The relationship between regional amyloid deposition and executive function decline in adults with Down syndrome

Abstract

AbstractBackgroundAn increase in global deposition of amyloid is known to be related to declines in a variety of cognitive domains among people with Down syndrome (DS). Less known is the correspondence between increased regional amyloid load and declines in specific functions. Since a decline in frontal lobe functions (e.g., attention, inhibitory control, shifting, motivation) is considered by many to be a key early indicator of AD dementia in adults with DS, the current study aims to identify regional amyloid changes that are associated with executive function (EF) decline in both pre‐symptomatic and symptomatic adults with DS.MethodLongitudinal data from participants of the Biomarkers of Alzheimer’s Disease in Adults with Down Syndrome (ADDS) consortium, at all stages of AD (pre‐clinical, prodromal, and clinical dementia), were examined. Forty‐two participants received amyloid PET and MRI scans and extensive neuropsychological testing of select cognitive functions at two time points, approximately 16 months apart. Changes in amyloid accumulation in the anterior and posterior cingulate, frontal lobe, superior temporal lobe, and parietal lobe were hypothesized to be related to performance on three measures of EF: Rapid Assessment of Developmental Disabilities (RADD) Digit Span Forward and Stroop Cats and Dogs Naming and Switching. PET data were co‐registered with T1‐weighted MRIs, converted to SUVR units using the cerebellum cortex reference region, and spatially normalized using a DS MRI template in MNI space. We modeled relationships between amyloid SUVR and EF using multiple regression in SPM12 with covariates accounting for time difference between the scans and neurocognitive assessment acquisition and sex.ResultsConsistent with our hypothesis, we found clear associations between increased amyloid deposition and decline in EF in people with DS in approximately the same regions as found in neurotypical populations without AD (Figure 1). Frontal lobe amyloid deposition disrupts dorsal and ventral attention network processes.ConclusionsWe found amyloid deposition in specific functional networks correspond to EF decline in a population with lifelong amyloid production and cognitive impairments. These findings bring us one step closer to validating biomarkers of early AD in DS.