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.

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.

Please see https://docs.google.com/spreadsheets/d/1j53\_NBnEVQik4Ps5a9pZOvuHm1mWHCRZ3DAvI0y8NO8/edit?usp=sharing or Appendix A (https://drive.google.com/file/d/1uC\_G8TJ1ujoJbas1p1gFaYFzY7Hw7xMq/view?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. No prior use of Salbutamol and Long-acting Muscarinic Antagonists (LAMA) anytime prior to cohort entry date
• 3. Enrollment in Medicare Part A, B, and D with no HMO coverage for 365 days prior to and including cohort entry date
• 4. At least two claims with COPD 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 in the 365 days prior to the cohort entry date

This study will employ a new user, active comparator, observational cohort study design comparing Salbutamol versus Long-acting muscarinic antagonists (LAMAs). 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).