Default mode network and medial temporal lobe functional connectivity changes with Alzheimer’s disease severity and cognitive impairment in individuals with Down syndrome

Abstract

AbstractBackgroundBy age 40, virtually all people with Down syndrome (DS) have sufficient beta‐amyloid and tau pathologies present to meet the criteria for pathological Alzheimer's disease (AD). Determining the timing and location of neurobiological changes caused by AD is critically important for effective intervention within this high‐risk population and more broadly in the general population, but little is known about the brain changes associated with clinical onset of AD in DS. Previous studies in sporadic AD suggest that functional connectivity of the default mode network (DMN) and medial temporal lobe (MTL) is vulnerable to AD pathology‐related impairment.MethodSeventy‐five individuals with DS (mean age 49.9±6.6, 36% women) from a subset of the Alzheimer’s Biomarkers Consortium ‐ Down Syndrome study underwent MRI, including an MPRAGE scan and a resting state functional scan. Participants completed a battery of neuropsychological tests and were assigned a consensus diagnosis for the presence or absence of mild cognitive impairment (MCI‐DS) or AD dementia. Forty‐eight participants were classified as cognitively stable (CS) (mean age 48±6.1, 42% women), 16 participants had MCI‐DS (mean age 50.8±4.2, 19% women), and 11 participants had dementia (mean age 57.2±6.6, 36% women).ResultParticipants with dementia had lower functional connectivity between the posterior DMN and the MTL relative to the CS and MCI‐DS groups. MCI‐DS participants had greater functional connectivity within the MTL relative to the CS group. Functional connectivity differences in these networks tracked with memory performance as well.ConclusionChanges in DMN and MTL functional connectivity are related to the progression of clinical symptoms of AD‐DS and may reflect synaptic changes stemming from AD pathology.