Association Between Dietary Intake and Function in Amyotrophic Lateral Sclerosis.

IMPORTANCE: There is growing interest in the role of nutrition in the pathogenesis and progression of amyotrophic lateral sclerosis (ALS). OBJECTIVE: To evaluate the associations between nutrients, individually and in groups, and ALS function and respiratory function at diagnosis. DESIGN, SETTING, AND PARTICIPANTS: A cross-sectional baseline analysis of the Amyotrophic Lateral Sclerosis Multicenter Cohort Study of Oxidative Stress study was conducted from March 14, 2008, to February 27, 2013, at 16 ALS clinics throughout the United States among 302 patients with ALS symptom duration of 18 months or less. EXPOSURES: Nutrient intake, measured using a modified Block Food Frequency Questionnaire (FFQ). MAIN OUTCOMES AND MEASURES: Amyotrophic lateral sclerosis function, measured using the ALS Functional Rating Scale-Revised (ALSFRS-R), and respiratory function, measured using percentage of predicted forced vital capacity (FVC). RESULTS: Baseline data were available on 302 patients with ALS (median age, 63.2 years [interquartile range, 55.5-68.0 years]; 178 men and 124 women). Regression analysis of nutrients found that higher intakes of antioxidants and carotenes from vegetables were associated with higher ALSFRS-R scores or percentage FVC. Empirically weighted indices using the weighted quantile sum regression method of "good" micronutrients and "good" food groups were positively associated with ALSFRS-R scores (ß [SE], 2.7 [0.69] and 2.9 [0.9], respectively) and percentage FVC (ß [SE], 12.1 [2.8] and 11.5 [3.4], respectively) (all P < .001). Positive and significant associations with ALSFRS-R scores (ß [SE], 1.5 [0.61]; P = .02) and percentage FVC (ß [SE], 5.2 [2.2]; P = .02) for selected vitamins were found in exploratory analyses. CONCLUSIONS AND RELEVANCE: Antioxidants, carotenes, fruits, and vegetables were associated with higher ALS function at baseline by regression of nutrient indices and weighted quantile sum regression analysis. We also demonstrated the usefulness of the weighted quantile sum regression method in the evaluation of diet. Those responsible for nutritional care of the patient with ALS should consider promoting fruit and vegetable intake since they are high in antioxidants and carotenes.

Cognitive-behavioral screening reveals prevalent impairment in a large multicenter ALS cohort.

OBJECTIVES: To characterize the prevalence of cognitive and behavioral symptoms using a cognitive/behavioral screening battery in a large prospective multicenter study of amyotrophic lateral sclerosis (ALS). METHODS: Two hundred seventy-four patients with ALS completed 2 validated cognitive screening tests and 2 validated behavioral interviews with accompanying caregivers. We examined the associations between cognitive and behavioral performance, demographic and clinical data, and C9orf72 mutation data. RESULTS: Based on the ALS Cognitive Behavioral Screen cognitive score, 6.5% of the sample scored below the cutoff score for frontotemporal lobar dementia, 54.2% scored in a range consistent with ALS with mild cognitive impairment, and 39.2% scored in the normal range. The ALS Cognitive Behavioral Screen behavioral subscale identified 16.5% of the sample scoring below the dementia cutoff score, with an additional 14.1% scoring in the ALS behavioral impairment range, and 69.4% scoring in the normal range. CONCLUSIONS: This investigation revealed high levels of cognitive and behavioral impairment in patients with ALS within 18 months of symptom onset, comparable to prior investigations. This investigation illustrates the successful use and scientific value of adding a cognitive-behavioral screening tool in studies of motor neuron diseases, to provide neurologists with an efficient method to measure these common deficits and to understand how they relate to key clinical variables, when extensive neuropsychological examinations are unavailable. These tools, developed specifically for patients with motor impairment, may be particularly useful in patient populations with multiple sclerosis and Parkinson disease, who are known to have comorbid cognitive decline.

Phenotypic and molecular analyses of primary lateral sclerosis.

OBJECTIVE: To understand phenotypic and molecular characteristics of patients with clinically "definite" primary lateral sclerosis (PLS) in a prospective study. METHODS: Six sites enrolled 41 patients who had pure upper motor neuron dysfunction, bulbar symptoms, a normal EMG done within 12 months of enrollment, and onset of symptoms ≥5 years before enrollment. For phenotypic analyses, 27 demographic, clinical, and cognitive variables were analyzed using the k-means clustering method. For molecular studies, 34 available DNA samples were tested for the C9ORF72 mutation, and exome sequencing was performed to exclude other neurologic diseases with known genetic cause. RESULTS: K-means clustering using the 25 patients with complete datasets suggested that patients with PLS can be classified into 2 groups based on clinical variables, namely dysphagia, objective bulbar signs, and urinary urgency. Secondary analyses performed in all 41 patients and including only variables with complete data corroborated the results from the primary analysis. We found no evidence that neurocognitive variables are important in classifying patients with PLS. Molecular studies identified C9ORF72 expansion in one patient. Well-characterized pathogenic mutations were identified in SPG7, DCTN1, and PARK2. Most cases showed no known relevant mutations. CONCLUSIONS: Cluster analyses based on clinical variables indicated at least 2 subgroups of clinically definite PLS. Molecular analyses further identified 4 cases with mutations associated with amyotrophic lateral sclerosis, Parkinson disease, and possibly hereditary spastic paraplegia. Phenotypic and molecular characterization is the first step in investigating biological clues toward the definition of PLS. Further studies with larger numbers of patients are essential.

Depression and wish to die in a multicenter cohort of ALS patients.

Our objective was to determine prevalence of depressive disorders and wish to die at the baseline visit of a longitudinal multisite study of patients with ALS. Structured telephone interviews were conducted with patients diagnosed in past 18 months at 16 U.S. ALS centers. Demographic, medical, psychiatric and other psychological measures were administered. Of 329 patients assessed, mean ALSFRS-R score was 36.6; 88% (289/329) had no depressive disorder, 7% (24/329) had minor depression, and 5% (16/329) had current major depressive disorder (DSM-IV criteria). Demographic, financial and employment factors were unrelated to depression, as were duration of ALS symptoms and respiratory status, although depressed patients had lower scores on the total ALSFRS-R (p = 0.004) and gross motor function (p < 0.001). Depressed patients reported less pleasure, greater suffering, weariness and anxiety, more stress, were less hopeful, felt less control over illness management, reported lower quality of life, more often had thoughts about ending their lives and hastening death (all p < 0.001). Of the 62 patients (19% of the sample) who expressed a wish to die, only 37% (23/62) were clinically depressed. In conclusion, depressive disorders are not necessarily to be expected of ALS patients. Wish to die is not always expressed in the context of depression and does not necessarily represent psychopathology as such.

Mortality among cocaine users: a systematic review of cohort studies.

AIMS: To conduct a systematic review of mortality among cohort studies of cocaine users. METHODS: Three electronic databases were searched (EMBASE, Medline and PsychINFO); other online databases were searched using online libraries and repositories of reports and literature in the drug and alcohol field, with requested contributions from trained librarians and experts. Searches and extraction were undertaken using protocols and cross-checking of decisions by two authors. Additional data were requested from study investigators where studies did not report relevant data. RESULTS: 1911 articles and 2 reports were identified from searches, with data from another four studies located from review articles. Seven cohorts of "problem" or dependent cocaine users reported data that permitted mortality rates to be estimated. Crude mortality rates ranged from 0.53 (95% CI: 0.10-1.58) to 6.16 (95% CI: 5.21-7.11) per 100 PY. Standardised mortality ratios (SMRs) reported in four studies suggested that mortality was four to eight times higher among cocaine users than age and sex peers in the general population. CONCLUSIONS: There are limited data on the extent of elevated mortality among problematic or dependent cocaine users and it is unclear how generalisable the results of these studies may be to other populations of problematic cocaine users. Greater attention to both the method of recruitment, and the characteristics of cocaine users, would enhance our understanding of the mortality risks of problematic cocaine use.

Mortality among amphetamine users: a systematic review of cohort studies.

AIMS: To report the results of a comprehensive literature search of studies of mortality among people who use amphetamines. DESIGN AND SETTING: Three electronic databases were searched (EMBASE, Medline and PsycINFO) and "grey" literature was located. Shortlists of papers were circulated to experts to ascertain whether any important papers had been missed. Papers were hand-searched to retrieve any additional relevant articles. MEASUREMENTS: Studies meeting inclusion criteria were prospective cohort studies examining mortality risk among dependent and problematic amphetamine users. Crude mortality rates (CMR/100PY) and standardised mortality ratios (SMRs) were the primary outcome measures considered. Data on overall mortality, and rates for specific causes of death, were of interest. FINDINGS: 2187 articles and 9 grey literature sources were obtained. After thorough review, 72 articles were identified as reporting on amphetamine-related mortality, 7 provided data from cohort studies of users. An additional study of Swedish military conscripts was identified by the authors during correspondence with other researchers. The geographic spread of cohorts was restricted to high income countries with the exception of one Thai study; reporting of standard parameters in mortality studies was often sparse. The estimated CMRs ranged from 0 in Australia to 2.95 (1.46-4.59) in Thailand. The Czech cohort reported the only SMR: 6.22 overall, males: 5.87, females: 7.84. CONCLUSIONS: Given the widespread use of amphetamines, the known non-fatal adverse effects of use and the mortality rates reported here, cohort studies investigating the morbidity and mortality associated with such drug use should be a research priority.