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Multicenter Study
. 2017 Dec;32(12):1772-1779.
doi: 10.1002/mds.27198. Epub 2017 Oct 30.

Cognitive impairment in progressive supranuclear palsy is associated with tau burden

Shunsuke Koga  1 , Adam Parks  2 , Koji Kasanuki  1 , Monica Sanchez-Contreras  1 , Matthew C Baker  1 , Keith A Josephs  3 , J Eric Ahlskog  3 , Ryan J Uitti  4 , Neill Graff-Radford  4 , Jay A van Gerpen  4 , Zbigniew K Wszolek  4 , Rosa Rademakers  1 , Dennis W Dickson  1
Affiliations
Multicenter Study

Cognitive impairment in progressive supranuclear palsy is associated with tau burden

Shunsuke Koga et al. Mov Disord. 2017 Dec.

Abstract

Background: 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.

Methods: 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.

Results: 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 ɛ4 carriers had more severe amyloid pathology, but total tau burden and a global cognitive impairment index did not differ from APOE ɛ4 noncarriers.

Conclusion: Cognitive impairment in progressive supranuclear palsy, most notably executive dysfunction, is associated with severity of progressive supranuclear palsy-related tau pathology. © 2017 International Parkinson and Movement Disorder Society.

Keywords: Alzheimer's disease; neuropathology; neuropsychology; progressive supranuclear palsy; tau.

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Conflict of interest statement

Financial Disclosures of all authors

Dr. Koga reports no disclosures.

Dr. Parks reports no disclosures.

Dr. Kasanuki reports no disclosures.

Dr. Sanchez-Contreras reports no disclosures.

Mr. Matthew C. Baker reports no disclosures.

Dr. Josephs receives research support from the NIH (R01-DC010367, R01-DC012519 & R01-AG037491) and the Alzheimer’s Association. Dr. Josephs is an editorial board member of Acta Neuropathologica, Journal of Neurology and Parkinsonism and Related Disorders.

Dr. Ahlskog reports no disclosures.

Dr. Uitti receives research support by the NIH (P50-NS072187, and from Advanced Neuromodulation Systems, Inc./St. Jude Medical, Dr. Uitti is an Associate Editor of Neurology and an editorial board member of Parkinsonism & Related Disorders.

Dr. Graff-Radford reports no disclosures.

Dr. van Gerpen receives research funds from the Mayo Clinic CR program and NIH (P50-NS072187). This research received no specific grant from any funding agency in the public, commercial or not-for-profit sectors.

Dr. Wszolek is partially supported by the NIH/NINDS P50 NS072187, NIH/NIA (primary) and NIH/NINDS (secondary) 1U01AG045390-01A1, Mayo Clinic Center for Regenerative Medicine, Mayo Clinic Center for Individualized Medicine, Mayo Clinic Neuroscience Focused Research Team (Cecilia and Dan Carmichael Family Foundation, and the James C. and Sarah K. Kennedy Fund for Neurodegenerative Disease Research at Mayo Clinic in Florida), the gift from Carl Edward Bolch, Jr., and Susan Bass Bolch, and The Sol Goldman Charitable Trust. Dr. Wszolek serves as Co-Editor-in-Chief of Parkinsonism and Related Disorders, Associate Editor of the European Journal of Neurology, and on the editorial boards of Neurologia i Neurochirurgia Polska, the Medical Journal of the Rzeszow University, and Clinical and Experimental Medical Letters; holds and has contractual rights for receipt of future royalty payments from patents re: A novel polynucleotide involved in heritable Parkinson’s disease; receives royalties from editing Parkinsonism and Related Disorders (Elsevier, 2015, 2016) and the European Journal of Neurology (Wiley- Blackwell, 2015, 2016).

Dr. Rademakers receives research support from the NIH (P50-NS072187, R01-NS076471 and R01-NS080882).

Dr. Dickson receives support from the NIH (P50-NS072187). Dr. Dickson is an editorial board member of Acta Neuropathologica, Annals of Neurology, Brain, Brain Pathology, and Neuropathology, and he is editor in chief of American Journal of Neurodegenerative Disease, and International Journal of Clinical and Experimental Pathology.

Figures

Figure 1
Figure 1
Spearman correlation analyses show that overall test battery mean score is negatively correlated with PSP-related tau burden (A, Spearman’s rho −0.49, P = 0.005), but not with the number of senile plaques (B, Spearman’s rho 0.03, P = 0.87) or neurofibrillary tangles (C, Spearman’s rho −0.09, P = 0.62).
See this image and copyright information in PMC

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