Abstract Introduction The impact of menopausal hormone therapy (HT) on age‐associated Alzheimer's and neurodegenerative diseases (NDDs) remains unresolved. To determine the effect of HT, formulation, type, and duration on risk of NDDs, a retrospective analysis was performed using a 10‐year Humana claims dataset. Methods Study population included women aged 45 years or older with or without claim records of HT medications. Patients diagnosed with NDDs including Alzheimer's disease (AD), Parkinson's disease (PD), dementia, multiple sclerosis (MS), and amyotrophic lateral sclerosis (ALS) were identified. Relative risk (RR) ratios and 95% confidence intervals (CI) for combined NDDs, or AD, PD, dementia, MS, and ALS were determined. Cumulative hazard ratios were determined to investigate the association between HT and NDDs at different age groups. Results In 379,352 women with or without claim records of HT, use of HT was associated with significantly reduced risk for combined NDDs (RR 0.42, 95% CI 0.40–0.43, P 1 year) on combined NDDs, AD, PD, and dementia was greater compared to short‐term therapy (≤1 year). Discussion HT was associated with reduced risk of all NDDs including AD and dementia, with greater duration of therapy and natural steroid formulations associated with greater efficacy. These findings advance precision HT to prevent NDDs including AD.