Hypersynchronized Magnetoencephalography Brain Networks in Patients with Mild Cognitive Impairment and Alzheimer's Disease in Down Syndrome

Introduction: The majority of individuals with Down syndrome (DS) show signs of Alzheimer's disease (AD) neuropathology in their fourth decade. However, there is a lack of specific markers for characterizing the disease stages while considering this population's differential features. Methods: Forty-one DS individuals participated in the study, and were classified into three groups according to their clinical status: Alzheimer's disease (AD-DS), mild cognitive impairment (MCI-DS), and controls (CN-DS). We performed an exhaustive neuropsychological evaluation and assessed brain functional connectivity (FC) from magnetoencephalographic recordings. Results: Compared with CN-DS, both MCI-DS and AD-DS showed a pattern of increased FC within the high alpha band. The neuropsychological assessment showed a generalized cognitive impairment, especially affecting mnestic functions, in MCI-DS and, more pronouncedly, in AD-DS. Discussion: These findings might help to characterize the AD-continuum in DS. In addition, they support the role of the excitatory/inhibitory imbalance as a key pathophysiological factor in AD. Impact statement The pattern of functional connectivity (FC) hypersynchronization found in this study resembles the largely reported Alzheimer's disease (AD) FC evolution pattern in population with typical development. This study supports the hypothesis of the excitatory/inhibitory imbalance as a key pathophysiological factor in AD, and its conclusions could help in the characterization and prediction of Down syndrome individuals with a greater likelihood of converting to dementia.