Study on Safety, Feasibility and Neural Activation of Non-Invasive Light Therapy System

Induction of neural oscillations by flickering light is a well established method used for diagnostic of various neural diseases (5,6).

Recent studies in mice have shown promising results indicating that induction of gamma oscillation at 40 Hz leads to a reduction in amyloid-β an tau in mice models of Alzheimer's disease (1-4). This study will use flickering light to induce 40 Hz gamma oscillation as the previously mentioned studies.

This study will utilize a novel way of masking the light by alternating the spectral composition of a white light, rendering the flicker invisible to the conscience perception while still entraining 40 Hz oscillations in the brain.

In the study subject will be exposed to invisible spectral flickering light (active setting) or continuous non-flickering white light (sham setting) for 1 hour each day. The sham setting is a high quality sham intervention as subjects will be blinded to the setting, both appears as white light.

As this is the first trial, the focus will be on 1) safety of the intervention 2) feasibility of the proposed intervention time and method 3) indication of efficacy.

In stage 1 of the trial 4 age-matched subjects with no Alzheimer's disease will be recruited and be exposed for 1 week. In stage 2 10 patients with Alzheimer's disease will be recruited and exposed for 6 consecutive weeks. Following the 6 weeks of intervention the subject will have 6 weeks of no intevention and assesed agian.

Inclusion criteria

• Adult competent persons able to understand the nature of the study and give written informed consent.
• Stage I: Healthy elderly subject.
• Stage II: Diagnosed with probable mild to moderate AD based on NIA-AA diagnostic criteria.
• Age >55 years and <80 years. Females must be post-menopausal.
• Fluent in Danish
• > 8 year of normal school education
• Pass a colour-blindness test (Ishihara colour test)
• Have visual and auditory capabilities, and language skills necessary for neuropsychological testing.
• Furthermore, subjects must have a person, hereafter named designated caregiver, who is available to the participant and can provide the necessary assistance with using the LTS device and Actigraph wearable at home and can assist with clinic visits and other practical issues.

Exclusion criteria

• Profound visual impairment provided correction with spectacles, if needed.
• Significant abnormalities related to important parts of the brain e.g. the visual system, pre-frontal cortex or hippocampus, or relevant lesions detected by MRI.
• Prior history of significant diseases related to the visual system or the brain.
• Medication Any patient using antiepileptic drugs, neuromodulating drugs or high dose of sedatives will be excluded.
• Prior history of substance abuse within the past 2 years.
• Any significant systemic illness or unstable medical condition, which could lead to difficulty complying with the protocol.