Insulin-Like Growth Factor-1 but Not Insulin Predicts Cognitive Decline in Huntington's Disease.

BACKGROUND: Huntington's disease (HD) is one of several neurodegenerative disorders that have been associated with metabolic alterations. Changes in Insulin Growth Factor 1 (IGF-1) and/or insulin input to the brain may underlie or contribute to the progress of neurodegenerative processes. Here, we investigated the association over time between changes in plasma levels of IGF-1 and insulin and the cognitive decline in HD patients. METHODS: We conducted a multicentric cohort study in 156 patients with genetically documented HD aged from 22 to 80 years. Among them, 146 patients were assessed at least twice with a follow-up of 3.5 ± 1.8 years. We assessed their cognitive decline using the Unified Huntington's Disease Rating Scale, and their IGF-1 and insulin plasmatic levels, at baseline and once a year during the follow-up. Associations were evaluated using a mixed-effect linear model. RESULTS: In the cross-sectional analysis at baseline, higher levels of IGF-1 and insulin were associated with lower cognitive scores and thus with a higher degree of cognitive impairment. In the longitudinal analysis, the decrease of all cognitive scores, except the Stroop interference, was associated with the IGF-1 level over time but not of insulin. CONCLUSIONS: IGF-1 levels, unlike insulin, predict the decline of cognitive function in HD.

Effectiveness of anti-psychotics and related drugs in the Huntington French-speaking group cohort.

PURPOSE: Huntington's disease is a rare condition. Patients are commonly treated with antipsychotics and tetrabenazine. The evidence of their effect on disease progression is limited and no comparative study between these drugs has been conducted. We therefore compared the effectiveness of antipsychotics on disease progression. METHODS: 956 patients from the Huntington French Speaking Group were followed for up to 8 years between 2002 and 2010. The effectiveness of treatments was assessed using Unified Huntington's Disease Rating Scale (UHDRS) scores and then compared using a mixed model adjusted on a multiple propensity score. RESULTS: 63% of patients were treated with antipsychotics during the survey period. The most commonly prescribed medications were dibenzodiazepines (38%), risperidone (13%), tetrabenazine (12%) and benzamides (12%). There was no difference between treatments on the motor and behavioural declines observed, after taking the patient profiles at the start of the drug prescription into account. In contrast, the functional decline was lower in the dibenzodiazepine group than the other antipsychotic groups (Total Functional Capacity: 0.41 ± 0.17 units per year vs. risperidone and 0.54 ± 0.19 vs. tetrabenazine, both p<0.05). Benzamides were less effective than other antipsychotics on cognitive evolution (Stroop interference, Stroop color and Literal fluency: p<0.05). CONCLUSIONS: Antipsychotics are widely used to treat patients with Huntington's disease. Although differences in motor or behavioural profiles between patients according to the antipsychotics used were small, there were differences in drug effectiveness on the evolution of functional and cognitive scores.

The unified Huntington's Disease Rating Scale for advanced patients: validation and follow-up study.

The Unified Huntington's Disease Rating Scale (UHDRS) adequately measures decline in patients at early and moderate stages of Huntington's disease (HD). In patients with advanced HD, floor effects hamper the evaluation, thus calling for an adjusted scale. We designed the UHDRS-For Advanced Patients (UHDRS-FAP) to improve longitudinal assessment of patients at the advanced disease stage. Sixty-nine patients with a Total Functional Capacity score ≤ 5 were recruited in France and the Netherlands. Among them, 45 patients were followed longitudinally (mean ± standard deviation, 1.6 ± 1.2 years) with the UHDRS-FAP; 30 patients also were assessed with the UHDRS. In cross-sectional analyses, the psychometric properties and inter-rater reliability of the scale were evaluated. Longitudinal analyses were used to evaluate the sensitivity to decline of the UHDRS-FAP compared with the UHDRS. Internal consistency was higher for motor (0.84) and cognitive (0.91) scores than for somatic (0.70) and behavioral (0.49) scores. Inter-rater reliability was ≥ 0.88 for all scores. The somatic score, which was specific to the UHDRS-FAP, declined over time along with motor and cognitive performance on both scales. Although performance with the two scales was correlated, the UHDRS-FAP appeared to be more sensitive to change and was the only scale that detected decline in patients with a Total Functional Capacity score ≤ 1. Neither scale detected a significant decline in behavioral scores. The results indicate that the UHDRS-FAP is reliable and more sensitive to change than the original UHDRS for cognitive and motor domains. It offers items that are relevant for daily care. Behavioral scores tended to decline, but this may reflect the decline in patients' communicative abilities.

Unified Huntington's disease rating scale for advanced patients: validation and follow-up study.

The Unified Huntington's Disease Rating Scale (UHDRS) adequately measures decline in patients at early and moderate stages of Huntington's disease (HD). In advanced patients, floor effects hamper the evaluation, thus calling for an adjusted scale. We designed the UHDRS-For Advanced Patients (UHDRS-FAP), in order to improve longitudinal assessment of patients at advanced disease stage. Sixty-nine patients with a Total Functional Capacity (TFC) ≤ 5 were recruited in France and in the Netherlands. Among them, 45 patients were followed longitudinally (mean 1.6 ± 1.2 years) with the UHDRS-FAP; 30 were also assessed with the UHDRS. Cross-sectional analyses evaluated psychometric properties and interrater reliability of the scale. Longitudinal analyses evaluated the sensitivity to decline compared to the UHDRS. Internal consistency was higher for motor and cognitive scores than for somatic and behavioral scores (0.84, 0.91, 0.70, and 0.49, respectively). Interrater reliability was ≥ 0.88 in all scores. The somatic score, specific to the UHDRS-FAP, declined over time, as well as motor and cognitive performance with both scales. Although performance with the 2 scales correlated, the UHDRS-FAP appeared more sensitive to change and was the only scale that detected decline in patients with a TFC ≤ 1. Neither scale detected a significant decline in behavioral scores. The UHDRS-FAP is reliable and more sensitive to change than the original UHDRS for cognitive and motor domains. It offers items relevant for daily care. Behavioral scores tended to decline but this may reflect the decline in the communicative abilities of the patients.

Relationship between short-term blood pressure variability and large-artery stiffness in human hypertension: findings from 2 large databases.

Short-term blood pressure (BP) variability predicts cardiovascular complications in hypertension, but its association with large-artery stiffness is poorly understood and confounded by methodologic issues related to the assessment of BP variations over 24 hours. Carotid-femoral pulse wave velocity (cfPWV) and 24-hour ambulatory BP were measured in 911 untreated, nondiabetic patients with uncomplicated hypertension (learning population) and in 2089 mostly treated hypertensive patients (83% treated, 25% diabetics; test population). Short-term systolic BP (SBP) variability was calculated as the following: (1) SD of 24-hour, daytime, or nighttime SBP; (2) weighted SD of 24-hour SBP; and (3) average real variability (ARV), that is, the average of the absolute differences between consecutive SBP measurements over 24 hours. In the learning population, all of the measures of SBP variability showed a direct correlation with cfPWV (SD of 24-hour, daytime, and nighttime SBP, r=0.17/0.19/0.13; weighted SD of 24-hour SBP, r=0.21; ARV, r=0.26; all P<0.001). The relationship between cfPWV and ARV was stronger than that with 24-hour, daytime, or nighttime SBP (all P<0.05) and similar to that with weighted SD of 24-hour SBP. In the test population, ARV and weighted SD of 24-hour SBP had stronger relationships with cfPWV than SD of 24-hour, daytime, or nighttime SBP. In both populations, SBP variability indices independently predicted cfPWV along with age, 24-hour SBP, and other factors. We conclude that short-term variability of 24-hour SBP shows an independent, although moderate, relation to aortic stiffness in hypertension. This relationship is stronger with measures of BP variability focusing on short-term changes, such as ARV and weighted 24-hour SD.

Offline exhaled nitric oxide in emergency department and subsequent acute asthma control.

BACKGROUND: Few studies have evaluated exhaled NO measurement during acute asthma. OBJECTIVES: To evaluate exhaled NO fraction (FE(NO)) and peak expiratory flow (PEF) time-courses during acute asthma treatment (beta 2-agonist plus systemic steroid) and to assess whether FE(NO) time-course predicts subsequent asthma control. METHODS: Sixty-five asthmatic patients (mean +/- SD, 34 +/- 10 years) were prospectively enrolled in three Emergency Departments. RESULTS: Sixteen patients were excluded (failure of offline FE(NO) measurement at 100 mL/s [FE(NO 0.1)], n = 4, and early discharge). The 49 remaining patients performed FE(NO 0.1) and PEF on admission, at the 2nd (H2) and 6th hour (H6). Follow-up using an Asthma Control Diary was obtained in 27 of 49 patients, whether they were hospitalized (n = 9) or discharged (n = 18). All but 2 patients had elevated FE(NO) on admission (median [interquartile], 49 [26-78] ppb). Unlike PEF, mean FE(NO 0.1) of our sample was not significantly modified by treatment. No significant relationship was evidenced between exhaled NO and PEF variations. The variation of FE(NO 0.1) [H0 minus H6] was different in patients who were hospitalized (decrease of 8 +/- 20 ppb) versus discharged (increase of 5 +/- 20 ppb, p = 0.04). This variation of FE(NO 0.1) was correlated with the Diary score (control of subsequent week), an initial increase in FE(NO 0.1) being associated with better asthma control. Nevertheless, neither exhaled NO nor PEFR were good predictors of asthma control. CONCLUSIONS: An increase in FE(NO) is observed in almost all patients with acute asthma, and its subsequent increase within 6 hours is associated with a better degree of asthma control in the subsequent week.

Different effects of ambulatory blood pressure monitoring on subjective and objective sleep quality.

OBJECTIVE: To determine whether ambulatory blood pressure monitoring affects objective and subjective sleep quality in patients tested at home. METHODS: Seventy consecutive patients (40 women and 30 men, aged 53+/-15 years), having ambulatory blood pressure monitoring to monitor the efficacy of antihypertensive treatment or to distinguish between hypertension or white-coat hypertension had an evaluation of their sleep quality on a first night with ambulatory blood pressure monitoring and the three following nights without ambulatory blood pressure monitoring. Ambulatory blood pressure monitoring was performed with an auscultatory device with a measure every 15 min during 24 h. Sleep evaluation criteria were both subjective (sleep quality score and sleep questionnaire) and objective (wrist actigraphy monitoring). Sleep parameters during night 1 with ambulatory blood pressure monitoring were compared with those during night 4 without ambulatory blood pressure monitoring. Usual quality of sleep of the patients was assessed by the mean sleep quality score over 7 consecutive days. RESULTS: The sleep quality score was significantly higher for night 4 than for night 1 (7.3+/-2.1 vs. 5.3+/-2.3; P<0.0001). In contrast, actigraphy parameters (actual sleep time, mean activity score, and fragmentation index) were similar on night 1 and night 4 (6.7+/-1.2 vs. 6.9+/-1.2, 13.2+/-9.8 vs. 12.1+/-8.4, and 31.0+/-14.5 vs. 29.9+/-14.3, respectively). Subjective sleep quality was significantly altered by ambulatory blood pressure monitoring in good sleepers (mean sleep quality score > or =7, 73% of patients) but not in poor sleepers. The effect of ambulatory blood pressure monitoring on subjective sleep quality did not differ between dippers and nondippers. CONCLUSIONS: Objective sleep quality as assessed by wrist actigraphy is not significantly altered by ambulatory blood pressure monitoring, whereas subjective sleep quality is adversely affected in good sleepers.

Cognitive impairment related to apathy in early Huntington's disease.

OBJECTIVE: To investigate the relationships between cognitive impairment and apathy in patients with early Huntington's disease (HD) and to further explore the influence of depression on the outcome of cognitive changes associated with apathy. METHODS: We included 36 early HD patients, among them 20 were apathetic (HDA) and 16 were not (HDnA). The two groups were matched by age, education and severity of disease. Cognitive functions were evaluated by a comprehensive neuropsychological battery that measures memory, attention, executive function, language and visuospatial abilities. RESULTS: The HDA patients had significantly lower scores on memory, attention and executive function tests when compared with the HDnA patients (p values <0.05). We compared the performance of patients with (50%) and without depression on cognitive tasks and showed that depression per se did not influence performance. Finally, the results demonstrate that interactions between apathy and motor disturbance have a significant effect on cognitive impairment in HD. DISCUSSION: The presence of apathy is associated with more severe deficits of attention, executive function and episodic memory in early HD patients. Furthermore, the findings suggest that depression has little or no effect on cognitive deficits. Finally, apathy increased in parallel with both motor and cognitive dysfunction.