One HOM patient was excluded because MMSE administration was not feasible owing to the severe motor and cognitive disability. Thus, the HOM group included 3 subjects (including HOM3 who scored 21 on the MMSE). Demographic and clinical features of HOM and HET subjects are displayed in Table 1. Clinical information of PD and CTR subjects have been already described in detail elsewhere and are reported in Table S1.
HOM were significantly younger than CTR, PD, and HET (P < 0.001) and presented more-severe motor symptoms than PD, as measured with UPDRS-III (P < 0.001). Gender distribution and smoking habits were not significant different between groups. When considering UPSIT raw scores, both HET and CTR performed significantly better on the UPSIT than PD (P < 0.001). HOM and PD did not present significantly different UPSIT raw scores. After adjusting for age, gender, and current smoking status, HOM presented significantly worse UPSIT scores, as compared to both HET and CTR, but not as compared to PD (HET = 9.1-point difference, P = 0.029; CTR = 9.8,P = 0.003; PD = 0.7, P = 0.8). In addition, HET showed significant higher UPSIT scores, as compared to PD, but not as compared to CTR, when considering age, gender, and current smoking status as covariates (PD = 8.3, P = 0.002; CTR = 0.7, P = 0.7). When repeating the regression analysis considering the MMSE scores instead of smoking status, HOM presented only a trend toward significance for worse UPSIT scores, as compared to HET (HET = 9.2-point difference, P = 0.066). On the other hand, the other results were largely confirmed. In detail, HOM presented significantly worse UPSIT scores, as compared to CTR, but not as compared to PD (CTR = 9.5, P = 0.015; PD = 1.6, P = 0.7), whereas HET showed significant higher UPSIT scores, as compared to PD, but not as compared to CTR (PD = 7.5,P = 0.005; CTR = 0.2, P = 0.9).
The proportion of subjects with severe olfactory impairment, computed according to previously published normative data, was higher in both HOM and PD (66.6% and 50%, respectively), as compared to both HET and CTR (0% and 6.6%, respectively, P < 0.001; Fig. 1).No significant association was found between severity of olfactory deficit and overall severity of phenotype (data not shown).