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


METHODS
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.


RESULTS
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.


CONCLUSIONS
We conclude that PART has cognitive consequences that should be considered in the context of emerging tau-targeted therapies in age-associated neurodegenerative diseases.
Department of Neurology, University of Pennsylvania, Philadelphia, PA, USA.
Kyra S
KS
Jefferson-George
Department of Neurology, University of Pennsylvania, Philadelphia, PA, USA.
David A
DA
Wolk
Department of Pathology and Laboratory Medicine, University of Pennsylvania, Philadelphia, PA, USA.
Edward B
EB
Lee
Department of Neurology, University of Pennsylvania, Philadelphia, PA, USA. Electronic address: mcmillac@upenn.edu.
Corey T
CT
McMillan
D000368:Aged; D000369:Aged, 80 and over; D000375:Aging; D003072:Cognition Disorders / Q000209:etiology*; D016208:Databases, Factual / Q000706:statistics & numerical data; D018450:Disease Progression; D005260:Female; D006801:Humans; D008137:Longitudinal Studies; D008297:Male; D008609:Mental Status Schedule; D016874:Neurofibrillary Tangles / Q000473:pathology*; D009483:Neuropsychological Tests; D018709:Statistics, Nonparametric; D024801:Tauopathies / Q000150:complications*
Clinical prognosis; Cognition; Primary age-related tauopathy; Tau