FUNCTIONAL CHANGES IN THE LANGUAGE NETWORK IN COGNITIVELY INTACT OLDER ADULTS IN RELATION TO CEREBRAL AMYLOID LOAD

Abstract

Background: Word finding symptoms are frequent early in the course of Alzheimer’s disease. The posterior superior temporal sulcus (STS) is the earliest language area affected in amnestic MCI and in early-stage probable AD (Vandenbulcke et al., 2007; Nelissen et al., 2007). We examined how amyloid load affects the network for language and associative-semantic processing in cognitively intact older adults. Methods: Fifty-seven community-recruited right-handed adults (mean age1⁄465, SD1⁄45.5, range 52-74) underwent 18 F-flutemetamol PET, volumetric and functional MRI, and neurolinguistic evaluation. The fMRI design contained two factors: task (associative-semantic versus visuoperceptual judgment) and input modality (written words versus pictures). Standardized uptake value ratios (SUVR) were calculated on normalized PET images with cerebellar grey matter as reference region. As primary outcome analysis, we conducted a whole-brain linear regression analysis between SUVR calculated in a composite cortical VOI (SUVRcomp) and activity levels obtained from the contrast of the associative-semantic minus the visuoperceptual control condition for words and pictures (cluster-level P 0.7). Stepwise multiple linear regression analysis showed that mean fMRI response in the posterior left STS and mTG during associative-semantic contitions minus visuoperceptual conditions was best predicted by SUVRcomp (r1⁄40.62, P<0.001) rather than age (P1⁄40.18). Conclusions: In cognitively intact older adults, amyloid load is associated with functional changes in left posterior STS, an area involved in lexical-semantic processing. Increased activity with higher amyloid load in cognitively intact individuals together with decreased activity inMCI and early AD is reminiscent of the activity pattern seen in the medial temporal cortex in episodic memory (Sperling, 2007; Reiman et al., 2012) across the different stages of AD.