PhD defence by Marcus Schultz Carstensen

The global prevalence of Alzheimer’s disease is expected to triple by 2050, with the majority of afflicted individuals residing in low- and middle-income nations. Currently, only symptomatic treatments are available to the vast population on earth, and two recently approved medications, Aducanumab and Lecanemab, are prohibitively expensive. This thesis aims to explore whether a new type of light-based brain stimulation, coined invisible spectral flicker, can be used as a possible substitute or supplement to medication for the symptomatic or disease-modifying treatment of Alzheimer’s disease. This treatment approach builds on studies in animal models showing a potential to target a new type of disease process, designated neuronal dysfunction in the context of the thesis. It is presumed to target the vicious cycle of toxic protein-dependent neuronal hyperactivation through enhanced inhibitory capacity, which is essential for the brain to function, be healthy, and age properly. Ten sequential studies within this thesis develop the technology, investigate its feasibility, as well as evaluate and demonstrate that mild-to-moderate Alzheimer’s disease patients may possibly improve in cognition, gamma activity, activities of daily living, and brain volume while seeming safe to use. Due to the complexity of substantial precedents from previous pharmaceutical Phase 3 trials and the rapidly changing regulatory landscape, a confirmatory Phase 3 trial is needed to validate the current results before approval and patient access. Consequently, further clinical research is required before we can answer with strong certainty whether we can substitute or supplement pharmaceutical medication, but the safety and feasibility evidence seems encouraging.