Alzheimer Disease, Late OnsetNCT06561906
Establish Diagnostic and Prognostic Models for Preclinical AD Patients Based on Multimodal MRI, Behavioral, Genetic, and Plasma Biomarkers
An observational study of Alzheimer Disease, Late Onset and Mild Cognitive Impairment, run by The Affiliated Nanjing Drum Tower Hospital of Nanjing University Medical School at 1 site in China.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 50 to 79 yearsHealthy volunteers can take part
- Conditions the study is for
- Alzheimer Disease, Late Onset, Mild Cognitive Impairment, Subjective Cognitive Decline
- What is being tested?
- Multimodal magnetic resonance imaging scanning, behavioral, genetic and plasma biomarker testing
- How many people
- 1,000 participants
- Where
- 1 siteChina
- Study dates
- 1 Sep 2020to Dec 2027
- Phase
- Observational
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 50 to 79 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Study population: Chinese Han nationality
Who may be able to join
- The inclusion criteria were 50-79 years old and having 8 or more years of education.
Who cannot join
- 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.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
China1 site, 1 recruiting
- Recruiting
Nanjing Drum Tower Hospital
Nanjing, Jiangsu, 210008
Bing Zhang, PhD, 15851803070, zhangbing_nanjing@nju.edu.cn
Bing Zhang, PhD
About this study
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.
Read the 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.
- Being tested
- Multimodal magnetic resonance imaging scanning, behavioral, genetic and plasma biomarker testing
- Keywords
- magnetic resonance imaging, spatial navigation, olfaction, genetic, plasma biomarkers
- Medical subject headings
- Alzheimer Disease, Cognitive Dysfunction, Spatial Navigation, Anosmia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Multimodal magnetic resonance imaging scanning, behavioral, genetic and plasma biomarker testingOther
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
| Study group | Role | What they receive |
|---|---|---|
| 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). Receives: Other: Multimodal magnetic resonance imaging scanning, behavioral, genetic and plasma biomarker testing | |
| 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). Receives: Other: Multimodal magnetic resonance imaging scanning, behavioral, genetic and plasma biomarker testing | |
| 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. Receives: Other: Multimodal magnetic resonance imaging scanning, behavioral, genetic and plasma biomarker testing | |
| Alzheimer's disease dementia | Patients are diagnosed as AD dementia by an experienced neurologist based on MMSE and CSF/PET biomarker evidence. Receives: Other: Multimodal magnetic resonance imaging scanning, behavioral, genetic and plasma biomarker testing |
What is being measured
The primary outcome is the main question the study is designed to answer.
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)
Measured: Baseline, Year 1, Year 2, Year 3
Secondary outcomes (1)
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.
Measured: Baseline
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted20 Aug 2024
- Study start1 Sep 2020
- Primary completionJul 2027 (estimated)
- Study completionDec 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Alzheimer Disease, Late OnsetStudies of the same condition, open and under way.
- More trials run by The Affiliated Nanjing Drum Tower Hospital of Nanjing University Medical SchoolThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Case-control
- Time perspective
- Prospective
- Enrolment
- 1,000 participants (estimated)
Sponsor and investigators
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06561906
- Sponsor's protocol ID
- 2023-341-01
- Status last verified
- Jun 2024
- First submitted
- 16 Aug 2024
- Last updated
- 20 Aug 2024
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided: 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.
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.
PubMed 37098612
Study at a glance
From the registry record, last updated by the sponsor on 20 Aug 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Establish Diagnostic and Prognostic Models for Preclinical AD Patients Based on Multimodal MRI, Behavioral, Genetic, and Plasma Biomarkers
- ClinicalTrials.gov ID
- NCT06561906
- Acronym / sponsor ID
- 2023-341-01
- Keywords
- magnetic resonance imaging, spatial navigation, olfaction, genetic, plasma biomarkers
- Study type
- Observational
- Recruitment status
- Recruiting
- Enrolment
- 1,000 participants (estimated)
- Lead sponsor
- The Affiliated Nanjing Drum Tower Hospital of Nanjing University Medical SchoolUniversity, hospital or other
- Study start
- 1 Sep 2020 (actual)
- Primary completion
- Jul 2027 (estimated)
- Study completion
- Dec 2027 (estimated)
- First posted
- 20 Aug 2024 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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
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 design
- Observational model
- Case-control
- Time perspective
- Prospective
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| Normal control | – | Other: Multimodal magnetic resonance imaging scanning, behavioral, genetic and plasma biomarker testingSubjects without memory complaints and associated worries and do not meet the diagnostic criteria for mild cognitive impairment (MCI) are recruited as normal control (NC). |
| Subjective cognitive decline | – | Other: Multimodal magnetic resonance imaging scanning, behavioral, genetic and plasma biomarker testingSubjects 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). |
| Mild cognitive impairment | – | Other: Multimodal magnetic resonance imaging scanning, behavioral, genetic and plasma biomarker testingParticipants 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. |
| Alzheimer's disease dementia | – | Other: Multimodal magnetic resonance imaging scanning, behavioral, genetic and plasma biomarker testingPatients are diagnosed as AD dementia by an experienced neurologist based on MMSE and CSF/PET biomarker evidence. |
Who may qualify
- Ages
- 50 to 79 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
- Study population
- Chinese Han nationality
Key inclusion criteria (1 listed)
- The inclusion criteria were 50-79 years old and having 8 or more years of education.
Key exclusion criteria (1 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Multimodal magnetic resonance imaging scanning, behavioral, genetic and plasma biomarker testingMultimodal 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 | Other | Alzheimer's disease dementia, Mild cognitive impairment, Normal control, Subjective cognitive decline |
Primary outcome
the area under the curve of the classification analysis between progressors and nonprogressors
Time frame: Baseline, Year 1, Year 2, Year 3
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)
1 secondary outcome
mediation effects of MRI on the associations between gene/plasma biomarker and cognition/behavior
Time frame: Baseline
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 20 Aug 2024.
- Background: PubMed 37098612Chen 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.
- Individual participant dataSharing planned: Undecided. 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Alzheimer Disease, Late Onset and Mild Cognitive Impairment, run by The Affiliated Nanjing Drum Tower Hospital of Nanjing University Medical School at 1 site in China.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 1 inclusion and 1 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 20 Aug 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in China. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Each site lists its own contact: choose the nearest one under Trial locations. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
the area under the curve of the classification analysis between progressors and nonprogressors (time frame: Baseline, Year 1, Year 2, Year 3). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT06561906, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 20 Aug 2024.