Cognitive trajectory in mild cognitive impairment due to primary age-related tauopathy

Merilee Teylan, Charles Mock, Kathryn Gauthreaux, Yen Chi Chen, Kwun C.G. Chan, Jason Hassenstab, Lilah M. Besser, Walter A. Kukull, John F. Crary

Research output: Contribution to journalArticlepeer-review

32 Scopus citations


Primary age-related tauopathy is increasingly recognized as a separate neuropathological entity different from Alzheimer’s disease. Both share the neuropathological features of tau aggregates and neuronal loss in the temporal lobe, but primary age-related tauopathy lacks the requisite amyloid plaques central to Alzheimer’s disease. While both have similar clinical presentations, individuals with symptomatic primary age-related tauopathy are commonly of more advanced ages with milder cognitive dysfunction. Direct comparison of the neuropsychological trajectories of primary age-related tauopathy and Alzheimer’s disease has not been thoroughly evaluated and thus, our objective was to determine how cognitive decline differs longitudinally between these two conditions after the onset of clinical symptoms. Data were obtained from the National Alzheimer’s Coordinating Center on participants with mild cognitive impairment at baseline and either no neuritic plaques (i.e. primary age-related tauopathy) or moderate to frequent neuritic plaques (i.e. Alzheimer neuropathological change) at subsequent autopsy. For patients with Alzheimer’s disease and primary age-related tauopathy, we compared rates of decline in the sum of boxes score from the CDRÕ Dementia Staging Instrument and in five cognitive domains (episodic memory, attention/working memory, executive function, language/semantic memory, and global composite) using z-scores for neuropsychological tests that were calculated based on scores for participants with normal cognition. The differences in rates of change were tested using linear mixed-effects models accounting for clinical centre clustering and repeated measures by individual. Models were adjusted for sex, age, education, baseline test score, Braak stage, apolipoprotein e4 (APOE e4) carrier status, family history of cognitive impairment, and history of stroke, hypertension, or diabetes. We identified 578 participants with a global CDR of 0.5 (i.e. mild cognitive impairment) at baseline, 126 with primary age-related tauopathy and 452 with Alzheimer’s disease. Examining the difference in rates of change in CDR sum of boxes and in all domain scores, participants with Alzheimer’s disease had a significantly steeper decline after becoming clinically symptomatic than those with primary age-related tauopathy. This remained true after adjusting for covariates. The results of this analysis corroborate previous studies showing that primary age-related tauopathy has slower cognitive decline than Alzheimer’s disease across multiple neuropsychological domains, thus adding to the understanding of the neuropsychological burden in primary age-related tauopathy. The study provides further evidence to support the hypothesis that primary age-related tauopathy has distinct neuropathological and clinical features compared to Alzheimer’s disease.

Original languageEnglish
Pages (from-to)611-621
Number of pages11
Issue number2
StatePublished - 1 Feb 2020


  • Alzheimer’s disease
  • Cognitive decline
  • Neuropathology
  • Neuropsychology
  • Primary age-related tauopathy


Dive into the research topics of 'Cognitive trajectory in mild cognitive impairment due to primary age-related tauopathy'. Together they form a unique fingerprint.

Cite this