FRACTALz- Fractal Dynamics as a Diagnostic Tool in Alzheimer’s Disease

Under healthy conditions, many physiological signals, such as locomotor activity and electroencephalography (EEG) signal, exhibit a nonlinear complex regulation, yielding fractal or scale-invariant patterns. People with Alzheimer’s disease (AD) exhibit altered fractal dynamics (FD) that precede clinical symptoms by several years. Recent evidence suggests that these alterations are associated with changes in subcortical brain regions, particularly the hypothalamus, which are implicated in the regulation of circadian rhythms. Amongst those, the suprachiasmatic nucleus (SCN) of the anterior hypothalamus and wake-promoting postero-lateral hypothalamic structures are affected at early (preclinical) disease stages.
This study aims to investigate the relationship between FD of locomotor activity and sleep EEG, and the integrity of subcortical brain structures in individuals with AD. We aim at recruiting 50 early-stage AD patients and 50 age- and sex-matched healthy individuals as a control group. Using ultra-high field (7T) MRI, we will divide hypothalamic nuclei into different structural compartments using a deep-learning parcellation tool. Quantitative MRI (qMRI) metrics (R2*, MT, R1, PD) will be extracted from these parcels to gain insights into tissue composition, such as myelin and axonal integrity. Furthermore, diffusion imaging will characterize microstructural integrity and connectivity.
Complementing the MRI measures, actimetry will monitor locomotor activity over three weeks, and polysomnography will identify sleep EEG signatures, providing a comprehensive view of physiological dynamics. We hypothesize that AD patients show reduced structural integrity in the anterior and postero-lateral hypothalamic compartments which mediate altered FD in locomotor activity and sleep EEG signatures. Our data will offer novel insights into the neural mechanisms underpinning AD. The use of 7T MRI is pivotal in resolving small, subcortical structures, bridging the gap between physiological changes and underlying pathology, and paving the way for early detection strategies in AD.