Neuropsychological And Neurophysiological Characterization Of Mild Cognitive Impairment And Alzheimer´S Disease In Down Syndrome

Abstract Down syndrome (DS) has been considered a unique model for the investigation of Alzheimer’s disease (AD) but intermediate stages in the continuum are poorly defined. Considering this, we investigated the neurophysiological (i.e. MEG) and neuropsychological patterns of Mild Cognitive Impairment (MCI) and AD in middle-aged adults with DS. The sample was composed of four groups: Control-DS (n=14, mean age 44.64±3.30 years), MCI-DS (n=14, 51.64±3.95 years), AD-DS (n=13, 53.54±6.58 years), and Control-no-DS (healthy controls, n=14, 45.21±4.39 years). DS individuals were studied with neuropsychological tests and MEG, while the Control-no-SD group completed only the MEG session. Our results showed that the AD-DS group exhibited a significantly poorer performance as compared with the Control-DS group in all tests. Further, this effect was crucially evident in AD-DS individuals when compared to the MCI-DS group in verbal and working memory abilities. In the neurophysiological domain, the Control-DS group showed a widespread increase of theta activity when compared with the Control-no-DS group. With disease progression, this increased theta was substituted by an augmented delta, accompanied with a reduction of alpha activity. Such spectral pattern —specifically observed in occipital, posterior temporal, cuneus and precuneus regions— correlated with the performance in cognitive tests. This is the first MEG study in the field incorporating both neuropsychological and neurophysiological information, and demonstrating that this combination of markers is sensitive enough to characterize different stages along the AD continuum in DS.