KEEPS Continuation: Long-term effects of menopausal hormone therapy on AD biomarkers

Clinical Score: 0.950 Price: $0.50 Alzheimer's disease recently menopausal women with good cardiovascular health Status: proposed

What This Experiment Tests

Clinical experiment designed to assess clinical efficacy targeting APOE in recently menopausal women with good cardiovascular health. Primary outcome: Amyloid beta burden on PET, hippocampal atrophy, and dorsolateral prefrontal cortex thickness on MRI

Description

This is a follow-up study to the Kronos Early Estrogen Prevention Study (KEEPS) that investigated the long-term effects of short-term menopausal hormone therapy on Alzheimer's disease biomarkers. The original KEEPS trial randomized recently menopausal women with good cardiovascular health to receive either oral conjugated equine estrogens (oCEE), transdermal 17β-estradiol (tE2) with micronized progesterone, or placebo for 4 years. Ten years after completion of the original trial, participants were reassessed using amyloid beta PET imaging, structural MRI to measure hippocampal atrophy and dorsolateral prefrontal cortex thickness. The study aimed to determine whether previous exposure to hormone therapy had any lasting effects on brain health and AD pathophysiology. The researchers also examined whether apolipoprotein E ε4 carrier status modified any observed effects. This represents one of the first long-term follow-up studies of a hormone therapy clinical trial using advanced neuroimaging biomarkers for Alzheimer's disease.

TARGET GENE
MODEL SYSTEM
recently menopausal women with good cardiovascular health
ESTIMATED COST
$0
TIMELINE
0 months
PATHWAY
amyloid beta metabolism, neurodegeneration
SOURCE
extracted_from_pmid_41618732
PRIMARY OUTCOME
Amyloid beta burden on PET, hippocampal atrophy, and dorsolateral prefrontal cortex thickness on MRI

Scoring Dimensions

Info Gain 0.00 (25%) Feasibility 0.00 (20%) Hyp Coverage 0.00 (20%) Cost Effect. 0.00 (15%) Novelty 0.00 (10%) Ethical Safety 0.00 (10%) 0.950 composite

📖 Wiki Pages

apoe-genotype-guided-preventiontherapeuticApoE (Apolipoprotein E)proteinAPOE Lipid Metabolism Pathway in Alzheimer's DiseamechanismAPOE Lipid Dysregulation Causal Chain in ADmechanismAPOE contributes to Alzheimer's disease by regulathypothesisAPOE contributes to Alzheimer's disease by regulathypothesisAPOE — Apolipoprotein EgeneAPOE Genotyping for Neurodegenerative Disease RiskdiagnosticAPOE-Expressing AstrocytescellPET Imaging for Neurodegenerative DiseasestechnologyMRI for Neurodegenerative DiseasestechnologyPET Imaging Combined with Fluid BiomarkerseventPET Imaging in NeurodegenerationdiagnosticMRI and Imaging Findings in Corticobasal SyndromediagnosticMRI Atrophy Patterns in CBS/PSPbiomarker

Protocol

Participants from the original KEEPS trial were recontacted 10 years after completion. Amyloid beta burden was assessed using positron emission tomography. Structural MRI was performed to measure hippocampal atrophy and dorsolateral prefrontal cortex thickness. APOE ε4 genotyping was performed to assess genetic modifying effects.

Expected Outcomes

The study hypothesized that imaging biomarkers would reveal early detection of evolving brain pathology if hormone therapy had long-term effects on AD risk

Success Criteria

Differences in amyloid beta burden and structural MRI biomarkers between hormone therapy groups and placebo

Related Hypotheses (5)

APOE4-Specific Lipidation Enhancement Therapy0.889
Prime Editing Precision Correction of APOE4 to APOE3 in Microglia0.641
Selective APOE4 Degradation via Proteolysis Targeting Chimeras (PROTACs)0.595
Competitive APOE4 Domain Stabilization Peptides0.561
APOE4 Isoform Correction via Lipidation Enhancement as CTE Risk Mitigation0.552

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