Rosalyn Hithersay

Transfer of cognitive training across magnitude dimensions achieved with concurrent brain stimulation of the parietal lobe

Improvement in performance following cognitive training is known to be further enhanced when coupled with brain stimulation. Here we ask whether training-induced changes can be maintained long term and, crucially, whether they can extend to other related but untrained skills. We trained overall 40 human participants on a simple and well established paradigm assessing the ability to discriminate numerosity–or the number of items in a set–which is thought to rely on an “approximate number sense” (ANS) associated with parietal lobes. We coupled training with parietal stimulation in the form of transcranial random noise stimulation (tRNS), a noninvasive technique that modulates neural activity. This yielded significantly better and longer lasting improvement (up to 16 weeks post-training) of the precision of the ANS compared with cognitive training in absence of stimulation, stimulation in absence of cognitive training, and cognitive training coupled to stimulation to a control site (motor areas). Critically, only ANS improvement induced by parietal tRNS + Training transferred to proficiency in other parietal lobe-based quantity judgment, i.e., time and space discrimination, but not to quantity-unrelated tasks measuring attention, executive functions, and visual pattern recognition. These results indicate that coupling intensive cognitive training with tRNS to critical brain regions resulted not only in the greatest and longer lasting improvement of numerosity discrimination, but importantly in this enhancement being transferable when trained and untrained abilities are carefully chosen to share common cognitive and neuronal components.

Assessment of an incentivised scheme to provide annual health checks in primary care for adults with intellectual disability: a longitudinal cohort study

BACKGROUND People with intellectual disabilities (ID) have many comorbidities but experience inequities in access to health care. National Health Service England uses an opt-in incentive scheme to encourage annual health checks of patients with ID in primary care. We investigated whether the first 3 years of the programme had improved health care of people with ID. METHODS We did a longitudinal cohort study that used data from The Health Improvement Network primary care database. We did multivariate logistic regression to assess associations between various characteristics and whether or not practices had opted in to the incentivised scheme. FINDINGS We assessed data for 8692 patients from 222 incentivised practices and those for 918 patients in 48 non-incentivised practices. More blood tests (eg, total cholesterol, odds ratio [OR] 1·88, 95% CI 1·47-2·41, p<0·0001) general health measurements (eg, smoking status, 6·0, 4·10-8·79, p<0·0001), specific health assessments (eg, hearing, 24·0, 11·5-49·9, p<0·0001), and medication reviews (2·23, 1·68-2·97, p<0·0001) were done in incentivised than in non-incentivised practices, and more health action plans (6·15, 1·41-26·9, p=0·0156) and secondary care referrals (1·47, 1·05-2·05, p=0·0256) were made. Identification rates were higher in incentivised practices for thyroid disorder (OR 2·72, 95% CI 1·09-6·81, p=0·0323), gastrointestinal disorders (1·94, 1·03-3·65, p=0·0390), and obesity (2·49, 1·76-3·53, p<0·0001). INTERPRETATION Targeted annual health checks for people with ID in primary care could reduce health inequities. FUNDING National Institute for Health Research.

The LonDownS adult cognitive assessment to study cognitive abilities and decline in Down syndrome.

Background: Down syndrome (DS), the most common genetic cause of intellectual disability, is associated with an ultra-high risk of developing Alzheimer’s disease. However, there is individual variability in the onset of clinical dementia and in baseline cognitive abilities prior to decline, particularly in memory, executive functioning, and motor coordination. The LonDownS Consortium aims to determine risk and protective factors for the development of dementia and factors relating to cognitive abilities in people with DS. Here we describe our cognitive test battery and related informant measures along with reporting data from our baseline cognitive and informant assessments. Methods: We developed a cognitive test battery to assess general abilities, memory, executive function, and motor coordination abilities in adults with DS, with informant ratings of similar domains also collected, designed to allow for data on a broad range of participants. Participants (n=305) had a range of ages and abilities, and included adults with and without a clinical diagnosis of dementia. Results: Results suggest the battery is suitable for the majority of adults with DS, although approximately half the adults with dementia were unable to undertake any cognitive task. Many test outcomes showed a range of scores with low floor and ceiling effects. Non-verbal age-adjusted IQ scores had lower floor effects than verbal IQ scores. Before the onset of any cognitive decline, females aged 16-35 showed better verbal abilities compared to males. We also identified clusters of cognitive test scores within our battery related to visuospatial memory, motor coordination, language abilities, and processing speed / sustained attention. Conclusions: Our further studies will use baseline and longitudinal assessments to explore factors influencing cognitive abilities and cognitive decline related to ageing and onset of dementia in adults with DS.

Cognitive decline and dementia in Down syndrome

Purpose of review Alzheimers disease is most likely universal in older individuals with Down syndrome, due to having three copies of the amyloid precursor protein gene, resulting in amyloid-beta plaque deposition. Down syndrome is an important population in which to consider clinical trials of treatments to prevent or delay the development of dementia. However, assessment of subtler cognitive changes is challenging due to the presence of intellectual disability. Recent findings Recent research confirmed that older adults with Down syndrome often present with cognitive decline: more than 80% may experience dementia by age 65 years. Efforts have been made to improve and validate neuropsychological assessment and to describe the relationship with comorbidities such as epilepsy and haemorrhagic stroke. There have also been advances in biomarkers such as neuroimaging using amyloid PET. Summary Clinical trials of treatments, particularly in the presymptomatic phase of Alzheimers disease, are important to consider in individuals with Down syndrome given their high dementia burden, and may also serve as proof of concept for other forms of Alzheimers disease. However, further work is required to improve outcome measures and better understand the biomarkers of progression of disorder and their relationship with symptom development during the presymptomatic period.

Carer-led health interventions to monitor, promote and improve the health of adults with intellectual disabilities in the community: a systematic review.

Using carers to help assess, monitor, or promote health in people with intellectual disabilities (ID) may be one way of improving health outcomes in a population that experiences significant health inequalities. This paper provides a review of carer-led health interventions in various populations and healthcare settings, in order to investigate potential roles for carers in ID health care. We used rapid review methodology, using the Scopus database, citation tracking and input from ID healthcare professionals to identify relevant research. 24 studies were included in the final review. For people with ID, the only existing interventions found were carer-completed health diaries which, while being well received, failed to improve health outcomes. Studies in non-ID populations show that carers can successfully deliver screening procedures, health promotion interventions and interventions to improve coping skills, pain management and cognitive functioning. While such examples provide a useful starting point for the development of future carer-led health interventions for people with ID, the paucity of research in this area means that the most appropriate means of engaging carers in a way that will reliably impact on health outcomes in this population remains, as yet, unknown.

Aging related cognitive changes associated with Alzheimer's disease in Down syndrome

Individuals with Down syndrome (DS) have an extremely high genetic risk for Alzheimers disease (AD), however, the course of cognitive decline associated with progression to dementia is ill‐defined. Data‐driven methods can estimate long‐term trends from cross‐sectional data while adjusting for variability in baseline ability, which complicates dementia assessment in those with DS.

Sequence of cognitive changes associated with development of Alzheimer's disease in Down syndrome - data driven analysis

Objective Individuals with Down syndrome (DS) have an extremely high genetic risk for Alzheimer’s disease (AD) however the course of cognitive decline associated with progression to dementia is ill-defined. Data-driven methods can estimate long-term trends from cross-sectional data while adjusting for variability in baseline ability, which complicates dementia assessment in those with DS. Methods We applied an event-based model to cognitive test data and informant-rated questionnaire data from 283 adults with DS (the largest study of cognitive functioning in DS to date) to estimate the sequence of cognitive decline and individuals’ disease stage. Results Decline in tests of memory, sustained attention / motor coordination, and verbal fluency occurred early, demonstrating that AD in DS follows a similar pattern of change to other forms of AD. Later decline was found for informant measures. Using the resulting staging model, we showed that adults with a clinical diagnosis of dementia and those with APOE 3:4 or 4:4 genotype were significantly more likely to be staged later, suggesting the model is valid. Interpretation Our results identify tests of memory and sustained attention may be particularly useful measures to track decline in the preclinical/prodromal stages of AD in DS whereas informant-measures may be useful in later stages (i.e. during conversion to dementia, or post-diagnosis). These results have implications for the selection of outcome measures of treatment trials to delay or prevent cognitive decline due to AD in DS. As clinical diagnoses are generally made late into AD progression, early assessment is essential.

GENETIC DISSECTION OF SEVERITY AND ONSET MODULATORS FOR ALZHEIMER’S PATHOLOGY IN DOWN SYNDROME USING CELLULAR SYSTEMS

Madhav Thambisetty, Cristina Legido-Quigley, King’s College London, London, United Kingdom; Kings College London, London, United Kingdom; Institute of Psychiatry, Psychology and Neuroscience, King’s College London, London, United Kingdom; NIHR Biomedical Research Centre for Mental Health and Biomedical Research Unit for Dementia at South London and Maudsley NHS Foundation, London, United Kingdom; Johns Hopkins University School of Medicine, Baltimore, MD, USA; Duke University, Durham, NC, USA; National Institute on Aging, Baltimore, MD, USA. Contact e-mail: stuart.snowden@kcl.ac.uk

USING FUNCTIONAL NEAR INFRARED SPECTROSCOPY (FNIRS) TO MEASURE FRONTAL CORTICAL ACTIVITY IN ADULTS WITH DOWN SYNDROME

ADNI1 to 2 transition, ADNI3 updates the study with recent MRI advances. ADNI2 included DTI, but only for GE scanners. ADNI3 includes diffusion for all manufacturers involved (GE, Philips, and Siemens), and emphasizes consistency across scanners. The resolution has been improved from 2.7 to 2.0mm (isotropic), and, where simultaneous multislice (SMS) acceleration is available, acquires three diffusion shells, supporting advanced diffusion analyses such as NODDI and DKI. Methods: To serve the general dementia research community, the diffusion protocol was designed to support three different analyses: DTI, with an emphasis on cross-sectional and longitudinal consistency; tractography, calling for more directions at higher diffusion weighting (b); and multi-compartment analyses such as NODDI and DKI, which require > 2 b values. Each depends on spatial resolution and SNR, but the time available for diffusion in ADNI3 is limited to around 8 minutes, and most scanners will not have SMS capability until partway through ADNI3. This strongly favors a HARDI-type acquisition with two protocols, a basic b1⁄41000 s/mm shell, and for SMScapable scanners, the addition of shells at b 1⁄4 500 and 2000s/mm. The directions were evenly spaced using an electrostatic repulsion algorithm. Results: Figure 1 shows the ADNI3 diffusion parameters. Conclusions:All ADNI3 sessions will acquire diffusion scans, with sites switching from Basic to Advanced protocol as SMS becomes available. The Advanced protocol includes the Basic one as a subset for consistency. References: 1. Zhang, H., Schneider, T., Wheeler-Kingshott, C. A. & Alexander, D. C. NODDI: Practical in vivo neurite orientation dispersion and density imaging of the human brain. NeuroImage 61,1000–1016 (2012). 2. Jensen, J. H., Helpern, J. A., Ramani, A., Lu, H. & Kaczynski, K. Diffusional kurtosis imaging: The quantification of non-gaussian water diffusion by means of magnetic resonance imaging. Magn. Reson. Med. 53,1432–1440 (2005). 3. Caruyer, E., Lenglet, C., Sapiro, G. & Deriche, R. Design of multishell sampling schemes with uniform coverage in diffusion MRI. Magn. Reson. Med. 69, 1534–1540 (2013). P3-328 USING FUNCTIONAL NEAR INFRARED