The association between AD pathology and sleep-dependent memory consolidation

JRCT ID: jRCT1030230197

Registered date:01/07/2023

Basic Information

• Recruitment status: Recruiting
• Health condition(s) or Problem(s) studied: Alzheimer's disease
• Date of first enrollment: 01/07/2023
• Target sample size: 50
• Study type: Interventional
• Intervention(s): Participants perform a pair-word association task (PWAT) and a mirror drawing task (MDT) for initial acquisition of declarative and procedural memory. They are assessed immediate memory performances in both mnemonic modalities. On the night of learning, participants sleep under polysomnography (PSG) and retest the next morning to assess delayed memory performances.

Outcome(s)

• Primary Outcome: Sleep-dependent improvement ratios in the PWAT and MDT

Secondary Outcome

1. Declarative memory score in the PWAT
2. Procedural memory score in the MDT
The following variables, derived from secondary data usage from the AT-Sleep study, will also be evaluated to consider as covariates for the primary endpoint.
a. Discrepancies between subjective and objective sleep variables
b. Self-assessments of sleep state (sleep diary, PSQI score, AIS score, ESS score)
c. PSG sleep variables (total recording time, total sleep time, sleep duration, bedtime, sleep onset latency, sleep efficiency, number and duration of awakenings, respiratory disturbance variables, periodic limb movement variables, EEG power spectrum variables, amount and rate of spindle wave appearance)
d. PSG sleep stage-related variables (rate of occurrence of each sleep stage, amount of occurrence of each sleep stage, REM latency, REM density, RWA, CAP, number of sleep cycles, arousal index, number of sleep stage transitions)
e. Actigraphy evaluation variables (sleep-wake variables, activity level)
f. Cognitive functions (MMSE score, MoCA-J score, WMS-R score, CDR score, IADL score)
g. T1-weighted, T2-weighted, FLAIR, and diffusion-weighted MRI brain structural imaging (brain volume, white matter volume, grey matter volume, fractional anisotropy, mean diffusivity),
h. PET images (amyloid accumulation, tau fractional anisotropy)
i. The presence or absence of the APOE gene 4 allele.

Key inclusion & exclusion criteria

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

Include criteria

Participants who will participate to the AT-Sleep study (jRCT1031220550) are enrolled. Individual selection criteria for healthy volunteers and patients on the Alzheimer's disease (AD) spectrum (mild AD, mild cognitive impairment (MCI), and preclinical AD) are as follows;
Healthy volunteers
1. Normal cognitive function (MMSE score is 28 points or higher)
2. Comprehensive CDR score is 0
3. MRI and PET have already been performed or will be performed in the AT-Sleep study.
4. Polysomnography will be performed in the AT-Sleep study.
5. Participants must fully understand the study and give written consent of their own free will.

Patients with AD spectrum
(Common part)
1. The participants are currently attending our hospital or have a history of research participation, and meet one of the following criteria (A, B, and C.)
2. They fully understand the content of the research and give written consent of their own will.
3. They have a partner who contacts the participant at least once a week and is willing to participate in the study as an informant.
4. They maintain vision, hearing, and writing skills that do not affect cognitive function tests.
5. They have already performed MRI and PET or will perform in the AT-Sleep study.
6. They will undergo polysomnography in the AT-Sleep study.

A. Mild AD
a. Probable AD on NIAAA diagnostic criteria
b. MMSE score is 23 or less
c. 0.5 or 1 on the comprehensive CDR
B. MCI (due to AD)
a. MCI due to AD by NIAAA diagnostic criteria
b. MMSE score is 27 or less
c. Comprehensive CDR score is 0.5 with memory score is 0.5 or 1
C. Preclinical AD
a. Probable AD by NIAAA diagnostic criteria (previously participated in amyloid PET studies, and the amyloid positive finding have been revealed)
b. MMSE core is 28 points or higher
c. Comprehensive CDR score is 0

Exclude criteria

Healthy volunteers
1. The participants who have been diagnosed certain neurodegenerative diseases or conditions including AD spectrum, also with multiple cerebral infarctions, normal pressure hydrocephalus, brain tumors, epilepsy, subdural hematoma, multiple sclerosis, or head trauma that results residual damage or abnormal brain structure.
2. They have a focal lesion, such as a cerebral infarction, that could affect infection or cognitive function on MRI.
3. They suffer from cardiac pacemakers, aneurysm clips, cochlear implants, other magnetic or electrically conductive metals, or claustrophobia that causes problems with MRI imaging.
4. They show hypersensitivity to thioflavin derivatives.
5. They have major depression or bipolar disorder defined by DSM-5 within the past year, or have a history of schizophrenia defined by DSM-5 in the past.
6. They have a history of alcohol or drug dependence defined by the DSM-5 within the past 2 years.
7. They have some sleep disorders under treatment.
8. They have a serious systemic illness or unstable conditions.
9. They are judged to be ineligible by the M.D. investigators.
Patients with AD spectrum
1. The participants have a specific neurodegenerative disease other than AD spectrum, including multiple cerebral infarctions, normal pressure hydrocephalus, brain tumor, epilepsy, subdural hematoma, multiple sclerosis, or head injury that has left residual effects or abnormal brain structure.
2. They have a focal lesion, such as a cerebral infarction, that could affect infection or cognitive function on MRI.
3. They suffer from cardiac pacemakers, aneurysm clips, cochlear implants, other magnetic or electrically conductive metals, or claustrophobia that causes problems with MRI imaging.
4. They show hypersensitivity to thioflavin derivatives.
5. They have major depression or bipolar disorder defined by DSM-5 within the past year, or have a history of schizophrenia defined by DSM-5 in the past.
6. They have a history of alcohol or drug dependence defined by the DSM-5 within the past 2 years.
7. They have exhibited psychiatric symptoms, excitability, and behavioral abnormalities to such an extent that adhering to the protocol has become difficult within the past 3 months.
8. They have a serious systemic illness or unstable conditions.
9. They have been admitted to a nursing home or hospital.
10. They are participating in a clinical intervention study or trial at the time of enrollment, or have a history of participation in anti-amyloid therapy trials.
11. They are judged to be ineligible by the M.D. investigators.

Related Information

• Primary Sponsor: Kuriyama Kenichi
• Source(s) of Monetary Support: JSPS KAKENHI Grant Number 20H03609