Phenotype differences between corticobasal syndrome and progressive supranuclear palsy with and without Alzheimer's disease biomarkers: Neuroimaging / Optimal neuroimaging measures for tracking disease progression. (7th December 2020) - Vasilevskaya, Anna
Abstract: Background: Progressive supranuclear palsy (PSP) and corticobasal syndrome (CBS) are usually caused by a tauopathy. Comorbid Alzheimer's disease (AD) pathology can be seen in PSP and is causative in a number of CBS cases. The contribution of different pathologies to the phenotypes is poorly characterized. Our aim was to compare PSP/CBS without AD biomarker (CBS/PSP‐non‐AD) to CBS/PSP with AD biomarkers (CBS/PSP‐AD). Method: Twenty‐four patients [11 males, 13 females; age (68.46±7.23)] with a diagnosis of PSP or CBS underwent MRI and PET imaging with tau specific [18F]‐AV1451 tracer as well as cerebrospinal fluid (CSF) analysis. PSP rating scale (PSPRS) and unified Parkinson's disease rating scale (UPDRS) motor exam were used to assess for motor disturbances. Cognitive testing was completed. Patients were divided into AD and non‐AD based on CSF or PET Tau imaging. Seventeen patients were negative for AD biomarkers (6 CBS, 11 PSP)] while7 tested positive [diagnoses (6 CBS‐AD, 1 PSP‐AD)]. Result: The CBS/PSP‐non‐AD group [age (70.18±6.65)] was significantly older (p=0.028) than the CBS/PSP‐AD group [age (64.29±7.32)]. There were no differences between the groups in terms of gender, education, or disease duration. The CBS/PSP‐non‐AD group compared to the CBS/PSP‐AD group had significantly lower PET [18F]‐AV1451 SUVR values in AD‐specific brain regions of hippocampus [1.20±0.28 vs. 1.80±0.39; p=0.002] and inferior parietal area [1.49±0.56 vs. 3.26±1.53; p=0.001]. The CBS/PSP‐non‐AD group compared to the CBS/PSP‐AD group scored significantly higher on PSPRS [40.76±18.61 vs. 18.29±6.65; respectively, p=0.004] and UPDRS motor exam [36.06±21.49 vs. 15.71±8.34; respectively, p=0.045]. Finally, CBS/PSP‐non‐AD group compared to the CBS/PSP‐AD group scored significantly higher scores on digit span forward [5.76±1.52 vs. 3.86±1.77; p=0.025]. Two participants refused to complete the sentence repetition task but CBS/PSP‐non‐AD group (N=15) scored significantly higher on sentence repetition compared to the CBS/PSP‐AD group (N=7) [4.13±1.46 vs. 2.43±1.90; p=0.031]. Conclusion: The CBS/PSP‐non‐AD group had higher motor signs but had better working memory and sentence repetition than the CBS/PSP‐AD group despite being older. These results show that the presence of AD biomarkers has an effect on CBS and PSP phenotypes. This has implications for monitoring progression and response to treatment.