Exploring electrophysiological markers of auditory predictive processes and pathological ageing in adults with Down's syndrome.

Down's syndrome is associated with pathological ageing and a propensity for early-onset Alzheimer's disease. The early symptoms of dementia in people with Down's syndrome may reflect frontal lobe vulnerability to amyloid deposition. Auditory predictive processes rely on the bilateral auditory cortices with the recruitment of frontal cortices and appear to be impaired in pathologies characterized by compromised frontal lobe. Hence, auditory predictive processes were investigated to assess Down's syndrome pathology and its relationship with pathological ageing. An auditory electroencephalography (EEG) global-local paradigm was presented to the participants, in which oddball stimuli could either violate local or higher level global rules. We characterised predictive processes in individuals with Down's syndrome and their relationship with pathological ageing, with a focus on the EEG event-related potential called Mismatch Negativity (MMN) and the P300. In Down's syndrome, we also evaluated the EEG components as predictor of cognitive decline 1 year later. We found that predictive processes of detection of auditory violations are overall preserved in Down's syndrome but also that the amplitude of the MMN to local deviancies decreases with age. However, the 1-year follow-up of Down's syndrome found that none of the ERPs measures predicted subsequent cognitive decline. The present study provides a novel characterization of electrophysiological markers of local and global predictive processes in Down's syndrome.

Test-retest reliability on the Cambridge Neuropsychological Test Automated Battery: Comment on Karlsen et al. (2020).

Test-retest reliability is essential to the development and validation of psychometric tools. Here we respond to the article by Karlsen et al. (Applied Neuropsychology: Adult, 2020), reporting test-retest reliability on the Cambridge Neuropsychological Test Automated Battery (CANTAB), with results that are in keeping with prior research on CANTAB and the broader cognitive assessment literature. However, after adopting a high threshold for adequate test-retest reliability, the authors report inadequate reliability for many measures. In this commentary we provide examples of stable, trait-like constructs which we would expect to remain highly consistent across longer time periods, and contrast these with measures which show acute within-subject change in response to contextual or psychological factors. Measures characterized by greater true within-subject variability typically have lower test-retest reliability, requiring adequate powering in research examining group differences and longitudinal change. However, these measures remain sensitive to important clinical and functional outcomes. Setting arbitrarily elevated test-retest reliability thresholds for test adoption in cognitive research limits the pool of available tools and precludes the adoption of many well-established tests showing consistent contextual, diagnostic, and treatment sensitivity. Overall, test-retest reliability must be balanced with other theoretical and practical considerations in study design, including test relevance and sensitivity.

Transcutaneous vagus nerve stimulation (t-VNS): A novel effective treatment for temper outbursts in adults with Prader-Willi Syndrome indicated by results from a non-blind study.

Temper outbursts are a severe problem for people with Prader-Willi Syndrome (PWS). Previous reports indicate that vagus nerve stimulation (VNS) may reduce maladaptive behaviour in neurodevelopmental disorders, including PWS. We systematically investigated the effectiveness of transcutaneous VNS (t-VNS) in PWS. Using a non-blind single case repeat measures modified ABA design, with participants as their own controls, t-VNS was evaluated in five individuals with PWS [three males; age 22-41 (M = 26.8)]. After a baseline phase, participants received four-hours of t-VNS daily for 12 months, followed by one month of daily t-VNS for two-hours. The primary outcome measure was the mean number of behavioural outbursts per day. Secondary outcomes included findings from behavioural questionnaires and both qualitative and goal attainment interviews. Four of the five participants who completed the study exhibited a statistically significant reduction in number and severity of temper outbursts after approximately nine months of daily four-hour t-VNS. Subsequent two-hour daily t-VNS was associated with increased outbursts for all participants, two reaching significance. Questionnaire and interview data supported these findings, the latter indicating potential mechanisms of action. No serious safety issues were reported. t-VNS is an effective, novel and safe intervention for chronic temper outbursts in PWS. We propose these changes are mediated through vagal projections and their effects both centrally and on the functioning of the parasympathetic nervous system. These findings challenge our present biopsychosocial understanding of such behaviours suggesting that there is a single major mechanism that is modifiable using t-VNS. This intervention is potentially generalizable across other clinical groups. Future research should address the lack of a sham condition in this study along with the prevalence of high drop out rates, and the potential effects of different stimulation intensities, frequencies and pulse widths.

Age-related retinal thickness in Down's syndrome: A high-risk population for dementia.

INTRODUCTION: People with Down's syndrome (DS) have a high prevalence of early-onset Alzheimer's disease. Early markers of Alzheimer's disease pathology identifiable before clinical change are needed for the evaluation of preventative treatments. The retina, an extension of the brain, may provide a noninvasive imaging site. METHODS: Forty-nine adults with DS and 36 age-matched controls completed retinal nerve fibre layer (RNFL) assessments using optical coherence tomography. RNFL thickness was analyzed in relation to cognitive status and age and previously acquired cortical thickness and cerebral amyloid ß binding data in a subgroup. RESULTS: RNFL thickness was greater in the DS group and did not show age-related thinning. RNFL correlated positively with cognitive scores and cortical thickness and was reduced in participants with positive cerebral amyloid ß binding. DISCUSSION: Increased RNFL in adults with DS may represent early Alzheimer's disease-related changes. Thinning was present in those with cerebral amyloid ß binding, independent of age.

Do the public share practitioners' views about the best evidence?

OBJECTIVE: To investigate whether general practitioners (GPs) and patients agree on what constitutes the best evidence for the effectiveness of treatments. METHODS: GPs and members of the public aged 18-83 read five scenarios describing comparisons between hypothetical treatments for common ailments. Each scenario reported that one treatment was the more effective, as determined by randomised controlled trial (RCT), audit of treatment outcomes from many doctors' patients, a single doctor's clinical experience, a friend's experience, or a web-based sales site. Participants rated how confident they would be that the treatment reported to be more effective would work for them. RESULTS: All participants had least confidence in the web-based sales site, more confidence in a friend's experience and more still in one doctor's experience. For doctor's experience, audit and RCT, amongst the public there were some differences by age but, importantly, only GPs had most confidence in evidence from an RCT. CONCLUSION: GPs may treat evidence from RCTs as the gold standard while members of the public (their patients) may not afford it that same respect. PRACTICE IMPLICATIONS: GPs engaged in shared decision-making should be alert to possible differences from their patients in the weight given to different types of evidence.