Is it time to change the way we detect Alzheimer’s disease and monitor its progression? Towards affordable and theory-driven approaches from cognitive neurosciences

A large proportion of people suffering from Alzheimer’s disease (AD) worldwide are not receiving a timely diagnosis. The tools currently used to detect AD and monitor its progression are not sensitive to the preclinical stages and lack specificity for correctdiagnosis. Available biomarkers show acceptable levels of sensitivity but remain littlespecific and not accessible to everyone. We embrace the view that enhancing cognitive assessment of AD should be a research priority. This Perspective paper focuses on issues which, to our view, have been preventing cognitive tests from meeting outstanding needs in the early of detection, monitoring, and treatment development of AD dementia.We first outline the limitations of current diagnostic procedures both theoretically and practically. We then provide a rationale for theory-driven cognitive approaches which would allow mapping assessment tools to specific neuropathological stages of the neurodegenerative course of AD. Finally, we propose research strategies that would help test a hypothesis which, though launched five years ago, remains untested.That is: “Which memory system is impaired first in Alzheimer’s disease?

Feature binding of common everyday items is not affected by age

There is a surge of studies confirming that old age spares the ability to bind in visual working memory (VWM) multiple features within singular object representations. Furthermore, it has been suggested that such ability may also be independent of the cultural background of the assessed individual. However, this evidence has been gathered with tasks that use arbitrary bindings of unfamiliar features. Whether age spares memory binding functions when the memoranda are features of everyday life objects remains less well explored. The present study investigated the influence of age, memory delay, and education, on conjunctive binding functions responsible for representing everyday items in VWM. We asked 32 healthy young and 41 healthy older adults to perform a memory binding task. During the task, participants saw visual arrays of objects, colours, or coloured objects presented for 6 s. Immediately after they were asked either to select the objects or the colours that were presented during the study display from larger sets of objects or colours, or to recombine them by selecting from such sets the objects and their corresponding colours. This procedure was repeated immediately after but this time providing a 30 s unfiled delay. We manipulated familiarity by presenting congruent and incongruent object-colour pairings. The results showed that the ability to bind intrinsic features in VWM does not decline with age even when these features belong to everyday items and form novel or well-known associations. Such preserved memory binding abilities held across memory delays. The impact of feature congruency on item-recognition appears to be greater in older than in younger adults. This suggests that long-term memory (LTM) supports binding functions carried out in VWM for familiar everyday items and older adults still benefit from this LTM support. We have expanded the evidence supporting the lack of age effects on VWM binding functions to new feature and object domains (i.e., everyday items). We have confirmed that education does not negatively impact on such ability at old age. Such results have important implications for the selection of culturally unbiased tests to screen for abnormal ageing trajectories

Accelerated Long-Term Forgetting Can Become Apparent Within 3-8 Hours of Wakefulness in Patients With Transient Epileptic Amnesia

OBJECTIVE: Accelerated long-term forgetting (ALF) is typically defined as a memory disorder in which information that is learned and retained normally over standard intervals (∼30 min) is forgotten at an abnormally rapid rate thereafter. ALF has been reported, in particular, among patients with transient epileptic amnesia (TEA). Previous work in TEA has revealed ALF 24 hr - 1 week after initial memory acquisition. It is unclear, however, if ALF observed 24 hr after acquisition reflects (a) an impairment of sleep consolidation processes taking place during the first night's sleep, or (b) an impairment of daytime consolidation processes taking place during the day of acquisition. Here we focus on the daytime-forgetting hypothesis of ALF in TEA by tracking in detail the time course of ALF over the day of acquisition, as well as over 24 hr and 1 week. METHOD: Eleven TEA patients who showed ALF at 1 week and 16 matched controls learned 4 categorical word lists on the morning of the day of acquisition. We subsequently probed word-list retention 30 min, 3 hr, and 8 hr postacquisition (i.e., over the day of acquisition), as well as 24-hr and 1-week post acquisition. RESULTS: ALF became apparent in the TEA group over the course of the day of acquisition 3-8 hr after learning. No further forgetting was observed over the first night in either group. CONCLUSIONS: The results of this study show that ALF in TEA can result from a deficit in memory consolidation occurring within hours of learning without a requirement for intervening sleep. (PsycINFO Database Record (c) 2015 APA, all rights reserved)

Biplanar versus conventional two-dimensional ultrasound guidance for radial artery catheterisation

Background: Ultrasound guidance increases first-pass success rates and decreases the number of cannulation attempts and complications during radial artery catheterisation but it is debatable whether short-, long-, or oblique-axis imaging is superior for obtaining access. Three-dimensional (3D) biplanar ultrasound combines both short- and long-axis views with their respective benefits. This study aimed to determine whether biplanar imaging would improve the accuracy of radial artery catheterisation compared with conventional 2D imaging. Methods: This before-and-after trial included adult patients who required radial artery catheterisation for elective cardiothoracic surgery. The participating anaesthesiologists were experienced in 2D and biplanar ultrasound-guided vascular access. The primary endpoint was successful catheterisation in one skin break without withdrawals. Secondary endpoints were the numbers of punctures and withdrawals, scanning and procedure times, needle visibility, perceived mental effort of the operator, and posterior wall puncture or other mechanical complications. Results: From November 2021 until April 2022, 158 patients were included and analysed (2D=75, biplanar=83), with two failures to catheterise in each group. First-pass success without needle redirections was 58.7% in the 2D group and 60.2% in the biplanar group (difference=1.6%; 95% confidence interval [CI], –14.0%–17.1%; P=0.84), and first-pass success within one skin break was 77.3% in the 2D group vs 81.9% in the biplanar group (difference=4.6%; 95% CI, 8.1%–17.3%; P=0.473). None of the secondary endpoints differed significantly. Conclusions: Biplanar ultrasound guidance did not improve success rates nor other performance measures of radial artery catheterisation. The additional visual information acquired with biplanar imaging did not offer any benefit. Clinical trial registration: N9687 (Dutch Trial Register).</p

Monitoring of the Sublingual Microcirculation During Cardiac Surgery:Current Knowledge and Future Directions

Handheld vital microscopes allow for direct observation of the sublingual microcirculatory perfusion during cardiac surgery. Through the use of handheld vital microscopes, it has been shown that cardiac surgery with cardiopulmonary bypass is associated with reduced and heterogenous microcirculatory perfusion. Microcirculatory impairment can result in inadequate tissue perfusion, leading to perioperative complications and poor outcome. Because microcirculatory impairment can occur despite stable or improved global hemodynamics, there is a yet unmet need for specific monitoring of the microcirculation. Technological advancements may facilitate point-of-care monitoring of microcirculatory perfusion using automated real-time analysis of microcirculatory measurements. Thus, microcirculatory monitoring may create new opportunities for specific microcirculatory treatment as part of hemodynamic management. The implementation of microcirculatory variables into personalized treatment concepts has the potential to improve hemodynamic management during cardiac surgery and thereby improve patient outcomes. Therefore, specific treatment strategies need to be developed to prevent or treat alterations of the microcirculatory perfusion. In the future, the use of handheld vital microscopes for microcirculatory monitoring may help to improve hemodynamic management and outcomes for patients undergoing cardiac surgical procedures

New perspectives on binding in visual working memory.

How does visual working memory (WM) store the binding between different features of a visual object (like colour, orientation, and location), and does memorizing these bindings require additional resources beyond memorizing individual features? These questions have traditionally been addressed by comparing performance across different types of change detection task. More recently, experimental tasks such as analogue (cued) recall, combined with analysis methods including Bayesian hypothesis testing and formal model comparison, have shed new light on the properties of WM. A significant new perspective is that noise in neural representation limits the precision of recall, and several recent models incorporate this view to account for failures of binding in WM. We review the literature on feature binding with a focus on these new developments and discuss their implications for the interpretation of classical findings

Accelerated long-term forgetting in presymptomatic autosomal dominant Alzheimer's disease: a cross-sectional study.

Tests sensitive to presymptomatic changes in Alzheimer's disease could be valuable for clinical trials. Accelerated long-term forgetting-during which memory impairment becomes apparent over longer periods than usually assessed, despite normal performance on standard cognitive testing-has been identified in other temporal lobe disorders. We assessed whether accelerated long-term forgetting is a feature of presymptomatic autosomal dominant (familial) Alzheimer's disease, and whether there is an association between accelerated long-term forgetting and early subjective memory changes.This article is available via Open Access. Click on the Additional Link above to access the full-text via the publisher's site