Prospective Cohort Study of Patients With Early Alzheimer's Disease Treated With Lecanemab

Second Affiliated Hospital, School of Medicine, Zhejiang University120 enrolled

Overview

As the population increases and aging intensifies, cognitive disorders represented by Alzheimer's disease (AD) not only pose a severe threat to public health but also bring significant social and economic burdens. Previously, treatment options for Alzheimer's disease were very limited, mainly providing symptomatic relief with few available medications. Lecanemab, an FDA-approved clinical treatment drug in 2023, targets the core pathology of AD-abnormal amyloid-beta (Aβ) aggregation in the brain-and has been validated through both biomarker and clinical scale assessments. The optimal dosage and safety-efficacy profile of lecanemab for treating early AD have been observed in phase 2 and phase 3 clinical trials. However, the use of lecanemab may lead to certain adverse effects, including infusion-related reactions, amyloid-related imaging abnormalities (ARIA), such as microhemorrhages or hemosiderin deposits (ARIA-H), and ARIA-E. This study aims to establish a prospective follow-up cohort of patients treated with lecanemab to observe changes in cranial imaging characteristics and clinical symptoms, assess the cognitive improvement effects of lecanemab in early AD patients (stages 3-4), and monitor the risk factors for adverse event occurrence.

Study Type

OBSERVATIONAL

Enrollment

120

Conditions

Alzheimer Disease Mild Cognitive Impairment (MCI)

Interventions

Eligibility

Sex: ALLMax age: 85 Years

Medical Language ↔ Plain English

Inclusion Criteria: * Mini-Mental State Examination (MMSE) score between 22 and 30, Clinical Dementia Rating Scale Sum of Boxes (CDR-SB) score between 0.5 and 1; * Confirmation of positive amyloid pathology by Amyloid-PET or cerebrospinal fluid Aβ testing; * Completion of APOE gene testing. * Willingness to use Lecanemab. Exclusion Criteria: * Unable to tolerate MRI scans; * MRI showing hemorrhagic manifestations, including \>4 microbleeds, surface iron deposition in any region, previous major hemorrhage, or potential brain lesions or vascular malformations; * Use of anticoagulants or antiplatelet drugs, presence of hemorrhagic diseases, or any other conditions that increase the risk of central nervous system bleeding; * With unstable physical conditions, unstable mental disorders, or those who are pregnant or breastfeeding.

Outcomes

Primary Outcomes

CDR-SB Score

All study subjects underwent Clinical Dementia Rating Scale Sum of Boxes (CDR-SB) assessment by a specialist before the 1st dose (V1) and at 3, 6, 12, and 18 months after treatment (V7, V14, V25, V39). CDR-SB, with total scores ranging from 0 to 18, can be used to measure cognitive changes in the early stages of Alzheimer's disease, with higher scores indicating more severe symptoms.

Time frame: CDR-SB scales by baseline before the 1st dose(V1) and at 3, 6, 12, and 18 months after treatment (V7, V14, V25, V39)

MMSE

All study subjects underwent Mini Mental State Examination (MMSE) assessment by a specialist before the 1st dose (V1) and at 3, 6, 12, and 18 months after treatment (V7, V14, V25, V39). MMSE, with total scores ranging from 0 to 30, can be used to measure cognitive changes in the early stages of Alzheimer's disease, with lower scores indicating more severe symptoms.

Time frame: MMSE scales by baseline before the 1st dose(V1) and at 3, 6, 12, and 18 months after treatment (V7, V14, V25, V39)

ADCs-ADL

All study subjects underwent Alzheimer's Disease Cooperative Study-Activity of Daily Life (ADCs-ADL) assessment by a specialist before the 1st dose (V1) and at 3, 6, 12, and 18 months after treatment (V7, V14, V25, V39). CDR-SB, with total scores ranging from 0 to 78, can be used to measure activity of daily life changes in the early stages of Alzheimer's disease, with lower scores indicating more severe symptoms.

Time frame: ADCs-ADL scales by baseline before the 1st dose(V1) and at 3, 6, 12, and 18 months after treatment (V7, V14, V25, V39)

NPI

All study subjects underwent Neuropsychiatric Inventory (NPI) assessment by a specialist before the 1st dose (V1) and at 3, 6, 12, and 18 months after treatment (V7, V14, V25, V39). CDR-SB, with total scores ranging from 0 to 18, can be used to measure cognitive changes in the early stages of Alzheimer's disease, with higher scores indicating more severe symptoms.

Time frame: NPI scales by baseline before the 1st dose(V1) and at 3, 6, 12, and 18 months after treatment (V7, V14, V25, V39)

Secondary Outcomes

Aβ-PET Burden

All study subjects underwent Aβ positron emission tomography (PET) before the 1st dose (V1) ,at 12 and 18 months after treatment (V26,V39). The investigators quantified participants' Aβ burden using the average cortical standard uptake value ratio (SUVR), that is, tracer uptake in medial orbital frontal, lateral temporal, parietal, anterior cingulate, posterior cingulate, and precuneus regions divided by uptake in the cerebellar reference region.

Time frame: Aβ-PET tested by baseline before the 1st dose(V1) , at 12 and 18 months after treatment (V25,V39)

MRI

All study subjects underwent magnetic resonance imaging (MRI) before the 1st dose (V1) ,at 2, 3, 6,12 and 18 months after treatment. The scan includes T1, T2 fluid attenuated inversion recovery (FLAIR, 5 mm slice thickness), susceptibility weighted imaging (SWI, 1 mm slice thickness) and diffusion weighted imaging (DWI). The MRI scan can be used to meature the study subjects' hippocampus atrophy and white matter hyperintensities and to detect whether adverse events such as amyloid-related imaging abnormalities happen.

Time frame: Time Frame: MRI tested by baseline before the 1st dose(V1) , at 2, 3, 6, 12 and 18 months after treatment (V5, V7, V14, V25, V39)

Biospecimen

All study subjects underwent blood collection before the 1st dose (V1) and at 3, 6, 12, and 18 months after treatment (V7, V14, V25, V39) for routine blood tests, liver and kidney function, plasma biomarkers, and other indicators. Among them, the APOE genotype of subjects will be tested before the 1st dose.

Time frame: Blood tested by baseline before the 1st dose(V1) , at 3, 6,12 and 18 months after treatment(V7, V14, V25, V39)