David A. Loewenstein, Rosie E. Curiel, Clinton Wright, Xiaoyan Sun, Noam Alperin, Elzabeth Crocco, Sara J. Czaja, Arlene Raffo, Ailyn Penate, Jose Melo, Kimberly Capp, Monica Gamez, Ranjan Duara

There is growing evidence that proactive semantic interference (PSI) and failure to recover from PSI may represent early features of Alzheimer's disease (AD). This study investigated the association between PSI, recovery from PSI, and reduced MRI volumes in AD signature regions among cognitively impaired and unimpaired older adults. Performance on the LASSI-L (a novel test of PSI and recovery from PSI) and regional brain volumetric measures were compared between 38 cognitively normal (CN) elders and 29 older participants with amnestic mild cognitive impairment (MCI). The relationship between MRI measures and performance on the LASSI-L as well as traditional memory and non-memory cognitive measures was also evaluated in both diagnostic groups. Relative to traditional neuropsychological measures, MCI patients' failure to recover from PSI was associated with reduced volumes in the hippocampus (rs = 0.48), precuneus (rs = 0.50); rostral middle frontal lobules (rs = 0.54); inferior temporal lobules (rs = 0.49), superior parietal lobules (rs = 0.47), temporal pole (rs = 0.44), and increased dilatation of the inferior lateral ventricle (rs = -0.49). For CN elders, only increased inferior lateral ventricular size was associated with vulnerability to PSI (rs = -0.49), the failure to recover from PSI (rs = -0.57), and delayed recall on the Hopkins Verbal Learning Test-Revised (rs = -0.48). LASSI-L indices eliciting failure to recover from PSI were more highly associated with more MRI regional biomarkers of AD than other traditional cognitive measures. These results as well as recent amyloid imaging studies with otherwise cognitively normal subjects, suggest that recovery from PSI may be a sensitive marker of preclinical AD and deserves further investigation.