Para-infectious brain injury in COVID-19 persists at follow-up despite attenuated cytokine and autoantibody responses

To understand neurological complications of COVID-19 better both acutely and for recovery, we measured markers of brain injury, inflammatory mediators, and autoantibodies in 203 hospitalised participants; 111 with acute sera (1–11 days post-admission) and 92 convalescent sera (56 with COVID-19-associated neurological diagnoses). Here we show that compared to 60 uninfected controls, tTau, GFAP, NfL, and UCH-L1 are increased with COVID-19 infection at acute timepoints and NfL and GFAP are significantly higher in participants with neurological complications. Inflammatory mediators (IL-6, IL-12p40, HGF, M-CSF, CCL2, and IL-1RA) are associated with both altered consciousness and markers of brain injury. Autoantibodies are more common in COVID-19 than controls and some (including against MYL7, UCH-L1, and GRIN3B) are more frequent with altered consciousness. Additionally, convalescent participants with neurological complications show elevated GFAP and NfL, unrelated to attenuated systemic inflammatory mediators and to autoantibody responses. Overall, neurological complications of COVID-19 are associated with evidence of neuroglial injury in both acute and late disease and these correlate with dysregulated innate and adaptive immune responses acutely

Discovering interesting classification rules with genetic programming

Data mining deals with the problem of discovering novel and interesting knowledge from large amount of data. This problem is often performed heuristically when the extraction of patterns is difficult using standard query mechanisms or classical statistical methods. In this paper a genetic programming framework, capable of performing an automatic discovery of classification rules easily comprehensible by humans, is presented. A comparison with the results achieved by other techniques on a classical benchmark set is carried out. Furthermore, some of the obtained rules are shown and the most discriminating variables are evidenced

Attentional control in Alzheimer's disease

Attentional control of executive function declines during the early stages of Alzheimer's disease. Controversy exists as to whether this decline results from a single global deficit or whether attentional control can be fractionated, with some aspects being more vulnerable than others. We investigated three proposed domains of attention, namely (i) focal attention, based on simple and choice reaction times; (ii) the capacity to resist distraction in a visual search task; and (iii) the capacity to divide attention between two simultaneous tasks. For each domain, two levels of difficulty were used to study Alzheimer's disease patients, who were compared with elderly and young control subjects. The unitary attentional hypothesis predicted that the impacts of level of difficulty, age and disease would be qualitatively similar across the three attentional domains. In fact we observed different patterns for each domain. We obtained no differential impairment for patients in the focal attentional task, whereas patients were somewhat more susceptible than control subjects to the similarity of the distractor items in visual search. Finally, we observed marked impairment in the capacity of Alzheimer's disease patients to combine performance on two simultaneous tasks, in contrast to preserved dual-task performance in the normal elderly group. These results suggest a need to fractionate executive processes, and reinforce earlier evidence for a specific dual-task processing deficit in Alzheimer's disease

Neuropsychological prediction of conversion to dementia from questionable dementia: Statistically significant but not yet clinically useful

Background: Verbal memory impairment, one of the earliest signs of Alzheimer’s disease (AD), may help identify people with cognitive impairment, insufficient for a diagnosis of dementia (questionable dementia: QD), at risk of developing AD. Other cognitive parameters have been found that may indicate which people with QD will go on to develop dementia. Nevertheless, some researchers have reported only partial success in differentiating between mild AD and age related cognitive impairment.Objectives: To discover if there are early, pre-clinical cognitive markers that could help identify patients attending our memory clinic who were at risk of developing dementia.Methods: Multidisciplinary assessment of a consecutive sample of 195 patients with QD seen in a National Health Service hospital outpatient clinic; 135 seen for a mean follow up of 24.5 months.Results: Conversion rate to dementia was 27.4% (37 of 135). A diagnosis of probable or possible AD was made in 15.6% (21 of 135) of cases. Despite statistically significant differences in some cognitive tasks between those who did and those who did not go on to dement, Cox regression analyses failed to improve prediction rates markedly above base rates and were unstable.Conclusion: A large number of studies claim good prediction of conversion to dementia using cognitive test scores. Although this study produced similarly good sensitivity and specificity values, proper consideration of the statistical analyses and their clinical significance suggested that these prediction methods are currently too imprecise for clinical use. Use of cognitive indicators combined with neuroradiological, neuropathological, and genetic factors for predicting conversion to dementia might prove more reliable but may be beyond the scope of many geriatric services