Journal of Alzheimer's Disease - Volume 83, issue 4

Authors: Hamblin, Michael R. | Salehpour, Farzad

Article Type: Introduction

DOI: 10.3233/JAD-210743

Citation: Journal of Alzheimer's Disease, vol. 83, no. 4, pp. 1395-1397, 2021

Authors: Johnstone, Daniel M. | Hamilton, Catherine | Gordon, Luke C. | Moro, Cecile | Torres, Napoleon | Nicklason, Frank | Stone, Jonathan | Benabid, Alim-Louis | Mitrofanis, John

Article Type: Review Article

Abstract: In recent times, photobiomodulation has been shown to be beneficial in animal models of Parkinson’s disease, improving locomotive behavior and being neuroprotective. Early observations in people with Parkinson’s disease have been positive also, with improvements in the non-motor symptoms of the disease being evident most consistently. Although the precise mechanisms behind these improvements are not clear, two have been proposed: direct stimulation, where light reaches and acts directly on the distressed neurons, and remote stimulation, where light influences cells and/or molecules that provide systemic protection, thereby acting indirectly on distressed neurons. In relation to Parkinson’s disease, given that the major …zone of pathology lies deep in the brain and that light from an extracranial or external photobiomodulation device would not reach these vulnerable regions, stimulating the distressed neurons directly would require intracranial delivery of light using a device implanted close to the vulnerable regions. For indirect systemic stimulation, photobiomodulation could be applied to either the head and scalp, using a transcranial helmet, or to a more remote body part (e.g., abdomen, leg). In this review, we discuss the evidence for both the direct and indirect neuroprotective effects of photobiomodulation in Parkinson’s disease and propose that both types of treatment modality, when working together using both intracranial and extracranial devices, provide the best therapeutic option. Show more

Keywords: Animal models, behavior, mitochondrial activity, neuroprotection, neurotrophic factors

DOI: 10.3233/JAD-210052

Citation: Journal of Alzheimer's Disease, vol. 83, no. 4, pp. 1399-1413, 2021

Authors: Yang, Luodan | Wu, Chongyun | Tucker, Lorelei | Dong, Yan | Li, Yong | Xu, Peisheng | Zhang, Quanguang

Article Type: Research Article

Abstract: Background: Anxious-depressive-like behavior has been recognized as an early endophenotype in Alzheimer’s disease (AD). Recent studies support early treatment of anxious-depressive-like behavior as a potential target to alleviate memory loss and reduce the risk of developing dementia. We hypothesize that photobiomodulation (PBM) could be an effective method to alleviate depression and anxiety at the early stage of AD pathogenesis. Objective: To analyze the effect of PBM treatment on anxious-depressive-like behavior at the early stage of AD. Methods: Using a novel transgenic AD rat model, animals were divided into wild-type, AD+sham PBM, and AD+PBM groups. Two-minute daily …PBM (irradiance: 25 mW/cm2 and fluence: 3 J/cm2 at the cortical level) was applied transcranially to the brain of AD animals from 2 months of age to 10 months of age. After completing PBM treatment at 10 months of age, behavioral tests were performed to measure learning, memory, and anxious-depressive-like behavior. Neuronal apoptosis, neuronal degeneration, neuronal damage, mitochondrial function, neuroinflammation, and oxidative stress were measured to test the effects of PBM on AD animals. Results: Behavioral tests showed that: 1) no spatial memory deficits were detected in TgF344 rats at 10 months of age; 2) PBM alleviated anxious-depressive-like behavior in TgF344 rats; 3) PBM attenuated neuronal damage, degeneration, and apoptosis; and 4) PBM suppresses neuroinflammation and oxidative stress. Conclusion: Our findings support our hypothesis that PBM could be an effective method to alleviate depression and anxiety during the early stage of AD development. The mechanism underlying these beneficial effects may be due to the improvement of mitochondria function and integrity and the inhibition of neuroinflammation and oxidative stress. Show more

Keywords: Anxiety, depression, low-level laser therapy, photobiomodulation, TgF344 rats

DOI: 10.3233/JAD-201616

Citation: Journal of Alzheimer's Disease, vol. 83, no. 4, pp. 1415-1429, 2021

Authors: Salehpour, Farzad | Khademi, Mahsa | Hamblin, Michael R.

Article Type: Research Article

Abstract: Background: Photobiomodulation (PBM) involves the use of red and/or near-infrared light from lasers or LEDs to improve a wide range of medical disorders. Transcranial PBM, sometimes accompanied by intranasal PBM, has been tested to improve many brain disorders, including dementia. Objective: To conduct a systematic review according to PRISMA guidelines of pre-clinical and clinical studies reporting the use of PBM, which were considered relevant to dementia. Methods: Literature was searched between 1967 and 2020 using a range of keywords relevant to PBM and dementia. The light source and wavelength(s), output power, irradiance, irradiation time, fluence or …total energy (dose), operation mode (continuous or pulsed) irradiation, approach and site, number of treatment sessions, as well as study outcome(s) were extracted. Results: Out of 10,473 initial articles, 36 studies met the inclusion criteria. Nine articles reported in vitro studies, 17 articles reported studies in animal models of dementia, and 10 studies were conducted in dementia patients. All of the included studies reported positive results. The clinical studies were limited by the small number of patients, lack of placebo controls in some instances, and only a few used objective neuroimaging methods. Conclusion: The preliminary evidence of clinical benefit, the lack of any adverse effects, and the remarkable ease of use, suggest larger clinical trials should be conducted as soon as possible. Show more

Keywords: Alzheimer’s disease, cognition, dementia, learning, low-level light therapy, memory, photobiomodulation

DOI: 10.3233/JAD-210029

Citation: Journal of Alzheimer's Disease, vol. 83, no. 4, pp. 1431-1452, 2021

Authors: Caldieraro, Marco Antonio | Laufer-Silva, Tatiana | Cassano, Paolo

Article Type: Research Article

Abstract: Background: Major depressive disorder (MDD) is prevalent and has significant impact on individuals and society. Cognitive symptoms are frequent in MDD and insufficiently treated by antidepressant medications. Transcranial photobiomodulation (t-PBM) is a novel device therapy which shows promise as an antidepressant and pro-cognitive treatment. To date, despite the encouraging results, the optimal stimulation parameters of t-PBM to treat MDD are not established, and clinical studies are very heterogeneous in terms of these parameters. While the literature provides guidance on the appropriate fluence to achieve therapeutic results, little is known on the other parameters. Objective: To evaluate the relationship …between different parameters and the antidepressant effect of t-PBM. Methods: We reviewed clinical studies on MDD and on depressive symptoms comorbid with other diseases. We calculated the standardized effect size of the change in symptoms severity before and after t-PBM and we performed a descriptive analysis of the reviewed papers. Results: The greatest effect sizes for the antidepressant effect were found in studies using pulse-wave t-PBM with high peak irradiance (but low average irradiance) over large skin surface. One well-designed and sufficiently powered, double-blind, sham-controlled trial indicated that t-PBM with low irradiance over a small skin surface is ineffective to treat depression. Conclusion: The use of t-PBM for Alzheimer’s disease and for dementia is still at its inception; these dosimetry lessons from the use of t-PBM for depression might serve as guidance. Show more

Keywords: Alzheimer’s disease, cognition disorders, depression, low-level light therapy, photobiomodulation

DOI: 10.3233/JAD-210586

Citation: Journal of Alzheimer's Disease, vol. 83, no. 4, pp. 1453-1469, 2021

Authors: Chan, Agnes S. | Lee, Tsz-lok | Hamblin, Michael R. | Cheung, Mei-chun

Article Type: Research Article

Abstract: Background: Recent studies of photobiomodulation (PBM) in patients with cognitive or psychological disorders (including traumatic brain injury, stroke, and dementia) have yielded some encouraging results. Objective: In this study, we aimed to investigate the effect of a single stimulation on memory in older adults with mild cognitive impairment (MCI). Methods: After PBM, hemodynamic changes, as a measure of functional brain activity, were evaluated using functional near-infrared spectroscopy (fNIRS). Eighteen subjects who met the criteria of MCI were randomly assigned to control and experimental groups. A single real or sham PBM session was administered to the forehead …of each patient in the experimental and control groups, respectively. All subjects performed a visual memory span test before and after the stimulation, and their hemodynamic responses during the tasks were measured using fNIRS. Results: The results showed that among the MCI subjects, only those who received PBM, but not those who received the sham stimulation, demonstrated significant improvement in the visual memory performance and a reduction in the hemodynamic response during the tasks. Conclusion: These findings suggest that PBM may reduce the cognitive efforts needed to complete tasks that require high memory loads, and thus improve the cognitive performance of individuals with MCI. Show more

Keywords: Functional near-infrared spectroscopy, mild cognitive impairment, photoneuromodulation, visual memory

DOI: 10.3233/JAD-201600

Citation: Journal of Alzheimer's Disease, vol. 83, no. 4, pp. 1471-1480, 2021

Authors: Spera, Vincenza | Sitnikova, Tatiana | Ward, Meredith J. | Farzam, Parya | Hughes, Jeremy | Gazecki, Samuel | Bui, Eric | Maiello, Marco | De Taboada, Luis | Hamblin, Michael R. | Franceschini, Maria Angela | Cassano, Paolo

Article Type: Research Article

Abstract: Background: Transcranial photobiomodulation (tPBM) has recently emerged as a potential cognitive enhancement technique and clinical treatment for various neuropsychiatric and neurodegenerative disorders by delivering invisible near-infrared light to the scalp and increasing energy metabolism in the brain. Objective: We assessed whether transcranial photobiomodulation with near-infrared light modulates cerebral electrical activity through electroencephalogram (EEG) and cerebral blood flow (CBF). Methods: We conducted a single-blind, sham-controlled pilot study to test the effect of continuous (c-tPBM), pulse (p-tPBM), and sham (s-tPBM) transcranial photobiomodulation on EEG oscillations and CBF using diffuse correlation spectroscopy (DCS) in a sample of ten healthy …subjects [6F/4 M; mean age 28.6±12.9 years]. c-tPBM near-infrared radiation (NIR) (830 nm; 54.8 mW/cm2 ; 65.8 J/cm2 ; 2.3 kJ) and p-tPBM (830 nm; 10 Hz; 54.8 mW/cm2 ; 33%; 21.7 J/cm2 ; 0.8 kJ) were delivered concurrently to the frontal areas by four LED clusters. EEG and DCS recordings were performed weekly before, during, and after each tPBM session. Results: c-tPBM significantly boosted gamma (t  = 3.02, df = 7, p  < 0.02) and beta (t  = 2.91, df = 7, p  < 0.03) EEG spectral powers in eyes-open recordings and gamma power (t  = 3.61, df = 6, p  < 0.015) in eyes-closed recordings, with a widespread increase over frontal-central scalp regions. There was no significant effect of tPBM on CBF compared to sham. Conclusion: Our data suggest a dose-dependent effect of tPBM with NIR on cerebral gamma and beta neuronal activity. Altogether, our findings support the neuromodulatory effect of transcranial NIR. Show more

Keywords: Cerebral blood flow, EEG oscillations, light-emitting diode, photobiomodulation, transcranial light therapy, transcranial near-infrared light

DOI: 10.3233/JAD-210058

Citation: Journal of Alzheimer's Disease, vol. 83, no. 4, pp. 1481-1498, 2021

Authors: Bullock-Saxton, Joanne | Lehn, Alexander | Laakso, E-Liisa

Article Type: Research Article

Abstract: Background: Neuroprotection against Parkinson’s disease degeneration by photobiomodulation has been reported in animal models but no true placebo-controlled human studies have been published. Objective: To understand if photobiomodulation therapy can produce clinically significant differences in physical performance measures in people with Parkinson’s disease; and what frequency of treatment is necessary to initiate clinical change. Methods: In a participant and assessor-blinded, randomized, placebo-controlled pilot study, 22 participants received either sham and/or active laser photobiomodulation (904 nm, 60 mW/diode, 50 Hz) for 33 s to each of 21 points at the cranium and intra-orally, on one, two or three times/week for …4 weeks. Two treatment phases were separated by a 4-week wash-out (Phase 2). Upper and lower limb physical outcome measures were assessed before and after each treatment phase. The Montreal Cognitive Assessment was evaluated prior to treatment Phase 1, and at the end of treatment Phase 3. Results: Montreal Cognitive Assessment remained stable between start and end of study. No measures demonstrated statistically significant changes. With regular treatment, the spiral (writing) test and the dynamic step test were most sensitive to change in a positive direction; and the 9-hole peg test demonstrated a minimum clinically important difference worthy of further investigation in a larger, adequately powered clinical trial. A placebo effect was noted. Conclusion: The results support the notion that combined transcranial and intra-oral photobiomodulation therapy needs to be applied at least 2 to 3 times per week for at least four weeks before some improvement in outcome measures becomes evident. Longer courses of treatment may be required. Show more

Keywords: Cognition, Parkinson’s disease, photobiomodulation, physical functional performance

DOI: 10.3233/JAD-210170

Citation: Journal of Alzheimer's Disease, vol. 83, no. 4, pp. 1499-1512, 2021

Authors: Baik, Ji Soo | Lee, Tae Young | Kim, Nam Gyun | Pak, Kyoungjune | Ko, Sung-Hwa | Min, Ji Hong | Shin, Yong-Il

Article Type: Research Article

Abstract: Background: Photobiomodulation (PBM) affects local blood flow regulation through nitric oxide generation, and various studies have reported on its effect on improving cognitive function in neurodegenerative diseases. However, the effect of PBM in the areas of the vertebral arteries (VA) and internal carotid arteries (ICA), which are the major blood-supplying arteries to the brain, has not been previously investigated. Objective: We aimed to determine whether irradiating PBM in the areas of the VA and ICA, which are the major blood-supplying arteries to the brain, improved regional cerebral blood flow (rCBF) and cognitive function. Methods: Fourteen patients …with mild cognitive impairments were treated with PBM. Cognitive assessment and single-photon emission computed tomography were implemented at the baseline and at the end of PBM. Results: Regarding rCBF, statistically significant trends were found in the medial prefrontal cortex, lateral prefrontal cortex, anterior cingulate cortex, and occipital lateral cortex. Based on the cognitive assessments, statistically significant trends were found in overall cognitive function, memory, and frontal/executive function. Conclusion: We confirmed the possibility that PBM treatment in the VA and ICA areas could positively affect cognitive function by increasing rCBF. A study with a larger sample size is needed to validate the potential of PBM. Show more

Keywords: Low-level light therapy, mild cognitive impairment, photobiomodulation, photobiomodulation therapy, regional cerebral blood flow

DOI: 10.3233/JAD-210386

Citation: Journal of Alzheimer's Disease, vol. 83, no. 4, pp. 1513-1519, 2021

Authors: Wang, Ziqi | Zhang, Yige | Dong, Li | Zheng, Zihao | Zhong, Dayong | Long, Xunqin | Cai, Qingyan | Jian, Wei | Zhang, Songge | Wu, Wenbin | Yao, Dezhong

Article Type: Research Article

Abstract: Background: Given that there is no specific drug to treat Alzheimer’s disease, non-pharmacologic interventions in people with subjective cognitive decline (SCD) and amnestic mild cognitive impairment (aMCI) are one of the most important treatment strategies. Objective: To clarify the efficacy of blue-green (500 nm) light therapy on sleep, mood, and physiological parameters in patients with SCD and aMCI is an interesting avenue to explore. Methods: This is a monocentric, randomized, and controlled trial that will last for 4 weeks. We will recruit 150 individuals aged 45 years or older from memory clinics and divide them into 5 …groups: SCD treatment (n  = 30), SCD control (n  = 30), aMCI treatment (n  = 30), aMCI control (n  = 30), and a group of healthy adult subjects (n  = 30) as a normal control (NC). Results: The primary outcome is the change in subjective and objective cognitive performance between baseline and postintervention visits (4 weeks after baseline). Secondary outcomes include changes in performance assessing from baseline, postintervention to follow-up (3 months after the intervention), as well as sleep, mood, and physiological parameters (including blood, urine, electrophysiology, and neuroimaging biomarkers). Conclusion: This study aims to provide evidence of the impact of light therapy on subjective and objective cognitive performance in middle-aged and older adults with SCD or aMCI. In addition, we will identify possible neurophysiological mechanisms of action underlying light therapy. Overall, this trial will contribute to the establishment of light therapy in the prevention of Alzheimer’s disease. Show more

Keywords: Alzheimer’s disease, low-level light therapy, mild cognitive impairment, non-pharmacologic interventions, subjective cognitive decline

DOI: 10.3233/JAD-201560

Citation: Journal of Alzheimer's Disease, vol. 83, no. 4, pp. 1521-1536, 2021