Alzheimer’s Disease Concurrent With Patent Foramen Ovale-Related Lacunar Infarcts and Extensive White Matter Hyperintensities: A Case Highlighting Biomarker-Clinical Staging Discordance

An elderly man with progressive memory decline met the 2024 National Institute on Aging and the Alzheimer's Association (NIA-AA) biological criteria for Alzheimer's disease (AD) - classified as stage C biologically but mild dementia clinically - revealing a clear staging mismatch. Recognizing this discordance led us to investigate additional comorbidities. He was found to have extensive white matter hyperintensities (WMHs) (Fazekas grade 3) and experienced multiple recurrent lacunar infarcts. Subsequent evaluation identified a patent foramen ovale (PFO) causing right-to-left shunting and paradoxical embolism. This case underscores the necessity of detecting biological-clinical discordance in AD, actively screening for cerebrovascular comorbidities such as WMHs and infarcts, and accurately identifying underlying causes to optimize patient management and enrich AD clinical research.