline and follow‐up (mean difference=13.8 months): CDR‐0 Stables (maintained CDR=0), CDR‐0.5 Stables (maintained CDR=0.5), CDR‐0 to CDR‐0.5 (Migrators), and CDR‐0.5 to CDR‐0 (Reverters). Baseline T1 MRI scans were assessed for gray‐matter volume and analyzed using voxel‐based morphometry in SPM12 for group differences. Statistical design was a two‐sample t‐test controlling for age, sex, education and whole brain volume in contrasts of interest (thresholded at k=25 voxels, p<0.01 uncorrected).ResultTable lists the baseline demographic and clinical characteristics for significant differences between groups. CDR‐0.5 Stables and Migrators had lower gray‐matter density (GMD) than CDR‐0 Stables and Reverters, most significantly in hippocampal (HC), temporal pole (BA38) and angular (BA39) regions (Figure).ConclusionOur analyses suggest that lower GMD in HC and BA38/39 may predict cognitive migration in early stages of disease pathology. OGTT tracks cognitive migration status in this cohort with Reverters having the lowest and Migrators having the highest mean OGTT. Validating these biomarkers may guide clinical diagnosis and treatments in ADRD. Cognitive and functional changes identified within one year can inform disease profiling.