New insights from a multi-ethnic Asian progressive supranuclear palsy cohort

Abstract

Background: Progressive supranuclear palsy (PSP) is a rare, disabling, neurodegenerative disease, with few studies done in Asian populations.

Methods: We prospectively characterized the clinical features and disease burden in a consecutively-recruited multi-ethnic Asian PSP cohort. Patients were extensively phenotyped using the Movement Disorder Society (MDS-PSP) clinical diagnostic criteria and the PSP-Clinical Deficits Scale (PSP-CDS). Caregiver burden was measured using the modified Zarit Burden Interview (ZBI). Investigations (neuroimaging and genetic tests) were reviewed.

Results: There were 104 patients (64.4% male; 67.3% Chinese, 21.2% Indians, 9.6% Malays), consisting of 48.1% Richardson syndrome (PSP-RS), 37.5% parkinsonian phenotype (PSP-P), and 10.6% progressive gait freezing phenotype (PSP-PGF). Mean age at motor onset was 66.3 ± 7.7 years, with no significant differences between the PSP phenotypes. Interestingly, REM-sleep behaviour disorder (RBD) symptoms and visual hallucinations (considered rare in PSP) were reported in 23.5% and 22.8% of patients, respectively, and a family history of possible neurodegenerative or movement disorder in 20.4%. PSP-CDS scores were highest (worst) in PSP-RS; and correlated moderately with disease duration (r_s = 0.45, P < 0.001) and weakly with caregiver burden (r_s = 0.22, P = 0.029) in the overall cohort. Three of 48 (6.3%) patients who had whole-exome sequencing harboured pathogenic/likely pathogenic GBA variants.

Conclusions: Significant heterogeneity in clinical features and disease burden, and high rates of RBD symptoms, visual hallucinations, and familial involvement were observed in this relatively large cohort. Our findings highlight important considerations when assessing Asian patients, and provide further support for the notion of overlapping neurobiology between PSP and Lewy body disorders.

Keywords: CADASIL; Caregiver burden; Diagnostic criteria; GBA; Genetics; LRRK2; PSP-CDS; Progressive supranuclear palsy; REM-sleep behaviour disorder; Visual hallucinations; Zarit Burden Interview.