In an aging population with increasing incidence of dementia and cognitive impairment, strategies are needed to slow age-related decline and reduce disease-related cognitive impairment in older ...adults. Physical exercise that targets modifiable risk factors and neuroprotective mechanisms may reduce declines in cognitive performance attributed to the normal aging process and protect against changes related to neurodegenerative diseases such as Alzheimer's disease and other types of dementia. In this review we summarize the role of exercise in neuroprotection and cognitive performance, and provide information related to implementation of physical exercise programs for older adults. Evidence from both animal and human studies supports the role of physical exercise in modifying metabolic, structural, and functional dimensions of the brain and preserving cognitive performance in older adults. The results of observational studies support a dose-dependent neuroprotective relationship between physical exercise and cognitive performance in older adults. Although some clinical trials of exercise interventions demonstrate positive effects of exercise on cognitive performance, other trials show minimal to no effect. Although further research is needed, physical exercise interventions aimed at improving brain health through neuroprotective mechanisms show promise for preserving cognitive performance. Exercise programs that are structured, individualized, higher intensity, longer duration, and multicomponent show promise for preserving cognitive performance in older adults.
Abstract Introduction Research suggests an association between global cognition and postural instability/gait disturbance (PIGD) in Parkinson disease (PD), but the relationship between specific ...cognitive domains and PIGD symptoms is not clear. This study examined the association of cognition (global and specific cognitive domains) with PIGD symptoms in a large, well-characterized sample of individuals with PD. Methods Cognitive function was measured with a detailed neuropsychological assessment, including global cognition, executive function, memory, visuospatial function, and language. PIGD symptoms were measured using the Movement Disorder Society Unified Parkinson's Disease Rating Scale (MDS-UPDRS) Part III, Motor Examination subscale. Multiple linear regression analyses were performed to assess the relationship between cognition and PIGD symptoms with models adjusting for age, sex, education, enrollment site, disease duration, and motor symptom severity. Results The analysis included 783 participants, with mean (standard deviation) age of 67.3 (9.7) years and median (interquartile range) MDS-UPDRS Motor Subscale score of 26 (17, 35). Deficits in global cognition, executive function, memory, and phonemic fluency were associated with more severe PIGD symptoms. Deficits in executive function were associated with impairments in gait, freezing, and postural stability, while visuospatial impairments were associated only with more severe freezing, and poorer memory function was associated only with greater postural instability. Discussion While impairments in global cognition and aspects of executive functioning were associated with more severe PIGD symptoms, specific cognitive domains were differentially related to distinct PIGD components, suggesting the presence of multiple neural pathways contributing to associations between cognition and PIGD symptoms in persons with PD.
Clinically impairing irritability affects 25% to 45% of children with attention-deficit/hyperactivity disorder (ADHD); yet, we know little about what interventions are effective in treating children ...with ADHD and co-occurring irritability. We used data from the Multimodal Treatment Study of Children With ADHD (MTA) to address 3 aims: to establish whether irritability in children with ADHD can be distinguished from other symptoms of oppositional defiant disorder (ODD); to examine whether ADHD treatment is effective in treating irritability; and to examine how irritability influences ADHD treatment outcomes.
Secondary analyses of data from the MTA included multivariate analyses, and intent-to-treat random-effects regression models were used.
Irritability was separable from other ODD symptoms. For treating irritability, systematic stimulant treatment was superior to behavioral management but not to routine community care; a combination of stimulants and behavioral treatment was superior to community care and to behavioral treatment alone, but not to medication alone. Irritability did not moderate the impact of treatment on parent- and teacher-reported ADHD symptoms in any of the 4 treatment groups.
Treatments targeting ADHD symptoms are helpful for improving irritability in children with ADHD. Moreover, irritability does not appear to influence the response to treatment of ADHD.
Multimodal Treatment Study of Children With Attention Deficit and Hyperactivity Disorder (MTA); http://www.clinicaltrials.gov; NCT00000388.
OBJECTIVE: Risperidone has been found efficacious for decreasing severe tantrums, aggression, and self-injurious behavior in children and adolescents with autistic disorder (autism). The authors ...report on whether risperidone improves the core symptoms of autism, social and communication impairment and repetitive and stereotyped behavior. METHOD: The database from an 8-week double-blind, placebo-controlled trial (N=101) and 16-week open-label continuation study (N=63) of risperidone for children and adolescents with autism was used to test for drug effects on secondary outcome measures: scores on the Ritvo-Freeman Real Life Rating Scale, the Children's Yale-Brown Obsessive Compulsive Scale, and the maladaptive behavior domain of the Vineland Adaptive Behavior Scales. RESULTS: Compared to placebo, risperidone led to a significantly greater reduction in the overall score on the Ritvo-Freeman Real Life Rating Scale, as well as the scores on the subscales for sensory motor behaviors (subscale I), affectual reactions (subscale III), and sensory responses (subscale IV). No statistically significant difference was observed, however, on the subscale for social relatedness (subscale II) or language (subscale V). Risperidone also resulted in significantly greater reductions in scores on the Children's Yale-Brown Obsessive Compulsive Scale and Vineland maladaptive behavior domain. This pattern of treatment response was maintained for 6 months. CONCLUSIONS: Risperidone led to significant improvements in the restricted, repetitive, and stereotyped patterns of behavior, interests, and activities of autistic children but did not significantly change their deficit in social interaction and communication. Further research is necessary to develop effective treatments for the core social and communicative impairments of autism.
Treatment-emergent adverse events (AEs) were monitored during an 8-week, double-blind, placebo-controlled trial of risperidone (0.5-3.5 mg/day) in 101 children and adolescents with a lifetime ...diagnosis of autistic disorder. In addition, 37 placebo nonresponders received open-label risperidone for another 8 weeks. Of all the risperidone responders (n=65), 63 entered an open extension of another 16 weeks (6 months total risperidone exposure), and 32 of them were rerandomized to either continued risperidone therapy (n=16) or gradual replacement with placebo (n=16) over 8 weeks. We collected the following measures of safety and tolerability: (1) laboratory blood assessments (CBC with differential, electrolytes, and liver function tests) and urinalyses, (2) vital signs, (3) Side Effects Review of AEs thought to be associated with risperidone, (4) sleep records, (5) Simpson Angus Neurological Rating Scale (SARS), (6) Abnormal Involuntary Movement Scale (AIMS), and (7) height and weight. No clinically significant changes were found on the lab tests. During the 8-week acute trial, the most common AEs on the Side Effects Review, scored as moderate or higher, were as follows (placebo and risperidone, respectively): Somnolence (12% and 37%), enuresis (29% and 33%), excessive appetite (10% and 33%), rhinitis (8% and 16%), difficulty waking (8% and 12%), and constipation (12% and 10%). "Difficulty falling asleep" and anxiety actually favored the risperidone condition at statistically significant levels. The same AEs tended to recur through 6 months of treatment, although often at reduced levels. Using Centers for Disease Control (CDC) standardized scores, both weight and body mass index (BMI) increased with risperidone during the acute trial (0.5 and 0.6 SDs, respectively, for risperidone; 0.0 and 0.1 SDs, respectively, for placebo) and into open-label extension (0.19 and 0.16 SDs, respectively), although the amount of gain decelerated with time. Extrapyramidal symptoms, as assessed by the SARS, were no more common for drug than placebo, although drooling was reported more often in the risperidone group. There were no differences between groups on the AIMS. Two subjects had seizures (one taking placebo), but these were considered unrelated to active drug. Most AEs were mild to moderate and failed to interfere with therapeutic changes; there were no unanticipated AEs. The side effects of most concern were somnolence and weight gain.
This paper explains how the Autism Research Units on Pediatric Psychopharmacology (RUPP Autism Network) resolved common assessment problems including communication problems compromising use of the ...patient as informant, broad subject heterogeneity, difficulties in assessing low-end IQs, scarcity of autism-adapted cognitive and neuropsychological tests, and reliability of the Autism Diagnostic Interview. (Contains extensive references.) (DB)
This article has reviewed the background and rationale for the choice of risperidone as the first drug to be studied by the RUPP Autism Network. Risperidone has potent effects on 5-HT and DA neuronal ...systems, both of which have been implicated in the pathophysiology of autism. Unlike the typical antipsychotics, haloperidol and pimozide, which have been shown to be effective for reducing many of the maladaptive behaviors associated with autism, risperidone's 5-HT2A/DA D2 ratio of receptor blockade appears to produce a lower risk of acute and chronic extrapyramidal side effects, as well as enhanced efficacy for the "negative" symptoms of autism. Indirect clinical and preclinical evidence supports the use of risperidone to treat impaired social behavior, interfering repetitive phenomena, and aggression, targets of pharmacotherapy for many patients with autism. Numerous published open-label trials in children and adolescents with autism and related PDDs and one double-blind, placebo-controlled study in adults suggest that risperidone has promise for the treatment of children and adolescents with autism. Because most of these studies have been short-term, open-label trials in small samples, however, a large-scale controlled study of risperidone in children and adolescents with autism is needed to confirm these results. Finally, because it is likely that children who demonstrate short-term benefit from risperidone will remain on the medication indefinitely, the longer-term effectiveness and safety of risperidone in this population also needs to be determined. The design of this study and the assessments used are described separately.
OBJECTIVE: Patterns of psychiatric comorbidity were assessed in adults with and without attention deficit hyperactivity disorder (ADHD) identified through a genetic study of families containing ...multiple children with ADHD. METHOD: Lifetime ADHD and comorbid psychopathology were assessed in 435 parents of children with ADHD. Rates and mean ages at onset of comorbid psychopathology were compared in parents with lifetime ADHD, parents with persistent ADHD, and those without ADHD. Age-adjusted rates of comorbidity were compared with Kaplan-Meier survival curves. Logistic regression was used to assess additional risk factors for conditions more frequent in ADHD subjects. RESULTS: The parents with ADHD were significantly more likely to be unskilled workers and less likely to have a college degree. ADHD subjects had more lifetime psychopathology; 87% had at least one and 56% had at least two other psychiatric disorders, compared with 64% and 27%, respectively, in non-ADHD subjects. ADHD was associated with greater disruptive behavior, substance use, and mood and anxiety disorders and with earlier onset of major depression, dysthymia, oppositional defiant disorder, and conduct disorder. Group differences based on Kaplan-Meier age-corrected risks were consistent with those for raw frequency distributions. Male sex added risk for disruptive behavior disorders. Female sex and oppositional defiant disorder contributed to risk for depression and anxiety. ADHD was not a significant risk factor for substance use disorders when male sex, disruptive behavior disorders, and socioeconomic status were controlled. CONCLUSIONS: Adult ADHD is associated with significant lifetime psychiatric comorbidity that is not explained by clinical referral bias.
Older adults with amnestic mild cognitive impairment (aMCI) are at higher risk for developing Alzheimer disease. Physical performance decline on gait and mobility tasks in conjunction with executive ...dysfunction has implications for accelerated functional decline, disability, and institutionalization in sedentary older adults with aMCI.
The purpose of this study was to examine whether performance on 2 tests commonly used by physical therapists (usual gait speed and Timed "Up & Go" Test TUG) are associated with performance on 2 neuropsychological tests of executive function (Trail Making Test, part B TMT-B, and Stroop-Interference, calculated from the Stroop Word Color Test) in sedentary older adults with aMCI.
The study was a cross-sectional analysis of 201 sedentary older adults with memory impairment participating in a longitudinal intervention study of cognitive function, aging, exercise, and health promotion.
Physical performance speed on gait and mobility tasks was measured via usual gait speed and the TUG (at fast pace). Executive function was measured with the TMT-B and Stroop-Interference measures.
Applying multiple linear regression, usual gait speed was associated with executive function on both the TMT-B (β=-0.215, P=.003) and Stroop-Interference (β=-0.195, P=.01) measures, indicating that slower usual gait speed was associated with lower executive function performance. Timed "Up & Go" Test scores (in logarithmic transformation) also were associated with executive function on both the TMT-B (β=0.256, P<.001) and Stroop-Interference (β=0.228, P=.002) measures, indicating that a longer time on the TUG was associated with lower executive function performance. All associations remained statistically significant after adjusting for age, sex, depressive symptoms, medical comorbidity, and body mass index.
The cross-sectional nature of this study does not allow for inferences of causation.
Physical performance speed was associated with executive function after adjusting for age, sex, and age-related factors in sedentary older adults with aMCI. Further research is needed to determine mechanisms and early intervention strategies to slow functional decline.
A multidisciplinary panel of 18 physicians and 3 non-physicians from eight countries (Sweden, UK, Argentina, Australia, Italy, Finland, Norway and the USA) reviewed the literature on diagnosis and ...management of adult coeliac disease (CD). This paper presents the recommendations of the British Society of Gastroenterology. Areas of controversies were explored through phone meetings and web surveys. Nine working groups examined the following areas of CD diagnosis and management: classification of CD; genetics and immunology; diagnostics; serology and endoscopy; follow-up; gluten-free diet; refractory CD and malignancies; quality of life; novel treatments; patient support; and screening for CD.
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