The relation of anxiety and cognition in Parkinson's disease

OBJECTIVE: Parkinson’s disease (PD) has long been conceptualized as a motor disorder, but nonmotor symptoms also manifest in the disease and significantly reduce quality of life. Anxiety and cognitive dysfunction are prevalent nonmotor symptoms, even in early disease stages, but the relation between these symptoms remains poorly understood. We examined self-reported anxiety and neurocognitive function, indexed by measures of executive function (set-shifting and phonemic fluency), categorical fluency, and attention/working memory. We hypothesized that anxiety would correlate with cognitive performance. METHOD: The Beck Anxiety Inventory and cognitive tests (Trail Making, Verbal Fluency, Digit Span) were administered to 77 nondemented adults with mild to moderate idiopathic PD (39 men, 38 women; Mage = 62.9 years). RESULTS: Higher anxiety was associated with more advanced disease stage and severity and with poorer set-shifting when using a derived metric to account for motoric slowing. Depression correlated with greater anxiety and disease severity, but not with cognitive performance. CONCLUSIONS: Our findings support the association of anxiety with a specific domain of executive function, set-shifting, in nondemented individuals with mild to moderate PD, raising the possibility that treatment of anxiety may alleviate aspects of executive dysfunction in this population.Accepted manuscrip

The therapeutic potential of exercise to improve mood, cognition, and sleep in Parkinson's disease

Published in final edited form as: Mov Disord. 2016 January ; 31(1): 23–38. doi:10.1002/mds.26484.In addition to the classic motor symptoms, Parkinson's disease (PD) is associated with a variety of nonmotor symptoms that significantly reduce quality of life, even in the early stages of the disease. There is an urgent need to develop evidence‐based treatments for these symptoms, which include mood disturbances, cognitive dysfunction, and sleep disruption. We focus here on exercise interventions, which have been used to improve mood, cognition, and sleep in healthy older adults and clinical populations, but to date have primarily targeted motor symptoms in PD. We synthesize the existing literature on the benefits of aerobic exercise and strength training on mood, sleep, and cognition as demonstrated in healthy older adults and adults with PD, and suggest that these types of exercise offer a feasible and promising adjunct treatment for mood, cognition, and sleep difficulties in PD. Across stages of the disease, exercise interventions represent a treatment strategy with the unique ability to improve a range of nonmotor symptoms while also alleviating the classic motor symptoms of the disease. Future research in PD should include nonmotor outcomes in exercise trials with the goal of developing evidence‐based exercise interventions as a safe, broad‐spectrum treatment approach to improve mood, cognition, and sleep for individuals with PD.This work was supported by the National Institute of Mental Health (F31MH102961 to G.O.R.)

Cognitive-behavioral therapy for anxiety in Parkinson's disease

Parkinson's disease (PD) is characterized by motor symptoms, but nonmotor symptoms also significantly impair daily functioning and reduce quality of life. Anxiety is prevalent and debilitating in PD, but remains understudied and undertreated. Much affective research in PD focuses on depression rather than anxiety, and as such, there are no evidence-based treatments for anxiety in this population. Cognitive-behavioral therapy (CBT) has shown promise for treating depression in PD and may be efficacious for anxiety. This exploratory study implemented a multiple-baseline single-case experimental design to evaluate the utility and feasibility of CBT for individuals with PD who also met criteria for a DSM-5 anxiety disorder ( n = 9). Participants were randomized to a 2-, 4-, or 6-week baseline phase, followed by 12 CBT sessions, and two post treatment assessments (immediately post treatment and 6-week follow-up). Multiple outcome measures of anxiety and depression were administered weekly during baseline and intervention. Weekly CBT sessions were conducted in-person ( n = 5) or via secure videoconferencing ( n = 4). At post treatment, seven of the nine participants showed significant reductions in anxiety and/or depression, with changes functionally related to treatment and most improvements maintained at 6-week follow-up. Effects of CBT on secondary outcomes varied across participants, with preliminary evidence for reduction in fear of falling. Adherence and retention were high, as were treatment satisfaction and acceptability. The findings of this pilot study provide preliminary evidence for the utility of CBT as a feasible treatment for anxiety and comorbid depressive symptoms in PD and highlight the potential of telehealth interventions for mood in this population.Accepted manuscrip

The potential of cognitive-behavioral intervention for anxiety in Parkinson's disease

OBJECTIVES: Anxiety is a prevalent but understudied non-motor symptom of Parkinson’s disease (PD), for which pharmacological treatments yield mixed results. Cognitive-behavioral therapy (CBT) has shown promise in improving depression in PD, and case studies suggest that it may also alleviate anxiety. Because of the deleterious effects of anxiety on cognition and quality of life, there is need for evidence-based psychological interventions. METHODS: This study explores the utility and feasibility of a transdiagnostic intervention to improve anxiety in PD using a multiple-baseline, single-case experimental design. Following a two-, four-, or six-week baseline phase, five individuals with PD who met DSM-5 criteria for an anxiety disorder received/are receiving 12 weekly sessions of CBT1, followed by a post-intervention assessment and a 6-week no-contact follow-up. Weekly levels of anxiety and depression are measured throughout the study, with measures of cognition, quality of life, sleep, and motor function completed at all pre- and post-intervention assessments. RESULTS: Results to date (2 completers, 3 currently enrolled) suggest that CBT may produce clinically meaningful changes in anxiety, depression, quality of life, and fear of falling (Figure 01). Results are mixed regarding effects on cognition, sleep, and motor function. Treatment satisfaction has been high. CONCLUSIONS: CBT may improve anxiety, depression, quality of life, and fear of falling among adults with PD and clinical anxiety. These findings warrant further exploration of CBT for anxiety across various stages of PD.Accepted manuscrip

Visuospatial Attention to Single and Multiple Objects Is Independently Impaired in Parkinson's Disease

Parkinson’s disease (PD) is associated with deficits in visuospatial attention. It is as yet unknown whether these attentional deficits begin at a perceptual level or instead reflect disruptions in oculomotor or higher-order processes. In the present study, non-demented individuals with PD and matched normal control adults (NC) participated in two tasks requiring sustained visuospatial attention, both based on a multiple object tracking paradigm. Eye tracking was used to ensure central fixation. In Experiment 1 (26 PD, 21 NC), a pair of identical red dots (one target, one distractor) rotated randomly for three seconds at varied speeds. The task was to maintain the identity of the sole target, which was labeled prior to each trial. PD were less accurate than NC overall (p = .049). When considering only trials where fixation was maintained, however, there was no significant group difference, suggesting that the deficit’s origin is closely related to oculomotor processing. To determine whether PD had additional impairment in multifocal attention, in Experiment 2 (25 PD, 15 NC), two targets were presented along with distractors at a moderate speed, along with a control condition in which dots remained stationary. PD were less accurate than NC for moving (p = 0.02) but not stationary targets. This group difference remained significant when considering only trials where fixation was maintained, suggesting the source of the PD deficit was independent from oculomotor processing. Taken together, the results implicate separate mechanisms for single vs. multiple object tracking deficits in PD

Predicting Treatment Response in Social Anxiety Disorder From Functional Magnetic Resonance Imaging

Context: Current behavioral measures poorly predict treatment outcome in social anxiety disorder (SAD). To our knowledge, this is the first study to examine neuroimaging-based treatment prediction in SAD. Objective: To measure brain activation in patients with SAD as a biomarker to predict subsequent response to cognitive behavioral therapy (CBT). Design: Functional magnetic resonance imaging (fMRI) data were collected prior to CBT intervention. Changes in clinical status were regressed on brain responses and tested for selectivity for social stimuli. Setting: Patients were treated with protocol-based CBT at anxiety disorder programs at Boston University or Massachusetts General Hospital and underwent neuroimaging data collection at Massachusetts Institute of Technology. Patients: Thirty-nine medication-free patients meeting DSM-IV criteria for the generalized subtype of SAD. Interventions: Brain responses to angry vs neutral faces or emotional vs neutral scenes were examined with fMRI prior to initiation of CBT. Main Outcome Measures: Whole-brain regression analyses with differential fMRI responses for angry vs neutral faces and changes in Liebowitz Social Anxiety Scale score as the treatment outcome measure. Results: Pretreatment responses significantly predicted subsequent treatment outcome of patients selectively for social stimuli and particularly in regions of higher-order visual cortex. Combining the brain measures with information on clinical severity accounted for more than 40% of the variance in treatment response and substantially exceeded predictions based on clinical measures at baseline. Prediction success was unaffected by testing for potential confounding factors such as depression severity at baseline. Conclusions: The results suggest that brain imaging can provide biomarkers that substantially improve predictions for the success of cognitive behavioral interventions and more generally suggest that such biomarkers may offer evidence-based, personalized medicine approaches for optimally selecting among treatment options for a patient

Failure of Working Memory Training to Enhance Cognition or Intelligence

Fluid intelligence is important for successful functioning in the modern world, but much evidence suggests that fluid intelligence is largely immutable after childhood. Recently, however, researchers have reported gains in fluid intelligence after multiple sessions of adaptive working memory training in adults. The current study attempted to replicate and expand those results by administering a broad assessment of cognitive abilities and personality traits to young adults who underwent 20 sessions of an adaptive dual n-back working memory training program and comparing their post-training performance on those tests to a matched set of young adults who underwent 20 sessions of an adaptive attentional tracking program. Pre- and post-training measurements of fluid intelligence, standardized intelligence tests, speed of processing, reading skills, and other tests of working memory were assessed. Both training groups exhibited substantial and specific improvements on the trained tasks that persisted for at least 6 months post-training, but no transfer of improvement was observed to any of the non-trained measurements when compared to a third untrained group serving as a passive control. These findings fail to support the idea that adaptive working memory training in healthy young adults enhances working memory capacity in non-trained tasks, fluid intelligence, or other measures of cognitive abilities.</p

Failure of Working Memory Training to Enhance Cognition or Intelligence

Fluid intelligence is important for successful functioning in the modern world, but much evidence suggests that fluid intelligence is largely immutable after childhood. Recently, however, researchers have reported gains in fluid intelligence after multiple sessions of adaptive working memory training in adults. The current study attempted to replicate and expand those results by administering a broad assessment of cognitive abilities and personality traits to young adults who underwent 20 sessions of an adaptive dual n-back working memory training program and comparing their post-training performance on those tests to a matched set of young adults who underwent 20 sessions of an adaptive attentional tracking program. Pre- and post-training measurements of fluid intelligence, standardized intelligence tests, speed of processing, reading skills, and other tests of working memory were assessed. Both training groups exhibited substantial and specific improvements on the trained tasks that persisted for at least 6 months post-training, but no transfer of improvement was observed to any of the non-trained measurements when compared to a third untrained group serving as a passive control. These findings fail to support the idea that adaptive working memory training in healthy young adults enhances working memory capacity in non-trained tasks, fluid intelligence, or other measures of cognitive abilities.National Institutes of Health (U.S.) (Blueprint for Neuroscience Research (T90DA022759/R90DA023427)United States. Defense Advanced Research Projects Agency (government contract no. NBCHC070105)United States. Dept. of Defense (National Defense Science and Engineering Fellowship)Massachusetts Institute of Technology (Sheldon Razin (1959) Fellowship

Anatomical connectivity patterns predict face selectivity in the fusiform gyrus

A fundamental assumption in neuroscience is that brain structure determines function. Accordingly, functionally distinct regions of cortex should be structurally distinct in their connections to other areas. We tested this hypothesis in relation to face selectivity in the fusiform gyrus. By using only structural connectivity, as measured through diffusion-weighted imaging, we were able to predict functional activation to faces in the fusiform gyrus. These predictions outperformed two control models and a standard group-average benchmark. The structure–function relationship discovered from the initial participants was highly robust in predicting activation in a second group of participants, despite differences in acquisition parameters and stimuli. This approach can thus reliably estimate activation in participants who cannot perform functional imaging tasks and is an alternative to group-activation maps. Additionally, we identified cortical regions whose connectivity was highly influential in predicting face selectivity within the fusiform, suggesting a possible mechanistic architecture underlying face processing in humans.United States. Public Health Service (DA023427)National Institute of Mental Health (U.S.) (F32 MH084488)National Eye Institute (T32 EY013935)Poitras FoundationSimons FoundationEllison Medical Foundatio

Clinical Risk Factors Associated with Anti-Epileptic Drug Responsiveness in Canine Epilepsy

The nature and occurrence of remission, and conversely, pharmacoresistance following epilepsy treatment is still not fully understood in human or veterinary medicine. As such, predicting which patients will have good or poor treatment outcomes is imprecise, impeding patient management. In the present study, we use a naturally occurring animal model of pharmacoresistant epilepsy to investigate clinical risk factors associated with treatment outcome. Dogs with idiopathic epilepsy, for which no underlying cause was identified, were treated at a canine epilepsy clinic and monitored following discharge from a small animal referral hospital. Clinical data was gained via standardised owner questionnaires and longitudinal follow up data was gained via telephone interview with the dogs’ owners. At follow up, 14% of treated dogs were in seizure-free remission. Dogs that did not achieve remission were more likely to be male, and to have previously experienced cluster seizures. Seizure frequency or the total number of seizures prior to treatment were not significant predictors of pharmacoresistance, demonstrating that seizure density, that is, the temporal pattern of seizure activity, is a more influential predictor of pharmacoresistance. These results are in line with clinical studies of human epilepsy, and experimental rodent models of epilepsy, that patients experiencing episodes of high seizure density (cluster seizures), not just a high seizure frequency pre-treatment, are at an increased risk of drug-refractoriness. These data provide further evidence that the dog could be a useful naturally occurring epilepsy model in the study of pharmacoresistant epilepsy