J Neurol (2012) 259:1793–1800 scores, mean differences and their 95% conﬁdence inter- vals. Means were computed for the whole study sample, and for three subgroups according to the disease stage of persons living with HD (Early HD = At risk, Pre-symp- tomatic gene carriers and Stage 1; Moderate HD = Stages 2 and 3; Advanced HD = Stages 4 and 5). Two-way mixed-design analyses of variance were used to compare the effect of the patient’s HD stage subgroup and the type of rater (self or proxy) as independent variables on pairs of self- and proxy-rated Speciﬁc and Summary Scale scores (dependent variables). Multivariate and univariate analyses of covariance were used to examine whether proxy mean scores were accounted for by other potential determinants in addition to patients’ HD stage, including the proxy’s own HrQoL as reﬂected in EQ-5D and SF12v2 scores, the patient’s EQ- 5D and SFv12 scores, and measures of patient–proxy contact. To explore agreement in terms of correlation, we examined scatterplots of patient ratings against proxy rat- ings. Linear regression was used to assess the relationship between self and proxy ratings across the whole sample. Chi-square, Fisher Exact and t tests were used to explore associations between regression standardised residuals (residuals above ±1.96 being deﬁned as outliers) and other variables such as HD stage, gender of patients or proxies. Intraclass correlation coefﬁcients (ICCs) with a one-way random effects model and their respective conﬁdence intervals were calculated to quantify correlation between self and proxy scores. The criteria used were the following: ICC C 0.80 indicates excellent agreement; 0.80 [ ICC C 0.60 substantial agreement; 0.60 [ ICC C 0.40 moderate and ICC \ 0.40 poor agreement [16, 24]. ICCs were also calculated separately for patient HD stage subgroups and for cases with Advanced HD who did not receive any assistance in completing the questionnaires. Results Characteristics of the persons living with HD and their proxies are summarised in Table 1. Most of the participants with HD (87%) had conﬁrmed positive gene status and 67% had received a clinical diagnosis. Almost all of the proxies were spouses or partners (83%); 10% were parents; 5% were children of HD individuals and for 2% of proxies this information was missing. Proxies spent a lot of time per day or night caring for the person living with HD (mean 12.44 h, SD 9.59, range 0:24) and most of them (87%) had contact on a daily basis. The average time the proxies had known the person living with HD was 30.94 years (SD 15.49, range 1:60). One patient did not report their HD stage, so this patient and proxy were omitted from analyses 1795 involving HD stage, giving sample sizes of 36 for Early HD, 18 for Moderate HD and 50 for Advanced HD. The pair was included in whole-sample analyses (n = 105). The self-reported EQ-5D and SF-12v2 measures show that, as expected, patients scored worse than proxies on all indices of HrQoL. Proxies’ physical health (SF-12v2 PCS) was near the average of available normative data but their mental health (MCS) fell below the population norm [25, 26]. Figure 1 shows the patient and proxy ratings separated by patient’s HD stage subgroup (Early, Moderate or Advanced). Two-way mixed-design ANOVAs, rater (self vs. prox- y) 9 HD stage, yielded strong effects of HD stage on every measure; Fs(2,101) ranged from 7.47 (Hopes and Worries) to 72.8 (Physical and Functional), ps B 0.001, with HrQoL ratings becoming progressively poorer across the three groups. There were no signiﬁcant rater 9 HD stage inter- actions, Fs(2,101) B 2.71, suggesting that patterns of self and proxy HrQoL scores were broadly consistent across stages. The main effects of rater are reported in Table 2. These were again nonsigniﬁcant on the Summary Scale and on all Speciﬁc Scales except the Speciﬁc Hopes and Worries Scale, where proxy ratings were signiﬁcantly better than patients’ own, and there was a trend for both the Speciﬁc Cognitive and the Speciﬁc Physical and Func- tional Scales’ proxy ratings to be poorer than self-ratings. To explore what factors other than patient’s HD stage might affect proxies’ HDQoL scores, a multivariate anal- ysis of covariance tested the effect of HD stage along with potential covariates on the six Speciﬁc Scales and Sum- mary Scale. The covariates were indices obtained from patients’ and proxies’ EQ-5D and SF-12v2 self-ratings, plus proxy estimates of how long they had known the patient and how much they were in contact. Over and above the expected strong effect of HD stage, the only variable which signiﬁcantly affected proxy scores (Wilks’ lamda = 0.64, p = 0.006) was the patient’s mental state (as measured by SF-12v2 MCS). Univariate analyses showed that the proxy-rated scales which were affected by patient’s MCS were Speciﬁc Hopes and Worries, Speciﬁc Mood State, Speciﬁc Self and Vitality and the Summary Scale—Fs(1,48) C 4.21, ps \ 0.05. All slope parameters were positive (0.62–1.72), i.e. the proxy rating of HrQoL improved as the patient’s MCS score improved. The correlation between proxy and patient HDQoL Summary score ratings is illustrated in Fig. 2 Overall there is a strong linear relationship (b = 0.81, R2 = 0.73, F(1,103) = 276, p \ 0.001). However outliers (where a proxy’s score is greatly discrepant from the patient’s own) are evident, commonly in the mid-range of HrQoL and especially among patients with Moderate HD. There were eight regression outliers (cases with standardised residual 123