Cognitive impairment in progressive supranuclear palsy is associated with tau burden

Shunsuke Koga, Adam Parks, Koji Kasanuki, Monica Sanchez-Contreras, Matthew C. Baker, Keith Anthony Josephs, J. Eric Ahlskog, Ryan J. Uitti, Neill R Graff Radford, Jay A Van Gerpen, Zbigniew K Wszolek, Rosa V Rademakers, Dennis W Dickson

Research output: Contribution to journalArticle

8 Citations (Scopus)

Abstract

Cognitive impairment is one of the core features of progressive supranuclear palsy. This study aimed to clarify the profile of cognitive impairment and its underlying pathology in progressive supranuclear palsy. We retrospectively reviewed medical records to evaluate the pattern and severity of cognitive impairment in 121 autopsy-confirmed progressive supranuclear palsy patients. A subset of 37 patients underwent neuropsychological evaluation as part of their clinical workup. The burden of progressive supranuclear palsy-related tau pathology (neurofibrillary tangles/pretangles, coiled bodies, tufted astrocytes, and threads) was semiquantitatively scored in 20 vulnerable brain regions. Concurrent pathologies potentially associated with cognitive impairment, such as Alzheimer's-type pathology, were also assessed. To evaluate possible genetic risk factors for cognitive impairment, genetic analysis for APOE and MAPT was performed. Ninety patients (74%) had documented cognitive impairment based on neurologic evaluation. In a subgroup with neuropsychological testing (n = 37), executive functioning was the most severely impaired cognitive domain. A global cognitive impairment index (Spearman's rho, -0.49; P = 0.005) and executive functioning were negatively correlated with total tau burden (Spearman's rho, -0.51; P = 0.003), but not correlated with the Alzheimer's-type pathology. APOE ?4 carriers had more severe amyloid pathology, but total tau burden and a global cognitive impairment index did not differ from APOE ?4 noncarriers. Cognitive impairment in progressive supranuclear palsy, most notably executive dysfunction, is associated with severity of progressive supranuclear palsy-related tau pathology.

Original languageEnglish (US)
JournalMovement Disorders
DOIs
StateAccepted/In press - 2017

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Progressive Supranuclear Palsy
Pathology
Coiled Bodies
Cognitive Dysfunction
Neurofibrillary Tangles
Amyloid
Astrocytes
Nervous System
Medical Records
Autopsy

ASJC Scopus subject areas

  • Neurology
  • Clinical Neurology

Cite this

Cognitive impairment in progressive supranuclear palsy is associated with tau burden. / Koga, Shunsuke; Parks, Adam; Kasanuki, Koji; Sanchez-Contreras, Monica; Baker, Matthew C.; Josephs, Keith Anthony; Ahlskog, J. Eric; Uitti, Ryan J.; Graff Radford, Neill R; Van Gerpen, Jay A; Wszolek, Zbigniew K; Rademakers, Rosa V; Dickson, Dennis W.

In: Movement Disorders, 2017.

Research output: Contribution to journalArticle

Koga, Shunsuke ; Parks, Adam ; Kasanuki, Koji ; Sanchez-Contreras, Monica ; Baker, Matthew C. ; Josephs, Keith Anthony ; Ahlskog, J. Eric ; Uitti, Ryan J. ; Graff Radford, Neill R ; Van Gerpen, Jay A ; Wszolek, Zbigniew K ; Rademakers, Rosa V ; Dickson, Dennis W. / Cognitive impairment in progressive supranuclear palsy is associated with tau burden. In: Movement Disorders. 2017.
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