The Nun Study is an iconic longitudinal study of aging and dementia on a cohort of 678 Catholic nuns from the School Sisters of Notre Dame. Participants consented to undergoing annual neuropsychological assessments, allowing researchers access to convent archives and medical records and post mortem brain donation. This study investigated the associations between epidemiological factors, cognitive function, and brain pathology. By examining published literature that reports on or utilizes Nun Study data, we provide an overview of its methodology and key findings, emphasizing its significant contributions to understanding cognitive impairment and related neuropathologies. Seminal findings on early-life factors affecting cognitive health, clinicopathological correlations, and apparent resistance and resilience to neuropathology are discussed. Decades of Nun Study research have made critical contributions to our understanding of Alzheimer's disease and related dementias and highlight continuing objectives for future research. HIGHLIGHTS: The uniform lifestyles of participants minimized potential confounds of the study. Early-life cognitive ability influenced late-life cognitive outcomes. Some participants with AD pathology did not exhibit dementia. Neuropathological comorbidities were common and increased the risk of dementia.