Phototherapy, also known as photobiomodulation (PBM), refers to the use of non-thermal, non-invasive light to achieve a therapeutic outcome, and can apply to a variety of light-emitting devices of various wavelengths. It is the use of a low energy light source to elicit biological effects, also commonly referred to as Low-Level Light Therapy, LLLT, or Low-Intensity Light Therapy, LILT. Interest in recent advances in the use of light emitting diodes (LEDs) has led to their clinical application for a variety of medical and cosmetic uses [1]. Three distinct wavelength stretches of light, including blue (415nm), red (633nm), and near-infrared (830nm, 1060-80nm), have demonstrated efficacy or multiple therapeutic applications, [2]. A previous laboratory research study [3] has shown that human lymphocytes pre-irradiated with 1072 nm light are resistant against subsequent ultraviolet light toxicity. This was the optimal wavelength for cytoprotection in this study . Further studies have shown that this wavelength demonstrated a non-invasive beneficial effect, on spatial memory performance in a mouse model of premature ageing [4]. Furthermore, this wavelength was shown to elicit a range of positive effects upon cellular stress leading to reduced β-amyloid in a mouse model of Alzheimer’s disease (AD) [5]. The mechanism of action involves photon absorption in the mitochondria electron-transport chain (cytochrome c oxidase), and up-regulation of selective neuroprotective chaperone genes [5]. A recent pilot double blind, placebo-controlled study provided the first evidence for the utility of the 1060-1080 nm wavelength range in treating age-dependent neurodegenerative diseases. In this study, 28 daily 6-minute exposures (6 active, 3 controls) improved executive functions as measured by clock drawing, praxis memory, visual attention and task switching in patients with dementia [6].
In this present study, we explored, for the first time, the potential for the beneficial effects of 1068 nm upon normal healthy middle-aged individuals.
Cerebrolite Trans-cranial phototherapy device
An air cooled, LED helmet with a peak wavelength of 1068nm was used for 6 minutes twice daily. The peak power of the NIR light output was circa 37 Watts peak optical power achieved by using a unique pulse width modulation. The plan of the device with position of LED panels is shown in Figure 1.
Recruitment
Recruitment was over 3 years, age-matched participants (mean age 57 ± 10 years (Active) and 57 ± 8 years (Placebo) from the general population recruited from Barcelona in Spain and the north of England. The Spanish volunteers were recruited sooner as the local Spanish regulator came to a decision similar to that in the UK, but a year earlier. A total of 27 participants completed the study. Recruitment was facilitated by word of mouth, newspaper advertisements and by posts on social media.
Randomisation
A computer-generated randomisation table was used. The odd numbers were assigned to individuals in the placebo group, and the even numbers were assigned to individuals in the active group.
Assessment tools
FDA-approved computerised assessment test, Automated Neuropsychological Assessment Metrics (ANAM) [7-11].
The ANAM assessment tool identified 16 different modalities: 1. composite score (overall performance), 2. simple reaction time (SRT 1), 3. code substitution (learning), 4. procedural reaction time, 5. mathematical processing (working memory 1), 6. matching to sample (spatial working memory), 7. code substitution- delayed (delayed memory), 8. simple reaction time (SRT 2), 9. Go/no-go (inhibition), 10. logical relations (reasoning), 11. spatial processing, 12. tower puzzle (problem solving), 13. tapping R hand (motor speed), 14. tapping L hand (motor speed), 15. 2-choice reaction time (attention/processing speed), 16. running memory (working memory 2).