Rating scales for cognition in Huntington's disease: Critique and recommendations.

Cognitive impairment is one of the main features of Huntington's disease and is present across the disease spectrum. As part of the International Parkinson's Disease and Movement Disorder Society-sponsored project to review all clinical rating scales used in Huntington's disease, a systematic review of the literature was performed to identify cognitive scales used in Huntington's disease and make recommendations for their use. A total of 17 cognitive scales were identified and evaluated. None of the scales met criteria for a "recommended" status. For assessing severity of cognitive dysfunction, the Montreal Cognitive Assessment was "recommended with caveats." The UHDRS Cognitive Assessment, the UHDRS-For Advanced Patients cognitive section, the Alzheimer's Disease Assessment Scale-Cognitive Subscale, the Frontal Assessment Battery, the Mattis Dementia Rating Scale, the Mini-Mental State Examination, and the Repeatable Battery for the Assessment of Neuropsychological Status were "suggested" for evaluating severity of cognitive impairment. The MoCA was "suggested" as a screening tool for cognitive impairment. The major challenge in the assessment of cognition in Huntington's disease is the lack of a formal definition of dementia and/or mild cognitive impairment in this disease. The committee concluded that there is a need to further validate currently available cognitive scales in Huntington's disease, but that it is premature to recommend the development of new scales. Recently developed Huntington's disease-specific scales, such as the Huntington's Disease-Cognitive Assessment Battery, hold promise but require the completion of more comprehensive clinimetric development. © 2017 International Parkinson and Movement Disorder Society.

A randomized, double-blind, placebo-controlled trial of coenzyme Q10 in Huntington disease.

OBJECTIVE: To test the hypothesis that chronic treatment of early-stage Huntington disease (HD) with high-dose coenzyme Q10 (CoQ) will slow the progressive functional decline of HD. METHODS: We performed a multicenter randomized, double-blind, placebo-controlled trial. Patients with early-stage HD (n = 609) were enrolled at 48 sites in the United States, Canada, and Australia from 2008 to 2012. Patients were randomized to receive either CoQ 2,400 mg/d or matching placebo, then followed for 60 months. The primary outcome variable was the change from baseline to month 60 in Total Functional Capacity score (for patients who survived) combined with time to death (for patients who died) analyzed using a joint-rank analysis approach. RESULTS: An interim analysis for futility revealed a conditional power of <5% for the primary analysis, prompting premature conclusion in July 2014. No statistically significant differences were seen between treatment groups for the primary or secondary outcome measures. CoQ was generally safe and well-tolerated throughout the study. CONCLUSIONS: These data do not justify use of CoQ as a treatment to slow functional decline in HD. CLINICALTRIALSGOV IDENTIFIER: NCT00608881. CLASSIFICATION OF EVIDENCE: This article provides Class I evidence that CoQ does not slow the progressive functional decline of patients with HD.

FDA Regulation of Neurological and Physical Medicine Devices: Access to Safe and Effective Neurotechnologies for All Americans.

The United States Food and Drug Administration (FDA) ensures that patients in the U.S. have access to safe and effective medical devices. The Division of Neurological and Physical Medicine Devices reviews medical technologies that interface with the nervous system. This article addresses how to navigate the FDA's regulatory landscape to successfully bring medical devices to patients.

Optimal Cutoff Scores for Alzheimer's Disease Using the Chinese Version of Mini-Mental State Examination Among Chinese Population Living in Rural Areas.

To explore the optimal cutoff score for initial detection of Alzheimer's Disease (AD) through the Chinese version of Mini-Mental State Examination (CMMSE) in rural areas in China, we conducted a cross-sectional study within the Linxian General Population Nutritional Follow-up study. 16,488 eligible cohort members participated in the survey and 881 completed the CMMSE. Among 881 participants, the median age (Interquartile range) was 69.00 (10.00), 634 (71.92%) were female, 657 (74.57%) were illiterate, 35 (3.97%) had 6 years of education or higher, and 295 (33.48%) were diagnosed with AD. By reducing the CMMSE criteria for illiterate to 16 points, primary school to 19 points, and middle school or higher to 23 points, the efficiency of Chinese version of Mini-Mental State Examination can be significantly improved for initial detection of AD in rural areas in China, especially in those nutrition deficient areas.

Neurocognitive clinical outcome assessments for inborn errors of metabolism and other rare conditions.

Well-defined and reliable clinical outcome assessments are essential for determining whether a drug provides clinically meaningful treatment benefit for patients. In 2015, FDA convened a workshop, "Assessing Neurocognitive Outcomes in Inborn Errors of Metabolism." Topics covered included special challenges of clinical studies of inborn errors of metabolism (IEMs) and other rare diseases; complexities of identifying treatment effects in the context of the dynamic processes of child development and disease progression; and the importance of natural history studies. Clinicians, parents/caregivers, and participants from industry, academia, and government discussed factors to consider when developing measures to assess treatment outcomes, as well as tools and methods that may contribute to standardizing measures. Many issues examined are relevant to the broader field of rare diseases in addition to specifics of IEMs.

Safety and tolerability of high-dosage coenzyme Q10 in Huntington's disease and healthy subjects.

Coenzyme Q10 (CoQ(10)), a potential neuroprotective compound, was previously investigated at a dosage of 600 mg/day in Huntington's disease (HD) patients and demonstrated a trend toward slowing disease progression. Higher CoQ(10) dosages may prove beneficial. We investigated the tolerability and blood levels associated with 1,200, 2,400, and 3,600 mg/day of CoQ(10) in HD and healthy subjects. Twenty-eight subjects (20 HD, 8 healthy) enrolled in a 20-week open-label trial. Subjects started on 1,200 mg/day of CoQ(10), increasing every 4 weeks by 1,200 mg to a maximum dosage of 3,600 mg/day. Monthly evaluations included review of adverse events and CoQ(10) blood levels. Twenty-three subjects (82%) achieved the target dosage of 3,600 mg/day. Six subjects (2 healthy, 4 HD) withdrew prematurely (gastrointestinal (GI) symptoms in 3, worsening HD in 2, and 1 because of a fall). All three serious adverse events occurred in a single subject, and were deemed unrelated to CoQ(10). The most common adverse events seen were GI symptoms. Mean (± SD) CoQ10 blood levels achieved over the course of the trial were as follows: 1.26 ± 1.27 µg/mL (baseline, n = 28), 5.59 ± 2.24 µg/mL (1,200 mg/day, week 4, n = 26), 6.38 ± 3.25 µg/mL (2,400 mg/day, week 8, n = 25), 7.49 ± 4.09 µg/mL (3,600 mg/day, week 12, n = 23), and 6.78 ± 3.36 µg/mL (3,600 mg/day, week 20, n = 20). CoQ(10) was well tolerated with over 80% of subjects achieving the target dosage. Dosages of 2,400 mg/day may provide the best balance between tolerability and blood level achieved. Further studies examining the efficacy of 2,400 mg/day are planned.

The course of depressive symptoms in early Parkinson's disease.

Little is known about the course of depressive symptoms in Parkinson's disease (PD). We studied the course of clinically significant depressive symptoms using data from two clinical trials that followed 413 early, untreated PD subjects for 12 to 18 months. We measured depressive symptoms with the 15-item geriatric depression scale (GDS-15); a score of > or =5 indicates clinically significant depressive symptoms. We used a time-dependent Cox model to examine the association between demographic variables, PD severity, and medication use on the time to resolution of depressive symptoms. One hundred fourteen of 413 (27.6%) subjects were screened positive for depression during the study, with a median GDS-15 score of 6, indicating mild symptoms. Within 6 months, 47% of subjects experienced remission of clinically significant depressive symptoms. Subjects with mild depressive symptoms were more likely to develop moderate to severe depressive symptoms (GDS > or = 10) than those without prior symptoms (relative risk = 6.16). Increasing severity of depressive symptoms, older age, and longer PD duration predicted a lower likelihood of symptom resolution (hazard ratios 0.83-0.92). Mild depressive symptoms have a variable course, with remission and development of more sustained and severe symptoms occurring over time. More severe depressive symptoms may herald a protracted course.

Patient selection and assessment recommendations for deep brain stimulation in Tourette syndrome.

In response to recent publicity regarding the potential use of deep brain stimulation (DBS) for reducing tic severity in Tourette's syndrome (TS), the Tourette Syndrome Association convened a group of TS and DBS experts to develop recommendations to guide the early use and potential clinical trials of DBS for TS and other tic disorders. The goals of these recommendations are to ensure that all surgical candidates are (1) fully informed about the risks, benefits, and alternative treatments available; (2) receive a comprehensive evaluation before surgery to ensure that DBS is clearly the appropriate clinical treatment choice; and (3) that early clinical experience will be documented publicly to facilitate rational decision-making for both clinical care and future clinical trials.

Obsessive-compulsive disorder in Tourette's syndrome.

A substantial body of scientific evidence suggests that obsessive-compulsive behavior occurs in a large percentage of patients with TS. Reliable estimates suggest that nearly 50% of patients with TS have some degree of obsessive-compulsive features. Most patients with TS have only mild OCB and thus would not meet the DSM-IV diagnostic criteria for OCD. Therefore, OCB is perhaps a more appropriate characterization of this behavioral phenomenon that occurs in TS. OCB in TS appears similar to the spectrum of the tic disorder in terms of its onset, severity, and course. As with tics, OCB is typically mild and not always substantially disabling. Although clinical features between TS + OCB and primary OCD overlap considerably, patients with TS + OCB appear to experience different types of obsessive thoughts and compulsive rituals. Compelling genetic evidence suggests that OCB may be an alternative expression of the TS phenotype, which may selectively affect female gene carriers. Identifying the TS gene in the future will substantially broaden our knowledge of this intriguing neurobehavioral disorder. Finally, neurobiologic evidence points to similar anatomic and chemical substrates in the pathogenesis of TS and OCD, suggesting that these two disorders share a common pathophysiology. The clinical evaluation of patients with TS and their families should always include an assessment for OCB. Self-rated inventories of OCD such as the LOI, LOI-CV, and MOCI are useful screening scales. A more structured interview using the Y-BOCS (CY-BOCS) is useful for determining the degree and severity of OCB in TS as well as the response to therapy. Clinicians should keep in mind that OCB may be the most disabling feature of TS and may require treatment. Pharmacologic agents, such as SSRIs, and traditional behavioral therapy are proven effective treatments for OCB, which can substantially reduce the full effect of TS on patients and their families.

Relationship between blood pressure and Alzheimer's disease in Linxian County, China.

To investigate the relationship between hypertension and Alzheimer's disease(AD) and the change of Alzheimer's patients' blood pressure(BP) before and after the onset of AD, we conducted this epidemiological study. Subjects for this study were individuals who participated in a large scale, randomized controlled trial of nutritional intervention from 1984 to 1991. Participants were initially screened for dementia using Chinese Mini-Mental State Examination (CMMS) and Activities of Daily Living (ADL). Positive subjects were subsequently administered a detailed neuropsychological and neurobehavioral examination. The diagnosis of AD was made by a consensus conference of psychiatrists using Diagnostic And Statistical Manual Of Mental Disorders-Fourth Edition(DSM-IV) criteria. 16488 subjects were examined and 301 were diagnosed as AD. We compared the prevalence of AD in different populations that were stratified with 1984's systolic or diastolic blood pressure(those four stratifications being high blood pressure, borderline blood pressure, normal, low blood pressure), and compared the change of blood pressure of 301 AD patients between 1984 and 1999-2000, which is before and after the onset of AD respectively. Multiple Logistic Regression (1:1 nested case-control study) was used to assess if hypertension is an independent risk factor for AD, and Trend test was used to assess the relationship between blood pressure and AD. Here we demonstrate that there was a significant difference in AD prevalence among different populations stratified by systolic or diastolic blood pressure (P < 0.01). The prevalence is highest in hypertension group, and lowest in hypotension group. Multiple Logistic Regression identified high blood pressure as a risk factor for AD (OR = 1.97, 95%CI:1.09-3.54, P = 0.02). Trend test showed that there is a significant dose-response relationship between blood pressure and AD (P < 0.0002). For hypertensive AD patients, there was no significant difference in systolic blood pressure(SBP) before and after the onset of AD, but diastolic blood pressure(DBP) decreased dramatically after the onset of AD (P < 0.01); however, the result also showed that DBP decrease occurred in the non-demented group. Based on this, we think the DBP decrease is not related to AD. We further investigated whether BP values differed crossed-sectionally between the AD-patients and non-demented individuals. We found that regardless of SBP or DBP, the BP values of the AD group were all significantly higher than that of non-demented. In summary, these data suggest there is a strong relationship between hypertension and AD; however, the mechanism remains to be studied.

MMSE Result of a Population aged above 55 in Rural Area of North China / 中国心理卫生杂志

Objective:to do a population study with MMSE in rural area of north China.Method:13 962 farmers aged 55 or above from four villages in Linxian of Henan province were tested with MMSE, with 3 different cut-off points according to different level of education in our sample.Result:in our sample, the average total score of MMSE was lower than Chinese norm, especially that of calculation. Those aged, with poor education, female, with low SES had lower scores in MMSE test. There was a negative correlation between score of MMSE and that of ADL (acitivity of daily living).Conclusion:female, age, poor education, low SES are risk factors for dementia.