REGIONAL AV1451 UPTAKE AND CORTICAL THICKNESS IN RELATION TO MEMORY, LANGUAGE AND EXECUTIVE FUNCTIONING IN AMYLOID-POSITIVE SUBJECTS

Abstract

Tau pathology is thought to spread in a characteristic manner, leading to cell loss and inducing cognitive decline. However, it is unclear to what degree Tau-PET, a marker of neurofibrillary tau pathology (NFT) tracks cognitive symptoms relative to structural MRI, which more directly reflects neuronal injury. In a group of amyloid positive (Ab+) controls, patients with Mild Cognitive Impairment (MCI) and dementia, we investigate the association of memory, language and executive functioning with Tau-PET and MRI-based cortical thickness in brain regions putatively associated with these domains. We included Ab+ individuals, as determined by Florbetapir PET, (10 controls, 14 MCI and 5 dementia patients) from ADNI who had AV1451 Tau-PET, structural MRI and cognitive data within 6 months of each other. Cortical thickness and normalized SUVR from the Tau-PET scans were measured in regions of interest obtained using multi-atlas segmentation. Composite z-scores of delayed recall, recognition, language and executive functioning were calculated, adjusting for age, gender and education using the linear regression equation from 122 Ab- controls from ADNIGO/2. Significant associations of AV1451 uptake in medial temporal lobe (MTL) structures with memory were found (Table 1), but AV1451 uptake did not correlate significantly with language and executive functioning in regions generally considered to support these functions. Cortical thickness measures were significantly associated with all cognitive domains. Stepwise regression analyses showed that mainly structural measures were significant predictors of memory and executive functioning, but AV1451 uptake was also included in the models for memory (Table 2). None of the predictors significantly predicted language in regression models. These preliminary findings show a stronger association of cognitive functioning with structural brain measures than with AV1451 uptake. Perhaps atrophy provides a tighter link with cognitive decline than tau pathology, possibly because NFTs precede the neurodegeneration which produces cognitive impairment and/or because tau pathology does not capture other contributors to loss of neuronal integrity. The more complementary relationship of AV1451 uptake and structural MRI 5 may reflect that in early AD tangle pathology is the primary driver of neuronal integrity in this region, as opposed to language and executive networks.