Hyposmia and cognitive impairment in Gaucher disease patients and carriers

Abstract

The objective of this study was to assess a cohort of Gaucher disease patients and their heterozygous carrier relatives for potential clinical signs of early neurodegeneration. Gaucher disease patients (n = 30), heterozygous glucocerebrosidase mutation carriers (n = 30), and mutation-negative controls matched by age, sex, and ethnicity (n = 30) were recruited. Assessment was done for olfactory function (University of Pennsylvania Smell Identification Test), cognitive function (Mini-Mental State Examination, Montreal Cognitive Assessment), rapid eye movement sleep disorder, autonomic symptoms, and parkinsonian motor signs (Unified Parkinson's Disease Rating Scale part III, Purdue pegboard). Olfactory function scores were significantly lower in Gaucher disease patients (P = .010) and heterozygous carriers (P < .001) than in controls. Cognitive assessment scores were significantly lower in Gaucher disease patients (P = .002) and carriers (P = .002) than in controls. Unified Parkinson's Disease Rating Scale motor subscale scores were significantly higher in Gaucher disease patients (P < .001) and heterozygotes (P = .0010) than in controls. There was no difference in scores for symptoms of rapid eye movement sleep disorder or autonomic dysfunction. Impairment of olfaction, cognition, and parkinsonian motor signs occurs more frequently in Gaucher disease patients and carriers than in controls, which may indicate the early stages of neurodegeneration.

FIG. 1

UPSIT scores for controls, carriers, and Gaucher disease patients. The median UPSIT score for controls was 35.5/40, which was significantly higher than the median UPSIT score for carriers (31/40; Mann-Whitney U test, P < .001) and Gaucher disease patients (32.5/40; Mann-Whitney U test, P = .01). The median UPSIT scores did not differ significantly between carriers and Gaucher disease patients. UPSIT, University of Pennsylvania Smell Identification Test.

FIG. 2

Montreal cognitive assessment scores for controls, carriers, and Gaucher disease. The median Montreal cognitive assessment score for controls (28/30) was significantly higher than that of carriers (26/30; Mann-Whitney U test, P = .002) or Gaucher disease patients (26/30; Mann-Whitney, P = .002). The median Montreal cognitive assessment scores did not differ between carriers and Gaucher disease patients.

FIG. 3

Unified Parkinson’s Disease Rating Scale Part III scores for controls, carriers, and Gaucher disease patients. The median Unified Parkinson’s Disease Rating Scale Part III score for controls was significantly lower than the median score for carriers (Mann-Whitney U test, P = .001) and Gaucher disease patients (Mann-Whiney U test, P < .001). The Unified Parkinson’s Disease Rating Scale Part III score did not differ significantly between carriers and Gaucher disease patients.