How can I assess my patients with Parkinson's disease during a busy clinic day?

BACKGROUND: The evaluation of motor impairment in Parkinson's disease (PD) is mainly assessed with the motor subdomain of the Unified Parkinson's Disease Rating scale (UPDRS part III) and, lately, with the MDS-UPDRS part III. To optimize efforts and special needs during specific circumstances in clinical practice, we sought to identify the most sensitive items to assess motor impairment in PD. METHODS: We included the COPPADIS-PD cohort and collected the UPDRS part III at baseline (V0), 12 months (V1), and 24 months (V2). Factor analysis and effect size using Cohen's d formula were performed in the Off and On states at V0, V1, and V2. RESULTS: We included 667 patients with PD, mean age of 62.59 ± 8.91 years, 410 (60.2%) males, with a median HY stage of 2.00 (1.00; 4.00) at baseline. Over time, the most discriminating items were postural stability and body bradykinesia ("arise from chair" and "gait") in the Off state, right and left upper extremity bradykinesia ("finger tap", "hand movements" and "prono/supination") in the On state. Body bradykinesia and right-left finger tapping were the items with the largest effect size (0.93, 0.84, 0.83, respectively) to assess motor improvement after receiving antiparkinsonian medications over time. CONCLUSION: Under specific circumstances, selecting a few items of the UPDRS part III, including postural stability, body bradykinesia, and upper extremity bradykinesia, could be used to create a quick clinical judgment of motor status and improvement in PD.

Association Between Insulin-Like Growth Factor-1 and Social Cognition in Huntington's Disease.

Background: Insulin-like growth factor 1 (IGF-1) seems to be involved in the neural circuits associated with social cognition and brain structure. Objectives: To investigate the association of IGF-1 levels with social cognition and brain structure in Huntington's disease (HD). Methods: We evaluated social cognition using the Ekman test in 22 HD patients and 19 matched controls. Brain structure was assessed using standard volume-based voxel-based morphometry and surface-based cortical thickness pipeline. We analyzed the association of IGF-1 levels with social cognition and brain structure using adjusted regression analysis. Results: Social cognition was worse in HD patients (P < 0.001), on antidopaminergic drugs (P = 0.02), and with lower IGF-1 levels (P = 0.04). In neuroimaging analyses, lower IGF-1 levels were associated with social cognition impairment and atrophy mainly in frontotemporal regions (P < 0.05 corrected). Conclusions: In HD, abnormal IGF-1 function seems to be associated with brain atrophy leading to clinical deficits in social cognition.

Polymorphisms in the oxytocin receptor and their association with apathy and impaired social cognition in Huntington's disease.

BACKGROUND: Huntington's disease (HD) is a neurodegenerative disorder characterized by cognitive, motor, and neuropsychiatric manifestations. Oxytocin is a neuropeptide studied for its role as a neuromodulator regulating multiple behaviors linked to social cognition. Genetic variation of oxytocin receptor (OXTR) might interact in the etiology and development of several impaired social behaviors. Our aim was to study OXTR polymorphisms and their relationship with apathy and social cognition in HD. METHODS: OXTR was sequenced in 21 cases and 22 controls. We assessed apathy, anxiety, depression, and irritability (Hospital Anxiety and Depression Scale-Snaith Irritability scale, HADS-SIS) and social cognition (Ekman 60 faces test), motor symptoms and functionality with the total functional capacity (TFC), and the Unified HD rating Scale (UHDRS). RESULTS: We identified ten variants in OXTR. Three variants were classified as possibly damaging (p.Arg40Gly) or probably damaging (p.Leu46Pro, p.Thr102Asn). Subjects carrying the wild-type genotype of the synonymous variant p.Val45 showed a significantly lower score in the HADS-SIS scale, related to lower irritability (p = 0.013). The only subject carrying the heterozygous genotype of the synonymous variant p.Leu62 showed a significantly higher score on Ekman scale, compared to wild-type (p = 0.049); however, this finding was not confirmed after bootstrapping. CONCLUSION: Variations in OXTR could have a relevant role in the correct development of social and cognitive functions. Future approaches will include the molecular study of p.Arg40Gly, p.Leu46Pro, and p.Thr102Asn to confirm their pathogenicity, as well as the validation of the influence of p.Val45 and p.Leu62 variants for their involvement in irritability and social cognition in HD.

The Impact of Dietary Intake and Physical Activity on Body Composition in Parkinson's Disease.

BACKGROUND: Skeletal muscle loss has been associated with declining physical performance and a negative prognostic effect on falls, disability, and mortality risk in Parkinson's disease. OBJECTIVES: We aimed to analyze the clinical correlates associated with skeletal muscle wasting in Parkinson's disease. METHODS: This was a cross-sectional, case-control, observational study. We collected information on dietary intake with a 24-hour recall questionnaire, body composition with bioelectrical impedance, motor severity with the Unified Parkinson's disease Rating Scale, and physical activity with the Global Physical Activity Questionnaire. We used multivariate linear regression analysis to analyze the sociodemographic and clinical correlates associated with skeletal muscle loss after adjusting for confounding variables. RESULTS: Forty-three patients with Parkinson's disease and 21 matched family members were included. Patients and family members had similar body composition, anthropometrics, and nutritional parameters. Advanced patients had similar nutrient intakes compared to patients with mild-to-moderate Parkinson's disease. In the multivariate linear regression analysis, female patients with low physical activity and low energy intake were more likely to have skeletal muscle loss. CONCLUSIONS: Skeletal muscle wasting is a complex multifactorial problem. Dietary strategies and physical exercise should be recommended, especially to females with Parkinson's disease, to prevent significant skeletal muscle wasting.

Factors Associated with Low Body Mass Index in Huntington's Disease: A Spanish Multicenter Study of the European Huntington's Disease Registry.

BACKGROUND: Patients with Huntington's disease (HD) are at risk for body weight loss and increased risk for institutionalization, morbidity, and mortality. The aim of this study was to determine the factors associated with low body mass index (BMI) in patients with HD. METHODS: In this national, observational, cross-sectional study of the European Huntington's Disease Network, the frequency of food consumption, calories, and nutrient intake in patients with HD was assessed using questionnaires validated for the Spanish population and were calculated using the software package Alimentación and Salud (Diet and Health), version 2.0. Nutritional status was estimated using the BMI, and disease severity was assessed using the Unified Huntington's Disease Rating Scale and a total functional capacity (TFC) score. Linear regression models were performed using BMI as the dependent variable and using energy balance (energy caloric intake - energy expenditure); the TFC score; the presence of a caregiver; dysphagia; cytosine, adenine, guanine (CAG) repeats; comorbidities; intake of supplements; pharmacologic treatments; age; gender; education; and physical activity as the independent variables. RESULTS: Two hundred twenty-four patients with HD were included (59% women), and their mean age was 47.41 ± 14.26 years, a median TFC score of 9 (range, 3-13), normal BMI in 124 patients (55.4%), and low BMI in 13 patients (6.7%). In the linear regression model, older age (ß = 0.003; P = 0.01), male gender (ß = 0.13; P = 0.003), and lower energy balance (ß = -0.0001; P = 0.0003) were associated with a higher log-transformed BMI. CONCLUSIONS: Younger female HD patients are at risk for low BMI. To counteract the influence of the HD gene mutation on decreased BMI, an increase in kilocalories per day should be encouraged.

Factors associated with Mediterranean diet adherence in Huntington's disease.

BACKGROUND & AIMS: Little is known about the importance of the Mediterranean Diet (MeDi) and dietary intake as environmental neuroprotective factors in Huntington's disease (HD); so, we evaluated and analyzed the prevalence and factors associated with MeDi adherence, and dietary intake in HD. METHODS: Spanish participants of the European Huntington Disease Network (EHDN) Registry study diagnosed with HD or premanifest HD gene carriers were included from June 2012 to August 2013. Self-reported dietary intake was collected by 3-day dietary record, MeDi adherence was assessed by 0-9 range (proposed by Trichopoulou et al.) and, other contributing factors related to nutrition were collected by telephone. Demographics and clinical variables were obtained from the EHDN Registry study database. Association of HD with MeDi adherence and nutritional characteristics were performed using logistic regression models. RESULTS: Ninety eight participants were included in the study, median age of 48 years (38-60 range), and median total functional capacity (TFC) 9 (5-13 range). HD severity was similar between participants with low vs moderate/high MeDi; however, quality of life (P = 0.009) was significantly higher among participants with moderate/high MeDi adherence. In terms of nutrients, higher MUFA/SFA intake was moderately correlated with better TFC and Unified HD Rating Scale (UHDRS) cognitive. Better TFC was associated with having a caregiver (OR = 11.86, P < 0.001), and non-smoking (OR = 0.21, P = 0.013). Moderate adherence to MeDi, was associated with older participants (OR = 1.19, P = 0.031), lower comorbidity (OR = 0.18, P = 0.018), lower UHDRS motor (OR = 0.90, P = 0.041), and lower risk for abdominal obesity (OR = 0.02, P = 0.011). CONCLUSIONS: In HD the moderate MeDi adherence is associated with better quality of life, lower comorbidity, lower motor impairment and lower risk for abdominal obesity compared to those participants with low MeDi adherence.

Relationship between Nutritional Status and the Severity of Huntington's Disease. A Spanish Multicenter Dietary Intake Study.

BACKGROUND: Little is known about the impact of nutrition status on Huntington's disease (HD) severity. OBJECTIVE: To analyze the association of nutritional factors with HD severity. METHODS: Observational, cross-sectional, national multicenter study. Participants were selected from a Spanish cohort of patients who participate in the European Huntington Disease Network (EHDN). The frequency of food consumption, caloric and nutrients intake in patients with HD were assessed using validated questionnaires for the Spanish population, and calculated using Alimentaci´on and Salud, version 2.0, and the Spanish Dietary Recommended Intakes were used as the gold standard. Disease severity was assessed using the Unified HD Rating Scale (UHDRS) and Total Functional Capacity (TFC). Logistic regression models were performed using the TFC as the dependent variable, and the macro-micronutrients as the independent variables, adjusted for age, gender, education, physical activity, and intake of supplements. RESULTS: Two hundred and twenty four patients with HD were included (59% women), mean age of 47.41±14.26 years, median TFC 9 (3­13), median UHDRS motor score of 33.5 (3.75­56), 75.8% with normal-high caloric intake, 55.4% normal BMI, and 54.4% with medium-high adherence to the Mediterranean diet. Compared to patients with mild-moderate HD, patients with severe HD had higher caloric intake (p = 0.02), and similar BMI (p = 0.33). Advanced HD was associated with higher intake of water-soluble vitamins (OR = 2.08; 95% CI = 1.12­3.85, p = 0.02), and minerals (OR = 1.86; 95% CI = 1.09­ 3.19, p = 0.02). CONCLUSIONS AND RELEVANCE: An adequate dietary intake prevents against weight loss in patients with advanced HD, but it is not associated with better functional state.

Body composition analysis as an indirect marker of skeletal muscle mass in Huntington's disease.

BACKGROUND: Skeletal muscle wasting is likely to play an important role in the Huntington's disease (HD) pathogenesis. Our aim was to analyze the body composition, and specifically fat-free mass (FFM), as an indirect marker of skeletal muscle in patients with HD, and its association with HD severity and energy balance. METHODS: Cross-sectional, case-control study. Body composition was analyzed using bioelectrical impedance. Information was collected as regards of the anthropometrics, disease severity [Unified Huntington Disease Rating (UHDRS) and Total functional capacity (TFC) scores], CAG repeats, protein catabolism, energy intake and energy expenditure. RESULTS: Twenty two patients with HD [mean age 50.3±15.6, mean UHDRS of 27.9±23.7, median TFC of 11 (IQR: 7; 13); median body mass index 23.6 (IQR: 26.8; 22.5)], and 18 controls were included. Both groups were similar in terms of age, gender, body mass index, body composition, physical activity level, and protein catabolism. FFM was correlated with energy intake (r=0.73, p<0.001), resting energy expenditure (r=0.64, p=0.001) and physical activity (r=0.54, p=0.003), but not with CAG repeats, or HD severity. CONCLUSIONS: Our results do not support the presence of significant muscle wasting in patients with early-moderate Huntington's disease. However, to prevent muscle wasting in HD, dietary strategies, in addition to physical exercise, should be further investigated.