Test-retest reliability and short-term variability of quantitative light reflex pupillometry in a mixed memory clinic cohort.

BACKGROUND: Quantitative light reflex pupillometry (qLRP) may be a promising digital biomarker in neurodegenerative diseases such as Alzheimer's disease (AD), as neuropathological changes have been found in the midbrain structures governing the light reflex. Studies investigating test-retest reliability and short-term, intra-subject variability of qLRP in these patient groups are missing. Our objective was therefore to investigate the test-retest reliability and short-term, intra-subject variability of qLRP in a memory clinic setting, where patients with neurodegenerative disease are frequently evaluated. METHODS: Test-retest reliability study. We recruited patients from a tertiary memory clinic and qLRP was carried out at a baseline visit and then repeated on day 3-14 and on day 21-35 using a hand-held pupillometer. We evaluated the test-retest reliability of qLRP by calculating intraclass correlation coefficients (ICCs) and intra-subject, short-term variability by fitting linear mixed models. We compared ICCs for subgroups based on age, sex, disease severity (MCI vs. mild dementia), AD diagnosis, and amount of neurodegeneration (cerebrospinal fluid-total tau levels). RESULTS: In total, 40 patients (mean age 72 years, 15 female, 22 with mild dementia) were included in the study. We found good-excellent reliability (ICC range 0.86-0.93) for most qLRP parameters. qLRP parameters exhibited limited intra-subject variability and we found no large sources of variability when examining subgroups. CONCLUSION: qLRP was found to have acceptable test-retest reliability and the study results pave the way for research using longitudinal or cross-sectional measurements to assess the construct in identifying and prognosticating neurodegenerative diseases.

Christmas article: Christmas lasts a long time, but do Christmas article writers? A bibliometric case-control study.

Introduction Christmas-themed scientific articles are becoming increasingly popular and may represent a shortcut to scientific demise due to their demand for time better spent on "serious" research. We aimed to investigate whether authorship on Christmas-themed medical articles could damage the scientific careers of authors. We hypothesized that Christmas-authorships had a negative impact on core bibliometric outcomes such as publication rates. Methods We extracted demographic and bibliometric data on first- and last authors of medical papers written for the Christmas edition of Journal of The Danish Medical Association through the years 2010-2012. These cases were compared with controls representing authors of original "serious" research papers written in the same years. We performed a negative binomial regression with the number of publications ten years after the index date (defined as the publication year of Christmas/"serious" article) as the outcome and adjusted models for sex and age. Results We found that first authors of Christmas-themed papers had a publication rate ratio (PRR) of 3.8 (95% confidence interval (CI): 1.4-12.4) in unadjusted analysis and last authors had a PRR of 0.6 (95% CI: 0.2-1.6). The associations weakened and were statistically insignificant in adjusted analyses. Conclusion Our results indicate that first authors publish more in the years following the publication of a Christmas article, although the association may be entirely driven by sex and age. Causality remains uncertain and further studies (such as RCTs) which randomize authors to produce Christmas-themed (preferably in a Santa's workshop setting) or serious articles are needed. Funding. None. Trial registration. None.

Plasma glucose is not associated with performance on standard cognitive screening tests in a mixed memory clinic cohort-An observational cross-sectional study.

BACKGROUND: It has been shown under experimental conditions that cognitive performance, especially working memory, is impaired in patients with type I and type II diabetes mellitus during hyperglycemic and hypoglycemic conditions, perhaps due to altered cerebral glucose metabolism. It is not known if patients with neurodegenerative diseases, who also exhibit pathological cerebral glucose metabolism, are affected in a similar manner by their plasma glucose levels. OBJECTIVE: We aimed to test if performance on two cognitive screening tests was associated with plasma glucose levels in a memory clinic cohort. METHODS: We included patients from the Copenhagen Memory Clinic Cohort with an available Mini Mental-State Examination (MMSE) test score and a plasma glucose measurement performed in conjunction with cognitive testing. We built linear regression models with MMSE and Addenbrooke's Cognitive Examination (ACE) test scores as the outcome and plasma glucose as the explaining variable and adjusted models for age, sex, and diabetes (plasma glucose measurement >11.1 mmol/L). We explored non-linear relationships by adding quadratic terms and by fitting a cubic spline regression model. RESULTS: In total, 2714 patients had an available MMSE score and a plasma glucose measurement. MMSE and ACE total scores were not associated with plasma glucose in a linear or non-linear fashion when we adjusted for age, sex, and diabetes. CONCLUSION: Plasma glucose levels, predominantly within normal ranges, were not associated with performance on routinely applied cognitive tests and do not need to be taken into consideration when interpreting test results from memory clinic patients.

[Christmas article: Copenhagen Christmas Cognitive Examination].

Introduction Motivation is important when administering cognitive tests. Routine cognitive testing may become trivial both for the examiner and the test subject when using tests that only incorporate neutral items. We hypothesized that a Christmas themed cognitive test could improve motivation for cognitive testing and might elicit positive emotional reactions. Methods We devised the Copenhagen Christmas Cognitive Examination (CCCE), a quickly administered test with ten items, all with Christmas themed content. The CCCE evaluates various important areas of cognition including anterograde and retrograde memory, visuoconstruction, naming and executive function. In this cross-sectional pilot study, we tested feasibility and further explored the possible emotional and motivational effects by administering a questionnaire with a 5-point Likert scale indicating agreement with statements regarding mood and motivation after testing. Results A total of 14 cognitively healthy participants (mean age 42 years (SD 12.3)) underwent testing with the CCCE. A high level of positive mood and motivation was present for most subjects after testing. Being in a Christmas mood after testing was significantly associated with higher test scores (Spearman's correlation coefficient 0.53, p = 0.019). Conclusion It was feasible to administer a Christmas themed cognitive test, and test subjects experienced positive emotional reactions after testing. Further testing in a non-healthy population is warranted. Funding none. Trial registration none.

Effects of aerobic exercise on event-related potentials related to cognitive performance: a systematic review.

Introduction: Aerobic exercise interventions may affect different cognitive domains such as attention, working memory, inhibition, etc. However, the neural mechanisms underlying this relationship, remains uncertain. Objective: To perform a systematic review on exercise intervention studies that use event-related potentials (ERPs) as outcome for cognitive performance. Methods: We identified studies through searches in four databases reporting the effects of either an acute bout or chronic exercise on any ERP associated with cognitive performance. Study population included participants >17 years of age with or without a diagnosis. Results: A total of 5,797 records were initially identified through database searching of which 52 were eligible for inclusion. Most studies were of acute aerobic exercise with moderate intensity. Results were heterogenious across studies, but there was a trend that ERP amplitude increased and (to a lesser extent) latencies decreased post-exercise. The P3 ERP was the most often reported ERP. Conclusion: Heterogeneity across studies regarding methodology limited the possibility to draw definitive conclusions but the most consistent findings were that acute aerobic exercise was associated with higher amplitudes, and to a lesser extent shorter latencies, of ERPs.

Prognostic value of complementary biomarkers of neurodegeneration in a mixed memory clinic cohort.

BACKGROUND: Biomarkers of neurodegeneration, e.g. MRI brain atrophy and [18F]FDG-PET hypometabolism, are often evaluated in patients suspected of neurodegenerative disease. OBJECTIVE: Our primary objective was to investigate prognostic properties of atrophy and hypometabolism. METHODS: From March 2015-June 2016, 149 patients referred to a university hospital memory clinic were included. The primary outcome was progression/stable disease course as assessed by a clinician at 12 months follow-up. Intracohort defined z-scores of baseline MRI automatic quantified volume and [18F]FDG-PET standardized uptake value ratios were calculated for all unilaterally defined brain lobes and dichotomized as pronounced atrophy (+A)/ pronounced hypometabolism (+H) at z-score <0. A logistic regression model with progression status as the outcome was carried out with number of lobes with the patterns +A/-H, -A/+H, +A/+H respectively as predictors. The model was mutually adjusted along with adjustment for age and sex. A sensitivity analysis with a z-score dichotomization at -0.1 and -0.5 and dichotomization regarding number of lobes affected at one and three lobes was done. RESULTS: Median follow-up time was 420 days [IQR: 387-461 days] and 50 patients progressed. Patients with two or more lobes affected by the pattern +A/+H compared to patients with 0-1 lobes affected had a statistically significant increased risk of progression (odds ratio, 95 % confidence interval: 4.33, 1.90-9.86) in a multivariable model. The model was partially robust to the applied sensitivity analysis. CONCLUSION: Combined atrophy and hypometabolism as assessed by MRI and [18F]FDG-PET in patients under suspicion of neurodegenerative disease predicts progression over 1 year.

Resting State EEG in Exercise Intervention Studies: A Systematic Review of Effects and Methods.

Background: Exercise has been shown to alter brain plasticity and is explored as a therapeutic intervention in a wide variety of neurological diseases. Electroencephalography (EEG) offers an inexpensive method of studying brain electrocortical activity shortly after exercise and thus offers a way of exploring the influence of exercise on the brain. We conducted a systematic review to summarize the current body of evidence regarding methods of EEG analysis and the reported effects of exercise interventions on EEG. Methods: PubMed, Web of Science and EMBASE were searched for studies investigating resting state EEG in exercise intervention studies carried out in participants >17 years of age and with no history of epilepsy. Further, studies solely investigating event-related potentials as an outcome measure were excluded. Relevant data were extracted, and a risk-of-bias assessment was carried out using the Cochrane risk-of-bias tool. A qualitative synthesis of results was carried out. A protocol for the systematic review was uploaded to https://www.crd.york.ac.uk/PROSPERO/ (ID: CRD42019134570) and the Preferred Reporting Items for Systematic Reviews (PRISMA) statement was followed. Results: Out of 1,993 records screened, 54 studies were included in a final qualitative synthesis with a total of 1,445 participants. Our synthesis showed that studies were mainly carried out using frequency analysis as an analytical method. Generally, findings across studies were inconsistent and few were adjusted for multiple comparisons. Studies were mainly of low quality and usually carried out in small populations, lowering the significance of results reported. Conclusions: Changes in the EEG as a result of an exercise intervention are elusive and difficult to replicate. Future studies should provide biologically sound hypotheses underlying assumptions, include larger populations and use standardized EEG methods to increase replicability. EEG remains an interesting methodology to examine the effects of exercise on the brain.