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http://dx.doi.org/10.14336/AD.2021.0229
*Correspondence should be addressed to: Dr. Jason H. Huang, Department of Neurosurgery, Baylor Scott and White Health, Temple,
Texas 76508, USA. E-mail: Jason.Huang@bswhealth.org.
Copyright: © 2021 Nizamutdinov D et al. This is an open-access article distributed under the terms of the Creative Commons Attribution
License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
ISSN: 2152-5250 1
Short Communications
Transcranial Near Infrared Light Stimulations Improve
Cognition in Patients with Dementia
Damir Nizamutdinov1,2, Xiaoming Qi1, Marvin H. Berman3, Gordon Dougal4, Samantha
Dayawansa1,2, Erxi Wu1,2,5,6, S. Stephen Yi6, Alan B. Stevens1, Jason H. Huang1,2*
1Baylor Scott and White Health, Neuroscience Institute, Neurosurgery, Temple, TX, USA. 2Texas A&M
University, HSC, College of Medicine, Neurosurgery, Temple, TX, USA. 3Quietmind Foundation, Elkins Park,
PA, USA. 4Maculume Limited, Spennymoor, UK. 5Texas A&M University, HSC, College of Pharmacy,
Department of Pharmaceutical Sciences, College Station, TX, USA. 6Department of Oncology, Dell Medical
School, The University of Texas at Austin, TX, USA.
[Received December 8, 2020; Revised February 24, 2021; Accepted February 29, 2021]
ABSTRACT: Dementia is a complex syndrome with various presentations depending on the underlying
pathologies. Low emission of transcranial near-infrared (tNIR) light can reach human brain parenchyma and be
beneficial to a number of neurological and neurodegenerative disorders. We hereby examined the safety and
potential therapeutic benefits of tNIR light stimulations in the treatment of dementia. Patients of mild to moderate
dementia were randomized into active and sham treatment groups at 2:1 ratio. Active treatment consisted of low
power tNIR light stimulations with an active photobiomodulation for 6 min twice daily during 8 consequent
weeks. Sham treatment consisted of same treatment routine with a sham device. Neuropsychological battery was
obtained before and after treatment. Analysis of variance (ANOVA) was used to analyze outcomes. Sixty subjects
were enrolled. Fifty-seven subjects completed the study and had not reported health or adverse side effects during
or after the treatment. Three subjects dropped out from trial for health issues unrelated to use of tNIR light
treatment. Treatment with active device resulted in improvements of cognitive functions and changes were: an
average increase of MMSE by 4.8 points; Logical Memory Tests I and II by ~3.0 points; Trail Making Tests A
and B by ~24%; Boston Naming Test by ~9%; improvement of both Auditory Verbal Learning Tests in all subtest
categories and overall time of performance. Many patients reported improved sleep after ~7 days of treatment.
Caregivers noted that patients had less anxiety, improved mood, energy, and positive daily routine after ~14-21
days of treatment. The tNIR light treatments demonstrated safety and positive cognitive improvements in
patients with dementia. Developed treatment protocol can be conveniently used at home. This study suggests that
additional dementia treatment trials are warranted with a focus on mitigating caregivers’ burden with tNIR light
treatment of dementia patients.
Key words: transcranial near infrared light, photobiomodulation, dementia, tnir light treatment.
Dementia is a complex syndrome with different clinical
presentations. Although the course of disease and its
clinical progression vary largely contingent on the
underlying pathologies, the development of brain
dysfunction that typically progresses to diffuse deficits is
characteristic [1]. The most common cause of dementia is
Alzheimer’s Disease (AD), which contributes to 60-80%
of cases. The number of persons with AD is expected to
increase and escalate dramatically in the coming years
with aging of the baby boom generation. In 2019, there
Volume 12, Number 5; xxx-xx, October 2021
Nizamutdinov D., et al Effects of tNIR Light in Dementia Treatment
Aging and Disease • Volume 12, Number 5, October 2021 2
were an estimated 5.5 million Americans living with AD
(https://www.nia.nih.gov/health/alzheimers-disease-fact-
sheet). This number is projected to reach 13.8 million in
the year of 2050 [2]. Apart from AD, dementia can also
be caused by Alzheimer’s disease-related dementia (e.g.,
vascular dementia, Lewy body dementia, frontotemporal
dementia, and Parkinson-related dementia).
Low power transcranial near - infrared (tNIR) light
emitting diodes (LED) illuminate light which is outside of
visible spectrum of human eyes but can efficiently
penetrate skin and skull to reach brain parenchyma [3–5].
Recent biomedical reports indicate that low emission of
tNIR light not only can be beneficial to various acute and
chronic pathologic brain conditions, but also can help to
maintain a healthy brain state. There are several molecular
mechanisms how tNIR light stimulation can achieve
positive therapeutic effects in brain tissue. One of the
widely studied and recognized mechanism of action is the
stimulation of mitochondria by photons and the
consequent increase in intracellular production of
adenosine triphosphate (ATP). This contributes to
overcome the low ATP level associated with many
neurological disorders [6–9]. Low power tNIR can also
increase oxygenation, improve regional circulation and
nutritional supplementation to the brain parenchyma by
triggering nitric oxide (NO) production, which is an
effective vasodilator [10–13]. The tNIR light exerts anti-
inflammatory function through modulation of NF-κB
system [14], tumor necrosis factor (TNFα), and beneficial
regulation of other pro- and anti-inflammatory cytokines
in brain parenchyma [15]. Through complex regulation of
signaling molecules and TCF/LEF transcription factors
[16–18], tNIR light activates anti-apoptotic, and anti-
senescence cascades [17–19], and further exerts
neuroprotective effects on both healthy and impaired
brain cells and tissue [15]. The tNIR light can also
promote synaptogenesis and neurogenesis through
activation of brain derived neurotrophic factor (BDNF),
which contributes to the infrastructure of brain function
through environmental support by promoting new
synaptic and neuronal growth [20, 21]. Reactive oxygen
species (ROS) impair brain function and attribute to
different neurological diseases [22, 23]. Photobio-
modulation demonstrated effective regulation of
cytokine-induced nitric oxide synthase production which
helps to manage amount of ROS intracellularly and
control oxidative stress and damage associated with it [24,
25]. In addition, photons in low power tNIR light carry
low energy and deliver low power density, which makes
it safe and incapable of heating or burning exposed tissues
even with prolong and direct exposures [26].
In this study we examined the safety and potential
therapeutic benefits of tNIR light stimulation in the
treatment of patients with dementia.
MATERIALS AND METHODS
This placebo controlled, randomized, double-blinded
study was approved by institutional IRB, performed under
protection embodied in the Basic Principles of the
Declaration of Helsinki, and conducted at Baylor Scott &
White Health (BSWH) Medical Center in Temple, TX.
Sixty patients diagnosed with early and moderate
dementia were enrolled and randomized to the active arm
or control arm at a 2:1 ratio. Subjects, family caregivers,
and investigators were masked. Inclusion criteria: 1)
patients of all sex, age 50–85-year-old; 2) diagnosed with
early- to mid-stage dementia or dementia-related
symptoms; 3) generally healthy as indicated by recent
physical examination within the last 6 months. Exclusion
criteria: 1) diagnosed with actively growing, or a history
of recurrent intracranial neoplasms; 2) history of epilepsy;
3) history of acute ischemic/hemorrhagic stroke.
Both active and sham light treatment helmet devices
had 12 cranial modules with 70 LEDs/module and 2
foldable eye modules with 14 LEDs/module. Sham
helmet devices designed identical to active devices but did
not emit NIR light. Active helmet devices emitted low
power NIR light with wavelength of 1060-1080nm and
15,000mW, irradiance or power density= 23.1mW/cm2,
~650cm2 per treatment area. Treatment protocol was two
6 minutes sessions daily for 8 consequent weeks at home
with either active or sham device self-administered by
patient/family caregiver.
Neuropsychological assessments of behavior, mood
and cognitive performance were conducted at beginning
(before the treatment) and at the end (within one day after
the last treatment session) of study. Alzheimer’s Disease
Neuroimaging Initiative (ADNI) neuropsychological
battery was implemented to assess cognitive function of
participants. ADNI battery included: 1) mini‐mental state
exam (MMSE) – a cognitive screener that briefly
measures orientation, word recall, attention, working
memory, copying skills, and abilities; 2) ADAS‐Cog
(including evaluation of spoken language, word finding
ability and ability to comprehend, word recall, word
recognition, and number cancellation test); 3) clock
drawing test (CDT) – subjects asked to draw a clock to a
requested time; 4) logical memory (immediate) – subjects
asked to recall a story immediately after it is been read; 5)
auditory verbal learning test- immediate (A.V.L.T.-1) –
subjects asked to memorize and recall immediately list of
words presented verbally in several trials; 6) digit span
forward and backward (DSF and DSB) – subjects asked
to recall given different sequences of numbers in same
order (forward span) or reverse (backward span).; 7)
category fluency test – subjects asked to name words in
given category within one minute; 8) trail making tests A
and B – subjects asked to connect circles in numerical and
Nizamutdinov D., et al Effects of tNIR Light in Dementia Treatment
Aging and Disease • Volume 12, Number 5, October 2021 3
mixed (numerical-alphabetical) order, respectively in
limited time; 9) WAIS‐R digit symbol substitution test –
a cognitive test to assess visual motor coordination, motor
persistence, attention and response speed; 10) Boston
naming test – subjects asked to name 30 objects/items
printed in the book; 11) logical memory (delayed) –
subjects asked to recall a story after 30 min delay; 12)
auditory verbal learning test- delayed (A.V.L.T.-2) –
subjects asked to recall list of words presented verbally 30
min prior the recording in several trials. Daily subjective
responses record was documented by caregivers. Sleep
associated findings were collected from caregivers’ daily
logs and feedback notes from patients/caregivers during
assessment visits. All assessments/evaluations were
performed by the same examiner using same procedures
across the study.
Analysis of variance (one-way ANOVA) was used to
assess mean differences between testing occasions and
analyze outcomes inside of each group. Clock drawing
and clock copying tests were scored using Shulman
method. Analyzed data were considered to be statistically
significant when p < .05.
RESULTS
Total of 60 subjects were enrolled into the study. Three
subjects withdrew from the study due to health issues
unrelated to the use of tNIR light therapy. Fifty-seven
enrolled patients successfully completed the 8 weeks
study course. Mean age of overall study population was
74.2 ± 7.7 years old with 60% of male and 40% of female
distribution. Mean age of population treated with active
device was 72.4 ± 8.2 years old with 59% of male and
41% of female distribution. Mean age of population
treated with sham device was 77.8 ± 5.2 years old with
53% of male and 47% of female. Patients had no health or
adverse effects reported during or after completion of
study associated with use of tNIR light stimulation.
Notably, both patients and family caregivers from the
active arm shared positive feedback of noticeable changes
in cognition and improved daily routine activities.
In the active arm, some patients appreciated longer
and more peaceful night sleeps. Duration of sleep
increased by 1 hour in average after 8 ± 2 days of the
treatment. Recurring nightmares ceased in some patients
receiving tNIR light therapy. Patients reported being more
energetic, physically and mentally engaged in daily
living. Caregivers noted that patients had less anxiety,
improved mood, energy, and positive daily routine after
approximately 14-21 days of treatment, which was not
noted by caregivers in the placebo arm.
When results of active tNIR light treatments were
compared with placebo effects in the end of trial, several
improvements were noted as follows:
Mini-Mental State Exam (MMSE). In the active arm,
the average MMSE score improved from 22.8 ± 2.6 at the
beginning of treatment to 27.6 ± 2.8 (p < .001) at the end
of the treatment, which was 4.8 points improvement
(21.0% increase) over the course of treatment. In the
control arm, the average MMSE score changed from 23.2
± 1.6 at the beginning of treatment to 24.6 ± 2.5 (p = .066)
at the end of the treatment, which was 1.4 points
improvement (6.2% increase) over the course of treatment
(Table 1).
Table 1. Study demographics, Mini Mental State Exam, Clock Drawing and Copying Tests, and Logical Memory Test I
and II.
Characteristics
Sham Treatment
Active Treatment
Before
After
Before
After
Mean
S.D.
Mean
S.D.
p - value
Mean
S.D.
Mean
S.D.
p - value
MMSE
23.2
1.6
24.6
2.5
.06596
22.8
2.6
27.6
2.8
4.9E-11***
CDT
75.0
27.8
76.3
27.5
.89919
69.5
29.3
83.7
23.2
.08669
CCT
95.0
15.5
93.8
20.3
.84604
84.7
25.2
92.1
18.9
.15389
LMT-I
7.4
4.9
6.0
4.5
.39916
8.5
5.9
11.8
7.0
.03070*
LMT-II
4.3
4.6
2.7
4.0
.29372
6.5
5.9
9.5
7.8
.06417
MMSE: Mini-Mental State Exam. CDT: Clock Drawing Test. CCT: Clock Copying Test. LMT-I: Logical Memory Test – Immediate total story unit
recall. LMT-II: Logical Memory Test – Delayed total story unit recall. S.D.: standard deviation
* - p value < .05; ** - p value < .01; *** - p value < .001
Clock Drawing Test (CDT). Positive trends of
improved CDT scores were recorded in patients received
active tNIR light treatment with mean value going up
from 3.5 ± 1.5 at the beginning of treatment to 4.2 ± 1.2
(p = .08) at the end of the treatment. This was 0.7 points
improvement (20.5% increase) over the course of
treatment. Patients with sham treatment did not
demonstrate significant changes in CDT with average
scores shifting from 3.75 ± 1.39 to 3.81 ± 1.38 (p = .89),
which is a mere 1.7% change in mean CDT score over the
course of sham treatment (Fig. 1A, Table 1).
Nizamutdinov D., et al Effects of tNIR Light in Dementia Treatment
Aging and Disease • Volume 12, Number 5, October 2021 4
Figure 1. Cognitive improvements after treatment with t-NIR light twice a day for 8 consecutive weeks. (A) Clock Drawing Test.
Figure demonstrate representatives of clock drawing tests performed by two different patients with dementia. Arrows indicate transition
from results before to results after the course of the treatment. (B) Trail Making Test A and B. * - stands for statistically significant
result with p < 0.05.
Clock Copying Test (CCT). Subjects with active
tNIR light treatment showed trend of mean CCT score
value improvement from 4.2 ± 1.3 at the beginning of
treatment to 4.6 ± 0.9 (p = .15) at the end of the treatment
resulted in 8.7% increase over the course of treatment.
Subjects treated with sham devices demonstrated decrease
of CCT performance from an average of 4.8 ± 0.8 at the
beginning to 4.7 ± 1.0 (p = .84) at the end of the treatment
(Table 1).
Logical Memory Test- immediate recall (LMT-I).
Total story passage recall/learning trial in patients with
active tNIR light treatment demonstrated improved
performance. Average story recall scores increased
significantly from 8.5 ± 5.9 at the beginning of treatment
to 11.8 ± 7.0 (p = .03) at the end of the treatment and
resulted in 3.3 points increase over the course of
treatment. In comparison, placebo effect on execution of
logical memory- I test demonstrated decrease in
performance of story recall with average score shifting
from 7.4 ± 5.0 at the beginning to 6.0 ± 4.5 (p = .39) at the
end of the treatment. This resulted in 1.4 points decrease
over the course of treatment (Table 1).
Logical Memory Test- delayed recall (LMT-II).
Active device treated group also demonstrated improved
performance by increase of average score by 3.0 points
from 6.5 ± 5.9 at the beginning of treatment to 9.5 ± 7.8
(p = .06) at the end of the treatment. Sham treated group
demonstrated decrease in performance similar to LMT-I
test and resulted in test score decrease by 1.6 points from
4.3 ± 4.6 to 2.7 ± 4.0 (p = .29) over the course of treatment
(Table 1).
Trail Making Test A. Positive results demonstrated
by patients treated with active tNIR light device. They
could perform noticeably faster and stayed focused on
given task without being distracted or reminded with
instructions. This test resulted in increased speed of
performance, and the average time to completion of task
decreased from 67.8 ± 36.5 seconds at the beginning of
the treatment to 51.8 ± 22.7 seconds (p = .03) at the end
of the treatment which was 16.0 seconds (23.5%) faster
than the average performance before the treatment. This
finding is in stark contrast to sham treated patients’
performance which demonstrated a broad range of
responses from no change to slower performance.
Average time to completion of sham treated dyad changed
from 68.4 ± 35.5 seconds at the beginning of treatment to
70.6 ± 41.4 seconds (p = .87) at the end of treatment. This
resulted in average of 2.2 seconds (6%) slower
performance for the task when compared to results before
sham treatment (Fig. 1B).
Trail Making Test B. More comprehensive and
demanding in execution than Test A, Test B utilizes the
same cognitive skills as Test A, but incorporates a mental
flexibility component, and is given twice as much time for
execution. Study patients undergoing active tNIR light
treatment could successfully replicate Test A trends on
this test. The average time to completion of task decreased
from 170.3 ± 82.7 seconds at the beginning to 129.9 ±
55.3 seconds (p = .03) at the end of treatment, which is
40.4 sec (23.7%) faster performance compared to the
speed of execution prior to the treatment. On other hand,
sham treated patients, once again, demonstrated trend of
slower execution after completion of treatment course. In
this group, an average time of completion changed from
167.9 ± 80.8 seconds to 176.6 ± 88.0 seconds (p = .80)
resulted in slower performance by 8.7 sec (5.2%) when
compared with time of performance before the treatment
(Fig. 1B).
Nizamutdinov D., et al Effects of tNIR Light in Dementia Treatment
Aging and Disease • Volume 12, Number 5, October 2021 5
Boston Naming Test (BNT). Patients treated with
active device had significantly better average
performance on BNT compared to sham treated group.
Average score in this group improved from 24.4 ± 4.4 at
the beginning to 26.6 ± 3.8 (p = .02) at the end of
treatment, which is 2.2 points increase (8.8%) compared
to levels before treatment. Some responses to the
treatment resulted in up to 35.3% of score improvement.
These results were noted in three cases in patients
diagnosed with moderate dementia. Sham treated patients
demonstrated insignificant BNT average score change
from 23.4 ± 4.6 to 24.3 ± 4.9 (p = .58), which is 0.9 points
shift (4.0%) compared to the level before treatment.
Digit Span Forward (DSF) and Digit Span Backward
(DSB) Tests. Active device treatment resulted in positive
change of DSF test average score from 6.9 ± 2.2 at the
beginning to 7.6 ± 2.2 (p = .15) at the end of treatment,
resulted in 0.7 points (10.3%) increase. In the active
group, DSB test average score shifted from 4.8 ± 1.7 to
5.5 ± 2.1 (p = .17), a 0.6 point (12.4%) increase over the
course of treatment. In the control group, neither DSF nor
DSB had significant change in test performance compared
to levels prior the treatment. Average test scores shifted
from 6.4 ± 1.9 to 6.4 ± 2.0 (p = .92) and from 5.0 ± 1.4 to
5.0 ± 1.2 (p = 1.0) for DSF and DSB tests, respectively.
WAIS‐R Digit Symbol Substitution Test. Treatment
with active device resulted in trends of improvement of
performance from 29.9 ± 11.4 to 33.7 ± 12.5 (p = .19),
which is 3.8 (12.6%) points higher than before the
treatment. Placebo effect did not trigger significant
improvements of performance on this test and resulted in
change of average score from 29.25 ± 13.9 to 29.8 ± 14.8
(p = .91), which is a mere 0.6 (1.9%) points change over
the course of treatment.
Word Fluency Test. Both treated groups performed
similarly with an average score change from 20.3 ± 7.3 to
22.9 ± 7.6 (p = .14) in the active arm and from 17.6 ± 6.6
to 19.1 ± 8.1 (p = .56) in the control arm, respectively.
Auditory Verbal Learning Test - Immediate
(A.V.L.T. - 1). Treatment with active device resulted in
statistically significant positive cognitive improvement in
patients’ performance during the course of treatment.
Immediate A.V.L.T.-1 test resulted in improvement of
evaluated performance for Trial 1 by 48.6% (p < .001),
Trial 5 by 31.2% (p = .001), Trial 1-5 Sum by 33.9% (p <
.001), and Trial 7 by 47.7% (p = .002). On other hand,
sham treated patients did not demonstrate statistically
significant results in the end of the treatment. In most
subtests, response to sham treatment had no change in
performance (for Trial 1 and Trial 5) or insignificant trend
(Trial 1-5 Sum) of improvement (Table 2).
Auditory Verbal Learning Test - Delayed (A.V.L.T. -
2). Delayed (30 min) recall and recognition subtests were
evaluated in patients from both groups. Significant
improvement was noted in the active group in delayed
recall subtest with an average score improvement by 2.2
(63.5%) points increasing from 3.4 ± 2.9 to 5.6 ± 4.4 (p =
.015) over the course of treatment. Significant observation
was also noted for recognition subtest with performance
improvement by 14.5% (p = .05) compared to score at the
beginning of the treatment. However, sham treated
patients did not demonstrate significant improvements on
aforementioned subtests (Table 2).
Table 2. Auditory Verbal Learning Test - Immediate and Delayed Subsets.
Subtests
Sham Treatment
Active Treatment
Before
After
Before
After
Mean
S.D.
Mean
S.D.
p - value
Mean
S.D.
Mean
S.D.
p - value
A.V.L.T. - 1
Trial 1
2.6
1.5
2.6
1.3
1
2.9
1.4
4.4
1.8
.00031***
Trial 5
5.6
2.4
5.6
2.5
1
7.2
2.8
9.4
3.0
.0015**
Sum 1-5
21.3
10.6
22.6
9.3
.69
26.7
9.9
35.7
12.2
.00078***
Trial 7
2.8
2.4
3.6
3.1
.41
4.6
2.6
6.8
3.3
.0022**
A.V.L.T. – 2
Delay
1.0
2.1
2.0
3.3
.31
3.4
2.9
5.6
4.4
.015*
Recognition
6.5
4.6
7.3
4.5
.62
9.7
3.4
11.1
2.9
.058
A.V.L.T. - 1: Auditory Verbal Learning Test – Immediate. A.V.L.T. - 2: Auditory Verbal Learning Test – Delayed (30 min). S.D.: standard deviation
* - p value < .05; ** - p value < .01; *** - p value < .001
DISCUSSION
Our study successfully demonstrated home-implemented
tNIR light stimulation for the treatment of dementia. This
twice daily, eight weeks tNIR light sessions were self-
administered by an older adult’s study population (74.2 ±
7.7 years old enrolled patients with dementia) with ease in
the friendly environment of home and minimal
instructions. This approach indicates that such technology
can be used for a long period of time remotely by self-
administration or with the help of a family or friend
caregiver. A daily log was provided to patients and
Nizamutdinov D., et al Effects of tNIR Light in Dementia Treatment
Aging and Disease • Volume 12, Number 5, October 2021 6
caregivers to impose treatment adherence and
compliance. Portable and cushioned cases were provided
along with the helmet device to ensure safe storage of the
device and offer portability, increasing treatment
accessibility and minimizing the potential conflict
between treatment schedule and unexpected life events
(e.g., travelling). These positive aspects of the treatment
were represented in feedback from participants and their
family caregivers. In comparison, other commonly used
medical devices could be either invasive, such as a cardiac
pacemaker, or require long hours continuous use causing
discomfort, such as a continuous positive airway pressure
(CPAP) machine. This demonstrates the feasibility and
acceptability of a light emitting device, suggesting that the
device can be a part of normal living in patients with
dementia who need prolonged, continuous, and
uninterrupted treatment without compromising quality of
life.
Our study demonstrated safety of 1060-1080nm
emitting spectrum, low power near infrared light used
twice daily in this trial. This study is a second tNIR light
treatment trial completed in Baylor Scott and White
Health following a smaller recent pilot safety study using
same technology and safety protocol, which was
successfully conducted and completed in collaboration
with Dr. Marvin Berman and his group from Quiet Mind
Foundation, Elkins Park, PA, USA [27]. The two
successfully completed trials serve as a good evidence in
regard to the safety of the therapeutic protocol
implemented in these trials, which is twice daily 6-min
long non-invasive transcranial near infrared light
stimulation. Considering reported safety in this and other
clinical studies using NIR technology, more clinical
studies are warranted using this technology and non-
invasive route of NIR administration to investigate its full
potential in the treatment of other neurological and
neurodegenerative disorders.
As we look at the subtests from different individuals,
the outcomes are even more exciting over only 8-week of
active treatment: a participant with moderate dementia
(MMSE = 16 prior to treatment) achieved a 75%
improvement (MMSE = 28 at the end of the treatment);
another patient had 80% improvement in the clock
drawing tests (Schulman method scoring); two patients
had 60% and 80% performance improvement in the clock
copying test; two patients had 12 points (48%, from 7 to
19, total score 25) and 13 points (52%, from 7 to 20, total
score 25) improvement in logical memory immediate and
delayed subtests; executive function has improved by up
to 73% in some patients evidenced by both trail making
test A and B, and verbal learning and memory tests have
improved by up to 35% as shown in the active verbal
learning immediate and delayed tests. In general, across
multiple subtests, patients in the group treated with active
tNIR light emitting device demonstrated considerable
improvement while patients in the sham treated group did
not. These observed positive outcomes suggest beneficial
effects of tNIR light stimulation on degenerative
progression of neuropathological conditions associated
with dementia. In sham treated group, natural progression
of disease during the course of the study contributed to no
positive change or decline in performance outcomes.
In the LMT-I, LMT-II, A.V.L.T.-1, A.V.L.T.-2
subtests and trail making test A, the pre-treatment mean
values in the sham treated group appeared to be lower than
pre-treatment mean values in the active group. However,
the pre-treatment means values for sham treated group
were higher in MMSE, CDT, CCT, DSB and trail making
test B assessments. This could be attributed to the
difference in mean age of study population in active (72.4
± 8.2 y.o.) and sham (77.8 ± 5.2 y.o.) groups, to privilege
of male population in active (59%) versus sham (53%), to
relatively small sample size in the control group (n=17)
versus active group (n=40), as well as explained by the
underlying neuropathology. In addition, inherent ceiling
and flooring effects could limit the reliability of these
subtests. Nonetheless, further investigations with larger
sample size, contribution of sex, age and causing
neuropathology are warranted.
Our study also demonstrated improvement of sleep-
in active group compared to feedback from patients and
family caregivers in the sham group. Although without
any specific measurement, it carries scientific merit and
should be integrated into future studies given the
important role of long and uninterrupted sleep-in
dementia and elderly population, as sleep disturbance has
been well demonstrated in dementia patients [28].
Caregiver notes and patient feedback indicated that
patients treated with active tNIR light devices have
improved night sleep with an average of 1 hour longer
after 6-10 days of treatment. This was not reported in the
control group. Patients in the active group also reported
decreased episodes of recurrent nightmares they had for
years before the study. These feedbacks are indicative of
improved overall duration of night sleep which is
impaired in patients with dementia [28]. This
improvement alone could contribute to a better recovery.
Other important findings were positive changes in daily
routine, improved mood, less anxiety, more energy and
engagement after approximately 14 to 21 days of
treatment. These observations were shared by both the
patients and family members. Great importance noted by
many caregivers was improved patient’s engagement in
daily living, helping around the household, remembering
instructions and participation in activities. Further studies
with specific measurements are warranted to examine
patient-caregiver-family member relationship, activities
of daily living with a focus on how tNIR light treatment
Nizamutdinov D., et al Effects of tNIR Light in Dementia Treatment
Aging and Disease • Volume 12, Number 5, October 2021 7
can potentially mitigate family caregiver’s burden caring
for patients with dementia.
Recent pre-clinical and clinical studies using tNIR
light stimulation reported promising improvements in
treatment of traumatic brain injury (TBI), Parkinson’s
disease (PD), and Alzheimer’s disease (AD). Below we
discuss latest findings and mechanisms of PBM in
treatment of neuropathological conditions.
Transcranial NIR light stimulation in treatment of
traumatic brain injury.
A few studies have investigated the application of PBM
in the treatment of TBIs. Some demonstrated successful
treatment of TBI associated symptoms using red light
stimulation [29, 30]. As discussed previously, there are
several mechanisms known to be triggered by photons of
NIR light which can reduce inflammation, constrain ROS
damage, and activate ATP production in energy
compromised brain area affected by TBI. Continuous
production of ATP is required for successful coordination
of metabolic, synaptic and immune efforts to consolidate
the area of injury, facilitate recovery and manage local
immune response [14, 15, 31–33]. Moreover, PBM-
initiated neurogenesis and synaptogenesis promote
reestablishment of axonal connectivity and rebuild the
intrinsic nervous networks damaged in TBI [34].
With respect to TBI triggered inflammatory chain
reaction and initiated generalized immune response, we
support the idea that aforementioned pathological
processes can be effectively addressed by implementing
tNIR light therapy. This approach is supported by
literature to be quite effective in acute and chronic TBI
treatment, considering general safety and demonstrated
efficacy of tNIR light stimulation in-vitro, in-vivo and
growing number of recent human clinical trials in this
field [29, 30]. One of the first clinical trials (small cohort
study) using tNIR light stimulations to treat chronic and
mild TBI reported positive improvements in cognition,
behavior, and sleep of patients, but also suggested that
more robust placebo-controlled studies are needed to
ensure reliability of tNIR light in TBI treatment [30, 35].
Transcranial NIR light in treatment of Parkinson’s
disease.
Parkinson’s disease is a chronic CNS pathology caused by
slow degeneration of substantia nigra (SN) pars compacta
dopaminergic neurons. PD has various clinical
presentations with motor and non-motor characteristics
depending on the stage of disease. The most common
symptoms are resting tremor, slowness of movements,
rigidity of muscles, balance impairment, dementia,
anxiety, depression, hallucinations and delusions.
Recently, several studies have investigated the effects of
tNIR light and PBM in treatment of PD using mice and
monkey models [36–38]. Most commonly used disease-
models were transgenic mice and 1-methyl-4-phenyl-
1,2,3,6-tetrahydropyridine (MPTP) compound induced
Parkinson’s model [39, 40]. In these studies, PBM has
shown mostly neuroprotective and cell preserving effects
by decreasing levels of hyper-phosphorylated tau and
cellular degeneration caused by tau-protein in PD
transgenic mice [40]. Low power LED laser treatment was
effective in SN cells preservation in PD model [37]. In
monkey PD model, after low dose red-light stimulation
course have been observed improvement of facial
expression, bradykinesia, and general activity [41]. An
increased secretion of tyrosine hydroxylase in
dopaminergic cells in response to red-light therapy or
PBM stimulation might have attributed to the function
improvement of SN cells in PD pathology [37, 38].
In this study, we have observed reduction of tremor
with noticeable improvement of balance in patients with
PD associated dementia. This could be consolidated with
the improvement of micro-tremor observed during clock
drawing test in this study (Figure 1A). More clinical trials
are required to consolidate findings about benefits of tNIR
light stimulations for treatment of patients with PD.
Transcranial NIR light in treatment of Alzheimer’s
disease.
Alzheimer’s disease is the most common
neurodegenerative pathology of CNS with progressive
memory loss and cognitive function impairment [41]. In
AD, there are pathological buildup of toxic beta-amyloid
peptide (β42) with hyper-phosphorylated tau proteins
which result in formation of amyloid plaques and
neurofibrillary tangles within brain tissue, respectively
[42, 43]. Red light treatment can potentially benefit in
management of AD through: 1) inhibition of apoptosis in
AD targeted neurons [44]; 2) induction of resistance to
neurotoxicity associated with toxic accumulation of β42
peptide [20, 45, 46]; 3) reduction of amyloid plaques
formation in the brain parenchyma [47]. Recent clinical
study has demonstrated significant improvement in
MMSE scores, cognitive subscale behavior and mood
subtests of AD patients treated with only daily intranasal
applications of NIR light supplemented with only once a
week transcranial NIR light session in duration of 12
weeks [48]. Even with a limited number of sessions using
transcranial NIR light delivery could achieve positive
improvements and align with some of our findings in this
study. It is promising to construct more future clinical
studies with transcranial applications of NIR light, which
could potentially yield in more beneficial outcomes.
Nizamutdinov D., et al Effects of tNIR Light in Dementia Treatment
Aging and Disease • Volume 12, Number 5, October 2021 8
Limitation of the study
Patient with mild dementia may have less room for
improvement compared to patients diagnosed with
moderate dementia. Additionally, some tests may not be
powerful enough to detect fewer substantial changes.
Therefore, robust changes in individual performances can
be obscured by those with minimal changes and vice
versa, when analyzing combined datasets from different
stages of disease (different pathological states). This can
potentially be addressed by stratifying patients’ data
based on severity of dementia. Results of stratified
patients’ data by stage of disease may represent a full
potential of therapeutic range for each patient group.
Conclusion
Transcranial applications in this study demonstrated safe
and convenient approach to deliver NIR light to the brain
without local or systemic side effects and adverse
reactions. Treatment protocol designed for this trial was
simple and successfully used at the convenience of home
by elderly population. Observed positive cognitive,
executive, and mood changes can benefit patients with
dementia by improving quality of life and self-
independence in daily lives, and thus helping their
immediate family caregivers by decreasing their burden.
More studies are necessary to look into family caregivers’
burden and to ensure reproducibility of positive findings.
Acknowledgements
This study was supported by a research grant from Clarke
Brain Institute Charities Inc. We are grateful to our team
of Neurologists and Neuropsychologists under
leaderships of Dr. Jeffrey W. Clark and Dr. Jared Benge
for referring patients for this clinical research trial.
Conflict of interest
Authors declare no conflict of interest.
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