Electroencephalogram features support the retrogenesis hypothesis of Alzheimer's disease: Exploratory comparison of brain changes in aging and childhood

J Alzheimers Dis. 2025 Jun 30:13872877251352119. doi: 10.1177/13872877251352119. Online ahead of print.

Abstract

BackgroundThe retrogenesis hypothesis (RH) suggests that the functional and cognitive decline observed in Alzheimer's disease dementia mirrors in reverse order the brain development during childhood and adolescence.ObjectiveEquivalent electroencephalogram (EEG) patterns between older adults across different cognitive decline stages and children across different brain maturation stages were directly compared.MethodsTo capture the complex patterns that allow for such a comparison, a regression model was trained on EEG data from N = 510 older adults, at different stages of cognitive reserve, to identify EEG markers predictive of global cognitive status. The model was then applied on the same EEG markers of N = 696 children across different ages.ResultsThe model predicted MMSE scores with an average error of 2.53 and R2 of 0.80. When applied to children, predictions correlated positively with age (r = 0.73). Key predictors of cognitive function concordant in both populations were theta coherence (right frontal-left temporal/parietal), temporal Hjorth complexity, and beta edge frequency, supporting the RH.ConclusionsThese EEG features were inversely associated between older adults and children, supporting a functional underpinning of the retrogenesis model of dementia. Clinical validation of these biomarkers could favor their use in the continuous monitoring of cognitive function.

Keywords: Alzheimer's disease; Hjorth complexity; Mini-Mental State Exam; cognitive function; developmental age; electroencephalography; frontotemporal dementia; machine learning; spectral coherence.