To attain the aims of this review, we attempted to locate salient data housed on PUBMED and GOOGLE SCHOLAR using the key terms, transcranialphotobiomodulation/lower level laser therapy and depression/anxiety/older adults. All forms of publication were deemed acceptable if they addressed the topics of interest noted above and there were no yearly or methodological restrictions. The most salient articles related to the transcranial use of photobiomodulation therapy, rather than systemic approaches, were duly examined and those that were noteworthy are presented in narrative form. All modes of application employed in the various research studies were accepted as valid, as were all definitions of anxiety and depression. Moreover, since the article was designed to serve as a general one to introduce the topic, rather than a systematic review, it did not consider any of the currently reported research endeavors in depth, but rather the goals was to present a snapshot of the prevailing trends in this realm and the potential of this modality for clinical purposes. As per Hamblin 1016, the term photobiomodulation, which refers to the use of red or near-infrared light to stimulate, heal, regenerate, and protect tissues was used predominantly in this brief review. Also termed low level laser light or therapy in the past, as well as simply photobiomodulation to describe the therapeutic process these technical terms are used interchangeably in this report. For a succinct review of recent controlled clinical trials, the articles by de Oliviera Foncesca et al. 15, Askalsky and Iosifescu 3 and Hamblin 1016 are recommended.

Depression and anxiety, major health issues impacting older adults negatively and significantly remain extremely challenging to eliminate. This review discusses findings concerning the possible role of photobiomodulation, a form of light therapy that utilizes non-ionizing light sources, including lasers, light emitting diodes, or broadband light to treat brain tissues, while providing a safe means of modulating brain activity without any irreversible damage in this regard 48. According to Gutierrez-Menendez et al. 45 and an increasing number of researchers 16, photobiomodulation, a non invasive brain modulation technique that can be applied in different formats, shows considerable promise in this regard for being able to stimulate, preserve and regenerate cells and tissues, including mitochondrial photon absorption, function, and integrity, while activating signaling pathways, transcription factors and protective genes, and anti-inflammatory mechanisms 4753 associated with depressive symptoms and others 7.

Figure 1

Older adults were the specific focus in this review, given the high prevalence rates of mood disorders in this group, including those with Alzheimer s disease 47, which may worsen with unrelieved albeit preventable depression symptoms. A high number of depressed older adults with memory loss may not be amenable to psychotherapy or alternate mainstream forms of therapy, such as exercise. As well, as opposed to pharmacotherapy, which may only have a limited impact in severe cases, Disner et al. 24 note low-level light therapy with transcranial laser is a non-invasive form of therapy that can be applied selectively to the prefrontal lobe to reduce depression and anxiety symptoms through its ability to foster a state of potentially sustainable neuro enhancement 45. Additional research further shows features of depression, including impaired neuronal metabolism, chronic pain, and various degrees of cognition, may indeed be modified favorably by this approach.

Kerppers et al 30 -who examined transcranial photobiomodulation in an effort to heighten neural activity in anxious and/or depressed younger subjects did find this modality was able to stimulate brain activity. This was also the view of Maiello et al. 22 and Cassano et al. 44. Moreover, the fact that red and near infra red light stimuli can be selectively modulated and adjusted non invasively to effect cognitive targets associated with declines in emotional health and impaired psychological status 54 is expected to help minimize or reduce the complex challenges of excess distress attributable to mood disturbances and their oftentimes disabling immobilizing ramifications and negative health consequences 16. Indeed, numerous studies that do exist all tend to show that in agreement with the known structural and dysfunctional alterations of the brain in depression and anxiety states, this non invasive form of light stimulation does consistently appear to mitigate various degrees of mood disturbances, effectively and significantly, and can reverse abnormalities, including those associated with severe depression states, as well as cognitions deemed irreversible. In addition, these improvements can be explained by observable related changes in one or more brain sites, molecular pathways, and neural processes implicated in mediating one or both of these disabling psychological conditions 43. These include, but are not limited to favorable impacts on mitochondrial metabolism and other pathways relevant to major depressive disorders. In addition, studies on animal models indicate the benefits from this form of therapy appear to be comparable to those achieved by antidepressant medications. Clinical studies also indicate good tolerability.

Taken as a whole, and even if studies to the contrary have not been published, in accord with Hamblin 1016 and others ^eg.55, photo biomodulation, a novel form of light therapy that utilizes non-ionizing light sources, including lasers, light emitting diodes, or broadband light, does appear to be a highly promising safe means of modulating brain cortical activity in simulated as well as clinical depression and anxiety without any observable damage when delivered transcranially 43. Also associated with cognitive improvements, memory, and behavioral improvements, including attenuation of depression and anxiety, and increased cortical oxygenation, the application of TPBM may be especially helpful for alleviating suffering in older adults who cannot exercise readily, take medications, or interact effectively clinically or in a group 55, especially those with cognitive challenges and frail elders with multiple morbidities. Thus future work to validate these preliminary findings, as well as clarifying the apparent clinical value of TPBM for larger more diverse samples that may lead to more targeted and successful therapies is strongly warranted. As well, the role of TPBM as an adjunctive therapeutic tool should be examined. In the interim, since many current intervention approaches, it appears that subject to careful patient evaluation concerning the nature and etiology of any prevailing chronic mood disturbances, the carefully construed and monitored application of TPBM can be expected to safely reduce feelings of excess anxiety 56 and depression 45 to some degree, with minimal risk, regardless of age and extent of the severity of one or more mood disturbances. To shed more light on the potential for TPBM and its implications on health status as a whole, testing whether such an application yield important parallel improvements in parameters related to the function of the musculoskeletal and cardiorespiratory systems, plus the immune system will be valuable. Whether bone health, the degree of sleep and life quality, and the extent of premature or biological aging attributable to inflammation can be attenuated is also of possible value to ascertain 175557 and may be highly informative. Moreover, identifying whether targeted and repeated TPBM applications can foster a stronger desire among patients towards self care and other positive behaviors, as well as a greater ability to adhere to health recommendations and to feel efficacious in achieving favorable health and active aging outcomes in the short and long-term time periods could prove invaluable.

In the interim, and in line with growing evidence from multiple sources, the transcranial application of diverse forms of delivering low level laser light therapy to the prefrontal cotical region of depressed animals and humans appears to offer a consistently efficacious result as far as producing measureable favorable organic changes in the stimulated neural tissues and structures that are vital to emotional regulation and wellbeing. Furthermore, and importantly, the currently demonstrated benefits of TPBM may be expected to heighten favorable outcome expectations and thus more positive perspectives for many older adults-in general, especially in light of the unfavorable stance often accompanying the stigma of depression and anxiety, in addition to widespread ageism issues and perspectives, plus vulnerability to the use of psychotropic drugs. To further affirm and advance its clinical value, however, more comparative studies, as well as dose response and other studies assessing the degree to which TPBM can act as an effective approach for enhancing mainstream intervention approaches such as exercise, counseling, pharmacologic and stress control approaches may be insightful. Finally, in terms of cost benefit analyses, it appears the low monetary and energy costs of TPBM, along with its ease of usage might be better exploited in terms of its possible value for reducing the immense degree of suffering, as well as unwanted consequences of depression, such as cardiovascular disease 58, and more recently COVID-19, among the growing older adult population, if more clinical evidence from long-term prospective studies of various degrees of distress in healthy and chronically impaired older adults are forthcoming.

Indeed, by providing hope to many, as opposed to despair, along with cost savings to elder care organizations, health policy makers, and governmental agencies, the apparent merits of TPBM should be studied sooner rather than later by all those in the health field who seek to advance elder care and raise older adults life quality, while preventing undue suffering and emotional pain in a cost-effective and safe manner.

Attributes or factors and parameters that may impact or influence efficacy and outcomes in clinical and preclinical studies of TPBM that should be carefully examined in light of their possible differential effects on the quantity of light absorbed, and hence on the desired outcomes include:

the degree of prevailing irradiance

treatment timing and repetition

pulse attributes and wavelength/light color 

the degree of fluence

power density effects

Other mediating or moderating factors that can be examined to gain further insight into the efficacy of TPBM for intervening in depression and anxiety are the characteristics of the subject, and application site ^s, the methods of applying the light stimuli, and the prevailing degree of emotional and neural dysfunction 1015165960. Others not well studied to date are the role of: 1) caregiver empathy and knowledge; 2) patient attributes and beliefs; 3) general health status; 4) living conditions; 5) social support; 6) degree of follow up evaluations.

Successful results may also depend on the ability of the provider to personalize any recommended phototherapy application, as well as follow up plans and timely carefully construed evaluations.

In the meantime, the work to date not only embodies, but is consistent with the contemporary paradigm shift away from dysregulation of single neurotransmitter systems in cases of depression towards circuit level abnormalities impacting function across multiple brain regions and neurotransmitter systems that is comparable to the actions of antidepressant medications 4354, as well as efforts to foster successful aging. Combining transcranially induced light therapy alongside antidepressant and/or other medications and educational approaches can also be expected to help speed up the rate at which possible beneficial outcomes are realized. Moreover, those treated optimally will undoubtedly tend to experience better overall health status, sleep quality, and a higher life quality than those who do not - all things considered 261 ⁶².

In this regard, although ignored for many years, it appears hard to refute the idea that TPBM is a potentially effective, sustainable, safe, and compatible intervention mode for purposes of offsetting the immense suffering attributable to the presence and risk of multiple cognitive and health challenges faced by many elderly, if not all. Its optimal value too, which may yet be untapped, appears to merit considerable attention in this regard, and is strongly encouraged.