Establish Diagnostic and Prognostic Models for Preclinical AD Patients Based on Multimodal MRI, Behavioral, Genetic, and Plasma Biomarkers

NCT ID: NCT06561906

Last Updated: 2024-08-20

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Total Enrollment

1000 participants

Study Classification

OBSERVATIONAL

Study Start Date

2020-09-01

Study Completion Date

2027-12-31

Brief Summary

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To establish the diagnostic and prognostic models that could help the preclinical identification of subjects at higher risk of clinical progression to mild cognitive impairment and dementia based on combined features of baseline demographic, cognitive, behavioral, multimodal MRI, genetic, and plasma data.

Detailed Description

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Alzheimer's disease (AD) is a global concern. Due to the lack of effective therapeutic methods targeting late-stage AD patients, it is critical to investigate brain alterations in the preclinical stage to pave the way for early diagnosis and intervention. Structural and functional magnetic resonance imaging (MRI) has been proven to be an effective and non-invasive approach to explore the neural mechanisms underlying neurological disorders. Genetic factors such as apolipoprotein E and plasma biomarkers play important roles in AD development and progression. However, the interaction effects of risk genes and different pathologic pathways implicated in the pathogenesis of AD remain unclear. Furthermore, the diagnostic and prognostic models that could predict future cognitive decline or clinical progression based on objective features derived from baseline demographic, cognitive, behavioral, multimodal MRI, genetic, and plasma data need to be further explored.

We aim to investigate the neural basis underlying early cognitive deficits using structural and functional MRI data combined with novel analytical methods such as dynamic functional connectivity, surface-based morphometry, graph theory, multilayer network, functional-structural coupling, hidden Markov model, and connectome gradient mapping. Secondly, to explore the interaction effects of risk genes, which may help a better illustration of different biological pathways implicated in the pathogenesis of Alzheimer's disease. Thirdly, to investigate the divergent and dynamic abnormalities of multimodal imaging markers across different stages of Alzheimer's disease and their associations with plasma biomarkers, which may enhance our understanding of the neuropathological mechanisms. Fourthly, to provide scientific evidence on the potential targets for early intervention of neurodegenerative diseases. Lastly, to establish the diagnostic and prognostic models that could help the preclinical identification of subjects at higher risk of clinical progression to mild cognitive impairment and dementia based on combined features of baseline multimodal biomarkers. These studies may help a better understanding of the neural and biological basis underlying AD and pave the way for early diagnosis and intervention.

Conditions

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Alzheimer Disease, Late Onset Mild Cognitive Impairment Subjective Cognitive Decline

Study Design

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Observational Model Type

CASE_CONTROL

Study Time Perspective

PROSPECTIVE

Study Groups

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Normal control

Subjects without memory complaints and associated worries and do not meet the diagnostic criteria for mild cognitive impairment (MCI) are recruited as normal control (NC).

Multimodal magnetic resonance imaging scanning, behavioral, genetic and plasma biomarker testing

Intervention Type OTHER

Multimodal magnetic resonance imaging scanning, including 3DT1, 3DT2, 3DFLAIR, functional MRI, DTI, NODDI, ASL, QSM behavioral testing, such as olfaction and spatial navigation genetic testing, such as APOE, BDNF plasma biomarker testing, such as ptau, Aβ42/40、NfL、GFAP

Subjective cognitive decline

Subjects who complain of memory decline within the last 5 years and express worries associated with memory decline and do not meet the diagnostic criteria for MCI are defined as subjective cognitive decline (SCD).

Multimodal magnetic resonance imaging scanning, behavioral, genetic and plasma biomarker testing

Intervention Type OTHER

Multimodal magnetic resonance imaging scanning, including 3DT1, 3DT2, 3DFLAIR, functional MRI, DTI, NODDI, ASL, QSM behavioral testing, such as olfaction and spatial navigation genetic testing, such as APOE, BDNF plasma biomarker testing, such as ptau, Aβ42/40、NfL、GFAP

Mild cognitive impairment

Participants are considered MCI patients with scores \>1 standard deviation (SD) below the normative means in both subtests within one cognitive domain or \>1 SD below the normative means in three single tests in three different domains.

Multimodal magnetic resonance imaging scanning, behavioral, genetic and plasma biomarker testing

Intervention Type OTHER

Multimodal magnetic resonance imaging scanning, including 3DT1, 3DT2, 3DFLAIR, functional MRI, DTI, NODDI, ASL, QSM behavioral testing, such as olfaction and spatial navigation genetic testing, such as APOE, BDNF plasma biomarker testing, such as ptau, Aβ42/40、NfL、GFAP

Alzheimer's disease dementia

Patients are diagnosed as AD dementia by an experienced neurologist based on MMSE and CSF/PET biomarker evidence.

Multimodal magnetic resonance imaging scanning, behavioral, genetic and plasma biomarker testing

Intervention Type OTHER

Multimodal magnetic resonance imaging scanning, including 3DT1, 3DT2, 3DFLAIR, functional MRI, DTI, NODDI, ASL, QSM behavioral testing, such as olfaction and spatial navigation genetic testing, such as APOE, BDNF plasma biomarker testing, such as ptau, Aβ42/40、NfL、GFAP

Interventions

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Multimodal magnetic resonance imaging scanning, behavioral, genetic and plasma biomarker testing

Multimodal magnetic resonance imaging scanning, including 3DT1, 3DT2, 3DFLAIR, functional MRI, DTI, NODDI, ASL, QSM behavioral testing, such as olfaction and spatial navigation genetic testing, such as APOE, BDNF plasma biomarker testing, such as ptau, Aβ42/40、NfL、GFAP

Intervention Type OTHER

Eligibility Criteria

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Exclusion Criteria

* Participants with a history of stroke, other neurological disorders that could lead to cognitive impairment (Parkinson's disease, encephalitis, epilepsy, brain tumors, etc.), severe anxiety or depression, and contraindications for magnetic resonance imaging (MRI) were not enrolled.
Minimum Eligible Age

50 Years

Maximum Eligible Age

79 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

Yes

Sponsors

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The Affiliated Nanjing Drum Tower Hospital of Nanjing University Medical School

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Locations

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Nanjing Drum Tower Hospital

Nanjing, Jiangsu, China

Site Status RECRUITING

Countries

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China

Facility Contacts

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Bing Zhang, PhD

Role: primary

15851803070

References

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Chen Q, Chen F, Long C, Zhu Y, Jiang Y, Zhu Z, Lu J, Zhang X, Nedelska Z, Hort J, Zhang B. Spatial navigation is associated with subcortical alterations and progression risk in subjective cognitive decline. Alzheimers Res Ther. 2023 Apr 25;15(1):86. doi: 10.1186/s13195-023-01233-6.

Reference Type BACKGROUND
PMID: 37098612 (View on PubMed)

Other Identifiers

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2023-341-01

Identifier Type: -

Identifier Source: org_study_id

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