Cognitive decline associated with pathological burden in primary age-related tauopathy

Primary age-related tauopathy (PART) is a neuropathological diagnosis characterized by tau neurofibrillary tangles (NFTs) in the absence of amyloid plaque pathology. Although most individuals over 50 years of age have evidence of NFTs, the clinical and cognitive consequences of PART are not known.

We evaluated 226 neuropathologically confirmed PART cases from the National Alzheimer's Coordinating Center database who participated in a total of 846 longitudinal neuropsychological assessments from the Alzheimer's Disease Center program's Uniform Data Set. Mixed-effects statistical models tested whether cognitive decline was associated with Braak stage NFT burden.

Higher stages of NFT burden in PART, with no evidence or minimal evidence of amyloid pathology, were associated with more rapid decline on tasks involving episodic and semantic memory along with tests of processing speed and attention.

We conclude that PART has cognitive consequences that should be considered in the context of emerging tau-targeted therapies in age-associated neurodegenerative diseases.