Alzheimer Disease
Conditions
Keywords
Alzheimer Disease
Brief summary
The goal of this observational study is to learn about the efficacy of Lecanemab treatment for early-onset familial Alzheimer's disease (AD) in patients under 65 years of age with a family history of AD. Participants will receive Lecanemab at a dosage of 10 mg/kg every two weeks for a total of 18 months and will undergo cognitive assessments, PET and MRI scans, blood/fluid tests and whole genome sequencing. The study will explore the effects of genetic and hereditary factors on the efficacy of Lecanemab treatment in early-onset familial AD patients.
Interventions
None listed
Sponsors
RenJi Hospital
Study design
Observational model
COHORT
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Inclusion criteria
* Age at onset ≤ 65 years, with a minimum age of 18 years; no restriction on gender. * Diagnosis of Alzheimer's Disease (AD) and Mild Cognitive Impairment (MCI): Must meet the clinical diagnostic criteria for AD-related MCI and mild AD as defined by the National Institute on Aging and the Alzheimer's Association (NIA-AA) (2011); confirmed Aβ positivity through Aβ-PET/CT, Aβ-PET/MRI, or cerebrospinal fluid testing. * MMSE ≥ 21 or MoCA ≥ 17 or CDR = 0.5 * No significant signs found in the neurological examination * Participants must be capable of completing cognitive assessments and other tests. * Informed consent must be obtained from the participants and their legal guardians, with a dated signature, prior to any operations or tests related to the protocol, committing to comply with the research procedures and cooperate throughout the study process.
Exclusion criteria
* Cognitive decline caused by other reasons: cerebrovascular disease, central nervous system infections, Creutzfeldt-Jakob disease, Huntington's disease, Parkinson's disease, Lewy body dementia, traumatic dementia, other physical and chemical factors (drugs, alcohol, CO, etc.), significant systemic diseases (hepatic encephalopathy, pulmonary encephalopathy, etc.), intracranial space-occupying lesions (subdural hematoma, brain tumor), endocrine system disorders (thyroid disease, parathyroid disease), and dementia caused by vitamin deficiencies or any other reasons. * Patients with other unstable diseases, or those who have had a stroke or transient ischemic attack, bleeding disorders, or seizures within the previous 12 months. * Patients with psychiatric disorders who meet DSM-IV criteria for schizophrenia or other mental illnesses, bipolar disorder, major depression, or delirium. * Patients with unstable or severe heart, lung, liver, kidney, hematological diseases; those with known malignancies or other serious prognoses. * Exclusion of cerebral amyloid angiopathy-related inflammation/β-amyloid-related cerebral vasculitis (CAAri/ABRA). * Presence of uncorrectable visual or auditory impairments that prevent completion of relevant assessments or scales. * Patients who cannot undergo MRI due to claustrophobia, pacemakers, defibrillators, or metal implants. * MRI findings showing more than four microhemorrhages (diameter \< 10 mm), evidence of surface iron deposition, vascular edema, diffuse white matter disease, multiple lacunar strokes, or any strokes involving major vascular regions. Presence of evidence of cerebral contusions, brain softening, cerebral aneurysms, or other vascular malformations, central nervous system (CNS) infections, as well as brain tumors other than meningiomas or arachnoid cysts. * Patients taking warfarin, vitamin K antagonists, or direct oral anticoagulants (dabigatran, rivaroxaban, edoxaban, apixaban, betrixaban) or heparin; patients receiving thrombolysis; patients with coagulation disorders. * Pregnant or lactating women. * Patients deemed unsuitable for use by clinicians apart from the
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Chang of CDR-SB score | baseline, 9 month, 18 month | CDR-SB, clinical dementia rating-sum of boxes |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change of ADAS-cog score | baseline, 9 month, 18 month | ADAS-cog, the Alzheimer's Disease Assessment Scale-Cognitive Subscale |
| Change of ADCS-ADL score | baseline, 9 month, 18 month | ADCS-ADL, the Alzheimer's Disease Cooperative Study - Activities of Daily Living Scale (ADCS-ADL) |
| Change of MoCA score | baseline, 9 month, 18 month | MoCA, the Montreal Cognitive Assessment |
| Change of BNT score | baseline, 9 month, 18 month | BNT, the Boston Naming Test |
| Change of TMT score | baseline, 9 month, 18 month | TMT, the trail making test |
| Change of HAMA and HAMD score | baseline, 9 month, 18 month | HAMA, Hamilton Anxiety Scale; HAMD, Hamilton Depression Scale |
| Change of biomarkers | baseline, 9 month, 18 month | p-tau181, p-tau217, Aβ40, Aβ42 , pEAβ3-42, GFAP, NFL, TRPC6 ( blood, urine, feces, gingival crevicular fluid, cerebrospinal fluid) |
| Change of amyloid burden | baseline, 9 month, 18 month | AV45-PET |
| Change of structural MRI | baseline, 9 month, 18 month | 3D T1-weighted, 3D T2-weighted and Diffusion Tensor Imaging (DTI) |
| Change of functional MRI | baseline, 9 month, 18 month | Blood oxygenation level dependent (BOLD) imaging |
| Change of magnetic susceptibility | baseline, 9 month, 18 month | Quantitative susceptibility mapping (QSM) imaging |
| Change of perfusion imaging | baseline, 9 month, 18 month | Arterial spin labeling (ASL) imaging |
| Whole Genome Sequencing | baseline | — |
| Change of speech information | baseline, 9 month, 18 month | Speech recording of Cookie-theft description task, using self-developed ASR speech analysis software (China software copyright number: 2016RS164680) for speech analysis |
| Positron emission tomography (PET) | baseline, 9 month, 18 month | Other PET including FDG-PET, Tau-PET, TSPO-PET, SV2A-PET, exendin-4 (GLP-1R)-PET, colinergic receptor probe (ASEM) PET |
Countries
China
Contacts
Primary ContactJinwen Xiao
Outcome results
None listed