The National Institutes of Health INvestigation of Co-occurring conditions across the Lifespan to Understand Down syndromE (INCLUDE) Project: Accelerating research discoveries for people with Down syndrome across the lifespan.

The National Institutes of Health (NIH) has a long-standing history of support for research in Down syndrome (DS). In response to a 2018 congressional directive for a trans-NIH initiative to address medical issues in DS, NIH launched the INCLUDE Project (INvestigation of Co-occurring conditions across the Lifespan to Understand Down syndromE). Reflecting the three INCLUDE components of basic science research, cohort development, and clinical trials, the Project has published funding opportunities to address conditions such as immune disorders and Alzheimer's disease. Due to a steady expansion in dedicated funding over its first 5 years, INCLUDE has invested $258 M in over 250 new research projects. INCLUDE also supports training initiatives to expand the number and diversity of investigators studying DS. NIH has funded an INCLUDE Data Coordinating Center that is collecting de-identified clinical information and multi-omics data from research participants for broad data sharing and secondary analyses. Through the DS-Connect® registry, INCLUDE investigators can access recruitment support. The INCLUDE Research Plan articulates research goals for the program, with an emphasis on diversity of research participants and investigators. Finally, a new Cohort Development Program is poised to increase the impact of the INCLUDE Project by recruiting a large DS cohort across the lifespan.

Medicine Maker: An Outreach Activity for Pharmaceutical Manufacturing and Health Literacy.

Public engagement in medicine has become more important in promoting population health management and literacy. Medicine is a topic of great societal importance, and many public engagement activities have been developed to promote this area. However, they often narrowly focus on patient groups, diseases, a singular pharmaceutical drug or analytical technique. Despite the importance of these activities, general audiences are still heavily reliant on doctors and pharmacists for information about their medicine and lack basic knowledge around medication use and personal safety. Given this, a broader engagement approach is warranted to target health literacy among the wider public. "Medicine Maker" is a hands-on public engagement workshop that provides audiences with the opportunity to "manufacture" and inspect the quality of proxy or "dummy" medicine through guided inquiry. Here, we detail the development of the Medicine Maker workshop from its origins in the teaching of Irish third-level pharmacy students, to its initial application with a variety of lay audiences. Formal and informal feedback from participants indicates that the workshop can help foster a more critical understanding of medicine manufacturing, quality control, and personal health.

International Alzheimer's Disease Research Portfolio (IADRP) aims to capture global Alzheimer's disease research funding.

Alzheimer's disease (AD) is a recognized international public health crisis. There is an urgent need for public and private funding agencies around the world to coordinate funding strategies and leverage existing resources to enhance and expand support of AD research. To capture and compare their existing investments in AD research and research-related resources, major funding organizations are starting to utilize the Common Alzheimer's Disease Research Ontology (CADRO) to categorize their funding information. This information is captured in the International Alzheimer's Disease Research Portfolio (IADRP) for further analysis. As of January, 2014, over fifteen organizations from the US, Canada, Europe and Australia have contributed their information. The goal of the IADRP project is to enable funding organizations to assess the changing landscape of AD research and coordinate strategies, leverage resources, and avoid duplication of effort.

Obstacles and opportunities in Alzheimer's clinical trial recruitment.

The 2012 National Plan to Address Alzheimer's Disease set an ambitious goal: to both prevent and effectively treat Alzheimer's disease by 2025. To reach this goal, tens of thousands of volunteers will be needed to participate in clinical trials to test promising new interventions and therapies. To mobilize these volunteers and their health care providers to participate in future clinical trials, it will be necessary to achieve a better understanding of the barriers keeping people from participating in Alzheimer's research; form innovative partnerships among researchers, health care and social service providers, and the public; and develop more-effective outreach strategies. In this article we explore recruitment issues, including those unique to Alzheimer's studies, and we suggest concrete steps such as establishing a structured consortium linking all of the registries of Alzheimer's trials and establishing new partnerships with community and local organizations that can build trust and understanding among patients, caregivers, and providers.

Common Alzheimer's Disease Research Ontology: National Institute on Aging and Alzheimer's Association collaborative project.

Alzheimer's disease is recognized as a public health crisis worldwide. As public and private funding agencies around the world enhance and expand their support of Alzheimer's disease research, there is an urgent need to coordinate funding strategies and leverage resources to maximize the impact on public health and avoid duplication of effort and inefficiency. Such coordination requires a comprehensive assessment of the current landscape of Alzheimer's disease research in the United States and internationally. To this end, the National Institute on Aging at the National Institutes of Health and the Alzheimer's Association developed the Common Alzheimer's Disease Research Ontology (CADRO) as a dynamic portfolio analysis tool that can be used by funding agencies worldwide for strategic planning and coordination.

Assessment of cognition in early dementia.

Better tools for assessing cognitive impairment in the early stages of Alzheimer's disease (AD) are required to enable diagnosis of the disease before substantial neurodegeneration has taken place and to allow detection of subtle changes in the early stages of progression of the disease. The National Institute on Aging and the Alzheimer's Association convened a meeting to discuss state of the art methods for cognitive assessment, including computerized batteries, as well as new approaches in the pipeline. Speakers described research using novel tests of object recognition, spatial navigation, attentional control, semantic memory, semantic interference, prospective memory, false memory and executive function as among the tools that could provide earlier identification of individuals with AD. In addition to early detection, there is a need for assessments that reflect real-world situations in order to better assess functional disability. It is especially important to develop assessment tools that are useful in ethnically, culturally and linguistically diverse populations as well as in individuals with neurodegenerative disease other than AD.

Guidelines for the pharmacologic treatment of neurobehavioral sequelae of traumatic brain injury.

There is currently a lack of evidence-based guidelines to guide the pharmacological treatment of neurobehavioral problems that commonly occur after traumatic brain injury (TBI). It was our objective to review the current literature on the pharmacological treatment of neurobehavioral problems after traumatic brain injury in three key areas: aggression, cognitive disorders, and affective disorders/anxiety/ psychosis. Three panels of leading researchers in the field of brain injury were formed to review the current literature on pharmacological treatment for TBI sequelae in the topic areas of affective/anxiety/ psychotic disorders, cognitive disorders, and aggression. A comprehensive Medline literature search was performed by each group to establish the groups of pertinent articles. Additional articles were obtained from bibliography searches of the primary articles. Group members then independently reviewed the articles and established a consensus rating. Despite reviewing a significant number of studies on drug treatment of neurobehavioral sequelae after TBI, the quality of evidence did not support any treatment standards and few guidelines due to a number of recurrent methodological problems. Guidelines were established for the use of methylphenidate in the treatment of deficits in attention and speed of information processing, as well as for the use of beta-blockers for the treatment of aggression following TBI. Options were recommended in the treatment of depression, bipolar disorder/mania, psychosis, aggression, general cognitive functions, and deficits in attention, speed of processing, and memory after TBI. The evidence-based guidelines and options established by this working group may help to guide the pharmacological treatment of the person experiencing neurobehavioral sequelae following TBI. There is a clear need for well-designed randomized controlled trials in the treatment of these common problems after TBI in order to establish definitive treatment standards for this patient population.

Information processing following mild head injury.

Research has shown that individuals who have sustained mild head injury demonstrate a slowed speed of processing that is exacerbated by fatigue/stress. We administered the Paced Auditory Serial Addition Test (PASAT) at the beginning and at the end of a 4-h experimental protocol to determine whether fatigue or a stressor would result in poorer scores for individuals who had previously sustained mild head injury. A significant improvement was found between the first and second administration for both head-injured and control subjects, but difference scores revealed a significant between-groups difference for the first of the four trials, with the head-injured participants performing worse than controls. Apparently, head-injured participants were slower to develop, as well as slower to regain, a means of efficiently processing rapidly presented information.

Complex partial seizure symptom endorsement in individuals with a history of head injury.

Research has shown that subjects at risk for cerebral dysfunction endorse more complex partial seizure symptoms than low risk controls. It has been suggested that seizure activity be regarded as occurring on a continuum of neurobehavioral dysfunction, rather than as a discrete syndrome. The present study assessed seizure symptom endorsement in individuals reporting a positive history of head injury. There were three groups of college student participants: head injury with loss of consciousness (LOC; n=31); head injury followed by a dazed period or alteration of consciousness (AOC; n=36); non-injured controls (NHI; n=60). In general, the LOC group reported greater frequency of symptomatology and a greater number of clinically significant symptoms (above the 90th percentile) than the NHI group, and a greater number of clinically significant symptoms than the AOC group. The AOC group did not differ from the NHI group on either variable. These results lend credence to the concept of a continuum representing an epilepsy spectrum disorder.

An examination of the California Verbal Learning Test II to detect incomplete effort in a traumatic brain-injury sample.

Clinical neuropsychologists are frequently called on to distinguish people who appear impaired on neuropsychological testing due to putting forth incomplete effort from those who have genuine cognitive deficits. Because traditional measures of effort are becoming accessible over the Internet and within the legal community and their purpose may be obvious to potential malingerers, nontraditional effort measures have been newly investigated. Using discriminant function analysis, this study explores whether five California Verbal Learning Test-Second Edition (CVLT-II) variables could differentiate between head-injured patients who were putting forth full effort and those who were putting forth incomplete effort. The discriminant function seemed to best predict those who put forth adequate effort while testing (95.6% correct) but not those who failed to put forth adequate effort during testing (only 13.8% correct). Hence, although the overall classification rate was moderately impressive (75.8%), the model's sensitivity in classification of the incomplete effort group was low. Cautious applications for these findings are discussed.

Association of COMT Val158Met genotype with executive functioning following traumatic brain injury.

Catechol-O-methyltransferase (COMT) is thought to functionally modulate dopamine neurons, thus likely influencing frontal-executive functioning. High enzyme activity (COMT Val) and low enzyme activity (COMT Met) are functional polymorphisms resulting from a G to A transition in exon 4 (codon 158) of the human COMT gene. Decreased cortical dopamine should result in poorer executive functioning. Therefore, the authors hypothesized that individuals with traumatic brain injury (TBI) and the low enzyme activity polymorphism would perform better on tests of executive functioning than individuals with the high enzyme activity polymorphism. One hundred thirteen individuals referred to the Defense and Veterans Brain Injury Center underwent a comprehensive TBI evaluation and were genotyped for the COMT polymorphism. Comparison of mean differences among the COMT genotype groups for several measures of aspects of executive functioning was conducted using analysis of variance (ANOVA) with adjustment for multiple comparisons. Homozygotes for the higher activity allele made more perseverative responses on the Wisconsin Card Sorting Test, while homozygotes for the lower activity allele had the least number of perseverative responses. While it cannot be determined whether TBI influenced the association of COMT Val158Met to executive functioning, these data extend the known relationship of genotype to executive performance seen in healthy comparison subjects and individuals with schizophrenia to individuals with TBI.

Sensation seeking and risk behaviors in young adults with and without a history of head injury.

Research has demonstrated a relation between sensation seeking and risky behavior as well as an association between risky behavior and the occurrence of head injury. This study assessed sensation seeking in young adults with and without a history of head injury by administration of the Sensation Seeking Scale (SSS), the Driver Risk Index (DRI), and the MacAndrews Scale of the Minnesota Multiphasic Personality Inventory (MMPI). There was a significant difference between the groups for the Thrill and Adventure Seeking Subscale of the SSS and the MacAndrews Scale of the MMPI, with head-injured participants scoring higher. Gender differences were seen in both groups for subscales of the SSS, with men scoring higher. Significant correlations were found for head-injured participants between the DRI and the Boredom Susceptiblity Subscale of the SSS, suggesting that as knowledge of risk increased for these participants, so did their preferences for risky behaviors. However, non-head-injured participants indicated a lower interest in risky behaviors as their knowledge of risk increased.

Neuropsychological deficits of a U.S. Army pilot following an anoxic event as a function of cardiac arrest.

Anoxic encephalopathy occurs as a result of cardiac arrest, respiratory distress, or carbon monoxide poisoning. This is a case report on the neuropsychological deficits of anoxia in an otherwise previously healthy 36-year-old male pilot. The patient was taking an over-the-counter supplement that included an herb called Ma Huang on the day of his cardiac arrest. Ma Huang is reported to potentially present an increased risk of cardiac infarctions and central nervous system dysfunctions. Several instances of death have been linked to Ma Huang. The patient produced a neuropsychological profile that evidenced impairments in executive functioning, memory, language, attention, intellectual and academic functioning, as well as motor speed and coordination, all of which are consistent with diffuse brain damage. This case adds to the body of literature documenting the physical and neuropsychological effects of anoxia, as well as the effects of ephedrine-based supplements, such as Ma Huang.

Functional assessment of executive abilities following traumatic brain injury.

PRIMARY OBJECTIVE: The Test of Functional Executive Abilities (TOFEA) is a measure of real-world planning/problem-solving abilities. The present study sought to identify the relationship between the TOFEA and traditional executive measures. DESIGN: Correlational and principal components factor analyses were conducted using the TOFEA and traditional neuropsychological executive measures. METHODS: Participants were 340 patients with traumatic brain injury. All participants underwent neuropsychological and speech-language assessments. RESULTS: Factor analysis of the TOFEA yielded a two-factor solution, planning/initiation and awareness/comprehension. Correlational analysis between the TOFEA and traditional measures demonstrated only a weak relationship. Factor analysis indicated a four factor executive solution with the TOFEA loading on the third planning/initiation and reasoning factor. CONCLUSIONS: The data support the notion that there is no one single measure of frontal-executive functioning, but rather these tests represent different executive components and, as such, more than one measure should be used in a comprehensive assessment.

Post concussion syndrome.

Individuals sustaining mild traumatic brain injuries often report a constellation of physical, cognitive, and emotional/behavioral symptoms referred to as post concussion symptoms (PCS). The most commonly reported post concussion symptoms are headache, dizziness, decreased concentration, memory problems, irritability, fatigue, visual disturbances, sensitivity to noise, judgment problems, depression, and anxiety. Although these PCS often resolve within one month, in some individuals PCS can persist from months to years following injury and may even be permanent and cause disability. When this cluster of PCS is persistent in nature, it is often called the post concussion syndrome or persistent PCS. Both physiological and psychological etiologies have been suggested as causes for persistent post concussion symptoms and this has led to much controversy and debate in the literature. Most investigators now believe that a variety of pre-morbid, injury-related, and post-morbid neuropathological and psychological factors contribute to the development and continuation of these symptoms in those sustaining mild traumatic brain injury (MTBI).