Clinical diagnoses among individuals with primary age-related tauopathy versus Alzheimer’s neuropathology

Primary age-related tauopathy (PART) is increasingly recognized as a pathologic entity distinct from Alzheimer’s disease (AD). Given that the diagnosis of PART is an autopsy diagnosis, it is unclear how PART is perceived in clinical practice. Thus, we investigated the presumptive primary and contributing diagnoses in individuals who had cognitive impairment while alive and who met neuropathologic criteria for PART at autopsy. We also compared these clinical diagnoses for people with PART to those with AD neuropathology (ADNP). We used data on 1,354 participants from the National Alzheimer’s Coordinating Center, restricting to those with no neuritic plaques (PART) or moderate/frequent neuritic plaques (ADNP); clinical visit within two years of autopsy; and mild cognitive impairment (MCI) or dementia at last visit. To assess if PART participants were less likely to receive a clinical diagnosis of AD at their last visit prior to autopsy, we used logistic regression, controlling for age, sex, education, and APOE ε4 status. There were 161 PART individuals (n=49 MCI; n=112 dementia) and 1,193 individuals with ADNP (n=75 MCI; n=1,118 dementia). Primary clinical diagnosis of AD was more common in those with ADNP (MCI: 69%; demented: 86%) than PART (MCI: 57%; demented: 52%). In the adjusted analysis, primary and contributing clinical diagnoses of AD remained less likely in PART versus ADNP participants with dementia (OR: 0.22, 95% CI: 0.13–0.38). This study suggests that clinicians recognize a distinction in the clinical presentation between PART and ADNP, diagnosing AD less frequently in those with PART. Nonetheless, clinical AD was diagnosed greater than 50% of the time in PART participants with MCI or dementia. Ante-mortem criteria for diagnosis of PART need to be established, as PART is a neuropathological entity that is distinct from AD and has its own clinical and cognitive outcomes.