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

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.

Study Overview

• Status: Recruiting
• Conditions: Mild Cognitive Impairment; Alzheimer Disease, Late Onset; Subjective Cognitive Decline
• Intervention / Treatment: Other: Multimodal magnetic resonance imaging scanning, behavioral, genetic and plasma biomarker testing

Detailed Description

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.

• Study Type: Observational
• Enrollment (Estimated): 1000

Contacts and Locations

Study Locations

• China
  • Jiangsu
    • Nanjing, Jiangsu, China, 210008
      • Recruiting
      • Nanjing Drum Tower Hospital
      • Principal Investigator: Bing Zhang, PhD
      • Contact: Bing Zhang, PhD; Phone Number: 15851803070; Email: zhangbing_nanjing@nju.edu.cn
      • Sub-Investigator: Qian Chen, PhD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: Yes

• Sampling Method: Non-Probability Sample

Study Population

Chinese Han nationality

Description

Inclusion Criteria:

• The inclusion criteria were 50-79 years old and having 8 or more years of education.

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.

Study Plan

How is the study designed?

Number of groups / cohorts

4

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
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).	Other: 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
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).	Other: 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
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.	Other: 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
Alzheimer's disease dementia; Patients are diagnosed as AD dementia by an experienced neurologist based on MMSE and CSF/PET biomarker evidence.	Other: 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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
the area under the curve of the classification analysis between progressors and nonprogressors	We'll measure the area under the curve of the ROC curves based on combined features of baseline demographic, cognitive, behavioral, multimodal MRI, genetic, and plasma data in discriminating those convert to MCI or AD (progressors) from those do not convert (nonprogressors)	Baseline, Year 1, Year 2, Year 3

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
mediation effects of MRI on the associations between gene/plasma biomarker and cognition/behavior	We'll explore whether MRI features could act as mediators between genetic factors and cognition or behavior, as well as between plasma biomarkers and cognition or behavior.	Baseline

Collaborators and Investigators

• Sponsor: The Affiliated Nanjing Drum Tower Hospital of Nanjing University Medical School

Publications and helpful links

General Publications

• 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.

Study record dates

Study Major Dates

• Study Start (Actual): September 1, 2020
• Primary Completion (Estimated): July 1, 2027
• Study Completion (Estimated): December 1, 2027

Study Registration Dates

• First Submitted: August 16, 2024
• First Submitted That Met QC Criteria: August 16, 2024
• First Posted (Actual): August 20, 2024

Study Record Updates

• Last Update Posted (Actual): August 20, 2024
• Last Update Submitted That Met QC Criteria: August 16, 2024
• Last Verified: June 1, 2024

More Information

Terms related to this study

• Keywords: magnetic resonance imaging; genetic; olfaction; spatial navigation; plasma biomarkers
• Additional Relevant MeSH Terms: Mental Disorders; Pathologic Processes; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neurocognitive Disorders; Disease Attributes; Neurodegenerative Diseases; Dementia; Tauopathies; Cognition Disorders; Alzheimer Disease; Cognitive Dysfunction; Late Onset Disorders
• Other Study ID Numbers: 2023-341-01

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED
• IPD Plan Description: Due to the clinical nature of the data, the data that support the findings of this study are not freely available but can be made available by the corresponding author, upon reasonable request. A formal data-sharing agreement is needed before any data can be shared.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No