Intra-Individual Variability in Alzheimer's Disease and Cognitive Aging: Definitions, Context, and Effect Sizes

To explore different definitions of intra-individual variability (IIV) to summarize performance on commonly utilized cognitive tests (Mini Mental State Exam; Clock Drawing Test); compare them and their potential to differentiate clinically-defined populations; and to examine their utility in predicting clinical change in individuals from the Alzheimer's Disease Neuroimaging Initiative (ADNI).) were computed for each of these definitions in 500 simulated replicates using scores on the Mini Mental State Exam and Clock Drawing Test. IIV was computed based on test items separately (‘within test’ IIV) and the two tests together (‘across test’ IIV). The best performing definition was then used to compute IIV for a third test, the Alzheimer's Disease Assessment Scale-Cognitive, and the simulations and effect sizes were again computed. All effect size estimates based on simulated data were compared to those computed based on the total scores in the observed data. Association between total score and IIV summaries of the tests and the Clinician's Dementia Rating were estimated to test the utility of IIV in predicting clinically meaningful changes in the cohorts over 12- and 24-month intervals.ES estimates differed substantially depending on the definition of IIV and the test(s) on which IIV was based. IIV (coefficient of variation) summaries of MMSE and Clock-Drawing performed similarly to their total scores, the ADAS total performed better than its IIV summary.IIV can be computed within (items) or across (totals) items on commonly-utilized cognitive tests, and may provide a useful additional summary measure of neuropsychological test performance

Age and distraction are determinants of performance on a novel visual search task in aged Beagle dogs

Aging has been shown to disrupt performance on tasks that require intact visual search and discrimination abilities in human studies. The goal of the present study was to determine if canines show age-related decline in their ability to perform a novel simultaneous visual search task. Three groups of canines were included: a young group (N = 10; 3 to 4.5 years), an old group (N = 10; 8 to 9.5 years), and a senior group (N = 8; 11 to 15.3 years). Subjects were first tested for their ability to learn a simple two-choice discrimination task, followed by the visual search task. Attentional demands in the task were manipulated by varying the number of distracter items; dogs received an equal number of trials with either zero, one, two, or three distracters. Performance on the two-choice discrimination task varied with age, with senior canines making significantly more errors than the young. Performance accuracy on the visual search task also varied with age; senior animals were significantly impaired compared to both the young and old, and old canines were intermediate in performance between young and senior. Accuracy decreased significantly with added distracters in all age groups. These results suggest that aging impairs the ability of canines to discriminate between task-relevant and -irrelevant stimuli. This is likely to be derived from impairments in cognitive domains such as visual memory and learning and selective attention

Systematic screening for unsafe driving due to medical conditions: Still debatable

<p>Abstract</p> <p>Background</p> <p>Assessing people's ability to drive has become a public health concern in most industrialized countries. Although age itself is not a predictive factor of an increased risk for dangerous driving, the prevalence of medical conditions that may impair driving increases with age. Because the implementation of a screening for unsafe driving due to medical conditions is a public health issue, its usefulness should be judged using standardised criteria already proposed for screening for chronic disease. The aim of this paper is to propose standardised criteria suitable to assess the scientific validity of screening for unsafe driving due to medical conditions, and identify potential issues to be clarified before screening can be implemented and effective.</p> <p>Discussion</p> <p>Using criteria developed for screening for chronic diseases and published studies on driving with medical conditions, we specify six criteria to judge the opportunity of screening for unsafe driving due to medical conditions. This adaptation was needed because of the complexity of the natural history of medical conditions and their potential consequences on driving and road safety. We then illustrate that published studies pleading for or against screening for unsafe driving due to medical conditions fail to provide the needed documentation. Individual criteria were mentioned in 3 to 72% of 36 papers pleading for or against screening. Quantitative estimates of relevant indicators were provided in at most 42% of papers, and some data, such as the definition of an appropriate unsafe driving period were never provided.</p> <p>Summary</p> <p>The standardised framework described in this paper provides a template for assessing the effectiveness (or lack of effectiveness) of proposed measures for screening for unsafe driving due to medical conditions. Even if most criteria were mentioned in the published literature pleading for or against such a screening, the failure to find quantitative and evidence-based estimates of relevant indicators provides useful insight for further research.</p

A Quantitative RNAi Screen for JNK Modifiers Identifies Pvr as a Novel Regulator of Drosophila Immune Signaling

Drosophila melanogaster responds to gram-negative bacterial challenges through the IMD pathway, a signal transduction cassette that is driven by the coordinated activities of JNK, NF-κB and caspase modules. While many modifiers of NF-κB activity were identified in cell culture and in vivo assays, the regulatory apparatus that determines JNK inputs into the IMD pathway is relatively unexplored. In this manuscript, we present the first quantitative screen of the entire genome of Drosophila for novel regulators of JNK activity in the IMD pathway. We identified a large number of gene products that negatively or positively impact on JNK activation in the IMD pathway. In particular, we identified the Pvr receptor tyrosine kinase as a potent inhibitor of JNK activation. In a series of in vivo and cell culture assays, we demonstrated that activation of the IMD pathway drives JNK-dependent expression of the Pvr ligands, Pvf2 and Pvf3, which in turn act through the Pvr/ERK MAP kinase pathway to attenuate the JNK and NF-κB arms of the IMD pathway. Our data illuminate a poorly understood arm of a critical and evolutionarily conserved innate immune response. Furthermore, given the pleiotropic involvement of JNK in eukaryotic cell biology, we believe that many of the novel regulators identified in this screen are of interest beyond immune signaling

Transparent Meta-Analysis of Prospective Memory and Aging

Prospective memory (ProM) refers to our ability to become aware of a previously formed plan at the right time and place. After two decades of research on prospective memory and aging, narrative reviews and summaries have arrived at widely different conclusions. One view is that prospective memory shows large age declines, larger than age declines on retrospective memory (RetM). Another view is that prospective memory is an exception to age declines and remains invariant across the adult lifespan. The present meta-analysis of over twenty years of research settles this controversy. It shows that prospective memory declines with aging and that the magnitude of age decline varies by prospective memory subdomain (vigilance, prospective memory proper, habitual prospective memory) as well as test setting (laboratory, natural). Moreover, this meta-analysis demonstrates that previous claims of no age declines in prospective memory are artifacts of methodological and conceptual issues afflicting prior research including widespread ceiling effects, low statistical power, age confounds, and failure to distinguish between various subdomains of prospective memory (e.g., vigilance and prospective memory proper)