Alzheimer's pathology and sleep disturbance

JRCT ID: jRCT1031220550

Registered date:29/12/2022

Basic Information

• Recruitment status: Recruiting
• Health condition(s) or Problem(s) studied: Alzheimer Disease
• Date of first enrollment: 05/01/2023
• Target sample size: 50
• Study type: Interventional
• Intervention(s): amyloid PET, tau PET

Outcome(s)

• Primary Outcome: Associations between amyloid/tau pathology and reduction in the ratio of deep sleep (N3 sleep) or in the period and quantity of total sleep

Secondary Outcome

Discrepancies in subjective sleep and objective sleep indices and their relationship with cognitive function and AD pathology
Self-evaluation of sleep (sleep diary, Pittsburgh sleep quality index , Athens insomnia scale , and Epworth sleepiness scale scores)
PSG variables (total recorded time, total sleep period, sleep period, period in bed, sleep latency, sleep efficiency, number/time of arousals during sleep, respiratory disturbance, periodic limb movement, sleep electroencephalogram power spectrum, and amount/ratio of the incidence of spindle waves)
PSG sleep stage variables (incidences/amount of each sleep stage, rapid-eye movement (REM) latency, REM concentration, REM sleep without atonia, number of sleep cycles, and awake index)
Actigraphy (sleep/awake variables, amount of activity)
Associations between brain atrophy on MRI and the described sleep variables
Associations between the epsilon 4 allele of APOE and the sleep variables described above

Key inclusion & exclusion criteria

• Age minimum: >= 60age old
• Age maximum: <= 80age old
• Gender: Both

Include criteria

1. Alzheimer's dementia (AD) spectrum patients
1) Aged 60 years and above and 80 years and below at the time of obtaining consent. All of the sexes are included.
2) Being and outpatient or having a history of participation in research, and either A, B, or Cis applicable from among the following
3) Persons who can consent to participation of the study under their free will
4) Having a study partner who has contact with the participant at least once a week and who is willing to participate in this study as an information provider (in-person, telephone, and email were accepted contact methods)
5) Vision, hearing ability, and writing ability are maintained to a degree that has no effect on cognitive tests
6) Having consented to undergo all examinations, including magnetic resonance imaging (MRI), positron emission tomography (PET), sleep-related examinations such as polysomnography (PSG), and gene analysis
A. Mild AD
a) Probable AD according to the National Institute on Aging and Alzheimer's Association (NIA-AA) criteria
b) Total Mini-Mental State Examination (MMSE) scores equal to or less than 23
c) Scores of 0.5 or 1 in global clinical dementia scale (CDR)
B. Mild cognitive impairment (MCI) due to AD
a) MCI due to AD according to the NIA-AA criteria
b) Total MMSE scores equal to or less than 27
c) Scores of 0.5 in global CDR and 0.5 or 1 in the memory domain
C. Preclinical AD
a) Preclinical AD according to the criteria of NIA-AA (amyloid-positive in a previous amyloid PET or cerebrospinal fluid study)
b) Total MMSE scores equal to or more than 28
c) Score of 0 in global CDR

2. Healthy volunteers
1) Healthy individuals with normal cognitive function (MMSE scores equal to or above 28)
2) Aged 60-80 years. Any sex is included.
3) Score of 0 in global CDR
4) Consent to undergo all examinations, that is, MRI, PET, sleep-related examinations such as PSG, and gene analysis
5) Giving informed consent based on participant's free will after the participant understand the content of the study

Exclude criteria

1. AD spectrum
1) Having been diagnosed with a specific neurodegenerative disease other than AD, or proven to have multiple cerebral infarctions, normal pressure hydrocephalus, brain tumors, epilepsy, subdural hematoma, multiple sclerosis, or head trauma with residual symptoms or brain structural abnormalities
2) Exhibiting local lesions on MRI, such as infections and cerebral infarctions, which could affect cognitive function. Asymptomatic deep small infarctions and mild white matter changes are deemed acceptable for inclusion, but atheromal thrombosis and cardiac embolism, infarction with lesions in the cerebral cortex, or severe diffuse white matter changes (Fazekas grades equal to or above 3) are excluded.
3) Possessing an implanted pacemaker, aneurysm clip, artificial inner ear, or other magnetic/electric conductive metals or being unable to undergo MRI because of claustrophobia
4) Having allergy to thioflavin derivatives
5) Having a history of major depressive disorder or bipolar disorder defined by Diagnostic Statistical Manual (DSM)-V within 1 year prior or schizophrenia as defined by DSM-5
6) Being comorbid with or having a history of alcohol/drug dependence as defined by DSM-V within past 2 years
7) Exhibiting psychiatric symptoms, excitement, or behavioral disturbance to a degree that would have hindered their ability to follow the research protocol within the preceding three months
8) Having serious systemic diseases or unstable diseases
9) Residing in a nursing home or being hospitalized
10) Currently participating in a clinical interventional study/trial or a history of having participated in anti-amyloid trials
11) Other, when a patient is judged as unsuitable by the principal investigator or sub-principal investigator

2. Healthy volunteers
1) Being diagnosed with a specific neurodegenerative disease including the AD spectrum. Proven to have multiple cerebral infarctions, normal pressure hydrocephalus, epilepsy, subdural hematoma, multiple sclerosis, and head trauma, with residual symptoms or brain structural abnormalities.
2) Exhibiting local lesions on MRI, such as infections and cerebral infarctions, which could affect cognitive function. Asymptomatic deep small infarctions and mild white matter changes are deemed acceptable for inclusion, but atheromal thrombosis and cardiac embolism, infarction with lesions in the cerebral cortex, or severe diffuse white matter changes (Fazekas grades equal to or above 3) are excluded.
3) Possessing an implanted pacemaker, aneurysm clip, artificial inner ear, or other magnetic/electric conductive metals or being unable to undergo MRI because of claustrophobia
4) Having allergy to thioflavin derivatives
5) Having a history of major depressive disorder or bipolar disorder as defined by DSM-V within 1 year prior or schizophrenia as defined by DSM-5
6) Being co-morbid with or having a history of alcohol/drug dependence as defined by DSM-V within 2 years prior
7) Being under treatment for a sleep disorder
8) Having serious systemic diseases or unstable diseases
9) Others, judged to be unsuitable by principal investigator (PI) and co-PI.

Related Information

• Primary Sponsor: Takano Harumasa
• Source(s) of Monetary Support: Grants-in-Aid for Scientific Research