Longitudinal changes in the expression of Alzheimer’s disease‐related pattern and default mode network

Abstract

AbstractBackgroundThe Alzheimer’s disease‐related pattern (ADRP) is an imaging biomarker of AD, for which expression levels correlate with cognitive impairment in individual patients. The default mode network (DMN) is a dominant metabolic network expressed in healthy individuals. Longitudinal changes in ADRP and DMN expression levels have not been comprehensively studied in patients with AD or mild cognitive impairment (MCI), or in cognitively normal (CN) subjects.MethodWe obtained longitudinal data from Alzheimer’s Disease Neuroimaging Initiative (ADNI) database of participants who were CN (n=59), or who had MCI (n=128) at baseline and underwent 3 or more FDG PET scans (nscans=704) and had CSF amyloid and APOE information available. Groups were divided based on the conversion status, i.e., if they developed MCI/dementia at follow‐up. There were 36 stable and 23 converting CN participants and 73 stable (sMCI) and 55 converting (cMCI) participants. Amyloid positivity was defined as CSF Aβ42 < 880 pg/mL and APOE positivity as presence of one or more APOE4 allele. We used an automated algorithm to calculate standardized ADRP and DMN expression levels for each scan. Repeated measurements ANOVA (RMANOVA) was used to evaluate longitudinal changes in network expression in each group, as well as network interactions with conversion status, amyloid and APOE positivity.ResultsADRP expression increased over time, but at with different rates in the CN, sMCI and cMCI groups (p<0.001). The interaction effect was significant between CN and cMCI (p<0.001) and sMCI and cMCI (p=0.009), but not between CN and sMCI (p=0.51). There was no significant interaction between group and time on DMN expression (p=0.60). Analysis of each group separately revealed no significant interaction between APOE4 status and time on ADRP or DMN expression levels (all p>0.10). There was a significant interaction between conversion status and time on ADRP and DMN in CN group (p<0.04). There was also a significant main effect of time on ADRP and DMN in cMCI group (p<0.04) and a significant interaction between amyloid and time on DMN expression (p=0.03).ConclusionADRP progression was faster in cMCI compared to CN and sMCI. The longitudinal changes in DMN were not significantly different across groups.