As the US population ages, the prevalence of Alzheimer’s disease and related dementias (AD/RD) is on the rise. This is especially true in rural America, where mortality rates due to AD/RD are rising faster than in metropolitan areas. To date, however, people living in rural communities are severely underrepresented in aging research. The Nevada Exploratory Alzheimer’s Disease Research Center (NVeADRC) seeks to address this gap. Here, we present preliminary cognitive data from our rural-dwelling cohort, as well as relevant demographic and clinical characteristics.

Individuals with normal cognition (NC), mild cognitive impairment (MCI), and dementia due to Alzheimer’s disease (AD) living in rural communities, defined as a rural-urban commuting area (RUCA) code of 4 or higher, were enrolled through either clinic or community outreach. Eligibility for the observational cohort required: age >55 years, primarily English-speaking, primary residence in a rural community, and availability of a study partner. Measures included the Uniform Data Set (v3), blood-based biomarkers, structural brain MRI, and portions of the PhenX Social Determinants of Health toolkit. Participants are seen at baseline and followed annually, with interim remote visits every 6 months. A multidisciplinary consensus diagnosis is rendered after each visit. Where feasible, a harmonized urban cohort followed by the Nevada Center for Neurodegeneration and Translational Neuroscience (CNTN) was used for comparison.

Fifty-six rural-dwelling (age=70.4±7.1 years; edu=15.2±2.6 years; 61% female) and 148 urban-dwelling (age=72.9±6.8 years; edu=15.8±2.7 years; 46% female) older adults were included; age significantly differed between cohorts but education did not. The rural cohort was 46% NC (MoCA=26.8±2.3; CDRsob=0.3±0.6), 32% MCI (MoCA=22.8±3.1; CDRsob=1.2±1.0), and 22% AD (MoCA=16.9±5.5; CDRsob=5.2±3.0). The urban cohort was 39% NC (MoCA=26.4±2.6; CDRsob=0.3±0.8), 44% MCI (MoCA=22.3±3.1; CDRsob=2.0±1.5) and 17% AD (MoCA=18.6±3.9; CDRsob=4.7±2.3). Rural communities were significantly more disadvantaged, as measured by the Area Deprivation Index (ADI), than urban communities (rural ADI=6.3±2.6; urban ADI=3.4±2.3; p<.001). Fifty-percent of the rural cohort lives in a moderate to severely disadvantaged neighborhood (ADI Decile>7) compared to 12% of the urban cohort, and 11% of individuals in the rural cohort reported living more than 30 miles from the nearest medical facility. Across the combined cohort, education was significantly correlated with ADI deciles (r=-.30, p<.001), with people in the areas of highest disadvantage having the lowest education. Verbal memory was also inversely associated with ADI. There were no differences in clinical diagnosis as a function of ADI rank.

Living in a rural community conveys a multifaceted array of risks and benefits, some of which differ from urban settings. The literature to date suggests that older adults living in rural communities are at significantly increased risk for morbidity and mortality due to AD/RD, though it is unclear why. Preliminary data from the NVeADRC show that increasing levels of neighborhood disadvantage were associated with lower levels of education and worse verbal memory in this convenience sample. The combined effect of low education and increased disadvantage account for some of the urban-rural differences in mortality that have been reported, though additional research on representative samples in this underrepresented population is critical.

The National Institute for Health and Care Excellence (NICE) interventional procedures programme (IPP) issues guidance on the safety and efficacy of new interventional procedures (IPS). The IPP considers a range of evidence from randomized controlled trials (RCTs) to case series to make final recommendations. Real-world evidence (RWE) can provide additional information on long-term outcomes and patient population characteristics that are not easily captured by RCTs. This study explores the impact of RWE in complementing RCTs on long-term safety and efficacy for national guidance development.

We review the impact of RWE in IPS guidance (IPG) updates and change in guidance recommendations in the last 5 years. This is done by analyzing NICE guidance updates and supporting evidence. A range of RWE was considered in the supporting evidence, for example, registries and clinical audits.

The addition of RWE evidence to IPP guidance update has led to significant changes in the recommendations. For example, in one recent IPG, standard arrangements recommendation based on short-term RCT evidence was changed to a research recommendation when RWE showed an increase in long-term adverse effects. In another recent IPG update, special arrangements recommendation based on short-term RCT evidence was changed to a research recommendation when RWE reported long-term inferior efficacy and safety for the new intervention compared to current standard of care. A complete overview of results of the last 5 years will also be presented at the meeting.

These findings indicate that increased availability of RWE in HTA has the potential to impact national guidance recommendations. In addition, it shows how RWE can fill the evidence base gaps created by RCTs. Such data can confirm or contradict the findings of RCTs, or generate questions needing further research, or support disinvestment in non-effective technologies.

Executive functions (EF) drive health and educational outcomes and therefore are increasingly common treatment targets. Most treatment trials rely on questionnaires to capture meaningful change because ecologically valid, pediatric performance-based EF tasks are lacking. The Executive Function Challenge Task (EFCT) is a standardized, treatment-sensitive, objective measure which assesses flexibility and planning in the context of provocative social interactions, making it a “hot” EF task.

We investigate the structure, reliability, and validity of the EFCT in youth with autism (Autism Spectrum Disorder; n = 129), or attention deficit hyperactivity disorder with flexibility problems (n = 93), and typically developing (TD; n = 52) youth.

The EFCT can be coded reliably, has a two-factor structure (flexibility and planning), and adequate internal consistency and consistency across forms. Unlike a traditional performance-based EF task (verbal fluency), it shows significant correlations with parent-reported EF, indicating ecological validity. EFCT performance distinguishes youth with known EF problems from TD youth and is not significantly related to visual pattern recognition, or social communication/understanding in autistic children.

The EFCT demonstrates adequate reliability and validity and may provide developmentally appropriate, treatment-sensitive, and ecologically valid assessment of “hot” EF in youth. It can be administered in controlled settings by masked administrators.

Although apps are increasingly being used to support the diagnosis, treatment and management of mental illness, there is no single means through which costs associated with mental apps are being reimbursed. Furthermore, different apps are amenable to different means of reimbursement as not all apps generate value in the same way.

To provide insights into how apps are currently generating value and being reimbursed across the world, with a particular focus on the situation in the USA.

An international team performed secondary research on how apps are being used and on common pathways to remuneration.

The uses of apps today and in the future are reviewed, the nature of the value delivered by apps is summarised and an overview of app reimbursement in the USA and other countries is provided. Recommendations regarding how payments might be made for apps in the future are discussed.

Currently, apps are being reimbursed through channels with other original purposes. There may be a need to develop an app-specific channel for reimbursement which is analogous to the channels used for devices, drugs and laboratory tests.

The IDEAL (Idea, Development, Exploration, Assessment, Learning) Framework measures the maturity of evidence base behind surgical innovation. The NICE Interventional Procedures (IP) programme issues guidance for the United Kingdom National Health Service (NHS) on use of surgical innovation. One of four recommendations can be made: (a) standard arrangements, (b) special arrangements, (c) research only, and (d) do not use. This study aimed to investigate whether the recommendation of NICE IP guidance corresponded with the stage of innovation as determined by IDEAL, thus IDEAL's role in informing future guidance production.

A retrospective sample of 103 pieces of guidance issued between 2015 and 2018 was analysed. One researcher examined the evidence base and determined the corresponding stage of the IDEAL framework, numbered 1, 2, 2a, 3 and 4. The primary outcome measure was the association between stage of evidence on IDEAL framework and the recommendation of published NICE IP guidance.

There were twenty-one (20 percent), thirty-three (32 percent), three (3 percent), forty (39 percent) and six (6 percent) procedures at IDEAL stages 1, 2, 2a, 3 and 4, respectively. Of those at stage 1 (idea), 48 percent were given research only arrangements, 43 percent special arrangements, and 10 percent standard. Many of the procedures at stages 2 (development) and 2a (exploration) were given standard arrangements (39 percent and 67 percent respectively). Forty-three percent of stage 3 (assessment) and 67 percent of stage 4 (learning) guidance were identified standard. At stage 4 none were given a ‘research only’ recommendation.

Procedures given ‘standard’ arrangements guidance are more likely have a mature and robust evidence base as determined by IDEAL. Those with limited evidence are more likely to be given a more cautious ‘research only’ guidance. Routine use of this framework could help inform future guidance production however cannot replace the decision-making function of the NICE committee which also involves patient experiences, population characteristics, risk of serious safety events, and equity issues.

There is increasing evidence for shared genetic susceptibility between schizophrenia and bipolar disorder. Although genetic variants only convey subtle increases in risk individually, their combination into a polygenic risk score constitutes a strong disease predictor.

To investigate whether schizophrenia and bipolar disorder polygenic risk scores can distinguish people with broadly defined psychosis and their unaffected relatives from controls.

Using the latest Psychiatric Genomics Consortium data, we calculated schizophrenia and bipolar disorder polygenic risk scores for 1168 people with psychosis, 552 unaffected relatives and 1472 controls.

Patients with broadly defined psychosis had dramatic increases in schizophrenia and bipolar polygenic risk scores, as did their relatives, albeit to a lesser degree. However, the accuracy of predictive models was modest.

Although polygenic risk scores are not ready for clinical use, it is hoped that as they are refined they could help towards risk reduction advice and early interventions for psychosis.

R.M.M. has received honoraria for lectures from Janssen, Lundbeck, Lilly, Otsuka and Sunovian.