U.S. patent application number 16/837456 was filed with the patent office on 2020-07-16 for cognition and memory enhancement via multiple odorant stimulation.
This patent application is currently assigned to THE REGENTS OF THE UNIVERSITY OF CALIFORNIA. The applicant listed for this patent is THE REGENTS OF THE UNIVERSITY OF CALIFORNIA. Invention is credited to Michael Leon.
Application Number | 20200222658 16/837456 |
Document ID | / |
Family ID | 68161083 |
Filed Date | 2020-07-16 |
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United States Patent
Application |
20200222658 |
Kind Code |
A1 |
Leon; Michael |
July 16, 2020 |
COGNITION AND MEMORY ENHANCEMENT VIA MULTIPLE ODORANT
STIMULATION
Abstract
Disclosed herein are methods, kits, and devices for improving
cognitive function and memory through olfactory stimulation. In
some embodiments, olfactory stimulation is performed by releasing
one or more scents according to an olfactory stimulation regimen or
schedule. The methods, kits and devices described herein can
provide a large impact on cognition with minimal effort and cost.
They can be used widely and effectively among older adults,
children, and other populations in need of improved cognitive
performance.
Inventors: |
Leon; Michael; (San Juan
Capistrano, CA) |
|
Applicant: |
Name |
City |
State |
Country |
Type |
THE REGENTS OF THE UNIVERSITY OF CALIFORNIA |
Oakland |
CA |
US |
|
|
Assignee: |
THE REGENTS OF THE UNIVERSITY OF
CALIFORNIA
OAKLAND
CA
|
Family ID: |
68161083 |
Appl. No.: |
16/837456 |
Filed: |
April 1, 2020 |
Related U.S. Patent Documents
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Application
Number |
Filing Date |
Patent Number |
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16383186 |
Apr 12, 2019 |
10639448 |
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16837456 |
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62657621 |
Apr 13, 2018 |
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Current U.S.
Class: |
1/1 |
Current CPC
Class: |
A61M 2230/30 20130101;
A61B 5/4812 20130101; A61M 21/02 20130101; A61M 2205/07 20130101;
A61M 2205/3569 20130101; A61M 2230/10 20130101; A61M 2230/42
20130101; A61M 2021/0016 20130101; A61M 2230/06 20130101; A61M
21/00 20130101; A61M 2230/10 20130101; A61M 2230/005 20130101; A61M
2230/42 20130101; A61M 2230/005 20130101; A61M 2230/30 20130101;
A61M 2230/005 20130101; A61M 2230/06 20130101; A61M 2230/005
20130101 |
International
Class: |
A61M 21/02 20060101
A61M021/02; A61M 21/00 20060101 A61M021/00 |
Claims
1. A method of improving cognitive function of a human comprising:
establishing a daily treatment schedule including a plurality of
intervals separated by breaks; inputting the daily treatment
schedule into a scent-delivery device such that the device delivers
one of a plurality of scents during each interval, and stops the
delivery of the scent at the end of the interval; ensuring that
scents delivered during consecutive intervals are sufficiently
distinct from each other so as to be distinguished by said human;
ensuring that no scent is repeated more than once during the daily
treatment schedule; repeating the daily treatment schedule each day
for a predetermined treatment length.
2. The method of claim 1 wherein establishing the daily treatment
schedule including the plurality of intervals separated by breaks
comprises scheduling a plurality of 30 minute intervals separated
by 5 minute breaks.
3. The method of claim 1 wherein establishing the daily treatment
schedule including the plurality of intervals separated by breaks
comprises scheduling at least three intervals separated by
breaks.
4. The method of claim 1 wherein inputting the daily treatment
schedule into a scent-delivery device comprises wirelessly
connecting the device to a handheld electronic device having an
application that allows the schedule to be uploaded to the
scent-delivery device.
5. The method of claim 1 wherein inputting the daily treatment
schedule into a scent-delivery device comprises setting a start
time.
6. The method of claim 1 wherein establishing a daily treatment
schedule comprises basing an initiation of the schedule on an
activity signifying that a user is going to bed.
7. The method of claim 6 wherein said activity comprises plugging a
handheld device into the scent-delivery device.
8. The method of claim 6 wherein said activity comprises a
biometric sensor, wirelessly connected to the hand-held device,
providing data that indicates the user has begun a sleep-cycle.
9. A device for providing cognitive-improvement olfactory therapy
comprising: a housing defining at least one cavity, each of said at
least one cavity sized to receive a removable scent cartridge, and
a vent; at least one fan adjacent the at least one cavity and
capable of moving air through said at least one cavity; at least
one motor associated with the at least one fan; a control board
that controls the at least one motor according to a daily schedule
that includes a plurality of intervals separated by breaks, and
initiates the daily schedule at a start event; wherein during an
interval, the at least one fan is activated such that air is pushed
through the vent and an associated at least one cavity, thereby
emitting an odor when a scent cartridge is placed in the at least
one cavity; wherein during a break, the at least one fan is not
activated.
10. The device of claim 9 further comprising moveable covers
associated with each of said cavities and mechanized to move
between an open position to a closed position, said covers
controlled by said control board.
11. The device of claim 9 wherein the start event comprises a time
of day.
12. The device of claim 9 wherein the start event comprises data
received from a biometric sensor indicating a user has begun a
sleep cycle.
13. The device of claim 9 further comprising a personal electronic
device wirelessly connected to control board, and wherein said
personal electronic device provides said daily schedule.
14. The device of claim 13 wherein said start event determined by
said personal electronic device.
15. A method of improving cognitive function of a human comprising:
providing a plurality of scents categorized into scent families,
each family including scent sub groups, according to a fragrance
wheel arranged such that adjacent sub groups have similarities;
establishing a daily treatment schedule including a plurality of
intervals separated by breaks, wherein a scent is administered to a
recipient during an interval and no scent is administered during a
break; ensuring that scents delivered during consecutive intervals
are sufficiently distinct from each other so as to be distinguished
by said human; ensuring that no scent is repeated more than once
during the daily treatment schedule; repeating the daily treatment
schedule each day for a predetermined treatment length.
16. The method of claim 15 wherein administering the daily schedule
to the recipient comprises using a device that automatically emits
said scents according to said daily schedule.
17. The method of claim 15 the daily schedule is administered to a
recipient while the recipient is sleeping.
18. The method of claim 15 wherein said scent families comprise
floral notes, oriental notes, woody notes, and fresh notes.
19. The method of claim 15 wherein said scent families comprise
floral notes, fruity notes, resinous notes, and spicy notes.
20. The method of claim 16 wherein using a device comprises
programming the device to begin the daily schedule a predetermined
amount of time after the user has gone to bed.
Description
RELATED APPLICATIONS
[0001] This application claims benefit of and priority to U.S.
Provisional Application Ser. No. 62/657,621 filed Apr. 13, 2018,
entitled Cognition and Memory Enhancement Via Multiple Odorant
Stimulation, which is hereby incorporated herein by reference in
its entirety.
BACKGROUND OF THE INVENTION
[0002] Environmental enrichment has been shown to have a positive
impact on cognitive function such as in ameliorating cognitive
decline in various animal models. Enriching an environment can be
accomplished in a variety of ways including, but not limited to,
the introduction of various objects, sounds, smells, colors,
animals, etc. Thousands of research papers reaching this conclusion
have been published and the cognitive benefits have been shown to
reduce or overcome animal models of human neurological disorders
such as Alzheimer's disease, memory loss, vascular dementia,
neuronal death in aging, traumatic brain injury, head injury,
Parkinson's disease, seizures, stroke, multiple sclerosis, anxiety,
autism, ADHD, Huntington's disease, Down Syndrome, stress,
depression, cerebral palsy, chemo-brain, schizophrenia, prenatal
alcohol syndrome, lead exposure, addiction and cancer, to name a
few. Noticeable behavioral changes have been observed in children
with autism after as little as six months of environmental
enrichment exercises.
[0003] Of the various stimulants used in environmental enrichments,
it has been found that cognition is strongly associate with
olfaction. Olfaction is the only sense that has a large, direct
pathway to the cognitive and emotional areas of the brain. Loss of
olfaction precedes the memory loss from aging and from all forms of
dementia. Olfactory loss triggers a massive loss of neurons in the
brain. After the age of 50, it has been found that olfactory
ability accurately predicts all-cause mortality within the next
five years.
[0004] Biologically, olfactory stimulation activates the entorhinal
cortex. The entorhinal cortex diminishes with age and other factors
such as Alzheimer's and other forms of dementia. As the entorhinal
cortex diminishes, it releases the dentate gyrus and CA3
(hippocampal subfields) from inhibition, thereby interfering with
memory. Thus, a restoration of olfaction should increase
neurogenesis and/or neural complexity in the entorhinal cortex,
thereby normalizing dentate/CA3 activity and restoring memory.
[0005] Interventions based on environmental enrichment can be
expensive or difficult to maintain, as in the case of exercise.
Currently, there is a lack of environmental enrichment modalities
that effectively improve cognitive function and memory while being
low cost, and easy to use or maintain. More specifically, there is
a lack of environmental enrichment modalities that exploits the
strong association that olfaction has with the cognitive and
emotional areas of the brain.
OBJECTS AND SUMMARY OF THE INVENTION
[0006] Provided herein are methods, kits, and devices for improving
cognitive function and memory, as well as preventing loss of these
functions. In some embodiments, the environment of the aging brain
is improved by reversing and/or preventing the decline in sensory
systems in older adults and those suffering from or at risk for
neurodegenerative conditions and/or cognitive decline. In some
embodiments, the cognitive outcomes of children and/or younger
adults are improved. In other embodiments, the methods can be used
to decrease colic in a baby, normalize premature infant brain
development, decrease cognitive age in adults, and decrease or
prevent migraines and headaches. The methods, kits and devices
described herein can provide a large impact on cognition with
minimal effort and cost. They can be used widely and effectively
among older adults, children, and other populations in need of
improved cognitive performance.
[0007] Generally, the present invention is directed to methods and
devices for improving cognitive function in the brain by
stimulating the olfactory senses. Stimulation, in most embodiments,
is accomplished by subjecting a treatment recipient to unique
scents on a rotating schedule of intervals. It has been found that
a single, specific odor, while potentially pleasant, does not have
significant cognitive benefits. However, when a treatment recipient
is subjected to a daily rotation of different scents, the olfactory
stimulations trigger accelerated creation of new neurons
(neurogenesis), as has been shown in mice, and/or increased neural
complexity, leading to oversized improvements in general cognition
and memory (Far Transfer Effects), as compared to practice effects
on the same task (Near Transfer Effects).
[0008] Far Transfer is the improvement in memory unrelated to
practice on that specific task and it thereby improves people's
general memory. Near Transfer is the ability to get better at a
specific task with practice on that task, but does not result in an
improvement in other cognitive abilities. There are many computer
games and other activities that are advertised as brain improvement
activities. These activities are all examples of Near Transfer.
[0009] One aspect of the invention maximizes the Far Transfer
Effects by providing an olfactory stimulation schedule that
includes a variety of odors, some of which are novel to the
recipient.
[0010] Another aspect of the invention maximizes the Far Transfer
Effects by providing an olfactory stimulation schedule that rotates
the odors being presented to the recipient.
[0011] Still another aspect of the invention provides an olfactory
stimulation schedule that provides odors that are pleasing to the
recipient.
[0012] Yet another aspect of the invention provides an olfactory
stimulation schedule that is delivered consistently over several
months.
[0013] Treatment programs, especially those that are
self-administered, or administered by a family member in the home
over a prolonged period, require dedication and discipline.
Understandably, the efficacy of a treatment program improves if the
treatment is administered consistently. Thus, one aspect of the
invention seeks to maximize the likely administration consistency
by making the program as enjoyable, easy to administer, and as
non-disruptive to the lifestyle of the recipient as possible. This
is accomplished through "ease of use factors."
[0014] One aspect of the invention provides pleasant scents as an
ease of use factor.
[0015] Another aspect of the invention is a device that creates
rotating scents as an ease of use factor.
[0016] Another aspect of the invention is a device that rotates
scents on a schedule as an ease of use factor.
[0017] Another aspect of the invention presents an aroma schedule
automatically while a treatment recipient is sleeping as an ease of
use factor.
[0018] It has been determined that while a recipient is sleeping,
odors do not awaken that person. As such, a recipient will not
awaken when subjected to an unpleasant odor. As such, unpleasant
odors may generally be more novel to a recipient than pleasant
odors. With this in mind, one aspect of the invention provides
potentially unpleasant odors while the recipient is sleeping.
[0019] Another aspect of the invention provides a schedule that
includes odors that are likely to be pleasing and odors that are
likely to be less-pleasing, with the less-pleasing odors occurring
during intervals during which the recipient will not be awake. For
example, the pleasing odors will be scheduled at times when the
recipient may be falling asleep, and in the morning when the
recipient may be waking up. The less-traditional or potentially
unpleasant odors are schedule for exposure in the middle of the
night when the recipient is less likely to be awake.
[0020] Another aspect of the invention provides an identification
system whereby a recipient can tag a scent as unpleasant, or give
the scent a rating on a scale, and the scent delivery system thus
schedules scents with the lowest rating during hours when the
recipient is most likely to be asleep.
[0021] Yet another aspect of the invention tracks, over the entire
treatment program, the scents that the recipient has been subjected
to, in order to ensure that novelty is maintained. Through
experimentation, it has been determined that a variety of scents
provides the greatest efficacy. In one embodiment, at least seven
embodiments are used.
[0022] In another embodiment, at least four scents are used.
However, the device that provides these scents is capable of
"playing" or emitting one or more of the scents simultaneously. As
such, two or more base scents may be mixed together to create new
scents.
[0023] In another embodiment a device is provided that can play
multiple base scents simultaneously (also referred to as mixing the
scents), as well as varying the intensity of each base scent. Thus,
a nearly infinite number of scents may be created using only four
base scents.
[0024] As one skilled in the art is aware, the sleep cycle consists
of various stages that repeat every 90 to 110 minutes. One model
breaks the sleep cycle into five stages: Stage 1 is light sleep
characterized by a decreasing amount of muscle, brain and eye
activity; Stage 2 involves a slowing of heart rate and breathing
pattern, as well as a slight decrease in body temperature. Stage 3
is where deep sleep begins and involves very slow delta waves
produced by the brain; Stage 4 is very deep sleep with rhythmic
breathing, limited muscle activity, and continued delta wave
production; and the fifth stage is called the REM (Rapid Eye
Movement) stage. This is the dream stage characterized by a rise in
blood pressure, heart rate, breathing rate, and rapid eye movement.
It is likely that the treatment efficacy of the olfactory
stimulation therapy of the invention may vary depending on which
sleep stage the recipient is in. For example, it may be determined
that treatment delivered during stages 3 and 4 have no effect while
treatment delivered during REM is the most effective of all the
stages.
[0025] With this in mind, one aspect of the invention includes a
sleep stage tracking system, such as a heart rate monitor,
respiration monitor, blood pressure monitor, brain wave sensor, or
any combination thereof. The sleep stage tracking system is used in
conjunction with the scent delivery schedule to ensure that break
intervals (periods between the scent delivery intervals) occur
during sleep stages that are less effective, and that scent
intervals occur during sleep stages that are of maximum
effectiveness.
[0026] Described herein is a method of improving at least one of
cognitive function and memory by treating a subject in need thereof
according to an olfactory stimulation regimen. In one embodiment,
the method comprises: a) releasing one or more scents to the
subject in an initial step on a first day; and b) releasing one or
more scents to the subject in a later step on a later day the one
or more scents in the later step are not identical to the one or
more scents in the initial step, whereby at least one of cognitive
function and memory of the subject is improved. In some
embodiments, the method is provided in conjunction with other forms
of environmental, sensorial, or tactile stimulation. In other
embodiments, the olfactory stimulation is provided in the absence
of tactile stimulation, or in the absence of other forms of
environmental or sensorial stimulation.
[0027] In one embodiment, subjects treated with the method
experience statistically improved cognitive function compared to
untreated subjects as measured by Stroop test, Rey Auditory Verbal
Learning Test (RAVLT), Wechsler Adult Intelligence Scale (WAIS)
test, or a combination thereof. In one embodiment, the method
improves or reduces age-related memory loss for the subject. In one
embodiment, the memory of the subject is improved. In one
embodiment, the method improves cognition, memory, intelligence
quotient (IQ), or a combination thereof.
[0028] In one embodiment, the method prevents, reverses, stops, or
slows progression of a neurodegenerative disease or condition. In
one embodiment, the neurodegenerative disease or condition is
Alzheimer's disease, Parkinson's disease, motor neuron disease,
Huntington's disease, or dementia.
[0029] In one embodiment, the method improves memory, intelligence,
sleeping, brain normalization, gait, balance, Alzheimer's disease,
Parkinson's disease, motor neuron disease, Huntington's disease,
other forms of dementia, agitation, post-traumatic stress disorder
(PTSD), panic attacks, stress, generalized anxiety disorder (GAD),
obsessive compulsive disorder (OCD), social anxiety disorder (SAD),
phobias, depression, major depressive disorder (MDD), premenstrual
syndrome (PMS), high blood pressure, colic, migraines, sleep
disorder, or a combination thereof.
[0030] In one embodiment, the method improves progression or
outcome for stroke rehabilitation, seizures, prenatal alcohol
syndrome, lead exposure, multiple sclerosis, addiction,
schizophrenia, Down Syndrome, p-opioid receptor loss, Fragile X
Syndrome, Rett Syndrome, Potocki-Lupski Syndrome, repetitive
behavior, Lewy body dementia, fronterotemporal dementia, or
Creutzfeldt-Jakob disease.
[0031] In one embodiment, the method decreases dementia or
dementia-associated disruptive behaviors, increases self-esteem,
decreases stress, decreases blood pressure, increases relaxation,
prevents oxidative damage, improves postural stability, improves
gait, increases deep sleep, improves mood, decreases anxiety,
improves vigor, improves quality of life, improves cognition, or
improves depression or depressive symptoms.
[0032] In one embodiment, the method improves cognitive processing
speed, attention capacity, executive function, or a combination
thereof. In one embodiment, the method improves sequential
processing, mental manipulation, attention, concentration, memory
span, short-term auditory memory, verbal learning and memory,
sequential processing, rote learning and memory, encoding, auditory
processing, working memory, transformation of information,
visual-spatial imaging, or a combination thereof. In one
embodiment, the method improves cognition, memory, intelligence
quotient (IQ), or a combination thereof.
[0033] In one embodiment, the subject is elderly. In one
embodiment, the subject has experienced age-related deficits in
cognitive functions, including but not limited to, deficits in
memory. In one embodiment, the subject is at least about 35, 40,
45, 50, 55, 60, 65, 70, 75, 80, 85, 90, 95, or about 100 years old.
In one embodiment, the subject is an older adult, aged 55 years or
older. In another embodiment, the subject is a younger adult, aged
18-55 years.
[0034] In one embodiment, the subject is a child. In some
embodiments, the child is one who exhibits normal cognitive
capabilities (irrespective of achievements or performance on
cognitive assessments), such as a child who does not meet the
criteria for a diagnosis of autism. In some embodiments, the child
is a typical child who does not exhibit or experience any
particular challenges to his or her environment or cognitive
abilities. In some embodiments, the child has one or more
developmental disorders. Representative examples of developmental
disorders include, but are not limited to, autism, ADHD and
developmental delay. In one embodiment, the child is autistic. In
other embodiments, the child has one or more developmental
disorders other than autism.
[0035] In some embodiments, the olfactory stimulation regimen is
performed over a period of 2, 3, 4, 5, 6, 7, 8, 9, or 10 days. In
some embodiments, the olfactory stimulation regimen is performed
over a period of 2 or more days. In some embodiments, the olfactory
stimulation regimen is performed over a period of at least 1, 2, 3,
or 4 weeks. In some embodiments, the olfactory stimulation regimen
is performed over a period of at least 1, 2, 3, 4, 5, or 6 months.
In some embodiments, the olfactory stimulation regimen is performed
over a period of at least 7, 8, 9, 10, 11, or 12 months. In some
embodiments, the olfactory stimulation regimen is performed over a
period of about 3 months. In some embodiments, the olfactory
stimulation regimen is performed over a period of about 6
months.
[0036] In some embodiments, scents used in the olfactory
stimulation regimen are from one or more scent categories selected
from the group consisting of floral, woody, and aromatic. In some
embodiments, the scents used are from two or three of these
categories. Optionally, in some embodiments, additional scent
categories can be used, such as oriental and/or fresh.
[0037] In some embodiments, scents used in the olfactory
stimulation regimen are from one or more scent categories selected
from the group consisting of fruity, flowery, woody, resinous, and
aromatic. In some embodiments, the scents used are from two, three,
four or all five of these categories.
[0038] In some embodiments, scents used in the olfactory
stimulation regimen are selected from the group consisting of
lavender, citrus, jasmine, lilac, mint, cinnamon, peppermint,
cloves, lemongrass, coffee, anise, basil, thyme, chamomile,
rosemary, cucumber, coconut, fresh cotton, violet, vanilla, forest
pine, pomegranate, pear, orange, apple, rosehip, saffron, sage,
eucalyptus, frankincense, nutmeg, and sandalwood. In some
embodiments, the scents used are from any combination of two or
more of these group members.
[0039] In some embodiments, steps of the olfactory stimulation
regimen are performed during night time. In some embodiments, steps
of the olfactory stimulation regimen are performed during day time.
In some embodiments, steps of the olfactory stimulation regimen are
performed during both day time and night time.
[0040] In some embodiments, the olfactory stimulation regimen is
performed as a series of stimulation cycles, each stimulation cycle
comprising at least two olfactory stimulation steps. In some
embodiments, the olfactory stimulation regimen comprises at least
one stimulation cycle comprising at least 3, 4, 5, 6, 7, 8, 9, or
10 steps. In some embodiments, the olfactory stimulation regimen
comprises repeating the at least one stimulation cycle for a
specified period of time. In some embodiments, the olfactory
stimulation regimen comprises a stimulation cycle of 6 steps. In
some embodiments, the olfactory stimulation regimen comprises a
stimulation cycle of 7 steps.
[0041] In some embodiments, at least one step of the olfactory
stimulation regimen comprises: a) releasing at least one scent
continuously for a first duration; and b) ceasing release of the at
least one scent for a second duration. In one embodiment, the first
duration is about 5 minutes. In one embodiment, the second duration
is about 1 minute.
[0042] In one embodiment, the at least one step further comprises
repeating a) and b). In one embodiment, a) and b) are repeated
until the subject has been exposed to the at least one scent for a
specified exposure period. In one embodiment, the specified
exposure period is about 5 minutes, about 10 minutes, about 15
minutes, about 20 minutes, about 25 minutes, about 30 minutes,
about 35 minutes, about 40 minutes, about 45 minutes, about 50
minutes, about 55 minutes, or about 60 minutes. In one embodiment,
the specified exposure period is up to about 5 minutes, about 10
minutes, about 15 minutes, about 20 minutes, about 25 minutes,
about 30 minutes, about 35 minutes, about 40 minutes, about 45
minutes, about 50 minutes, about 55 minutes, or about 60
minutes.
[0043] In some embodiments, each step of the olfactory stimulation
regimen comprises: a) releasing at least one scent continuously for
a first duration; and b) ceasing release of the at least one scent
for a second duration.
[0044] In some embodiments, each step of the olfactory stimulation
regimen is administered using a nebulizer or diffuser. In some
embodiments, each step of the olfactory stimulation regimen is
administered through ventilation, heating, humidification or
vaporization, nebulization or atomization of one or more scents, or
a combination thereof. In some embodiments, each step of the
olfactory stimulation regimen is administered using at least one
candle, tea light diffuser, nebulizing diffuser, room spray,
evaporative diffuser, evaporative fan diffuser, vaporizing
diffuser, wearable evaporative diffuser, ultrasonic diffuser, heat
evaporative diffuser, evaporative pad diffuser, cream, wick, open
odorant container, or any combination thereof.
[0045] In some embodiments, at least one step of the olfactory
stimulation regimen exposes the subject to one scent. In some
embodiments, each step of the olfactory stimulation regimen exposes
the subject to one scent. In some embodiments, at least one of the
olfactory stimulation steps exposes the subject to a plurality of
scents. In some embodiments, each of the olfactory stimulation
steps exposes the subject to a plurality of scents.
[0046] In some embodiments, each step of the olfactory stimulation
regimen exposes the subject to one or more scents for at least
about 5 minutes, about 10 minutes, about 15 minutes, about 20
minutes, about 25 minutes, about 30 minutes, about 35 minutes,
about 40 minutes, about 45 minutes, about 50 minutes, about 55
minutes, or about 60 minutes. In some embodiments, each step of the
olfactory stimulation regimen exposes the subject to one or more
scents for up to about 5 minutes, about 10 minutes, about 15
minutes, about 20 minutes, about 25 minutes, about 30 minutes,
about 35 minutes, about 40 minutes, about 45 minutes, about 50
minutes, about 55 minutes, or about 60 minutes. In some
embodiments, each step of the olfactory stimulation regimen
comprises exposing the subject to one or more scents for about 30
minutes.
[0047] In some embodiments, the olfactory stimulation regimen
comprises performing at least 2, 3, 4, or 5 steps per day. In some
embodiments, the olfactory stimulation regimen comprises performing
two steps per day. In one embodiment, the two steps utilize one or
more scents that are identical.
[0048] In some embodiments, the olfactory stimulation regimen
comprises releasing one or more scents once per day. In some
embodiments, the olfactory stimulation regimen comprises
consecutive steps that expose the subject to different scents. In
some embodiments, the olfactory stimulation regimen comprises
consecutive steps that expose the subject to identical scents.
[0049] In some embodiments, the method comprises cyclic
administration of olfactory stimulation steps of the olfactory
stimulation regimen. In some embodiments, the olfactory stimulation
regimen comprises releasing one or more scents at least once per
day. In some embodiments, the olfactory stimulation regimen
comprises releasing one or more scents at least twice per day. In
some embodiments, the olfactory stimulation regimen comprises daily
release of one or more scents.
[0050] Also provided by the invention is a method of improving
cognitive function and/or memory by treating a subject in need
thereof with olfactory stimulation. In one embodiment, the method
comprises: a) an earlier step exposing the subject to one or more
scents; and b) a later step exposing the subject to one or more
scents that are not identical to the one or more scents from the
earlier step, whereby cognitive function of the subject is
improved. Additionally, provided is a method of improving cognitive
performance in a subject in need thereof. In one embodiment, the
method comprises exposing a subject to a plurality of scents during
a treatment period comprising a series of exposures at least two of
the series of exposures have sets of one or more scents that are
not identical.
[0051] Further provided is a method of improving cognitive
performance through olfactory stimulation using a series of odorant
exposure steps. In one embodiment, the method comprises an earlier
odorant exposure step comprising exposing a subject to a first set
of one or more odorants; and a later odorant exposure step
comprising exposing the subject to a second set of one or more
odorants the first set and the second set do not have identical
odorants. Also provided is a method of improving cognitive function
and/or memory by performing olfactory stimulation steps. In one
embodiment, the method comprises exposing a subject to a first set
of one or more scents; and exposing the subject to a second set of
one or more scents the first set and the second set do not have
identical scents.
[0052] Also provided is a method of improving cognitive function
and/or memory by exposing a subject to a plurality of scents over a
period of time. In one embodiment, the method comprises exposing a
subject to a first set of one or more scents; and exposing the
subject to a second set of one or more scents the first set and the
second set have different scents.
[0053] Also provided is a method of improving cognitive function
and/or memory by treating a subject in need thereof according to an
olfactory stimulation regimen. In one embodiment, the method
comprises a series of steps each releasing one or more scents to
the subject no two consecutive steps release identical scents.
[0054] Also provided is a method of improving cognitive function
and/or memory by treating a subject in need thereof according to an
olfactory stimulation regimen. In one embodiment, the method
comprises alternating olfactory stimulation steps each releasing
one or more scents to the subject no two consecutive steps release
identical scents.
[0055] Also provided is a method of improving cognitive function
and/or memory by treating a subject in need thereof according to an
olfactory stimulation regimen. In one embodiment, the method
comprises performing one olfactory stimulation step per day, each
step comprising releasing one or more scents to the subject at
least once no two consecutive olfactory stimulation steps release
identical scents. In one embodiment, at least one step comprises
releasing one or more scents to the subject at least 2, 3, 4, 5, 6,
7, 8, 9, or 10 times. In one embodiment, each step comprises
releasing one or more scents to the subject at least 2, 3, 4, 5, 6,
7, 8, 9, or 10 times.
[0056] Also provided is a method of improving cognitive function
and/or memory by treating a subject in need thereof according to an
olfactory stimulation regimen. In one embodiment, the method
comprises: a) performing an olfactory stimulation cycle comprising
a series of olfactory stimulation steps only one olfactory
stimulation step is performed per day, and each step comprises
releasing one or more scents to the subject at least once; and b)
repeating the olfactory stimulation cycle in a). In one embodiment,
further comprising repeating the olfactory stimulation cycle in a)
for a specified duration.
[0057] Also provided is an olfactory stimulation kit. In one
embodiment, the kit comprises: a) a scent-releasing device adapted
to release a plurality of scents; b) a schedule for releasing the
plurality of scents. In one embodiment, the schedule comprises: (i)
releasing, from the scent-releasing device, one or more scents in
an initial step on a first day; and (ii) releasing, from the
scent-releasing device, one or more scents in a later step on a
later day the one or more scents in the later step are not
identical to the one or more scents in the initial step. In one
embodiment, the schedule is provided on an instruction sheet.
[0058] In some embodiments, the plurality of scents is from one or
more scent categories selected from the group consisting of floral,
oriental, woody, aromatic, and fresh. In one embodiment, the
plurality of scents is from one or more scent categories selected
from the group consisting of floral, woody, and aromatic. In some
embodiments, the plurality of scents is from one or more scent
categories selected from the group consisting of fruity, flowery,
woody, resinous, and aromatic. In some embodiments, the plurality
of scents is selected from the group consisting of lavender,
citrus, jasmine, lilac, mint, cinnamon, peppermint, cloves,
lemongrass, coffee, anise, basil, thyme, chamomile, rosemary,
cucumber, coconut, fresh cotton, violet, vanilla, forest pine,
pomegranate, pear, orange, apple, rosehip, saffron, sage,
eucalyptus, frankincense, nutmeg, and sandalwood.
[0059] In some embodiments, the schedule comprises steps performed
during night time. In some embodiments, the schedule comprises
steps performed during day time. In some embodiments, the schedule
comprises steps performed over a period of 2, 3, 4, 5, 6, 7, 8, 9,
or 10 days. In some embodiments, the schedule comprises steps
performed over a period of 2 or more days. In some embodiments, the
schedule comprises steps performed over a period of at least 1, 2,
3, or 4 weeks. In some embodiments, the schedule comprises steps
performed over a period of at least 1, 2, 3, 4, 5, or 6 months. In
some embodiments, the schedule comprises steps performed over a
period of about 3 months. In some embodiments, the schedule
comprises steps performed over a period of about 6 months. In some
embodiments, the schedule comprises steps performed as a series of
stimulation cycles, each stimulation cycle comprising at least two
olfactory stimulation steps. In some embodiments, the schedule
comprises at least one stimulation cycle comprising at least 3, 4,
5, 6, 7, 8, 9, or 10 steps. In some embodiments, the schedule
comprises repeating the at least one stimulation cycle for a
specified period of time. In some embodiments, the schedule
comprises a stimulation cycle of 6 steps. In some embodiments, the
schedule comprises a stimulation cycle of 7 steps.
[0060] In some embodiments, at least one step of the schedule
comprises: a) releasing at least one scent continuously for a first
duration; and b) ceasing release of the at least one scent for a
second duration. In one embodiment, the first duration is about 5
minutes. In one embodiment, the second duration is about 1 minute.
In one embodiment, the at least one step further comprises
repeating a) and b). In one embodiment, a) and b) are repeated for
a specified release period. In one embodiment, the specified
release period is about 5 minutes, about 10 minutes, about 15
minutes, about 20 minutes, about 25 minutes, about 30 minutes,
about 35 minutes, about 40 minutes, about 45 minutes, about 50
minutes, about 55 minutes, or about 60 minutes. In one embodiment,
the specified exposure period is up to about 5 minutes, about 10
minutes, about 15 minutes, about 20 minutes, about 25 minutes,
about 30 minutes, about 35 minutes, about 40 minutes, about 45
minutes, about 50 minutes, about 55 minutes, or about 60
minutes.
[0061] In some embodiments, each step of the schedule comprises: a)
releasing at least one scent continuously for a first duration; and
b) ceasing release of the at least one scent for a second
duration.
[0062] In some embodiments, the scent-releasing device comprises a
nebulizer or diffuser.
[0063] In some embodiments, the scent-releasing device is adapted
to release the plurality of scents through ventilation, heating,
humidification or vaporization, nebulization or atomization, or a
combination thereof by the scent-releasing device. In some
embodiments, the scent-releasing device comprises at least one
candle, tea light diffuser, nebulizing diffuser, room spray,
evaporative diffuser, evaporative fan diffuser, vaporizing
diffuser, wearable evaporative diffuser, ultrasonic diffuser, heat
evaporative diffuser, evaporative pad diffuser, cream, wick, open
odorant container, or any combination thereof from the
scent-releasing device.
[0064] In some embodiments, at least one step of the schedule
releases one scent. In some embodiments, each step of the schedule
releases one scent. In some embodiments, at least one step of the
schedule releases a plurality of scents. In some embodiments, each
step of the schedule releases a plurality of scents. In some
embodiments, each step of the schedule releases one or more scents
for at least about 5 minutes, about 10 minutes, about 15 minutes,
about 20 minutes, about 25 minutes, about 30 minutes, about 35
minutes, about 40 minutes, about 45 minutes, about 50 minutes,
about 55 minutes, or about 60 minutes. In some embodiments, each
step of the schedule releases one or more scents for up to about 5
minutes, about 10 minutes, about 15 minutes, about 20 minutes,
about 25 minutes, about 30 minutes, about 35 minutes, about 40
minutes, about 45 minutes, about 50 minutes, about 55 minutes, or
about 60 minutes. In some embodiments, each step of the schedule
releases one or more scents for about 30 minutes. In some
embodiments, the schedule comprises releasing one or more scents at
least 2, 3, 4, or 5 times per day. In some embodiments, the
schedule comprises releasing one or more scents two times per
day.
[0065] In one embodiment, one or more scents released on a given
day are identical. In some embodiments, the schedule comprises
releasing one or more scents once per day. In some embodiments, the
schedule comprises consecutive steps that release different scents.
In some embodiments, the schedule comprises consecutive steps that
release identical scents. In some embodiments, the schedule
comprises cyclic administration of olfactory stimulation steps. In
some embodiments, the schedule comprises releasing one or more
scents at least once per day. In some embodiments, the schedule
comprises releasing one or more scents at least twice per day. In
some embodiments, the schedule comprises daily release of one or
more scents.
BRIEF DESCRIPTION OF THE DRAWINGS
[0066] These and other aspects, features and advantages of which
embodiments of the invention are capable of will be apparent and
elucidated from the following description of embodiments of the
present invention, reference being made to the accompanying
drawings, in which
[0067] FIG. 1 is a graph showing a decline in cognitive functions
over time;
[0068] FIG. 2 is a timeline depicting the administration of an
embodiment of a method of the invention;
[0069] FIG. 3 is a timeline depicting an embodiment of a daily
schedule of a method of the invention;
[0070] FIG. 4 is a graph showing a human sleep cycle;
[0071] FIG. 5 is a diagram of a fragrance wheel;
[0072] FIG. 6 is a chart showing an embodiment of a scent rotation
of the invention;
[0073] FIG. 7 is a diagram showing Henning's Prism;
[0074] FIG. 8 is a diagram of a fragrance wheel formed from one
side of Henning's Prism;
[0075] FIG. 9 is a perspective view of an embodiment of a device of
the invention;
[0076] FIG. 10 is a cutaway view of the embodiment of the device of
FIG. 9;
[0077] FIG. 11 is a perspective view of an embodiment of a
cartridge of the invention;
[0078] FIG. 12 is a cutaway view of the cartridge of FIG. 11;
[0079] FIG. 13 is an elevation of an embodiment of a scent pad
package of the invention;
[0080] FIG. 14 is a perspective view of an embodiment of a gel tab
of the invention; and,
[0081] FIG. 15 is a side elevation of an embodiment of a CPAP mask
of the invention;
[0082] FIG. 16 is a graph showing a change in Stroop score using
the invention;
[0083] FIG. 17 is a graph showing a change in Rey Auditory Verbal
Learning Test score using the invention;
[0084] FIG. 18 is a graph showing a change in Wechsler Adult
Intelligence Scale-Ill-Letter-Number Sequencing score using the
invention; and,
[0085] FIG. 19 is a graph showing a change in Wechsler Adult
Intelligence Scale-III Backwards Digit Span score using the
invention.
DESCRIPTION OF EMBODIMENTS
[0086] Specific embodiments of the invention will now be described
with reference to the accompanying drawings. This invention may,
however, be embodied in many different forms and should not be
construed as limited to the embodiments set forth herein; rather,
these embodiments are provided so that this disclosure will be
thorough and complete, and will fully convey the scope of the
invention to those skilled in the art. The terminology used in the
detailed description of the embodiments illustrated in the
accompanying drawings is not intended to be limiting of the
invention. In the drawings, like numbers refer to like
elements.
Definitions
[0087] All scientific and technical terms used in this application
have meanings commonly used in the art unless otherwise specified.
As used in this application, the following words or phrases have
the meanings specified.
[0088] As used herein, "releasing" a scent to a subject, or
"exposing" a subject to a scent, means that the scent is presented
into the environment of the subject in a manner sufficient for
stimulation of the subject's olfactory system.
[0089] As used herein, "decreases" or "increases" means reduces or
raises, respectively, by a detectable or noticeable amount. In some
embodiments, such a decrease or increase is measured using one of
the assessment tools described herein. In some embodiments, the
decrease or increase represents a "significant difference".
[0090] As used herein, "improves" means results in an improved
state, for example, the amelioration of symptoms of an adverse
condition, or the enhancement of a desired condition, such as
memory.
[0091] As used herein, a "significant difference" or "significantly
different" means a difference that can be detected in a manner that
is considered reliable by one skilled in the art, such as a
statistically significant difference, or a difference that is of
sufficient magnitude that, under the circumstances, can be detected
with a reasonable level of reliability. In one example, an increase
or decrease of 10% relative to a reference value is a significant
difference. In other examples, an increase or decrease of 20%, 30%,
40%, or 50% relative to the reference value is considered a
significant difference. In yet another example, an increase of
two-fold relative to a reference value is considered significant.
The reference value can be, for example, an untreated subject, or a
baseline (pretreatment) value for the same subject.
[0092] As used herein, ranges and amounts can be expressed as
"about" a particular value or range. About also includes the exact
amount. Hence "about 5 minutes" means "about 5 minutes" and also "5
minutes." Generally, the term "about" includes an amount that is
from 10% below to 10% above the particular value or range. For
example, "about 10 minutes" means "from 9 minutes to 11
minutes."
[0093] As used herein, "a" or "an" means at least one, unless
clearly indicated otherwise.
Environmental Enrichment
[0094] In more than a dozen animal models of human neurological
conditions, environmental enrichment has been shown to ameliorate
their human-like symptoms, including the cognitive decline in aging
(Patel, et al., 2012; Segovia, et al., 2006; Valero, et al., 2007)
and in Alzheimer's disease (Arendash, et al., 2004; Arranz, et al.,
2011; Basak, et al., 2008; Berardi, et al., 2007; Costa, et al.,
2007; Jankowsky, et al., 2015; Lazarov, et al., 2005; Polito, et
al., 2014). In humans, environmental enrichment, including
exercise, computer games, social behavior and nutrition have been
shown to reduce the risk of cognitive decline in aging and disease
(Herzog, et al., 2008; Kirk-Sanchez and McGough, 2014; Klimova,
2016; Williams and Kemper, 2010), but it has been difficult to show
that cognitive decline can be reversed, and when there are such
improvements, the effects tend to be modest in size (Herzog, et
al., 2008; Rodakowski, et al., 2015). Moreover, it has been shown
to be difficult to keep people on such interventions as a routine
program of physical exercise (Williams, et al., 2007).
[0095] The olfactory system experiences a clear deterioration in
older adults, with 18% of older adults having olfactory impairment
and 46% of those over 80 years old having very limited olfactory
ability (Doty, et al., 1984; Hoffman, et al., 1998; Liu, et al.,
2016; Murphy, et al., 2002; Pinto, et al., 2015; Toussaint, et al.,
2015). The initiation of this decline parallels that seen for
cognitive ability in older adults (Park, et al., 2003; Salthouse,
2009). The decline in cognitive function with age is illustrated in
FIG. 1, which shows an initial decline around the age of 60 that
continues as the individual ages with inductive reasoning, spatial
orientation, perceptual speed, numeric ability, verbal ability, and
verbal memory all being affected. The olfactory system has direct
projections to cognitive areas, unlike other sensory systems, and
the loss or compromise of the olfaction system results in massive
volume loss in these cognitive areas in humans at any age (Bitter,
et al., 2010a; 2010b; 2011; Yao, et al., 2014). Normal human aging
is accompanied by a deterioration of olfactory abilities (Dong, et
al., 2017; Hoffman, et al., 2016; Seubert, et al. 2017), along with
the deterioration of olfactory projection sites, which include the
cognitive areas of the brain (Kollndorfer, et al., 2015; Segura, et
al., 2013). Moreover, a degradation of olfactory ability predicts
both an elevated risk of minimal cognitive impairment (MCI) and
which of those with MCI will go on the develop Alzheimer's disease
(Adams, et al., 2017; Devanand, et al., 2000; Lafaille-Magnan, et
al., 2017; Peter, et al., 2003; Roberts, et al., 2016; Schubert, et
al., 2008; 2017; Swan and Carmelli, 2002). Remarkably, olfactory
function also predicts all-cause mortality in older adults
(Gopinath, et al., 2011; Pinto, et al., 2014).
[0096] The loss of olfactory function precedes or parallels the
initiation of a variety of cognitive disorders such as Alzheimer's
disease, Parkinson's disease, Lewy body dementia, fronterotemporal
dementia, Creutzfeldt-Jakob disease, minimal cognitive impairment,
and schizophrenia (Conti, et al., 2013; Devanand, et al., 2000;
Devanand, et al., 2010; Doty, et al., 1988; Li, et al., 2010;
Luzzi, et al., 2007; Meusel, et al., 2010; Nguyen, et al., 2010;
Parrao, et al., 2012; Ponson, et al., 2004; Ross, et al., 2006;
Tabaton, et al., 2004; Wattendorf, et al., 2009). Given that these
cognitive disorders have widely differing etiologies, it raises the
possibility that the loss of olfactory stimulation contributes to
the decline in cognitive ability in each of these disorders.
[0097] In humans who have experienced olfactory loss due to a
variety of problems, such as post-infectious olfactory dysfunction,
head trauma, Parkinson's, and aging) increased olfactory
experiences has been shown to improve olfactory identification,
olfactory discrimination, and to lesser extent, olfactory threshold
(Damm, et al., 2014; Gei ler, et al., 2014; Haehner, et al., 2013;
Hummel, et al., 2009; Konstantinidis, et al., 2013; Patel, et al.,
2017). These results were achieved through exposure to four
odorants taken from each of four odor groups: resinous
(eucalyptus), flowery (rose), fruity (lemon), and aromatic (clove).
There are further improvements in olfactory ability with increased
duration of exposure, increased concentration of the odorants and
an increased number of odorants (Altundag, et al., 2015; Damm, et
al., 2014; Konstantinidis, et al., 2016). In addition to
improvements in sensory ability, older adults exposed to increased
olfactory stimulation have an improvement in their cognitive
function, as evidenced by increased verbal fluency, an improvement
in their depressive symptoms, and an improved sense of wellbeing
(Wegener, et al., 2018). Olfactory stimulation in older adults also
decreases falls in this group (Sakamoto, et al., 2012).
[0098] Individuals with autism have olfactory dysfunction, both
with their abnormal sniff response to odors of different valences
(Rozenkrantz, et al., 2015) and to social odors (Endevelt-Shapira,
et al. 2018). They also have abnormal olfactory responses
(Boudjarane, et al., 2017; Tonacci, et al., 2017). Diverse rodent
models of autism have their human-like symptoms of this disorder
ameliorated when they are placed into an enriched environment
(Kerr, et al., 2010; Kondo et al., 2008; Lacaria, et al., 2012;
Lonetti et al., 2010; Nag et al., 2009; Restivo et al., 2005;
Reynolds, et al., 2013; Schneider & Przewlocki, 2005; Schneider
et al., 2006).
[0099] Environmental enrichment, which included olfactory
stimulation that was paired with tactile stimulation has been
successfully used to treat children with classic autism (Woo and
Leon, 2013, Woo, et al., 2015). In two randomized clinical trials,
parents delivered novel multisensory stimulation, featuring
olfactory stimulation, each morning and evening for 15-30 min over
the course of six months. 42% of the enriched children had a major
improvement in their symptoms as measured on the subjective
Childhood Autism Rating Scale, compared to 7% of the standard-care
controls who had that kind of improvement. IQ increased by more
than 8 points for enriched children, compared to about a point of
improvement in controls. The Short Sensory Profile revealed an
11-point improvement for enriched children and about a point for
controls. Receptive language, as measured by the objective Reynell
Developmental Language Scales, improved by more than 200% in
enriched with autism and less than 20% for controls. Finally, after
6 months, 21% of the children with autism were considered to have
lost that diagnosis using the objective Autism Diagnostic
Observation Schedule and no control child reached that level of
improvement.
[0100] A review of the outcomes of over 1,000 children along the
entire autism spectrum who were being given this treatment at home
(Aronoff, et al., 2016) revealed that these children did better
than those in the university clinical trials, with an effect size
of 1.85. Not only did the core symptoms of autism improve, but the
co-morbid symptoms, which accompany virtually every child with this
disorder have, including: sensory processing, self-awareness,
communication, mood, sleeping, eating, motor skills, learning,
memory, anxiety and attention span. This treatment had similar
effects on children across the entire autism spectrum, both girls
and boys improved equally, and the treatment worked for all ages
tested (2-18 years old). There was also a dose/response outcome for
parental compliance and the symptom improvement of their
children.
Schedules
[0101] Referring now to the Figures, and first to FIGS. 2 and 3,
there is shown a general illustration of a method 10 of the
invention. The method 10 generally involves subjecting a treatment
recipient to a daily schedule 20 of scent intervals 30 separated by
breaks 40. The daily schedule is administered for several days,
weeks, months or years, depending on the treatment recipient and
the desired results. As there are no negative side-effects or
downsides to the treatment method 10, other than perhaps the
expense of the fragrances, benefit may be found in continuing the
schedule 20 indefinitely.
[0102] FIG. 3 provides a non-limiting example of a daily schedule
20 that is initiated upon bedtime B. Bedtime is selected due to the
ease with which the treatment may be delivered to a person not
moving around, and the effectiveness which a scent may be delivered
to a person in a relatively-small, enclosed room, such as a
bedroom. It is noted however that treatment effectiveness may not
be diminished if the treatment is delivered during the day, such as
to a person sitting at a computer, driving a vehicle, or is
otherwise stationary relative to the delivery device; or if the
delivery device moves with the recipient throughout the recipient's
daily activities, such as would be the case with a wearable
device.
[0103] In the embodiment of FIG. 3, the recipient activates a
scent-delivery device (detailed below) that includes a timer that
is set to deliver various odors at predetermined intervals. In this
example, the intervals 30 are approximately 30 minutes long and are
separated by breaks 40 that are 5 minutes in duration. It is to be
understood, however, that these interval times and break times are
merely non-limiting examples and may vary based on recipient
preference, subjective results, doctor recommendations based on
empirical evidence, sleep duration, etc. Good results have been
attained with 30 minute intervals with 5 minute breaks, as a
starting point.
[0104] The daily schedule 20 begins each day at a start event. For
recipients with a regular daily routine, the start event may be a
set time of day, rather than being initiated at bedtime. For
example, in this embodiment, the first interval 30 of the daily
schedule 20 may begin at midnight and continue until 12:30 am. The
first break 40 thus spans from 12:30 to 12:35 am and the second
interval 30 begins at 12:35 am and lasts until 1:05 am. These
intervals 30 and breaks repeat this pattern until a predetermined
number N of intervals 30 and breaks 40 have occurred. The number N,
like the interval 30 length, may be varied based on the length of
sleep the recipient typically gets, as well as subjective or
objective results. Generally, N should be at least 3 for optimal
results.
[0105] In another embodiment, the start event may be tied to the
sleep cycle of the recipient. FIG. 4 is a diagram of the human
sleep cycle 50. The sleep cycle 50 consists of various stages that
repeat every 90 to 110 minutes. One model breaks the sleep cycle
into five stages: Stage 1 is light sleep characterized by a
decreasing amount of muscle, brain and eye activity; Stage 2
involves a slowing of heart rate and breathing pattern, as well as
a slight decrease in body temperature. Stage 3 is where deep sleep
begins and involves very slow delta waves produced by the brain;
Stage 4 is very deep sleep with rhythmic breathing, limited muscle
activity, and continued delta wave production; and the fifth stage
is called the REM (Rapid Eye Movement) stage. This is the dream
stage characterized by a rise in blood pressure, heart rate,
breathing rate, and rapid eye movement.
[0106] Referring again to FIG. 4, it is shown that the sleep cycle
begins in stage 1 and quickly progresses to stage 4 within the
first hour of falling asleep. After an hour or so, the heart rate,
blood pressure, and breathing rate increase rapidly as the person
enters REM sleep, which typically lasts only about 5 minutes. After
REM sleep, the cycle repeats to a certain extent.
[0107] Notably, throughout the night, the degree to which the
sleeper enters deep sleep diminishes. For example, as seen in the
graph of FIG. 4, during the second cycle, stage 4 is barely
attained. The end of the second cycle is also marked by a REM stage
that lasts 10 minutes, rather than 5 minutes. The third cycle only
drops into stage 2 sleep, followed by a 15 minute REM stage. The
fourth cycle also only drops into stage 2 sleep and is followed by
a REM stage that lasts 30-60 minutes.
[0108] Much is still to be learned about the human sleep cycle.
Scientists have often thought that experiences and lessons are
converted into long term memory during sleep, and further that REM
sleep plays an essential role in the acquisition of learned
material, both declarative and procedural memory, both forms of
Near Transfer. Researchers recently have begun to hypothesize that
deep, restorative sleep, also referred to as "slow-wave sleep
(SWS)" plays a significant role in declarative memory by processing
and consolidating newly acquired information.
[0109] With this in mind, one aspect of the invention includes a
sleep stage tracking system, such as a heart rate monitor,
respiration monitor, blood pressure monitor, brain wave sensor, or
any combination thereof. The sleep stage tracking system is used in
conjunction with the scent delivery schedule to ensure that break
intervals (periods between the scent delivery intervals) occur
during sleep stages that are less effective, and that scent
intervals occur during sleep stages that are of maximum
effectiveness. It is likely that the treatment efficacy of the
olfactory stimulation therapy of the invention may vary depending
on which sleep stage the recipient is in. For example, it may be
determined that treatment delivered during stages 3 and 4 have no
effect while treatment delivered during REM is the most effective
of all the stages.
[0110] Given that there would likely be no degradation in
effectiveness if a scent were to be delivered during a point in the
sleep cycle that is not optimal for Far Transfer, the benefit of
tracking the sleep cycle may be to simply avoid the occurrence of
breaks 40 that during periods of peak Far Transfer Effects. For
example, if it is determined that REM sleep is the best stage of
the sleep cycle for Far Transfer Effects, it may be beneficial to
avoid breaks 40 during the REM stages, especially the first two to
three REM stages, which last only 5-15 minutes.
[0111] Similarly, if it is determined that Stage 4 is the most
beneficial time for olfactory stimulation to be administered, it
would be important to ensure that intervals 30 are scheduled during
the first two sleep cycles, as the first two cycles are typically
the only cycles in which Stage 4 is entered.
[0112] One embodiment of the method of the invention provides
intervals 30 that coincide with the sleep cycles through the use of
monitoring. Because the sleep cycles coincide with variations in
biological factors such as blood pressure, heart rate, respiration
rate, brain wave activity, and eye movement, one skilled in the art
would realize that a number of technologies exist to monitor the
various sleep stages. As such, the interval 30 durations and break
40 durations could be selected to synchronize with the sleep
cycles. In this embodiment, there are as few as 3 intervals or as
many as 6 or 7 intervals, depending on the length of sleep by the
recipient.
[0113] One embodiment of this synchronized method involves
recording the sleep patterns of the recipient over a period of days
to establish a typical pattern. The delivery device is then
scheduled to approximate a synchronized schedule. Under this
method, the recipient would not have to use a monitoring device
unless recalibration is desired.
[0114] Another embodiment of this synchronized method involves
continuous monitoring of one or more of the above-mentioned
biological factors. For example, heart rate monitors are common in
many forms including, but not limited to, optical wearables, chest
straps, air-bed pulse detectors, and the like. The biological
factor is monitored continuously and the sleep cycle is determined
based on the data collected therefrom. The device then activates
and deactivates the various scents according to a schedule that is
created based on the data. As such, the schedule may differ
slightly from evening to evening. This method may be optimally
suited to recipients that have a varying daily routine.
Rotations
[0115] One aspect of the invention is that the scents being
delivered to the recipients be novel. This is not to imply that the
scent is completely unfamiliar to the recipient over his or her
lifetime, but simply that the scent changes each interval and is
not re-introduced for a predetermined number of intervals. In one
embodiment, at least seven different scents are used, and no scent
is repeated until the other six scents have been used. In other
embodiments, a vast number of scents are used such that it is
unlikely that a scent would be used twice during an entire
treatment program.
[0116] As a general guideline, it is believed that the more novel a
scent is, the greater impact it will have. Additionally, it is
believed that consecutive scents should differ as much as possible
during a particular daily schedule 20. In order to achieve this,
one embodiment provides a rotation that avoids placing two aromas
from a same scent group adjacent to each other.
[0117] Scents are sometimes classified into scent groups, commonly
referred to as the fragrance wheel or chart. There are many
different fragrance charts. One widely used chart, used herein
merely as an example, was developed by perfumery taxonomist Michael
Edwards in 1992, and modified several times since. The 2010 version
of the Michael Edwards fragrance wheel is provided as FIG. 4 and
was published in 2011 in Fragrances of the World, by Michael
Edwards & Co., incorporated by reference herein.
[0118] As seen in FIG. 5, there are four main fragrance families:
floral, oriental, woody and fresh. These are divided into
sub-groups and arranged such that the sub-groups show relationship
to each other. For example, the floral family is divided into
floral, sort floral and floral oriental. The oriental family is
divided into soft oriental, oriental and woody oriental. The floral
oriental sub group from the floral oriental family is arranged next
to the soft orient sub group from the oriental family because these
two are the most similar, despite being in different families.
[0119] The fragrance wheel of FIG. 5 is useful because the further
scent differences are easily visualized by their respective
proximity on the wheel. For example, scents from the mossy woods
sub group are found opposite the scents from the floral sub group.
Thus, it is easy to assess that the brain will process an amber
smell as very different from a fresh-cut flower smell.
[0120] In creating a rotation, a guideline for scent variety can be
established using the fragrance wheel of FIG. 5. For example, a
spacing of 1-5 subgroups between consecutive scents can maximize
the effectiveness of the olfactory stimulation schedule 20.
Similarly, it can be determined that during the course of a single
daily schedule 20, at least one fragrance from each of the four
families should be represented.
[0121] FIG. 6 provides an example rotation 60 in which there is at
least one sub group separating consecutive intervals 30, and all
four families are represented over the seven intervals 30 of the
schedule 20.
[0122] FIG. 7 provides another example of a fragrance schematic
developed by Hans Henning, a German psychologist, in 1916. Henning
H (1916) Der Geruch. Leipzig, Germany. The schematic of FIG. 7 is
known as Henning's Prism, and is a three-dimensional prism
consisting of three rectangular faces, each of which could be used
as a fragrance wheel. The corners of the prism include the
fragrance families: fragrant (flowery or floral), ethereal
(fruity), putrid, resinous, burned, and spicy. Each face shares two
families with an adjoining face. Thus, one face of the prism
includes the families: flowery, fruity, spicy and resinous. Another
face includes the families: flowery,spicy, burnt and putrid. The
third face includes the families: burnt, putrid, fruity and
resinous. Because the putrid and burnt families are generally less
desirable, it is thought that the face shown in FIG. 8 will be
preferred. FIG. 8 takes this face and forms a wheel including the
subgroups between the families.
Intensity
[0123] The strength or intensity of the aroma being produced during
the treatment must be strong enough to have an effect on the
treatment recipient, but not so strong as to create lingering odors
in the furniture or other objects in the room where the treatment
is being administered. Optimally, the scent being delivered during
each interval 30 will dissipate during the break 40 between the
intervals 30. Interestingly, are not affected by scents while they
sleep, so the scent being strong enough to interrupt sleep patterns
is not a concern. However, as discussed above, olfaction loss
occurs with age and should strengthen with treatment. As such, it
is an embodiment of the invention to adjust the intensity level
prior to the treatment program to a level that is easily detected
by the recipient without being overpowering.
[0124] Another embodiment of the invention includes a device that
allows fragrances to be mixed by "playing" two or more cartridges
simultaneously. The device also allows the intensity of each scent
cartridge to be adjusted by increasing or decreasing the airflow
passing through the cartridge. In this way, the "recipes" may be
altered by not only adjusting which cartridges are being played,
but by adjusting the intensities of each cartridge that is being
played. For example, if a "recipe" involves a mixture of cherry and
vanilla, the cherry cartridge could be played at a 50% intensity,
while the vanilla cartridge could be played at 10% intensity. This
would create a different scent that if the vanilla were played at
50% and the cherry were played at 10%, for example.
Devices
[0125] A variety of devices are envisioned that could be used to
practice the method 10 of the invention. These devices can
generally be broken down into two categories--forced air devices
and evaporative devices. The forced air devices generally include
one or more scent cartridges that are engaged with a machine that
pumps air, via one or more fans, bellows, turbine(s), etc., through
the cartridge, preferably at a selectable rate such that intensity
may be varied. Some embodiments include a plurality of cartridges
on a selectable carousel that plays one cartridge at a time. Other
devices include a plurality of cartridge engagement assemblies, or
"play heads" to allow the cartridges to be played
simultaneously.
[0126] The evaporative devices involve scent cartridges, pads or
gels that are either contained within a dispensing device, or may
be layered such that, once opened, an exposed layer having a first
scent begins to evaporate, thereby emitting the first scent. The
scent layers may be separated by odorless layers to provide breaks
40 between the scent intervals 30. The dispensing device may have
mechanized covers that selectively cover and uncover a scent
cartridge or may have heaters associated with each scent cartridge
that raises the temperature of the gel to a point that evaporation
occurs.
[0127] Referring now to FIG. 9, there is shown a first embodiment
of a device 100 of the invention. Device 100 is a forced air device
that accommodates four cartridges 102, 104, 106 and 108. Each of
the cartridges may be a disposable device that allows air to flow
through the cartridge to emit a fragrance. Alternatively, in the
interest of ecology and cost, the cartridges may be refillable and
reusable. More detail about the individual cartridges will be
provided below.
[0128] Referring to both FIGS. 9 and 10, an embodiment of the
device 100 includes a housing 110 with cavities 112, 114, 116 and
118 sized and shaped to accommodate cartridges 102, 104, 106 and
108, respectively. Each cavity 112, 114, 116 and 118 may be
equipped with a retractable cover 122, 124, 126 and 128,
respectively, such that the cartridges not being used are preserved
and aromas therefrom are not deployed.
[0129] It is envisioned that each of the cartridges and
corresponding cartridges have a unique shape corresponding to a
fragrance family. In this way, a recipient will be required to
place a cartridge belonging to each fragrance family in the device
100. In the example of device 100, the shapes selected are circle,
square, triangle and oval for cartridges 102, 104, 106 and 108.
Alternatively, each cartridge could be coded, and each cavity could
be equipped with a code reader such that the device 100 knows which
fragrance is inserted into each cavity.
[0130] The housing has a vent 110 formed in one wall through which
the fragrance from the cartridges is emitted. The sidewall was
selected as most users will place the device 100 on a bedside
table. The vent 110 may then be situated such that it faces the
recipient.
[0131] Internally, the device includes a fan or fans 130 situated
beneath the cavities. The fan 130 is powered by a motor 132 and is
connected to the motor with a shaft 134. A control board 140 drives
the logics that activate and deactivate each motor along with logic
functions discussed in detail below. In the embodiment having one
fan, flow through the individual cartridges is controlled by the
covers 122, 124, 126 and 128.
[0132] The device 100 is shown as drawing air downward through the
cartridges and into a central housing cavity 120. The air is forced
to exit through the vent 110 because the vent 110 is the only exit
for the cavity, considering that the covers are closed on cavities
not being used and that fans are running on each cavity with an
open cover. This design allows the central housing cavity 120 to be
used as a mixing chamber in the event that more than one fragrance
cartridge is being used simultaneously. In order to protect the
electronic componentry, such as the motors 132 and the control
board 140, a barrier 121 is provided, insulating these components
from the central housing cavity 120.
[0133] One skilled in the art will realize that the device 100 may
be designed such that air flow is reversed, without departing from
the spirit of the invention. A reversed air flow could be
accomplished by merely reversing the direction of the fans 130.
This design may be advantageous in that there would be less risk of
residue building up in the cavity 120.
[0134] The control board 140 is electrically connected to the fan
motors 132 and includes a wireless connection technology, such as
Bluetooth.RTM. that can be connected to an electronic device such
as a smart phone or reader. An application, downloadable onto the
device, includes control logics that allow a user to customize a
treatment schedule. Alternatively, a physician may create a
schedule 20 that is downloadable by the user.
[0135] The application provides various controls and options that
may be incorporated into the daily schedule, including scent
rotation, intensity, timing, reminders, scent shuffle, and the
like. The application preferably tracks the scent rotation to
assess which scents may have been played repeatedly over the course
of the treatment program. These scents can be marked by the
application as losing novelty and can thus be taken out of the
rotation, or mixed with another scent the next time they are
used.
[0136] The application can be wirelessly connected to a variety of
biometric sensors listed above, such that the schedule becomes
dynamically-timed. For example, the user may don a heart rate
monitor when going to bed. The activation of the heart rate monitor
is sensed by the application and the application begins to monitor
the sleep stage of the user to determine the timing of the daily
schedule 20, as discussed above.
[0137] Alternatively, if a biometric sensor is not used, the
handheld electronic device itself could be used by the control
board to indicate the beginning of a daily schedule 20. For
example, the device 100 may include a USB charging port 111 that is
connected to the control board. The user could use this USB port to
charge their phone during the evening. Plugging the phone into the
device 100 could be used as an indication that the daily schedule
20 should commence. Ease of use is thus maximized as the disruption
in routine is minimized, as most people are accustomed to charging
their smart phones in the evening.
[0138] The control board 140 is also used to track the usage of the
cartridges. Depending on the construction of the cartridge, the
application can be used to provide indications to the user that a
particular cartridge needs to be replaced.
[0139] FIG. 11 shows an embodiment of a cartridge 102 of the
invention. This embodiment is a disposable embodiment and includes
a housing 150 with a top 152 and a bottom 154. The top 152 and
bottom 154 are vented such that air may pass through. The cartridge
102 would be shipped with a removable film (not shown) covering the
top 152 and bottom 154 until the cartridge is ready to be used,
thus preserving the odorant contained therein.
[0140] FIG. 12 shows a cutaway view of the cartridge 102, allowing
an absorbent odorant pad 156 to be seen. The pad 156 may be formed
as a wad, such as a cotton ball or polyester fiberfill wad, and
should be loosely packed such that air may flow through it.
Alternatively, the pad 156 may be slightly smaller than an interior
of the cartridge such that air may flow around the pad 156. In this
embodiment, a denser wadding material may be used that might hold
more odorant than an embodiment that requires the air to flow
through the pad 156.
[0141] In one embodiment of the cartridge 150 of FIG. 12, the top
152 is removable and replaceable. This embodiment reduces plastic
waste and costs. Rather than replacing the entire cartridge,
odorant pads 156 could be provided or sold individually or in
packages containing multiple packages. FIG. 10 shows a package 160
of pads 156 arranged such that each row 162 represents a different
scent family and each column 164 thus represents a different day of
the week.
[0142] As introduced above, one aspect of the invention provides
evaporative devices that involve scent cartridges, pads or gels
that are either contained within a dispensing device, or may be
layered such that, once opened, an exposed layer having a first
scent begins to evaporate, thereby emitting the first scent. The
scent layers may be separated by odorless layers to provide breaks
40 between the scent intervals 30.
[0143] One embodiment 180 of an evaporative device is shown in FIG.
14. This device is a gel tab consisting of a plurality of odorant
layers 182 separated by odorless layers 184. In this example there
are six odorant layers 182 separated by five odorless layers. The
odorant layers are designed to evaporate at a desired rate such
that each odorant layer represents an interval 30. The odorless
layers are designed to evaporate at a desired rate such that each
odorless layer represents a break 40. The desired timing of each
layer may be controlled by the thickness of the layer during the
manufacturing process. The odorless layers 184 would then be
thinner than the odorant layers 182. The gel tabs 180 are provided
on a substrate 186 such that only the top layer evaporates.
[0144] The gel tab 180 provides a base for a variety of delivery
mechanisms encompassed in the invention. Additionally, it is
envisioned that the gel tab 180 could shaped such that it may be
removed from the substrate 186 and applied like tap directly to the
upper lip or chin of the recipient. In this embodiment, it may be
desired to include a odorless layer 184 as the top layer such that
the user has a few minutes to fall asleep prior to experiencing the
odorants.
[0145] FIG. 15 shows a CPAP mask 200 that has been modified
slightly to accommodate a gel tab 180. The mask 200 has a nozzle
206 that connects to the gas delivery tube of a typical CPAP
machine (not shown). The nozzle 206 includes a compartment 202 with
a lid 204 that can be opened so that a gel tab 180 may be placed
therein. The tab 180 is placed such that the substrate 186 is on
the top. During use, the gas flowing through the nozzle 206 from
the CPAP machine passes under the bottom, exposed layer of the tab
180 and is inhaled by the user. In the morning, the empty substrate
186 is discarded.
[0146] Other devices are envisioned that utilize the gel tab 180
including, but not limited to, plug-in style air fresheners,
non-CPAP masks, pendants and other wearable devices, nose plugs,
heat-activated devices, diffusers, etc.
EXAMPLES
[0147] The following examples are presented to illustrate the
present invention and to assist one of ordinary skill in making and
using the same. The examples are not intended in any way to
otherwise limit the scope of the invention.
Example 1: Environmental Enrichment in Inner-City Classrooms
[0148] This Example demonstrates enhancing brain responses with
multiple olfactory stimulation in school children. Children in an
inner-city school were exposed to 30 minutes of olfactory
stimulation daily in the classroom using essential oil fragrances,
one per day, rotating through 5 different scents (n=25 children),
for 3 months. Another group of 23 children was left without such
stimulation, serving as controls. Stroop test scores were monitored
over that period. This test assesses cognitive processing speed,
attention capacity, and executive function. In addition, the Stroop
test has a strong correlation with IQ, general behavior, and school
performance (Imbrosciano and Berlach, 2005).
[0149] As shown in FIG. 16, olfactory-enriched children had more
than 10 times the improvement observed in controls on that test.
The classes were team taught by the same teachers, making it
unlikely that this phenomenon was due to differences in the
teaching ability of their teachers. While there have been many
attempts to improve cognitive outcomes for children in elementary
school, such attempts have generally been unsuccessful in
increasing their cognitive capacity.
Example 2: Environmental Enrichment for Older Adults
[0150] This Example demonstrates the positive impact of olfactory
stimulation on the cognitive ability of older adults. The older
adults were tested using standard, validated cognitive assessments,
and then retested after they had received daily olfactory
stimulation. The stimulated older adults had improvements that were
181%, 268% and 1,258% better than controls.
[0151] Older adults were given a set of pleasant scents and asked
to expose themselves to the scents using a provided nebulizer for
30 min in the morning and 30 min in the evening every day for 6
months. 40 older adults (60-75 years old) gave themselves patterned
olfactory stimulation at home, or were assigned to a group that did
not experience increased olfactory stimulation. Three tests of
cognition were administered at the start of the trial, and then
again after 6 months.
[0152] In a test that reveals verbal learning and memory (Rey
Auditory Verbal Learning), olfactory-enriched older adults
performed 181% A better than controls (FIG. 17). In a test of
sequential processing, mental manipulation, attention,
concentration, memory span, and short-term auditory memory (WAIS
III Letter-Number Sequencing), the enriched group had a 268%
advantage over controls (FIG. 18). Finally, in a test of rote
learning and memory, attention, encoding, and auditory processing,
working memory, transformation of information, mental manipulation,
and visual-spatial imaging (WAIS III Backwards Digit Span), the
enriched group performed 1,258% better than controls (FIG. 19).
[0153] These cognitive benefits are about 1-2 orders of magnitude
better than computer games, direct brain stimulation, exercise or
social interactions (Clememson and Stark, 2015; Ezzyat, et al.,
2018; Hertzog, et al. 2009; Kirk-Sanchez and McGough, 2014;
Kucewisc, et al., 2018).
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[0240] Although the invention has been described in terms of
particular embodiments and applications, one of ordinary skill in
the art, in light of this teaching, can generate additional
embodiments and modifications without departing from the spirit of
or exceeding the scope of the claimed invention. Accordingly, it is
to be understood that the drawings and descriptions herein are
proffered by way of example to facilitate comprehension of the
invention and should not be construed to limit the scope
thereof.
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