Enhancing Patient Understanding of Medication Risks and Benefits.

OBJECTIVE: To evaluate the effectiveness of 2 interventions, including the DrugFactsBox format for presenting written medication information and the SMART (Strategic Memory Advanced Reasoning Training) program designed to enhance gist (i.e., "bottom-line" meaning) reasoning ability. METHODS: We used a 2 × 2 factorial research design. A total of 286 patients with rheumatoid arthritis were randomly assigned to 1 of 4 groups, including DrugFactsBox with the SMART program, DrugFactsBox without the SMART program, other consumer medication information (CMI) with the SMART program, and other CMI without the SMART program. Data were collected via telephone interviews and online questionnaires at 4 time points, including baseline and 6-week, 3-month, and 6-month time points following baseline. The primary outcome variable was informed decision-making, which was defined as making a value-consistent decision concerning use of disease-modifying antirheumatic drugs based on adequate knowledge. RESULTS: We found no main effects for the 2 interventions, either alone or in combination. However, there was a significant interaction between assignment to the SMART/no SMART groups and informed decision-making at baseline. Among participants in the SMART groups who did not meet the criteria for informed decision-making at baseline, 42.5% met the criteria at the 6-month follow-up, compared to 23.6% of participants in the no SMART groups (mean difference 18.9 [95% confidence interval 5.6, 32.2]; P = 0.007). This difference was driven by increased knowledge in the SMART groups. Among participants who met the criteria for informed decision-making at baseline, the difference between the SMART and no SMART groups was not statistically significant. CONCLUSION: Participation in a theory-driven program to enhance gist reasoning may have a beneficial effect on informed decision-making among patients with inadequate knowledge concerning therapeutic options.

Enhancing Innovation and Underlying Neural Mechanisms Via Cognitive Training in Healthy Older Adults.

Non-invasive interventions, such as cognitive training (CT) and physical exercise, are gaining momentum as ways to augment both cognitive and brain function throughout life. One of the most fundamental yet little studied aspects of human cognition is innovative thinking, especially in older adults. In this study, we utilize a measure of innovative cognition that examines both the quantity and quality of abstracted interpretations. This randomized pilot trial in cognitively normal adults (56-75 years) compared the effect of cognitive reasoning training (SMART) on innovative cognition as measured by Multiple Interpretations Measure (MIM). We also examined brain changes in relation to MIM using two MRI-based measurement of arterial spin labeling (ASL) to measure cerebral blood flow (CBF) and functional connectivity MRI (fcMRI) to measure default mode and central executive network (CEN) synchrony at rest. Participants (N = 58) were randomized to the CT, physical exercise (physical training, PT) or control (CN) group where CT and PT groups received training for 3 h/week over 12 weeks. They were assessed at baseline-, mid- and post-training using innovative cognition and MRI measures. First, the CT group showed significant gains pre- to post-training on the innovation measure whereas the physical exercise and control groups failed to show significant gains. Next, the CT group showed increased CBF in medial orbitofrontal cortex (mOFC) and bilateral posterior cingulate cortex (PCC), two nodes within the Default Mode Network (DMN) compared to physical exercise and control groups. Last, significant correlations were found between innovation performance and connectivity of two major networks: CEN (positive correlation) and DMN (negative correlation). These results support the view that both the CEN and DMN are important for enhancement of innovative cognition. We propose that neural mechanisms in healthy older adults can be modified through reasoning training to better subserve enhanced innovative cognition.

Modular Brain Network Organization Predicts Response to Cognitive Training in Older Adults.

Cognitive training interventions are a promising approach to mitigate cognitive deficits common in aging and, ultimately, to improve functioning in older adults. Baseline neural factors, such as properties of brain networks, may predict training outcomes and can be used to improve the effectiveness of interventions. Here, we investigated the relationship between baseline brain network modularity, a measure of the segregation of brain sub-networks, and training-related gains in cognition in older adults. We found that older adults with more segregated brain sub-networks (i.e., more modular networks) at baseline exhibited greater training improvements in the ability to synthesize complex information. Further, the relationship between modularity and training-related gains was more pronounced in sub-networks mediating "associative" functions compared with those involved in sensory-motor processing. These results suggest that assessments of brain networks can be used as a biomarker to guide the implementation of cognitive interventions and improve outcomes across individuals. More broadly, these findings also suggest that properties of brain networks may capture individual differences in learning and neuroplasticity. Trail Registration: ClinicalTrials.gov, NCT#00977418.

Distinct Brain and Behavioral Benefits from Cognitive vs. Physical Training: A Randomized Trial in Aging Adults.

Insidious declines in normal aging are well-established. Emerging evidence suggests that non-pharmacological interventions, specifically cognitive and physical training, may counter diminishing age-related cognitive and brain functions. This randomized trial compared effects of two training protocols: cognitive training (CT) vs. physical training (PT) on cognition and brain function in adults 56-75 years. Sedentary participants (N = 36) were randomized to either CT or PT group for 3 h/week over 12 weeks. They were assessed at baseline-, mid-, and post-training using neurocognitive, MRI, and physiological measures. The CT group improved on executive function whereas PT group's memory was enhanced. Uniquely deploying cerebral blood flow (CBF) and cerebral vascular reactivity (CVR) MRI, the CT cohort showed increased CBF within the prefrontal and middle/posterior cingulate cortex (PCC) without change to CVR compared to PT group. Improvements in complex abstraction were positively associated with increased resting CBF in dorsal anterior cingulate cortex (dACC). Exercisers with higher CBF in hippocampi bilaterally showed better immediate memory. The preliminary evidence indicates that increased cognitive and physical activity improves brain health in distinct ways. Reasoning training enhanced frontal networks shown to be integral to top-down cognitive control and brain resilience. Evidence of increased resting CBF without changes to CVR implicates increased neural health rather than improved vascular response. Exercise did not improve cerebrovascular response, although CBF increased in hippocampi of those with memory gains. Distinct benefits incentivize testing effectiveness of combined protocols to strengthen brain health.

Reasoning training in veteran and civilian traumatic brain injury with persistent mild impairment.

Traumatic brain injury (TBI) is a chronic health condition. The prevalence of TBI, combined with limited advances in protocols to mitigate persistent TBI-related impairments in higher order cognition, present a significant challenge. In this randomised study (n = 60), we compared the benefits of Strategic Memory Advanced Reasoning Training (SMART, n = 31), a strategy-based programme shown to improve cognitive control, versus an active learning programme called Brain Health Workshop (BHW, n = 29) in individuals with TBI with persistent mild functional deficits. Outcomes were measured on cognitive, psychological health, functional, and imaging measures. Repeated measures analyses of immediate post-training and 3-month post-training demonstrated gains on the cognitive control domain of gist reasoning (ability to abstract big ideas/goals from complex information/tasks) in the SMART group as compared to BHW. Gains following the SMART programme were also evident on improved executive function, memory, and daily function as well as reduced symptoms associated with depression and stress. The SMART group showed an increase in bilateral precuneus cerebral blood flow (CBF). Improvements in gist reasoning in the SMART group were also associated with an increase in CBF in the left inferior frontal region, the left insula and the bilateral anterior cingulate cortex. These results add to prior findings that the SMART programme provides an efficient set of strategies that have the potential to improve cognitive control performance and associated executive functions and daily function, to enhance psychological health, and facilitate positive neural plasticity in adults with persistent mild impairment after TBI.

Neural mechanisms of brain plasticity with complex cognitive training in healthy seniors.

Complex mental activity induces improvements in cognition, brain function, and structure in animals and young adults. It is not clear to what extent the aging brain is capable of such plasticity. This study expands previous evidence of generalized cognitive gains after mental training in healthy seniors. Using 3 MRI-based measurements, that is, arterial spin labeling MRI, functional connectivity, and diffusion tensor imaging, we examined brain changes across 3 time points pre, mid, and post training (12 weeks) in a randomized sample (n = 37) who received cognitive training versus a control group. We found significant training-related brain state changes at rest; specifically, 1) increases in global and regional cerebral blood flow (CBF), particularly in the default mode network and the central executive network, 2) greater connectivity in these same networks, and 3) increased white matter integrity in the left uncinate demonstrated by an increase in fractional anisotropy. Improvements in cognition were identified along with significant CBF correlates of the cognitive gains. We propose that cognitive training enhances resting-state neural activity and connectivity, increasing the blood supply to these regions via neurovascular coupling. These convergent results provide preliminary evidence that neural plasticity can be harnessed to mitigate brain losses with cognitive training in seniors.

Shorter term aerobic exercise improves brain, cognition, and cardiovascular fitness in aging.

Physical exercise, particularly aerobic exercise, is documented as providing a low cost regimen to counter well-documented cognitive declines including memory, executive function, visuospatial skills, and processing speed in normally aging adults. Prior aging studies focused largely on the effects of medium to long term (>6 months) exercise training; however, the shorter term effects have not been studied. In the present study, we examined changes in brain blood flow, cognition, and fitness in 37 cognitively healthy sedentary adults (57-75 years of age) who were randomized into physical training or a wait-list control group. The physical training group received supervised aerobic exercise for 3 sessions per week 1 h each for 12 weeks. Participants' cognitive, cardiovascular fitness and resting cerebral blood flow (CBF) were assessed at baseline (T1), mid (T2), and post-training (T3). We found higher resting CBF in the anterior cingulate region in the physical training group as compared to the control group from T1 to T3. Cognitive gains were manifested in the exercise group's improved immediate and delayed memory performance from T1 to T3 which also showed a significant positive association with increases in both left and right hippocampal CBF identified earlier in the time course at T2. Additionally, the two cardiovascular parameters, VO2 max and rating of perceived exertion (RPE) showed gains, compared to the control group. These data suggest that even shorter term aerobic exercise can facilitate neuroplasticity to reduce both the biological and cognitive consequences of aging to benefit brain health in sedentary adults.

Evaluating the effectiveness of reasoning training in military and civilian chronic traumatic brain injury patients: study protocol.

BACKGROUND: Individuals who sustain traumatic brain injuries (TBIs) often continue to experience significant impairment of cognitive functions mediated by the prefrontal cortex well into chronic stages of recovery. Traditional brain training programs that focus on improving specific skills fall short of addressing integrative functions that draw upon multiple higher-order processes critical for social and vocational integration. In the current study, we compare the effects of two short-term, intensive, group-based cognitive rehabilitation programs for individuals with chronic TBI. One program emphasizes learning about brain functions and influences on cognition, while the other program adopts a top-down approach to improve abstract reasoning abilities that are largely reliant on the prefrontal cortex. These treatment programs are evaluated in civilian and military veteran TBI populations. METHODS/DESIGN: One hundred individuals are being enrolled in this double-blinded clinical trial (all measures and data analyses will be conducted by blinded raters and analysts). Each individual is randomly assigned to one of two treatment conditions, with each condition run in groups of five to seven individuals. The primary anticipated outcomes are improvement in abstract reasoning and everyday life functioning, measured through behavioral tasks and questionnaires, and attention modulation, as measured by functional neuroimaging. Secondary expected outcomes include improvements in the cognitive processes of working memory, attention, and inhibitory control. DISCUSSION: Results of this trial will determine whether cognitive rehabilitation aimed at teaching TBI-relevant information about the brain and cognition versus training in TBI-affected thinking abilities (e.g., memory, attention, and executive functioning) can improve outcomes in chronic military and civilian TBI patient populations. It should shed light on the nature of improvements and the characteristics of patients most likely to benefit. This trial will also provide information about the sustainability of treatment-related improvements 3 months post-training. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT01552473.

Higher-order reasoning training years after traumatic brain injury in adults.

OBJECTIVE: To conduct a feasibility study to compare the effects of top-down Strategic Memory and Reasoning Training (SMART) versus information-based Brain Health Workshop (BHW, control) on gist-reasoning (ie, abstracting novel meaning from complex information), memory, executive functions, and daily function in adults with traumatic brain injury. PARTICIPANTS: Twenty-eight participants (of the 35 recruited), 16 men & 12 women, aged 20 to 65 years (M = 43, SD = 11.34) at chronic stages posttraumatic brain injury (2 years or longer) completed the training. Fourteen participants that received SMART and 14 participants that completed BHW were assessed both pre- and posttraining. Thirteen of the SMART trained and 11 from BHW participated in a 6-month testing. DESIGN: The study was a single blinded randomized control trial. Participants in both groups received a minimum of 15 hours of training over 8 weeks. RESULTS: The SMART group significantly improved gist-reasoning as compared to the BHW group. Benefits of the SMART extended to untrained measures of working memory and participation in functional activities. Exploratory analyses suggested potential transfer effects of SMART on memory and executive functions. The benefits of the SMART program as compared to BHW were evident at immediately posttraining and 6 months posttraining. CONCLUSION: This study provides preliminary evidence that short-term intensive training in top-down modulation of information benefits gist-reasoning and generalizes to measures of executive function and real life function at chronic stages of post-TBI.

Gist reasoning training in cognitively normal seniors.

OBJECTIVE: Cognitive impairment is a key factor that threatens functionality and quality of life in seniors. Given the projection that the population of individuals 65 years of age and older will double within the next 25 years, a critical need exists to identify and test effectiveness of protocols that target higher-order cognitive skills such as gist reasoning to maximize cognitive capacity in later life. METHODS: This study examined the effects of eight hours of gist reasoning training in 26 cognitively normal seniors between the ages of 64-85 years (M = 74.23, SD = 6.67). RESULTS: Findings suggest that top-down strategy-based gist reasoning training significantly improved abstraction ability, a skill relevant to everyday life, as well as generalized to untrained measures of executive function including concept abstraction, cognitive switching, and verbal fluency. Individuals with lower baseline ability to abstract gist showed the greatest gain in the target domain trained. CONCLUSIONS: These findings highlight the potential value of engaging in cognitively challenging activities that involve gist reasoning, to strengthen and preserve cognitive capacity with aging.