Data Analysis for Drug Repurposing for Effective Alzheimer's Medicines (DREAM)- Anastrozole vs Exemestane/Letrozole

This study aims to evaluate the comparative risk of dementia/Alzheimer's disease onset between patients treated with medications that target specific metabolic pathways and patients treated with alternative medications for the same indication.

Study Overview

• Status: Completed
• Conditions: Breast Cancer
• Intervention / Treatment: Drug: Anastrozole; Drug: Exemestane/Letrozole

Detailed Description

This is a non-randomized, non-interventional study that is part of the DREAM Study of Brigham and Women's Hospital. DREAM is led by Dr. Madhav Thambisetty, MD, PhD, Chief of the Clinical and Translational Neuroscience Section, Laboratory of Behavioral Neuroscience, National Institute on Aging (NIA) intramural research program. This study aims to evaluate the comparative risk of dementia/Alzheimer's disease onset between patients treated with medications that target specific metabolic pathways and patients treated with alternative medications for the same indication using healthcare claims data.

• Study Type: Observational
• Enrollment (Actual): 16989

Contacts and Locations

Study Locations

• United States
  • Massachusetts
    • Boston, Massachusetts, United States, 02120
      • Brigham and Women's Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 65 years and older (Older Adult)
• Accepts Healthy Volunteers: Yes

• Sampling Method: Non-Probability Sample

Study Population

This study will employ a new user, active comparator, observational cohort study design comparing Anastrozole vs Exemestane/Letrozole. The patients will be required to have continuous enrollment during the baseline period of 365 days before initiation of study drugs (cohort entry/index date). Follow-up for the outcome (dementia) differs between analyses. Follow-up begins the day after drug initiation (analysis 1, 3, 4); 180 days after drug initiation (analysis 2).

Description

Please see https://docs.google.com/spreadsheets/d/1GrnVsPCockqqdfxC9LWd6ndbzS2wpJVvTbCOAhn4DLM/edit?usp=sharing or Appendix A (https://drive.google.com/drive/folders/1I8FVmpPzC5wQN9DFIv1Rbwh1N0SLEv0B?usp=sharing) for full code and algorithm definitions.

Medicare timeframe: 2008 to 2018 (end of data availability)

Inclusion Criteria:

• 1. Aged >/= 65 years on the index date
• 2. Enrollment in Medicare Part A, B, and D with no HMO coverage for 365 days prior to and including cohort entry date
• 3. At least two claims with breast cancer diagnosis measured 365 days prior to drug initiation

Exclusion Criteria:

• 1. Prior history of dementia measured anytime prior to cohort entry date
• 2. Prior history of nursing home admission anytime prior to cohort entry date
• 3. Prior history of Anastrozole or Exemestane/Letrozole use anytime prior to cohort entry date

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Retrospective

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Anastrozole; Exposure group	Drug: Anastrozole; Anastrozole claim is used as the exposure group.
Exemestane/Letrozole; Reference group	Drug: Exemestane/Letrozole; Exemestane/Letrozole claim is used as the reference group.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time to dementia onset	Time to dementia onset, i.e., Alzheimer's disease, vascular dementia, senile, presenile, or unspecified dementia, or dementia in other diseases classified elsewhere. Please refer to uploaded protocol for full definition due to size limitations.	up to 6 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time to Alzheimer's disease onset	Time to Alzheimer's disease onset. Please refer to uploaded protocol for full definition due to size limitations.	up to 6 years

Collaborators and Investigators

• Sponsor: Brigham and Women's Hospital
• Collaborators: Johns Hopkins University; National Institute on Aging (NIA); Rutgers University
• Investigators: Principal Investigator: Madhav Thambisetty, MD, PhD, National Institute on Aging (NIA)

Study record dates

Study Major Dates

• Study Start (Actual): November 1, 2022
• Primary Completion (Actual): June 30, 2023
• Study Completion (Actual): December 31, 2023

Study Registration Dates

• First Submitted: November 21, 2022
• First Submitted That Met QC Criteria: December 1, 2022
• First Posted (Actual): December 2, 2022

Study Record Updates

• Last Update Posted (Actual): July 28, 2025
• Last Update Submitted That Met QC Criteria: July 25, 2025
• Last Verified: July 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Antineoplastic Agents; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Hormones, Hormone Substitutes, and Hormone Antagonists; Antineoplastic Agents, Hormonal; Enzyme Inhibitors; Steroid Synthesis Inhibitors; Hormone Antagonists; Estrogen Antagonists; Aromatase Inhibitors; Letrozole; Anastrozole; Exemestane
• Other Study ID Numbers: 2019P003607-11

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No