Structural brain imaging correlates of general intelligence in UK Biobank.

The associations between indices of brain structure and measured intelligence are unclear. This is partly because the evidence to-date comes from mostly small and heterogeneous studies. Here, we report brain structure-intelligence associations on a large sample from the UK Biobank study. The overall N = 29,004, with N = 18,426 participants providing both brain MRI and at least one cognitive test, and a complete four-test battery with MRI data available in a minimum N = 7201, depending upon the MRI measure. Participants' age range was 44-81 years (M = 63.13, SD = 7.48). A general factor of intelligence (g) was derived from four varied cognitive tests, accounting for one third of the variance in the cognitive test scores. The association between (age- and sex- corrected) total brain volume and a latent factor of general intelligence is r = 0.276, 95% C.I. = [0.252, 0.300]. A model that incorporated multiple global measures of grey and white matter macro- and microstructure accounted for more than double the g variance in older participants compared to those in middle-age (13.6% and 5. 4%, respectively). There were no sex differences in the magnitude of associations between g and total brain volume or other global aspects of brain structure. The largest brain regional correlates of g were volumes of the insula, frontal, anterior/superior and medial temporal, posterior and paracingulate, lateral occipital cortices, thalamic volume, and the white matter microstructure of thalamic and association fibres, and of the forceps minor. Many of these regions exhibited unique contributions to intelligence, and showed highly stable out of sample prediction.

Physical, Psychological, Social, and Existential Symptoms in Older Homeless-Experienced Adults: An Observational Study of the Hope Home Cohort.

BACKGROUND: The homeless population in the United States is aging. Aging-associated comorbidities are associated with increased symptoms. OBJECTIVE: To describe the prevalence of symptoms among older homeless-experienced adults, analyze factors associated with moderate-high physical symptom burden, and identify symptom clusters. DESIGN: Cross-sectional analysis within longitudinal cohort study. PARTICIPANTS: Using population-based sampling from shelters, meal programs, encampments, and a recycling center in Oakland, CA, we recruited homeless adults aged ≥ 50 for a longitudinal cohort. This study includes participants who participated in the 18-month follow-up visit. MAIN MEASURES: We assessed physical symptoms using the Patient Health Questionnaire-15 (PHQ-15); psychological symptoms using the Center for Epidemiologic Studies Depression Scale (CES-D), Primary Care PTSD Screen (PC-PTSD), and psychiatric section of the Addiction Severity Index (ASI); loneliness using the Three-Item Loneliness Scale; and regret using a six-item regret scale. KEY RESULTS: Two hundred eighty-three participants (75.6% men and 82.3% African-Americans) completed symptoms interviews. Over a third (34.0%) had moderate-high physical symptom burden. The most prevalent physical symptoms were joint pain, fatigue, back pain, and sleep trouble. Over half (57.6%) had psychological symptoms; 39.6% exhibited loneliness and 26.5% had high regret. In a multivariate model, being a woman (AOR 2.54, 95% CI 1.28-5.03), childhood abuse (AOR 1.88, 95% CI 1.00-3.50), cannabis use (AOR 2.59, 95% CI 1.38-4.89), multimorbidity (AOR 2.50, 95% CI 1.36-4.58), anxiety (AOR 4.30, 95% CI 2.24-8.26), hallucinations (AOR 3.77, 95% CI 1.36-10.43), and loneliness (AOR 2.32, 95% CI 1.26-4.28) were associated with moderate-high physical symptom burden. We identified four symptom clusters: minimal overall (n = 129), moderate overall (n = 68), high physical and high psychological (n = 67), and high physical and low psychological (n = 17). CONCLUSIONS: Older homeless-experienced adults exhibit a high prevalence of symptoms across multiple dimensions. To reduce suffering, clinicians should recognize the interaction between symptoms and address multiple symptom dimensions.

Genome-wide association study of cognitive functions and educational attainment in UK Biobank (N=112 151).

People's differences in cognitive functions are partly heritable and are associated with important life outcomes. Previous genome-wide association (GWA) studies of cognitive functions have found evidence for polygenic effects yet, to date, there are few replicated genetic associations. Here we use data from the UK Biobank sample to investigate the genetic contributions to variation in tests of three cognitive functions and in educational attainment. GWA analyses were performed for verbal-numerical reasoning (N=36 035), memory (N=112 067), reaction time (N=111 483) and for the attainment of a college or a university degree (N=111 114). We report genome-wide significant single-nucleotide polymorphism (SNP)-based associations in 20 genomic regions, and significant gene-based findings in 46 regions. These include findings in the ATXN2, CYP2DG, APBA1 and CADM2 genes. We report replication of these hits in published GWA studies of cognitive function, educational attainment and childhood intelligence. There is also replication, in UK Biobank, of SNP hits reported previously in GWA studies of educational attainment and cognitive function. GCTA-GREML analyses, using common SNPs (minor allele frequency>0.01), indicated significant SNP-based heritabilities of 31% (s.e.m.=1.8%) for verbal-numerical reasoning, 5% (s.e.m.=0.6%) for memory, 11% (s.e.m.=0.6%) for reaction time and 21% (s.e.m.=0.6%) for educational attainment. Polygenic score analyses indicate that up to 5% of the variance in cognitive test scores can be predicted in an independent cohort. The genomic regions identified include several novel loci, some of which have been associated with intracranial volume, neurodegeneration, Alzheimer's disease and schizophrenia.

Shared genetic aetiology between cognitive functions and physical and mental health in UK Biobank (N=112 151) and 24 GWAS consortia.

Causes of the well-documented association between low levels of cognitive functioning and many adverse neuropsychiatric outcomes, poorer physical health and earlier death remain unknown. We used linkage disequilibrium regression and polygenic profile scoring to test for shared genetic aetiology between cognitive functions and neuropsychiatric disorders and physical health. Using information provided by many published genome-wide association study consortia, we created polygenic profile scores for 24 vascular-metabolic, neuropsychiatric, physiological-anthropometric and cognitive traits in the participants of UK Biobank, a very large population-based sample (N=112 151). Pleiotropy between cognitive and health traits was quantified by deriving genetic correlations using summary genome-wide association study statistics and to the method of linkage disequilibrium score regression. Substantial and significant genetic correlations were observed between cognitive test scores in the UK Biobank sample and many of the mental and physical health-related traits and disorders assessed here. In addition, highly significant associations were observed between the cognitive test scores in the UK Biobank sample and many polygenic profile scores, including coronary artery disease, stroke, Alzheimer's disease, schizophrenia, autism, major depressive disorder, body mass index, intracranial volume, infant head circumference and childhood cognitive ability. Where disease diagnosis was available for UK Biobank participants, we were able to show that these results were not confounded by those who had the relevant disease. These findings indicate that a substantial level of pleiotropy exists between cognitive abilities and many human mental and physical health disorders and traits and that it can be used to predict phenotypic variance across samples.

GWAS for executive function and processing speed suggests involvement of the CADM2 gene.

To identify common variants contributing to normal variation in two specific domains of cognitive functioning, we conducted a genome-wide association study (GWAS) of executive functioning and information processing speed in non-demented older adults from the CHARGE (Cohorts for Heart and Aging Research in Genomic Epidemiology) consortium. Neuropsychological testing was available for 5429-32,070 subjects of European ancestry aged 45 years or older, free of dementia and clinical stroke at the time of cognitive testing from 20 cohorts in the discovery phase. We analyzed performance on the Trail Making Test parts A and B, the Letter Digit Substitution Test (LDST), the Digit Symbol Substitution Task (DSST), semantic and phonemic fluency tests, and the Stroop Color and Word Test. Replication was sought in 1311-21860 subjects from 20 independent cohorts. A significant association was observed in the discovery cohorts for the single-nucleotide polymorphism (SNP) rs17518584 (discovery P-value=3.12 × 10(-8)) and in the joint discovery and replication meta-analysis (P-value=3.28 × 10(-9) after adjustment for age, gender and education) in an intron of the gene cell adhesion molecule 2 (CADM2) for performance on the LDST/DSST. Rs17518584 is located about 170 kb upstream of the transcription start site of the major transcript for the CADM2 gene, but is within an intron of a variant transcript that includes an alternative first exon. The variant is associated with expression of CADM2 in the cingulate cortex (P-value=4 × 10(-4)). The protein encoded by CADM2 is involved in glutamate signaling (P-value=7.22 × 10(-15)), gamma-aminobutyric acid (GABA) transport (P-value=1.36 × 10(-11)) and neuron cell-cell adhesion (P-value=1.48 × 10(-13)). Our findings suggest that genetic variation in the CADM2 gene is associated with individual differences in information processing speed.

The association between C-reactive protein and delirium in 710 acute elderly hospital admissions.

BACKGROUND: Delirium is a common neuropsychiatric syndrome associated with poor outcomes. Evidence supports a neuroinflammatory etiology, but the role of the inflammatory marker C-reactive protein (C-RP) remains unclear. We investigated the relationship between C-RP and delirium and its severity as well as interaction with medical diagnosis. METHODS: From an existing database (710 patients over 70 years old admitted to a Medical Acute Admissions Unit) we analyzed data which included C-RP levels, delirium (using the Confusion Assessment Method), and other clinical and demographic factors. Primary diagnoses were grouped (cardiovascular, musculoskeletal, infection, metabolic, and other). RESULTS: There was a strong association between elevated C-RP and delirium (t = 5.09; p < 0.001), independent of other potential risk factors for delirium (odds ratio (OR) = 1.32 (95% CI: 1.10-1.58) p = 0.003). There was no significant association between C-RP and delirium severity, and between C-RP and delirium in the populations with cardiovascular disease, infection upon admission, or from the metabolic group despite an OR of 2.24 (95% CI: 0.92-5.45). There was an association in the musculoskeletal group (OR 2.19 (95% CI: 1.19-4.02)). CONCLUSIONS: There is an association between elevated C-RP and delirium. This is strongest in patients admitted with musculoskeletal disease but not in others, implying that C-RP is involved in the genesis of delirium in musculoskeletal disease, but that other factors or processes may be more important in those with cardiovascular disease or infection.

Shared learning for oral health therapy and dental students: enhanced understanding of roles and responsibilities through interprofessional education.

INTRODUCTION: To enhance interprofessional learning outcomes, The School of Dentistry at The University of Queensland redesigned first-year curricula. Courses for Bachelor of Oral Health (OHT) and Bachelor of Dental Science (DS) students were combined, and learning content created to support the development of skills, knowledge and attitudes required for the oral healthcare team to work effectively in providing the best possible care for patients. METHODS: Over a 2-year period, all commencing OHT and DS students were invited to participate in this study. One cohort (n = 93) was enrolled into a traditional, discipline-specific programme (TRAD), whereas the other cohort (n = 93) experienced an integrated learning programme (INT) with combined courses for OHT and DS students. The Readiness for Interprofessional Learning Scale (RIPLS) and a modified dental and dental care professional roles and responsibilities (DRR) survey were completed to determine students' awareness of dental professionals' roles and responsibilities, and their attitudes to interprofessional education and teamwork. RESULTS: Following completion of 1 year of learning, both INT and TRAD cohorts showed similar levels of readiness for shared learning. At the commencement of the second year of the study programme, however, there was a significantly better understanding of shared care amongst INT students. CONCLUSIONS: This study provides initial support for the integrated learning approach adopted by this university. The INT cohort had significantly improved understandings of the roles and responsibilities of dentists and oral health therapists. The results of this study have been used to refine ongoing curriculum developments.

Using a Claims-Based Frailty Index to Investigate Frailty, Survival, and Healthcare Expenditures among Older Adults Hospitalized for COVID-19 at an Academic Medical Center.

BACKGROUND: Frailty is associated with mortality in older adults hospitalized with COVID-19, yet few studies have quantified healthcare utilization and spending following COVID-19 hospitalization. OBJECTIVE: To evaluate whether survival and follow-up healthcare utilization and expenditures varied as a function of claims-based frailty status for older adults hospitalized with COVID-19. DESIGN: Retrospective cohort study. PARTICIPANTS: 136 patients aged 65 and older enrolled in an Accountable Care Organization (ACO) risk contract at an academic medical center and hospitalized for COVID-19 between March 11, 2020 - June 3, 2020. MEASUREMENTS: We linked a COVID-19 Registry with administrative claims data to quantify a frailty index and its relationship to mortality, healthcare utilization, and expenditures over 6 months following hospital discharge. Kaplan Meier curves and Cox Proportional Hazards models were used to evaluate survival by frailty. Kruskal-Wallis tests were used to compare utilization. A generalized linear model with a gamma distribution was used to evaluate differences in monthly Medicare expenditures. RESULTS: Much of the cohort was classified as moderate to severely frail (65.4%), 24.3% mildly frail, and 10.3% robust or pre-frail. Overall, 27.2% (n=37) of the cohort died (n=26 during hospitalization, n=11 after discharge) and survival did not significantly differ by frailty. Among survivors, inpatient hospitalizations during the 6-month follow-up period varied significantly by frailty (p=0.02). Mean cost over follow-up was $856.37 for the mild and $4914.16 for the moderate to severe frailty group, and monthly expenditures increased with higher frailty classification (p <.001). CONCLUSIONS: In this cohort, claims-based frailty was not significantly associated with survival but was associated with follow-up hospitalizations and Medicare expenditures.

Association between Longitudinal Cerebrospinal Fluid Alzheimer's Biomarkers and the Lifestyle for Brain Health (LIBRA) Index: Findings from the European Prevention of Alzheimer's Dementia Cohort Study (EPAD LCS).

BACKGROUND: In the absence of preventative pharmacological interventions for Alzheimer's Disease dementia, there is a growing interest in modifiable risk factors associated with AD. Such risk factors are thought to contribute up to 40% of the risk of dementia. The Lifestyle for Brain Health (LIBRA) index, a dementia risk score which focuses exclusively on modifiable factors, has been found to be associated with increased risk of dementia and cognitive decline. It is currently unclear how the LIBRA index relates to cerebrospinal fluid (CSF) biomarkers of Alzheimer's Disease. OBJECTIVES: To examine the association between LIBRA index scores and trajectories of phospho-tau 181 and total tau in the European Prevention of Alzheimer's Dementia Longitudinal Cohort Study (EPAD LCS), and to examine whether these trajectories differ between participants with high and low CSF amyloid-beta 1-42 (Aß42). DESIGN: Analysis of CSF biomarker and LIBRA index scores from the European Prevention of Alzheimer's Dementia Longitudinal Cohort Study. SETTING: The European Prevention of Alzheimer's Dementia Longitudinal Cohort Study is a multi-centre, pan-European study. MEASUREMENTS: Cerebrospinal fluid samples were taken by lumbar puncture and analysed using electrochemiluminescence. LIBRA index scores were calculated from self-reported variables, questionnaires, and physiological measurements. RESULT: In the total sample (n = 1715; mean age = 66.0, 56.4% female), there were no significant associations between LIBRA scores (mean = 0.73 points) and rate of change in cerebrospinal fluid biomarkers. In participants with high Aß, reflecting less deposition in the brain, (n = 1134), LIBRA scores were significantly associated with the rate of change in total tau, where higher LIBRA scores (denoting higher dementia risk) were associated with increases in t-tau. There were no significant associations between LIBRA scores and change in cerebrospinal biomarkers in participants with low Aß. CONCLUSION: We found an association between modifiable risk factors and total tau accumulation in participants without dementia and without Aß accumulation. This suggests that increasing levels of total tau may be driven by factors other than Aß accumulation and highlights the need for developing and examining tau-targeting drugs in Alzheimer's Disease development.

Screening over Speech in Unselected Populations for Clinical Trials in AD (PROSPECT-AD): Study Design and Protocol.

BACKGROUND: Speech impairments are an early feature of Alzheimer's disease (AD) and consequently, analysing speech performance is a promising new digital biomarker for AD screening. Future clinical AD trials on disease modifying drugs will require a shift to very early identification of individuals at risk of dementia. Hence, digital markers of language and speech may offer a method for screening of at-risk populations that are at the earliest stages of AD, eventually in combination with advanced machine learning. To this end, we developed a screening battery consisting of speech-based neurocognitive tests. The automated test performs a remote primary screening using a simple telephone. OBJECTIVES: PROSPECT-AD aims to validate speech biomarkers for identification of individuals with early signs of AD and monitor their longitudinal course through access to well-phenotyped cohorts. DESIGN: PROSPECT-AD leverages ongoing cohorts such as EPAD (UK), DESCRIBE and DELCODE (Germany), and BioFINDER Primary Care (Sweden) and Beta-AARC (Spain) by adding a collection of speech data over the telephone to existing longitudinal follow-ups. Participants at risk of dementia are recruited from existing parent cohorts across Europe to form an AD 'probability-spectrum', i.e., individuals with a low risk to high risk of developing AD dementia. The characterization of cognition, biomarker and risk factor (genetic and environmental) status of each research participants over time combined with audio recordings of speech samples will provide a well-phenotyped population for comparing novel speech markers with current gold standard biomarkers and cognitive scores. PARTICIPANTS: N= 1000 participants aged 50 or older will be included in total, with a clinical dementia rating scale (CDR) score of 0 or 0.5. The study protocol is planned to run according to sites between 12 and 18 months. MEASUREMENTS: The speech protocol includes the following neurocognitive tests which will be administered remotely: Word List [Memory Function], Verbal Fluency [Executive Functions] and spontaneous free speech [Psychological and/ or behavioral symptoms]. Speech features on the linguistic and paralinguistic level will be extracted from the recordings and compared to data from CSF and blood biomarkers, neuroimaging, neuropsychological evaluations, genetic profiles, and family history. Primary candidate marker from speech will be a combination of most significant features in comparison to biomarkers as reference measure. Machine learning and computational techniques will be employed to identify the most significant speech biomarkers that could represent an early indicator of AD pathology. Furthermore, based on the analysis of speech performances, models will be trained to predict cognitive decline and disease progression across the AD continuum. CONCLUSION: The outcome of PROSPECT-AD may support AD drug development research as well as primary or tertiary prevention of dementia by providing a validated tool using a remote approach for identifying individuals at risk of dementia and monitoring individuals over time, either in a screening context or in clinical trials.

The global distribution of oral and maxillofacial surgeons: a mixed-methods study.

Despite its role in treating the most dominant non-communicable diseases worldwide, the global workforce of oral and maxillofacial (OM) surgeons is not well-characterized. To address the current deficit in understanding of the global OM surgeon workforce and to elevate oral and maxillofacial surgery (OMS) in the global health discourse, we join other surgical specialties in evaluating global surgical capacity with a descriptive analysis of the distribution of OM surgeons worldwide. A mixed-methods study was implemented using a combination of literature review, in-country contacts, internet searches, and survey data. The survey was distributed globally from January to June 2022. Data regarding OM surgeon workforce estimates were obtained for 104 of 195 United Nations-recognized countries (53.3%). Among countries with available estimates, the median global workforce density was 0.518 OM surgeons per 100,000 population. Twenty-eight countries (26.9%) were reported to have two or fewer OM surgeons. The median OM surgeon workforce density for low-income countries was 0.015 surgeons per 100,000 population, compared to 1.087 surgeons per 100,000 population in high-income countries. low and middle-income countries countries have the least workforce density as well as the least data coverage. More work is needed to better understand the capacity of the global OM surgeon workforce and access to OMS care.

Impact of clinical symptoms and diagnosis: the electronic Person-Specific Outcome Measure (ePSOM) development programme.

INTRODUCTION: Regulatory bodies recommend that outcome measures used in Alzheimer's disease (AD) clinical trials capture clinically meaningful changes for the trial participant. However, commonly used outcome measures do not reflect the individual's views on what matters to them individually. The aim of the electronic Person-Specific Outcome Measure (ePSOM) programme is to better understand what outcomes matter to patients in early Alzheimer's disease. METHODS: As part of the ePSOM programme, we designed and ran an online study to understand what matters to individuals when developing new treatments for AD. The ePSOM survey ran Aug 2019-Dec 2019 (UK) and collected primarily free text responses which were analysed using Natural Language Processing (NLP) techniques. In this paper, we focus our analyses on individuals who reported having a neurodegenerative disease diagnosis (primarily Mild Cognitive Impairment (MCI) or AD), reporting the most frequent and most important brain health priorities for this group. Due to a small sample size, the Diagnosis group was analysed as a whole. Finally, we compared the Diagnosis group to an age and gender matched control group using chi-squared tests to look for any differences between the Diagnosis and control groups' priorities. RESULTS: The survey was completed by 5808 respondents, of whom 167 (2.9%) (women n = 91, men n = 69, other n = 7) had received one of our pre-defined neurodegenerative disease diagnosis: most commonly MCI n = 52, 1.1% (mean age 69.42, SD = 10.8); or Alzheimer's disease n = 48, 1.0% (mean age 71.24, SD = 9.79). Several thematic clusters were significantly more important for the target diagnostic group, e.g.: Expressing opinions; and less important, e.g., Cognitive Games. CONCLUSION: We conclude there are a range of outcomes which individuals consider important and what potential new treatments should help maintain or improve, suggesting that outcomes that matter shift along the preclinical, prodromal and overt dementia continuum. This has important implications for the development of outcome measures in long term prevention studies that last several years where participants may pass through different stages of disease. In the final stage of our project, we will design an electronic outcomes app which will employ the methodology tested in the large-scale survey to capture what matters to individuals about their brain health at an individual level.

The Scottish Brain Health Service Model: Rationale and Scientific Basis for a National Care Pathway of Brain Health Services in Scotland.

In order to address the oft-cited societal, economic, and health and social care impacts of neurodegenerative diseases, such as Alzheimer's disease, we must move decisively from reactive to proactive clinical practice and to embed evidence-based brain health education throughout society. Most disease processes can be at least partially prevented, slowed, or reversed. We have long neglected to intervene in neurodegenerative disease processes, largely due to a misconception that their predominant symptom - cognitive decline - is a normal, age-related process, but also due to a lack of multi-disciplinary collaboration. We now understand that there are modifiable risk factors for neurodegenerative diseases, that successful management of common comorbidities (such as diabetes and hypertension) can reduce the incidence of neurodegenerative disease, and that disease processes begin (and, crucially, can be detected, reduced, and delayed, prevented, or treated) decades earlier in life than had previously been appreciated. Brain Health Scotland, established by Scottish Government and working in partnership with Alzheimer Scotland, propose far-reaching public health and clinical practice approaches to reduce neurodegenerative disease incidence. Focusing here on Brain Health Scotland's clinical offerings, we present the Scottish Model for Brain Health Services. To our knowledge, the Scottish Model for Brain Health, built on foundations of personalised risk profiling, targeted risk reduction and prevention, early disease detection, equity of access, and harnessing comprehensive data to assist in clinical decision-making, marks the first example of a nationwide approach to overhauling clinical, societal, and political approaches to the prevention, assessment, and treatment of neurodegenerative disease.

The association between personality disorder and an act of deliberate self harm in the older person.

BACKGROUND: Suicide rates are higher in the over 65s than in younger adults and there is a strong link between deliberate self harm (DSH) and suicide in older people. The association between personality disorder (PD) and DSH in older adults remains uncertain. Our objective was to describe this association. METHODS: A case control study was conducted in which participants were: (i) those who had undertaken an act of DSH and (ii) a hospital-based control group drawn from a geographical contiguous population. PD was assessed using the Standardised Assessment of Personality (SAP). RESULTS: Seventy-seven cases of DSH were identified; 61 (79.2%) of these participants were interviewed. There were 171 potential controls identified of whom 140 (81.9%) were included. An SAP was completed in 45/61 (73.8%) of cases and 100/140 (71.4%) of controls. The mean age was 79.8 years (SD = 9, range 65-103). The crude odds ratio for the association between PD and DSH was 5.91 [(95% CI 2.3, 14.9) p<0.0001]. There was a strong interaction with age stratified at 80 years. There was no association between PD and DSH after age 80. The adjusted odds ratio for PD in the group <80 years was 20.5 [(95% CI 3, 141) p = 0.002]. Borderline and impulsive PD traits tended to be associated with an episode of DSH more than other personality types. CONCLUSIONS: PD appears to be a strong and independent risk for an act of DSH in people aged between 65 and 80 years and should be looked for as part of any risk assessment in this population. Access to specialist services may be required to optimally manage this problem and reduce the subsequent risk of suicide.

A UK-Wide Study Employing Natural Language Processing to Determine What Matters to People about Brain Health to Improve Drug Development: The Electronic Person-Specific Outcome Measure (ePSOM) Programme.

BACKGROUND: It is important to use outcome measures for novel interventions in Alzheimer's disease (AD) that capture the research participants' views of effectiveness. The electronic Person-Specific Outcome Measure (ePSOM) development programme is underpinned by the need to identify and detect change in early disease manifestations and the possibilities of incorporating artificial intelligence in outcome measures. OBJECTIVES: The aim of the ePSOM programme is to better understand what outcomes matter to patients in the AD population with a focus on those at the pre-dementia stages of disease. Ultimately, we aim to develop an app with robust psychometric properties to be used as a patient reported outcome measure in AD clinical trials. DESIGN: We designed and ran a nationwide study (Aug 2019 - Nov 2019, UK), collecting primarily free text responses in five pre-defined domains. We collected self-reported clinical details and sociodemographic data to analyse responses by key variables whilst keeping the survey short (around 15 minutes). We used clustering and Natural Language Processing techniques to identify themes which matter most to individuals when developing new treatments for AD. RESULTS: The study was completed by 5,808 respondents, yielding over 80,000 free text answers. The analysis resulted in 184 themes of importance. An analysis focusing on key demographics to explore how priorities differed by age, gender and education revealed that there are significant differences in what groups consider important about their brain health. DISCUSSION: The ePSOM data has generated evidence on what matters to people when developing new treatments for AD that target secondary prevention and therein maintenance of brain health. These results will form the basis for an electronic outcome measure to be used in AD clinical research and clinical practice.

Predictors of adherence to atypical antipsychotics (risperidone or olanzapine) in older patients with schizophrenia: an open study of 3(1/2) years duration.

OBJECTIVE: Although the evidence base for the use of antipsychotics in older people with schizophrenia is generally of low quality, it tends to support the use of atypical antipsychotics. Only limited information regarding longer term adherence to these apparently more effective drugs is available. The aim of this study was to determine predictors of adherence to risperidone or olanzapine in patients over 60. METHODS: Patients receiving care from old age psychiatrists for their schizophrenia were randomised to treatment with olanzapine or risperidone and were followed for up to 3(1/2) years. Kaplan-Meier curves were generated to assess the univariate effect of randomisation drug on long-term adherence and Cox regression adjusted for baseline variables which may have affected adherence. RESULTS: In total, 60.6% of the 66 patients in the study were still taking their randomised drug by the end of the interval in which they remained under observation (64.7% olanzapine and 56.3% risperidone). This difference was non-significant. No baseline variable was associated with an increased risk of non-adherence, though the delivery form of pre-randomisation drug (oral or depot) was weakly (p = 0.054) associated with patients originally on depot being less likely to be adherent to an atypical drug. CONCLUSIONS: Overall adherence with atypical medication was good with almost two-thirds of the patients remaining on their randomisation drug for the interval in which they were under observation. Patients taken off depot were less likely to be adherent but there was no significant difference in adherence between olanzapine and risperidone. Scrutiny of the survival curves suggested that non-adherence is an early event in treatment and patients adherent at 6 months were likely to remain adherent over a longer time period.

Cognitive speed of processing and functional declines in older cancer survivors: an analysis of data from the ACTIVE trial.

It has been suggested that chemotherapy treatment for cancer may contribute to cognitive decline in older cancer survivors. This issue is particularly important given that subtle cognitive impairment, particularly in cognitive processing speed, can affect functional status and quality of life for older adults. Multivariate regression of data from a longitudinal randomized controlled trial of older adults revealed a trend towards decreased performance after cancer treatment with chemotherapy on several functional measures associated with processing speed (as compared with matched individuals who did not have cancer). Additional analyses revealed that a subset of the chemotherapy-treated adults demonstrated a reliable negative change on several measures of processing speed. While inconclusive, this hypothesis generating work suggests that cognitive dysfunction following cancer treatment may contribute to disability observed in older cancer survivors. Further research is needed to determine the significance of the relationship between cognitive and functional impairment in older cancer survivors.

Self-Administered Cognitive Testing by Older Adults At-Risk for Cognitive Decline.

Self-administered computerized cognitive testing could effectively monitor older individuals at-risk for cognitive decline at home. In this study, we tested the feasibility and reliability of 3 tablet-based executive functioning measures and an executive composite score in a sample of 30 older adults (age 80±6) with high multimorbidity. The tests were examiner-administered at baseline and then self-administered by the participants at home across 2 subsequent days. Eight of the participants reported no prior experience with touchscreen technology. Twenty-seven participants completed both self-administered assessments, and 28 completed at least one. Cronbach's alpha (individual tests: .87-.89, composite: .93) and correlations between examiner-administered and self-administered performances (individual tests: .72-.91, composite: .93) were high. The participants who had never used a smartphone or a tablet computer showed comparable consistency. Remote self-administered tablet-based testing in older adults at-risk for cognitive decline is feasible and reliable, even among participants without prior technology experience.

The European Prevention of Alzheimer's Dementia (EPAD) Longitudinal Cohort Study: Baseline Data Release V500.0.

BACKGROUND: The European Prevention of Alzheimer's Dementia (EPAD) Programme is a pan-European project whose objective is to deliver a platform, adaptive, Phase 2 proof of concept (PoC) trial for the secondary prevention of Alzheimer's dementia. A component of this platform is the Longitudinal Cohort Study (LCS) which acts as a readiness cohort for the PoC Trial as well as generating data for disease modelling work in the preclinical and prodromal phases of Alzheimer's dementia. OBJECTIVES: The first data wave has been collected, quality checked, released and now available for analysis to answer numerous research questions. Here we describe the results from key variables in the EPAD LCS with the objective of using these results to compliment analyses of these data in the future. DESIGN: EPAD LCS is a cohort study whose primary objective is as a readiness cohort for the EPAD PoC Trial. As such recruitment is not capped at any particular number but will continue to facilitate delivery of the EPAD PoC Trial. Research Participants are seen annually (with an additional 6 month visit in the first year). SETTING: The EPAD Trial Delivery Network comprises currently 21 centres across Europe. PARTICIPANTS: Research participants are included if they are over 50 years old and do not have a diagnosis of dementia. MEASUREMENTS: All research participants undergo multiple assessments to fully characterise the biology of Alzheimer's disease and relate this to risk factors (both fixed and modifiable) and biomarker expression of disease through brain imaging, fluid samples (CSF, blood, urine and saliva), cognitive performance, functional abilities and neuropsychiatric symptomatology. RESULTS: V500.0 represents the first 500 research participants baselined into EPAD LCS. The mean age was 66.4 (SD=6.7) and 47.8% were male. The data was split for presentation into 4 groups: [1] CDR=0 and Amyloid + (preclinical AD), [2] CDR=0 and Amyloid -, [3] CDR=0.5 and Amyloid + (prodromal AD) and [4] CDR=0.5 and Amyloid -. CONCLUSIONS: The EPAD LCS is achieving its primary objective of trial readiness and the structured approach to data release as manifest by this first data release of V500.0 will assist researchers to describe and compare their findings as well as in systematic reviews and meta-analyses. It is anticipated given current recruitment rates that V1500.0 data release will take place in Autumn 2019. V500.1 (when the 1 year follow up is completed on the V500.0 (sub)cohort will be in Autumn 2019 also.

Involving research participants in a pan-European research initiative: the EPAD participant panel experience.

BACKGROUND: Including participants in patient and public involvement activities is increasingly acknowledged as a key pillar of successful research activity. Such activities can influence recruitment and retention, as well as researcher experience and contribute to decision making in research studies. However, there are few established methodologies of how to set up and manage participant involvement activities. Further, there is little discussion of how to do so when dealing with collaborative projects that run across countries and operate in multiple linguistic and regulatory contexts. METHODS: In this paper we describe the set-up, running and experiences of the EPAD participant panel. The EPAD study was a pan-European cohort study with the aim to understand risks for developing Alzheimer's disease and build a readiness cohort for Phase 2 clinical trials. Due to the longitudinal nature of this study, combined with the enrolment of healthy volunteers and those with mild cognitive impairments, the EPAD team highlighted participant involvement as crucial to the success of this project. The EPAD project employed a nested model, with local panels meeting in England, France, Scotland, Spain and The Netherlands, and feeding into a central study panel. The local panels were governed by terms of reference which were adaptable to local needs. RESULTS: The impact of the panels has been widespread, and varies from feedback on documentation, to supporting with design of media materials and representation of the project at national and international meetings. CONCLUSIONS: The EPAD panels have contributed to the success of the project and the model established is easily transferable to other disease areas investigating healthy or at-risk populations.