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| Name | Class |
|---|---|
| The Swedish Research Council | OTHER_GOV |
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The main purpose of this project is to establish whether changes in brain connectivity can be used to predict the development of Alzheimer's disease (AD).
To achieve this aim, the investigators will perform six different studies that have been designed to achieve the following specific objectives:
1.1. Identify changes of brain connectivity in individuals who show abnormal AD amyloid biomarkers in the cerebrospinal fluid and blood.
1.2. To assess the correlation between brain connectivity changes and biomarkers of synaptic dysfunction and inflammation as well as alterations of electrical brain signals.
1.3. Establish whether alterations of brain connectivity could be improved after patients start treatment with cholinesterase inhibitors.
1.4. Assess differences in brain connectivity between patients receiving treatment with statins and those not taking this medication.
1.5. Determine whether brain connectivity changes can predict longitudinal cognitive decline and conversion to AD dementia.
1.6. Assess whether different microorganisms can grow more rapidly in the cerebrospinal fluid from AD patients compared to controls and whether their levels are associated with brain connectivity.
1.7. Evaluate the relationship between brain connectivity and the integrity of the locus coeruleus, which is the earliest site of AD pathology
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| SCI normal | Subjects with subjective cognitive impairment with normal amyloid levels. |
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| SCI abnormal | Subjects with subjective cognitive impairment with low amyloid levels. |
| |
| MCI abnormal | Subjects with mild cognitive impairment with low amyloid levels. |
| |
| AD abnormal | Subjects with Alzheimer's disease with low amyloid levels. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Neuroimaging | Other | The investigators will collect imaging sequence, cognitive test scores, clinical data and biofluid samples |
|
| Measure | Description | Time Frame |
|---|---|---|
| Brain connectivity can predict the development of Alzheimer's disease | The investigators will build a multilayer network for each patient using DWI and fMRI images, following a methodology similar to that described in Multiplex Connectome Changes Across the Alzheimer's Disease Spectrum Using Gray Matter and Amyloid Data. Specifically, each patient's brain connectivity will be modeled as a multiplex network, where distinct imaging modalities define different layers. The structural connectivity layer will be derived from diffusion-weighted imaging (DWI), capturing white matter fiber tract connections between brain regions. The functional connectivity layer will be built using functional MRI (fMRI), measuring temporal correlations of neural activity across regions. Nodes in the network will correspond to anatomically defined brain regions, and inter-layer edges will be established to link homologous regions across layers, enabling integration of structural and functional information. | 4 years |
| Measure | Description | Time Frame |
|---|---|---|
| Relationship between multilayer connectivity and other imaging sequences, cognition and biofluid biomarkers | The investigators will measure the association between multilayer brain connectivity with biomarkers and clinical measures from the participants, including markers of amyloid, tau, vascular pathology and tests measuring memory, executive function, language and visuospatial skills. These analyses will be conducted using linear regression and linear mixed effects models for longitudinal outcomes. |
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Inclusion Criteria:
Inclusion criteria for subjects with subjective cognitive complaints:
Inclusion criteria for patients with mild cognitive impairment:
Specific inclusion criteria for patients with Alzheimer's disease:
Exclusion Criteria:
In addition, participants who have claustrophobia or some form of metal implant in their body that may interfere with the brain imaging scan will be excluded from the study.
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Subjects across the AD continuum
| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Joana B. Pereira, PhD | Contact | +46709966186 | joana.pereira@ki.se |
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| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Karolinska University Hospital | Recruiting | Stockholm | Solna | 171 64 | Sweden |
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| ID | Term |
|---|---|
| D000544 | Alzheimer Disease |
| ID | Term |
|---|---|
| D003704 | Dementia |
| D001927 | Brain Diseases |
| D002493 | Central Nervous System Diseases |
| D009422 | Nervous System Diseases |
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| ID | Term |
|---|---|
| D059906 | Neuroimaging |
| D000073216 | Mental Status and Dementia Tests |
| ID | Term |
|---|---|
| D003952 | Diagnostic Imaging |
| D019937 | Diagnostic Techniques and Procedures |
| D003933 | Diagnosis |
| D003943 | Diagnostic Techniques, Neurological |
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Cerebrospinal fluid and blood plasma.
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| 4 years |
| D024801 |
| Tauopathies |
| D019636 | Neurodegenerative Diseases |
| D019965 | Neurocognitive Disorders |
| D001523 | Mental Disorders |
| D008919 | Investigative Techniques |
| D009483 | Neuropsychological Tests |
| D011581 | Psychological Tests |
| D004191 | Behavioral Disciplines and Activities |