Aberrant brain criticality as a neural basis of preclinical Alzheimer’s disease

Alzheimer’s disease (AD) is a chronic, nonlinearly progressive neurodegenerative disease that affects multiple domains of behaviour and is the most common form of dementia. However, there is scarce understanding of its biological basis nor there are reliable markers for the earliest disease stages preceding AD. Here we investigated whether AD progression is predicted by increasingly aberrant critical brain dynamics driven by underlying E/I imbalance using magnetoencephalography (MEG) data from cross-sectional (N=343) and longitudinal (N=45) cohorts. As a hallmark of brain criticality, we quantified long-range temporal correlations (LRTCs) in neuronal oscillations and tracked changes in neuronal excitability. We demonstrate that attenuation and progressive changes of LRTCs characterize the earliest stages of disease progression and yield accurate classification to individuals with subjective cognitive decline (SCD) and mild cognitive impairment (MCI). Our data indicate that pathological brain critical dynamics in AD progression provide a clinical marker for targeting specific treatments to individuals at increased risk.