Clinical trial NCT03370744: Prediction of Cognitive Decline by Neuroimaging Techniques and the Application in Diagnosis and Treatment of Preclinical AD
Official title: Prediction of Cognitive Decline by Neuroimaging Techniques and the Application in Diagnosis and Treatment of Preclinical AD (Sino Longitudinal Study on Cognitive Decline, SILCODE)
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Subjective Cognitive Decline
Preclinical Alzheimer's Disease
Keywords: subjective cognitive decline
brain network
multi-modality
magnetic resonance imaging
Lead sponsor: Xuanwu Hospital, Beijing
Sponsor class: OTHER
First posted: 2017-12-12
Enrollment: 300
Sex: ALL
Minimum age (years): 60
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Observational model: CASE_CONTROL
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Volunteers recrewed from communities, and signed up with informed consent.

Brief summary: This study is affiliated to Sino Longitudinal Study on Cognitive Decline, SILCODE. To establish models of normal and pathological cognitive aging.To collect the longitudinal data of SCD population, to study the dynamic changes of brain networks so as to explore the progressive mechanisms of AD on brain networks and to construct a high-precision multi-modal model for early diagnosis.

Detailed description: This study is affiliated to Sino Longitudinal Study on Cognitive Decline, SILCODE. Alzheimer's disease (AD) is the most common cause of dementia, which severely injures multiple domains of cognitive functions in the aging people, bringing heavy burden to the society and families. Studying the cognitive brain damage mechanism of subjective cognitive decline (SCD), the preclinical stage of AD, would provide great opportunities for understanding the pathogenesis of AD and clinical value for early diagnosis and intervention in AD. The project intends to utilize amyloid-PET and FDG-PET for screening and then employ the comprehensive neuropsychological examination combined with multi-modal MRI neuroimaging techniques to study the brain functions and structures of the normal aging and SCD. The imaging data would be analyzed from several levels, including the cognitive dimensions, brain activation patterns, and especially functional and structural networks to establish the models of normal and pathological cognitive aging, which mainly be modulated by frontal-parietal control system. We aim to establish models of normal and pathological cognitive aging. Furthermore, the longitudinal data of SCD population would be collected to study the dynamic changes of brain networks so as to explore the progressive mechanisms of AD on brain networks and to construct a high-precision multi-modal model for early diagnosis

Eligibility criteria: 1. NC Inclusion Criteria:

1. Older than 60, right handedness, Han nationality;
2. Have no cognitive decline complains, with neither worry nor concern about their cognition;
3. Scores of standardized neuropsychological tests scale adjusted for age, sex and education are in normal range;
4. Physical examination is negative;
5. Review medical history and family history is negative, accessory examination don't show disease could cause cognitive decline;
6. Could cooperate collection of multi-modal magnetic resonance imaging, once a year, for continueously five years.

2. SCD Inclusion Criteria:

1. Presence of self-perceived continuous cognitive decline compared to previous normal status and unrelated to an acute event;
2. Failure to meet the following criteria for MCI.

3.SCD-plus Inclusion Criteria:

1. Presence of self-perceived continuous cognitive decline compared to previous normal status and unrelated to an acute event;
2. Concerns (worries) associated with memory complaint;
3. Failure to meet the following criteria for MCI.

3. MCI Inclusion Criteria:

1. Clinical Dementia Rating (CDR) score of 0.5 as well as failure to meet the criteria for dementia
2. Having impaired scores (defined as \>1 SD below the age-corrected normative mean) on both measures within at least one cognitive domain (i.e., memory, language, or speed/executive function);
3. Having impaired scores in each of the three cognitive domains sampled;
4. the Functional Activities Questionnaire (FAQ) ≥9.

4. AD Inclusion Criteria The diagnosis of AD syndrome is based on the diagnostic guidelines for dementia due to AD delivered by the National Institute on Aging-Alzheimer's Association workgroups (NIA-AA)with a total CDR score of 1.

Exclusion Criteria:

1. Claustrophobia, with metals in the body that cannot be examined by MRI, including metal dentures or other contraindications for examination;
2. Left handedness or ambidextrality.

Primary outcomes:
measure: The altered volume pattern in SCD/SCD-plus with progression.
timeFrame: 5 years
measure: The altered DTI pattern in SCD/SCD-plus with progression.
timeFrame: 5 years
measure: The altered functional MRI pattern in SCD/SCD-plus with progression.
timeFrame: 5 years
measure: The altered FDG-PET pattern in SCD/SCD-plus with progression.
timeFrame: 5 years
measure: The altered AV45-PET pattern in SCD/SCD-plus with progression.
timeFrame: 5 years
measure: Genotype of SCD/SCD-plus with progression.
timeFrame: 5 years
measure: AD7c-NTP level of SCD/SCD-plus with progression.
timeFrame: 5 years
measure: Gut microbiota of SCD/SCD-plus with progression.
timeFrame: 5 years
Secondary outcomes:
Other outcomes:
Locations:
city: Beijing
country: China
facility: Department of Neurolgy,Xuanwu Hospital of Capital Medical University
state: Beijing
Study officials:
affiliation: Xuanwu Hospitial Capital Medical University
name: Ying Han, Doctor
role: STUDY_CHAIR
References:
citation: Wang T, Wang X, Yao Y, Zhao C, Yang C, Han Y, Cai Y. Association of plasma apolipoproteins and levels of inflammation-related factors with different stages of Alzheimer's disease: a cross-sectional study. BMJ Open. 2022 Apr 6;12(4):e054347. doi: 10.1136/bmjopen-2021-054347.
citation: Sheng C, Yang K, He B, Du W, Cai Y, Han Y. Combination of gut microbiota and plasma amyloid-beta as a potential index for identifying preclinical Alzheimer's disease: a cross-sectional analysis from the SILCODE study. Alzheimers Res Ther. 2022 Feb 14;14(1):35. doi: 10.1186/s13195-022-00977-x.
citation: Ding C, Du W, Zhang Q, Wang L, Han Y, Jiang J. Coupling relationship between glucose and oxygen metabolisms to differentiate preclinical Alzheimer's disease and normal individuals. Hum Brain Mapp. 2021 Oct 15;42(15):5051-5062. doi: 10.1002/hbm.25599. Epub 2021 Jul 22.
citation: Dong QY, Li TR, Jiang XY, Wang XN, Han Y, Jiang JH. Glucose metabolism in the right middle temporal gyrus could be a potential biomarker for subjective cognitive decline: a study of a Han population. Alzheimers Res Ther. 2021 Apr 7;13(1):74. doi: 10.1186/s13195-021-00811-w.
citation: Sheng C, Sun Y, Wang M, Wang X, Liu Y, Pang D, Liu J, Bi X, Du W, Zhao M, Li Y, Li X, Jiang J, Han Y. Combining Visual Rating Scales for Medial Temporal Lobe Atrophy and Posterior Atrophy to Identify Amnestic Mild Cognitive Impairment from Cognitively Normal Older Adults: Evidence Based on Two Cohorts. J Alzheimers Dis. 2020;77(1):323-337. doi: 10.3233/JAD-200016.
citation: Li X, Wang X, Su L, Hu X, Han Y. Sino Longitudinal Study on Cognitive Decline (SILCODE): protocol for a Chinese longitudinal observational study to develop risk prediction models of conversion to mild cognitive impairment in individuals with subjective cognitive decline. BMJ Open. 2019 Jul 26;9(7):e028188. doi: 10.1136/bmjopen-2018-028188.
citation: Sun Y, Wang X, Wang Y, Dong H, Lu J, Scheininger T, Ewers M, Jessen F, Zuo XN, Han Y. Anxiety correlates with cortical surface area in subjective cognitive decline: APOE epsilon4 carriers versus APOE epsilon4 non-carriers. Alzheimers Res Ther. 2019 Jun 3;11(1):50. doi: 10.1186/s13195-019-0505-0.