Promoting Growth in Behavioral Neurology: A Path Forward.

Behavioral neurology & neuropsychiatry (BNNP) is a field that seeks to understand brain-behavior relationships, including fundamental brain organization principles and the many ways that brain structures and connectivity can be disrupted, leading to abnormalities of behavior, cognition, emotion, perception, and social cognition. In North America, BNNP has existed as an integrated subspecialty through the United Council for Neurologic Subspecialties since 2006. Nonetheless, the number of behavioral neurologists across academic medical centers and community settings is not keeping pace with increasing clinical and research demand. In this commentary, we provide a brief history of BNNP followed by an outline of the current challenges and opportunities for BNNP from the behavioral neurologist's perspective across clinical, research, and educational spheres. We provide a practical guide for promoting BNNP and addressing the shortage of behavioral neurologists to facilitate the continued growth and development of the subspecialty. We also urge a greater commitment to recruit trainees from diverse backgrounds so as to dismantle persistent obstacles that hinder inclusivity in BNNP-efforts that will further enhance the growth and impact of the subspecialty. With rapidly expanding diagnostic and therapeutic approaches across a range of conditions at the intersection of neurology and psychiatry, BNNP is well positioned to attract new trainees and expand its reach across clinical, research, and educational activities.

BDNF mediates improvement in cognitive performance after computerized cognitive training in healthy older adults.

Introduction: The often-cited mechanism linking brain-derived neurotrophic factor (BDNF) to cognitive health has received limited experimental study. There is evidence that cognitive training, physical exercise, and mindfulness meditation may improve cognition. Here, we investigated whether improvements in cognition after these three types of structured interventions are facilitated by increases in BDNF. Methods: A total of 144 heathy older adults completed a 5-week intervention involving working memory/cognitive training, physical exercise, mindfulness meditation, or an active control condition. Serum BDNF levels and Digit Symbol Test (DST) performance were measured pre- and post-intervention. Results: Linear mixed models suggested that only the cognitive training group demonstrated augmentation of BDNF and DST performance relative to the control condition. Path analysis revealed that changes in BDNF mediate intervention-related improvement in task performance. Regression analyses showed that, across all intervention conditions, increased BDNF levels were associated with increased DST scores. Discussion: This study appears to be the first to suggest that BDNF helps mediate improvements in cognition after working memory training in healthy older adults. Highlights: Older adults were randomized to physical activity, mindfulness, cognitive training (computerized cognitive training (CCT), or control.CCT, but no other condition, led to increased serum brain-derived neurotrophic factor (BDNF) levels.CCT led to improvement on the untrained Digit Symbol Test (DST) of speed/working memory.Path analysis: increases in BDNF mediate intervention-related improvement on DST.Increases in BDNF associated with improved DST across all experimental groups.

Promoting Successful Cognitive Aging: A Ten-Year Update.

A decade has passed since we published a comprehensive review in this journal addressing the topic of promoting successful cognitive aging, making this a good time to take stock of the field. Because there have been limited large-scale, randomized controlled trials, especially following individuals from middle age to late life, some experts have questioned whether recommendations can be legitimately offered about reducing the risk of cognitive decline and dementia. Despite uncertainties, clinicians often need to at least make provisional recommendations to patients based on the highest quality data available. Converging lines of evidence from epidemiological/cohort studies, animal/basic science studies, human proof-of-concept studies, and human intervention studies can provide guidance, highlighting strategies for enhancing cognitive reserve and preventing loss of cognitive capacity. Many of the suggestions made in 2010 have been supported by additional research. Importantly, there is a growing consensus among major health organizations about recommendations to mitigate cognitive decline and promote healthy cognitive aging. Regular physical activity and treatment of cardiovascular risk factors have been supported by all of these organizations. Most organizations have also embraced cognitively stimulating activities, a heart-healthy diet, smoking cessation, and countering metabolic syndrome. Other behaviors like regular social engagement, limiting alcohol use, stress management, getting adequate sleep, avoiding anticholinergic medications, addressing sensory deficits, and protecting the brain against physical and toxic damage also have been endorsed, although less consistently. In this update, we review the evidence for each of these recommendations and offer practical advice about behavior-change techniques to help patients adopt brain-healthy behaviors.

Cognitive Impairment in Aging Physicians: Current Challenges and Possible Solutions.

Aging physicians are at a higher risk of cognitive impairment, undermining patient safety and unraveling physicians' careers. Neurologists, occupational health physicians, and psychiatrists will participate in both health system policy decisions and individual patient evaluations. We address cognitive impairment in aging physicians and attendant risks and benefits. If significant cognitive impairment is found after an appropriate evaluation, precautions to confidentially support physicians' practicing safely for as long as possible should be instituted. Understanding that there is heterogeneity and variability in the course of cognitive disorders is crucial to supporting cognitively impaired, practicing physicians. Physicians who are no longer able to practice clinically have other meaningful options.

Capacity-limited resources are used for managing sensory degradation and cognitive demands: Implications for age-related cognitive decline and dementia.

Older adults with sensory deficits are at higher risk for developing cognitive impairment and dementia. It remains uncertain if the link between sensory and cognitive functioning reflects a common underlying factor or whether sensory deficits directly undermine cognitive processing. This issue was addressed by comparing behavioral and event-related potential responses of 16 older and 16 young adults during a working memory paradigm that parametrically varied visual contrast level (100%, 69%, 22%) and cognitive task load (1-4 face pairs to remember). The groups were well-matched on demographic and neuropsychological variables; however, older adults had worse corrected visual acuity and contrast sensitivity. The study's major finding was an interaction between visual contrast level and task load on performance accuracy (percent of correct responses) and the allocation of resources for decision making/updating (as indexed by the P3b amplitude). The negative impact of degraded visual processing was greater at higher levels of task demand. This result suggests that a shared pool of processing resources is used to mediate cognitive operations and manage the processing of degraded images. The study also demonstrated that older adults reach the limits of their processing capacity at lower levels of task load. The interaction between visual degradation and task demand, accompanied by the age-related reduction in available processing resources highlight the increased vulnerability of older adults. Specifically, an age-associated decline in visual acuity and contrast sensitivity puts older adults at risk for depleting their limited resources in the service of processing degraded visual images. The results of this study underscore the potential importance of optimizing vision in older adults to help mitigate age-associated cognitive decline.

New-Onset Delusions Heralding an Underlying Neurodegenerative Condition: A Case Report and Review of the Literature.

OBJECTIVE: To present a striking case of new-onset psychosis in a middle-aged woman subsequently diagnosed with behavioral variant frontotemporal dementia (bvFTD). To review the data regarding key red-flag features that may suggest a diagnosis of a neurodegenerative process, and specifically bvFTD, rather than a primary psychotic disorder. To examine the role of genetics, especially mutations of the microtubule-associated protein tau (MAPT) gene, in familial cases of frontotemporal dementia (FTD). DATA SOURCES: The pertinent literature was searched online (PubMed, Google Scholar) using the following search terms: frontotemporal dementia (FTD), Pick's disease, behavioral variant FTD (bvFTD), psychosis, delusions, MAPT, and genetics. No date or language limit was applied. STUDY SELECTION: The case report was generated through detailed assessment of clinical notes, imaging studies, and laboratory results. The brain autopsy was carried out and summarized by our neuropathology team. Previously published literature was selected for inclusion in the review section based on relevance to the topic. RESULTS: A neurodegenerative etiology for psychosis (and specifically bvFTD) should be suspected in patients with progressive deficits in executive function, language, or memory. Other key warning features include the presence of a strong family history of a late-life psychotic disorder (or institutional placement or suicide), loss of empathy, impaired recognition of facial expression, or the development of emotional blunting and apathy, abnormal movements, or seizures. CONCLUSIONS: Neurodegenerative disease should be on the differential diagnosis for any patient presenting with new-onset psychosis and behavioral changes in mid to late adulthood. Should red-flag features be present, early referral to a clinic specializing in dementia is recommended for further evaluation. This case highlights that MAPT mutations can be associated with psychosis in FTD and should be considered in the genetic workup. Ongoing research into the cellular and neural circuit mechanisms of psychosis in neurodegenerative disease may shed light on pathologic processes underlying psychosis in primary psychiatric disorders.

Feasibility of an at-home, web-based, interactive exercise program for older adults.

INTRODUCTION: Increased physical exercise is linked to enhanced brain health and reduced dementia risk. Exercise intervention studies usually are conducted at facilities in groups under trainer supervision. To improve scalability, accessibility, and engagement, programs may need to be structured such that individuals can execute and adjust routines in their own homes. METHODS: One hundred eighty-three healthy older adults from two sites (the United States and Sweden) were screened. One hundred fifty-six subjects (mean age 73.2), randomly assigned to one of four interventions (PACE-Yourself physical exercise program, mindfulness meditation, or Cogmed® adaptive or nonadaptive computerized working memory training) began the study. All interventions were structurally similar: occurring in subjects' homes using interactive, web-based software, over five weeks, ∼175 minutes/week. In the PACE-Yourself program, video segments presented aerobic exercises at different pace and intensity (P&I). The program paused frequently, allowing subjects to indicate whether P&I was "too easy," "too hard," or "somewhat hard." P&I of the subsequent exercise set was adjusted, allowing subjects to exercise at a perceived exertion level of "somewhat hard." Program completion was defined as finishing ≥60% of sessions. RESULTS: A high percentage of participants in all groups completed the program, although the number (86%) was slightly lower in the PACE-Yourself group than the other three. Excluding dropouts, the PACE-Yourself group had a lower adherence rate of 93%, compared with the other three (∼98%). Over the five weeks, PACE-Yourself participants increased exercising at the highest intensity level, consistent with augmented aerobic activity over time. The number of exercise sessions completed predicted the postintervention versus preintervention increase in self-reported level of physical activity. DISCUSSION: This study supports the feasibility of a home-based, subject-controlled, exercise program in which P&I is regulated via real-time participant feedback, which may promote self-efficacy. Further study is needed to determine if similar results are found over longer periods and in more diverse populations.

The Brain Health Champion study: Health coaching changes behaviors in patients with cognitive impairment.

INTRODUCTION: Converging evidence suggests that increasing healthy behaviors may slow or prevent cognitive decline. METHODS: We piloted a six-month, randomized, controlled investigation of 40 patients with mild dementia, mild cognitive impairment, or subjective cognitive decline. The intervention consisted of weekly motivational interviewing phone calls and three visits with a "Brain Health Champion" health coach, who guided participants to achieve personalized goals. Changes in behavior were measured using validated questionnaires. RESULTS: Compared with the standard-of-care control group, Brain Health Champion participants had statistically significant and clinically meaningful increases in physical activity (Cohen's d = 1.37, P < .001), adherence to the Mediterranean diet (Cohen's d = 0.87, P = .016), cognitive/social activity (Cohen's d = 1.09, P = .003), and quality of life (Cohen's d = 1.23, P < .001). The magnitude of behavior change strongly predicted improvement in quality of life. DISCUSSION: Our results demonstrate the feasibility and potential efficacy of a health coaching approach in changing health behaviors in cognitively impaired and at-risk patients.

Markers of Novelty Processing in Older Adults Are Stable and Reliable.

Exploratory behavior and responsiveness to novelty play an important role in maintaining cognitive function in older adults. Inferences about age- or disease-related differences in neural and behavioral responses to novelty are most often based on results from single experimental testing sessions. There has been very limited research on whether such findings represent stable characteristics of populations studied, which is essential if investigators are to determine the result of interventions aimed at promoting exploratory behaviors or draw appropriate conclusions about differences in the processing of novelty across diverse clinical groups. The goal of the current study was to investigate the short-term test-retest reliability of event-related potential (ERP) and behavioral responses to novel stimuli in cognitively normal older adults. ERPs and viewing durations were recorded in 70 healthy older adults participating in a subject-controlled visual novelty oddball task during two sessions occurring 7 weeks apart. Mean midline P3 amplitude and latency, mean midline amplitude during successive 50 ms intervals, temporospatial factors derived from principal component analysis (PCA), and viewing duration in response to novel stimuli were measured during each session. Analysis of variance (ANOVA) revealed no reliable differences in the value of any measurements between Time 1 and 2. Intraclass correlation coefficients (ICCs) between Time 1 and 2 were excellent for mean P3 amplitude (ICC = 0.86), the two temporospatial factors consistent with the P3 components (ICC of 0.88 and 0.76) and viewing duration of novel stimuli (ICC = 0.81). Reliability was only fair for P3 peak latency (ICC = 0.56). Successive 50 ms mean amplitude measures from 100 to 1,000 ms yielded fair to excellent reliabilities, and all but one of the 12 temporospatial factors identified demonstrated ICCs in the good to excellent range. We conclude that older adults demonstrate substantial stability in ERP and behavioral responses to novel visual stimuli over a 7-week period. These results suggest that older adults may have a characteristic way of processing novelty that appears resistant to transient changes in their environment or internal states, which can be indexed during a single testing session. The establishment of reliable measures of novelty processing will allow investigators to determine whether proposed interventions have an impact on this important aspect of behavior.

Is Computerized Working Memory Training Effective in Healthy Older Adults? Evidence from a Multi-Site, Randomized Controlled Trial.

BACKGROUND: Developing effective interventions to attenuate age-related cognitive decline and prevent or delay the onset of dementia are major public health goals. Computerized cognitive training (CCT) has been marketed increasingly to older adults, but its efficacy remains unclear. Working memory (WM), a key determinant of higher order cognitive abilities, is susceptible to age-related decline and a relevant target for CCT in elders. OBJECTIVE: To evaluate the efficacy of CCT focused on WM compared to an active control condition in healthy older adults. METHODS: Eighty-two cognitively normal adults from two sites (USA and Sweden) were randomly assigned to Cogmed Adaptive or Non-Adaptive (active control) CCT groups. Training was performed in participants' homes, five days per week over five weeks. Changes in the performance of the Cogmed trained tasks, and in five neuropsychological tests (Trail Making Test Part A and Part B, Digit Symbol, Controlled Oral Word Association Test and Semantic Fluency) were used as outcome measures. RESULTS: The groups were comparable at baseline. The Adaptive group showed robust gains in the trained tasks, and there was a time-by-group interaction for the Digit Symbol test, with significant improvement only after Adaptive training. In addition, the magnitude of the intervention effect was similar at both sites. CONCLUSION: Home-based CCT Adaptive WM training appears more effective than Non-Adaptive training in older adults from different cultural backgrounds. We present evidence of improvement in trained tasks and on a demanding untrained task dependent upon WM and processing speed. The benefits over the active control group suggest that the Adaptive CCT gains were linked to providing a continuously challenging level of WM difficulty.