Dose analysis on a cohort of Alzheimer's disease patients stimulated with transcranial alternating current stimulation

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Virtual-106 - DOSE ANALYSIS ON A COHORT OF ALZHEIMER’S DISEASE PATIENTS STIMULATED WITH TRANSCRANIAL ALTERNATING CURRENT STIMULATION (ID 659)Topic AS07. Neuromodulation Biomarkers and Outcomes IntroductionThe Neurotwin project ran a randomized controlled trial conducted at the Fundazione Santa Lucia (Rome) with 28 patients with Alzheimer’s disease (AD). Participants received transcranial alternating current stimulation (tACS) using personalized protocols derived from biophysical head models built from each patient’s MRI. We quantified dose as the average normal component of the electric field (〈En〉) within predefined cortical targets and tested whether dose predicted change on the Alzheimer’s Disease Assessment Scale–Cognitive Subscale 13 (ADAS-Cog 13), the primary cognitive outcome. Materials / Methods Baseline T1 MRIs were segmented into skin, skull, cerebrospinal fluid (CSF) (including ventricles), grey-matter (GM), and white-matter (WM). Finite-element models estimated electric fields for a bilateral AF3/AF4–T7/T8 montage with trial currents personalized across participants (frontal 1.56–1.77 mA; temporal 1.11–1.69 mA). Tissues were modeled as isotropic/homogeneous with conductivity values: 0.33, 0.008, 1.79, 0.40, and 0.15 S/m. 〈En〉 was calculated in dorsolateral prefrontal cortex (DLPFC),temporal cortex, precuneus, hippocampus, and inferior parietal lobule (IPL). Mixed linear models related linear combinations of regional 〈En〉 to ADAS-Cog-13 change. Principal components (PCs) summarized multiregional dose patterns. Sham-session results served as a control analysis. ResultsA PC capturing left-right hemispheric (LH/RH) asymmetry in temporal and IPL regions significantly predicted cognitive improvement at follow-up, surviving Bonferroni correction (p < 0.01, see figure 1). Greater LH 〈En〉 relative to the RH was associated with better outcomes. No robust dose-response associations were observed in the Figure 1: (a) Relationship between PC4 (dose pattern capturing LH/RH asymmetry) and percentage change in ADAS-Cog-13 from baseline with mixed-model fit. (b) PC4 loadings across ROIs. DiscussionThe asymmetry aligns with reports of earlier LH atrophy and hypometabolism in early stages of AD, suggesting that structural differences modulate delivered fields and clinical response. Increased atrophy in the left hemisphere, characteristic of AD progression, likely leads to structural changes (e.g., cortical thinning, increased CSF volumes) that inherently decrease the strength and modify the distribution of the induced electric fields in affected areas. Thus, this PC might be serving as an indirect proxy of structural degeneration, reflecting that patients with more pronounced LH atrophy, and thus inherently weaker LH fields, demonstrate a worse cognitive prognosis. This interpretation underscores the need to disentangle stimulation effects from underlying anatomical pathology. ConclusionsFuture analyses should test whether direct morphometric measures of hemispheric asymmetry predict outcomes comparably, or whether the dose-derived PC carries independent prognostic information. Such work could also inform whether dose asymmetry might serve as a practical biomarker for treatmentstratification in personalized tACS protocols. Acknowledgements This work was supported by European Unions Horizon 2020 research and innovation programme work-up under Grant Agreement No. 101017716 (Neurotwin) and by the European Research Council (ERC Synergy Galvani) under the European Union’s Horizon 2020 research and innovation programme Grant Number 855109.

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