Sleep and Alzheimer’s Disease: Lacking Sleep, Having Enough Sleep,

Sleeping Too Much, and Mental Activities during Daytime

Tingting Pan

The Second Foreign Language School Affiliated to Shanghai Normal University

Shanghai, 201399, China

Keywords:

Alzheimer’s Disease, Sleep Aβ Plaque, Tau Protein.

Abstract:

This work discusses how does sleep influences the incidence rate of Alzheimer’s Disease, from 3 scenarios:

lacking sleep, having enough sleep, and sleeping too much. Lack of sleep can be further divided into having

a snap during the daytime or not. Some studies proved that sleep disturbances are associated with Alzheimer’s

Disease from experiments by comparing mice with not enough sleep and with enough sleep. However, they

didn’t concern about the symptoms of oversleeping, and the mental activities during a human being’s life

compared to a mouse. Therefore, this work will try to demonstrate that sleep disturbances are associated with

the risk of developing AD inherently. Alzheimer’s Disease is incurable, but there are ways to reduce the

potential of getting it.

1 INTRODUCTION

Alzheimer's Disease is a progressive disease, with

symptoms like confusion, disorientation, poor

concentration, and change in personality, which

would become worsen over years. “There are over 55

million people worldwide living with dementia in

2020”(Alzheimer’s Disease International. (2020),

which means there are about 55 million families

suffered from it. Moreover, Alzheimer’s disease has

heredity, which means it is possible to continue this

suffering. More understanding of sleep and

Alzheimer’s Disease could promote the development

of new therapeutic approaches, and benefit all human

beings. Therefore, sleep as one of the factors of

Alzheimer’s Disease is essential to study.

Some studies proved that sleep disturbances are

associated with Alzheimer’s Disease from

experiments by comparing mice with not enough

sleep and with enough sleep. However, these

experiments are biased because they didn’t mention

the symptoms of oversleeping. Also, these

experiments are not clear about the situations of mice

in the daytime, because normal human beings would

have much more mental activities in the daytime than

mice, and these experimenters might only afford them

water and food during experiment days.

In order to determine different kinds of sleep

symptoms’ relationship to Alzheimer’s

Figure 1: Shows relationships between sleep and AD.

228

Pan, T.

Sleep and Alzheimer’s Disease: Lacking Sleep, Having Enough Sleep, Sleeping Too Much, and Mental Activities during Daytime.

DOI: 10.5220/0011248400003438

In Proceedings of the 1st International Conference on Health Big Data and Intelligent Healthcare (ICHIH 2022), pages 228-232

ISBN: 978-989-758-596-8

Disease, the experiment would compare the AD

pathogenesis in 4 experimental groups and 1 control

group. The results might demonstrate that sleep

disturbances are associated with the risk of

developing AD inherently and explain why people

with less sleep and less mental activities are more

vulnerable to AD progression.

Sleep can be divide into three kinds: not enough

(not enough time or poor quality), enough (about 7

hours), and oversleeping. Lack of sleep can be divide

into sleep (like siesta) or doesn’t sleep in the daytime.

However, all of them will cause the increase of

amyloid-β (Aβ) amount and result in Alzheimer’s

Disease at a later age.

Studies showed that, “People who slept six hours

or less per night in their 50s and 60s were more likely

to develop dementia later in life.” (Bryant, Erin.

2021). During the sleep, cerebrospinal fluid (CSF)

can wash away “harmful waste proteins that build up

between brain cells during waking hours.”(Hamilton,

Jon. 2013)

Figure 2: Shows change of Aβ levels in human between

wake and sleep periods. (Cedernaes, Jonathan., et al. 2017).

Therefore, if a person didn’t sleep for the whole

night, the Aβ level will increase extremely in his

bloodstream and cerebrospinal fluid (CSF).

Researchers also found people who are oversleeping

(over 9 hours a day) “were twice as likely to develop

Alzheimer’s” (British Neuroscience Association.

2017). The reason is that most people who are

oversleeping have metabolic dysfunction because of

obesity and inactivity, which can affect their sleep

quality, like diabetes which “can cause sleep loss”

(Mann, Denise. 2010). For example, people who are

overweight are more likely to have sleep apnea.

Moreover, people with Alzheimer’s Disease are

often tired during the day but with poor sleeping

quality, so it would also cause them to oversleep.

Besides, the two kinds (lack of sleep and

oversleeping) of sleep disturbances and the normal

kind of sleep (enough sleeping during the day) will all

be growing the risk of developing Alzheimer’s

Disease because of aging.

Figure 3: Shows ciucular relationshp between Obesity

(Type 2 Diabetes) and Sleep Apnea. (Framnes, Sarah., et al.

2018).

2 METHODS AND RESULTS

2.1 Animals

In this study, transgenic C57BL/6J mice are used as a

model of Alzheimer’s disease. The mice are most

commonly used as the human disease model because

of their availability of homogeneous strains and they

are easy to breed. Moreover, the C57BL/6J mice have

always been used to study sleep disturbances, because

after acute hypoxia, they showed different symptoms

of sleep disturbances, like “greater amount of

irregular breathing during rest” (Chai, Sam., et al.

2011), which would influence sleep quality.

Because of the average life span for C57BL/6J

mice is about 550 days, the experiment starts at the

ages of 10 months with 6 mice per cage (3 female and

3 male animals) as a group. Before the experiment

started, mice are ad libitum to access water and food

at 23 degrees Celsius with 12h-day/12h-night cycles.

When the experiment started, four groups of

C57BL/6J mice are used for these studies: normal

sleep with normal activity (eating, etc.) in the daytime

(n=6, 3 female and 3 male animals), abnormal sleep

with normal activities, and allowed to take a rest (like

siestas in human) during the daytime (n=6), abnormal

sleep with normal activities and not allowed to take a

rest in the daytime (n=6), and abnormal sleep with

mind training in the daytime (n=6). Non-transgenic

littermates with normal sleep and mind training in the

daytime (n=6) act as the control group because it's

closer to normal human beings’ daily routine. The

animal experiments mentioned above conform to the

requirements given by the institutional animal care

and animal use committee.

Sleep and Alzheimer’s Disease: Lacking Sleep, Having Enough Sleep, Sleeping Too Much, and Mental Activities during Daytime

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2.2 Brain Training

To simulate normal human beings' daily routine,

brain training is necessary for the experiment. Clicker

training is introduced to certain experiment groups

for the enrichment of the cognition of the mice. The

training session is last for three weeks, and studies

showed “trained mice displayed less of this

depression-related behavior” (Leidinger, Charlotte.,

et al. 2017).

One benefit of this training is that it could be

achieved successfully in almost all the mice (“100%

of female mice and 83% of male mice”) (Leidinger,

Charlotte., et al. 2017).

Figure 4: Shows training success rate (Leidinger,

Charlotte., et al. 2017)

2.3 HistologyAβ Plaque Detection

Positron emission tomography (PET) imaging can

“measure physiological function by looking at blood

flow, metabolism, neurotransmitters, and

radiolabelled drugs” (Berger, Abi. 2003), which

include Aβ plaques of a certain region. To detect the

Aβ plaques level in five groups of mice, 18F-FC119S,

which is a radiopharmaceutical is injected into the

mouse. Later, the Aβ plaque level in the brain and

also in the cerebrospinal fluid (CSF) can be seen by

using PET scanning.

Tau protein detection:

Positron emission tomography (PET) imaging can

also be used for tau protein detection in five groups

of mice. To detect the tau protein, 18F-AV-1451 is

injected into the mice's brain as a radio-diagnostic

agent. “F-FC119S is a positron emission tomography

(PET) tracer for imaging β-amyloid (Aβ) plaques in

Alzheimer’s disease (AD)” (Oh, Se Jong., et al.,

2018). After that, the tau protein aggregation can be

seen by using PET scanning.

Figure 5: Shows PET scans for Aβ plaque and Tau protein

from normal older adult (with low Aβ plaque and Tau

protein level), normal older adult (with high Aβ plaque and

Tau protein level), and AD patient. (Yang, Sarah. (2016)

2.4 Results

Experiment groups with abnormal sleep are assumed

to have higher tau protein and Aβ levels, whereas

groups with normal sleep have less tau protein

because the tau protein and Aβ protein are normally

cleared by the glymphatic system, “a cleaning

mechanism that functions in the removal of

potentially harmful metabolites and proteins from the

brain” (Cai, XueZhu., et al. 2020), during sleep.

Take the average and standard deviation of the

data (Aβ level, tau protein level) in each group. Then,

do the following tests:

T-test:

H0: There is no difference between 5groups

H1: group 1 < group 2, 3, 4 < group 5

If P≤ 0.05, then the results reject the null

hypothesis; if P> 0.05, then the results failed to reject

the null hypothesis.

One-way ANOVA test:

H0: There is no difference among the means of the

three test groups.

H1: There is a difference among means of five test

groups, and the data of the group 2, 3, 4 lies between

group 1 and group 5.

If p≤ 0.05, then the results reject the null

hypothesis; if p>0.05, then the results fail to reject the

null hypothesis.

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Figure 6: Shows experiment process of the work.

3 CONCLUSIONS

3.1 Experiments Review

It is no doubt that sleep can affect the risk of

Alzheimer’s Disease. Therefore, in the experiment,

four groups of transgenic C57BL/6J mice are used as

experiment groups, and the non-transgenic mice are

the control group.

①

Non-transgenic littermates with normal sleep and

mind training in the daytime (n=6, 3 female and 3

male animals) act as the control group.

②

normal sleep with normal activity (eating etc.) in

the daytime (n=6)

③

abnormal sleep with normal activities and allowed

to take a rest (like siestas in humans) during the

daytime (n=6)

④

abnormal sleep with normal activities and not

allowed to take a rest in the daytime (n=6)

⑤

abnormal sleep with mind training in the daytime

(n=6)

After the experiments, Aβ plaques level and Tau

protein are detected as AD pathogenesis. After

analyzing the data, if it matches the hypothesis that

the tau protein and Aβ plaques level in group 1 is less

than group 2, 3, 4, and less than group 5, the

experiments succeed, and if not, the experiments

failed.

3.2 Future Directions

As mentioned in the results, the glymphatic system in

the mice brain can clear amyloid-β and tau protein

during sleep, but it is only in the mice brain. The

glymphatic system in the human brain still needs to

explore.

Notably, sleep is related to inflammation in the

brain, and Alzheimer’s Disease can also lead to

inflammation. Therefore, the connection between

sleep, inflammation, and Alzheimer’s Disease is also

an essential area to be understood.

Along with aging, the sleeping time will normally

decrease in older people, how to improve their sleep

quality is a problem that remains unsolved.

Moreover, how to lengthen older people’s sleep, and

if that is helpful to reduce the risk of developing

Alzheimer’s Disease remains unknown.

The proposed model still needs further research to

improve, and here are some suggestions for decrease

the risk of developing Alzheimer’s Disease.

Sleep about 8 hours a day, not less than 6 hours

and no more than 9 hours.

Siesta should be less than 1 hour a day

Focus on sleep quality as well, can use eye patch

and sleep aromatherapy, etc. to improve sleep

quality.

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