Neutralising antibody activity against SARS-CoV-2 variants, including Omicron, in an elderly cohort vaccinated with BNT162b2

SARS-CoV-2 variants threaten the effectiveness of tools we have developed to mitigate against serious COVID-19. This is especially true in clinically vulnerable sections of society including the elderly. Using sera from BNT162b2 (Pfizer-BioNTech) vaccinated individuals aged between 70 and 89 (vaccinated with two doses 3-weeks apart) we examined the neutralising antibody (nAb) response to wildtype SARS-CoV-2. Between 3 and 20-weeks post 2nd dose, nAb titres dropped 4.9-fold to a median titre of 21.3 (ND80) with 21.6% of individuals having no detectable nAbs at the later time point. Experiments examining the neutralisation of twenty-one different SARS-CoV-2 variant spike proteins confirmed a significant potential for antigenic escape, especially for the Omicron (BA.1), Beta (B.1.351), Delta (B.1.617.2), Theta (P.3), C.1.2 and B.1.638 variants. Interestingly, however, the recently-emerged sub-lineage AY.4.2 was more efficiently neutralised than parental Delta pseudotypes. Combining pseudotype neutralisation with specific receptor binding domain (RBD) ELISAs we confirmed that changes to position 484 in the spike RBD were predominantly responsible for SARS-CoV-2 nAb escape, although the effect of spike mutations is both combinatorial and additive. Lastly, using sera from the same individuals boosted with a 3rd dose of BNT162b2 we showed that high overall levels of neutralising antibody titre can provide significant levels of cross-protection against Omicron. These data provide evidence that SARS-CoV-2 neutralising antibodies wane over time and that antigenically variable SARS-CoV-2 variants are circulating, highlighting the importance of ongoing surveillance and booster programmes. Furthermore, they provide important data to inform risk assessment of new SARS-CoV-2 variants, such as Omicron, as they emerge.

Swallowing Dynamics and Breathing-Swallowing Coordination Are Altered in Patients with Mild Cognitive Impairment

<b><i>Introduction:</i></b> Postinspiratory activity, which is essential for laryngeal closure during swallowing to prevent aspiration of food into the airways, is reduced in a mouse model of tauopathy. Therefore, we hypothesized that patients at the stage of mild cognitive impairment (MCI) exhibit alterations in swallowing dynamics and coordination between swallowing and breathing. <b><i>Methods:</i></b> We examined breathing-swallowing coordination in patients with MCI. Patients who scored ≥24 on the Mini-Mental State Examination and &#x3c;26 on the Japanese version of the Montreal Cognitive Assessment were recruited at Sumoto Itsuki Hospital. Parameters associated with breathing-swallowing coordination were assessed using a combination of two sensors: a respiratory flow sensor and a piezoelectric sensor attached to the skin surface of the anterior neck. <b><i>Results:</i></b> Nineteen patients met the criteria for MCI; 16 of these patients (79.5 ± 9.1 years old) scored &#x3c;3 on the 10-item Eating Assessment Tool and were enrolled in the study. Their data were compared with those of an age-matched elderly cohort (79.9 ± 2.9 years old). The frequencies of swallowing during inspiration and swallowing immediately followed by inspiration in patients with MCI were 6.9% and 9.6%, respectively; these frequencies were not significantly different from those of the age-matched elderly cohort. However, the timing of swallowing in the respiratory cycle was significantly delayed in the MCI patients, and both time from the onset to the peak of laryngeal elevation and the duration between the onset of rapid laryngeal elevation and the time when the larynx returned to the resting position were significantly lengthened in this group. <b><i>Conclusion:</i></b> At the stage of MCI, breathing-swallowing coordination has already started to decline.

The efficacy of cystoperitoneal shunting for the surgical management of intracranial arachnoid cysts in the elderly: A systematic review of the literature

Background: Intracranial arachnoid cysts (AC) are benign, cerebrospinal fluid filled spaces within the arachnoid layer of the meninges. Neurosurgical intervention in children and young adults has been extensively studied, but the optimal strategy in the elderly remains unclear. Therefore, we performed a single center retrospective study combined with a systematic review of the literature to compare cystoperitoneal (CP) shunting with other surgical approaches in the elderly cohort. Methods: Retrospective neurosurgical database search between January 2005 and December 2018, and systematic review of the literature using PRISMA guidelines were performed. Inclusion criteria: Age 60 years or older, radiological diagnosis of intracranial AC, neurosurgical intervention, and neuroradiological (NOG score)/clinical outcome (COG score). Data from both sources were pooled and statistically analyzed. Results: Our literature search yielded 12 studies (34 patients), which were pooled with our institutional data (13 patients). CP shunts (7 patients; 15%), cyst fenestration (28 patients; 60%) and cyst marsupialisation/resection (10 patients; 21%) were the commonest approaches. Average duration of follow-up was 23.6, 26.9, and 9.5 months for each approach, respectively. There was no statistically significant association between choice of surgical intervention and NOG score (P = 0.417), COG score (P = 0.601), or complication rate (P = 0.955). However, CP shunting had the lowest complication rate, with only one patient developing chronic subdural haematoma. Conclusion: CP shunting is a safe and effective surgical treatment strategy for ACs in the elderly. It has similar clinical and radiological outcomes but superior risk profile when compared with other approaches. We advocate CP shunting as first line neurosurgical intervention for the management of intracranial ACs in the elderly.

Incidence, Risk Factors, and Timing of Macrovascular Thrombosis in the Post-COVID-19 Elderly and Assessing the Need and Duration of Extended Thromboprophylaxis: A Prospective Study

Background: COVID-19 infection causes a wide spectrum of macrovascular thrombosis, which has contributed significantly to morbidity and mortality in the elderly. Guidelines have recommended extended prophylaxis following discharge from the hospital for variable periods. The risk of thrombosis and the optimal duration of extended anticoagulation remain uncertain. Objectives: This study aimed at determining the overall incidence and timing of macrovascular thrombosis in post-COVID-19 elderly patients. It also aimed at finding out the predictive value of clinical severity, in-hospital anticoagulation, and discharge D-dimer values for the incidence of macrovascular thrombosis and overall mortality within 13 weeks following clinical recovery from acute COVID-19 infection in the elderly. Methods: In this study, 288 elderly patients with symptomatic acute COVID-19 infection discharged between August 1, 2020, and November 30, 2020, were enrolled. Details regarding the incidence of macrovascular thrombosis were collected through a telephone interview after 90 days. Data were tabulated and analyzed with IBM SPSS Statistics for Windows, Version 23.0. (Armonk, NY: IBM Corp.) Results: The number of macrovascular thrombotic events was significantly higher in group C (critical illness) than in the other two groups (17.9 vs. 1.8 and 1.1%, respectively) (P = 0.0005). Three (10.7%) patients died within 13 weeks of discharge in group C, versus one (0.6%) patient in group M (mild to moderate illness) and none in group S (severe illness) (P = 0.0005). There were two macrovascular thrombotic events in the elevated D-dimer group versus one in the reduced D-dimer group (P = 0.135). The number of deaths was high in the elevated D-dimer group [2 (8.3%) vs. 0 (0), P = 0.053]. The cumulative incidence rate of macrovascular events in the post-COVID-19 elderly cohort 13 weeks after discharge was 3.12%. Conclusions: Elderly patients with a critical illness during hospitalization due to COVID-19 and elevated D-dimer values at discharge have the maximum risk of developing macrovascular thrombosis in the post-COVID-19 period. It is reasonable to recommend extended thromboprophylaxis for at least eight weeks in the post-COVID-19 elderly.

Efficacy, Outcome, and Safety of Elderly Patients with Glioblastoma in the 5-ALA Era: Single Center Experience of More Than 10 Years

Background: In the next decades, the incidence of patients with glioblastoma (GBM) will increase due to the growth of the elderly population. Fluorescence-guided resection using 5-aminolevulinic acid (5-ALA) is widely applied to achieve maximal safe resection of GBM and is identified as a novel intraoperative marker for diagnostic tissue during biopsies. However, detailed analyses of the use of 5-ALA in resections as well as biopsies in a large elderly cohort are still missing. The aim of this study was thus to investigate the efficacy, outcome, and safety of surgically- treated GBM in the 5-ALA era in a large elderly cohort. Methods: All GBM patients aged 65 years or older who underwent neurosurgical intervention between 2007 and 2019 were included. Data on 5-ALA application, intraoperative fluorescence status, and 5-ALA-related side effects were derived from our databank. In the case of resection, the tumor resectability and the extent of resection were determined. Potential prognostic parameters relevant for overall survival were analyzed. Results: 272 GBM patients with a median age of 71 years were included. Intraoperative 5-ALA fluorescence was applied in most neurosurgical procedures (n = 255/272, 88%) and visible fluorescence was detected in most cases (n = 252/255, 99%). In biopsies, 5-ALA was capable of visualizing tumor tissue by visible fluorescence in all but one case (n = 91/92, 99%). 5-ALA administration did not result in any severe side effects. Regarding patient outcome, smaller preoperative tumor volume (<22.75 cm3), gross total resection, single lesions, improved postoperative neurological status, and concomitant radio-chemotherapy showed a significantly longer overall survival. Conclusions: Our data of this large elderly cohort demonstrate the clinical utility and safety of 5-ALA fluorescence in GBM for improved tumor visualization in both resections as well as biopsies. Therefore, we recommend the use of 5-ALA not only in resections, but also in open/stereotactic biopsies to optimize the neurosurgical management of elderly GBM patients.

Association between depression and the risk of Alzheimer’s disease using the Korean National Health Insurance Service-Elderly Cohort

In this cohort study, we assessed the association between depression and the risk of Alzheimer’s disease from data obtained from the 2002 to 2013 Korean National Health Insurance Service-Elderly Cohort Database, which accounts for 10% of the South Korean population aged > 60 years. A total 518,466 patients were included in the analysis and followed up, unless they were excluded due to death or migration. Patients who sought treatment for depression or dementia within 1 year of the washout period and who were diagnosed with dementia within the 1-year period of the diagnosis of depression were excluded from the study. The risk of dementia was analysed using Cox proportional hazards models. Patients with a history of depression during the follow-up period were at a higher risk of Alzheimer’s disease than those without a history of depression (HR 3.35, CI 3.27–3.42). The severe-depression group exhibited the highest risk of Alzheimer’s disease (HR 4.41, CI 4.04–4.81), while the mild-depression group exhibited a relatively lower risk of Alzheimer’s disease (HR 3.31, CI 3.16–3.47). The risk of Alzheimer’s disease was associated with depression history and an increased severity of depression increased the risk of Alzheimer’s disease.

Clinical Outcomes after Intravenous Alteplase in Elderly Patients with Acute Ischaemic Stroke: A Retrospective Analysis of Patients Treated at a Tertiary Neurology Centre in England from 2013 to 2018

Intravenous thrombolysis with alteplase within 4.5 hours from symptom onset is a well-established treatment of acute ischaemic stroke (AIS). The aim was to compare alteplase for AIS between patients aged >80 and ≤80 years in our registry data, from 2013 to 2018. Mechanical thrombectomy cases were excluded. We assessed clinical outcomes over the six-year period and between patients aged over 80 and ≤80 years, using measures including the discharge modified Rankin Scale (mRS), 24-hour National Institutes of Health Stroke Scale (NIHSS) improvement, and symptomatic intracerebral haemorrhage (sICH) rate. Of a total of 805 AIS patients who received intravenous alteplase, 278 (34.5%) were over 80 years old, and 527 (65%) were younger. 616 (76.5%) received thrombolysis ≤ 3 hours after symptom onset and 189 (23.5%) within 3-4.5 hours. Median baseline mRS and NIHSS of the elderly cohort were 1 (IQR 0-5) and 13 (IQR 2-37), respectively, compared to the younger cohort 0 (IQR 0-5) and 9 (IQR 0-29). The sICH rate was 7.2% in the elderly and 4.6% in those ≤80 years, p = 0.05 . NIHSS improved within 24 hours in 34% of the elderly cohort compared to 35% in the younger cohort. At hospital discharge, the mortality rate was 9% in the elderly cohort compared to the 6% in the younger cohort, p = 0.154 . 25% of patients aged >80 years had mRS ≤ 2 compared to 47% in the younger patients ( p < 0.0001 ). In conclusion, thrombolysis in elderly patients results in clinical improvement comparable to younger patients.

Combining Navigator and Optical Prospective Motion Correction for High-Quality 500 μm Resolution Quantitative Multi-Parameter Mapping at 7T

PURPOSEHigh-resolution quantitative multi-parameter mapping shows promise for non-invasively characterizing human brain microstructure but is limited by physiological artifacts. We implemented corrections for rigid head movement and respiration-related B0-fluctuations and evaluated them in healthy volunteers and dementia patients.METHODSCamera-based optical prospective motion correction (PMC) and free-induction decay (FID) navigator correction were implemented in a gradient and RF-spoiled multi-echo 3D gradient echo sequence for mapping proton density (PD), longitudinal relaxation rate (R1) and effective transverse relaxation rate (R2*). We studied their effectiveness separately and in concert in young volunteers and then evaluated the navigator correction (NAVcor) with PMC in a group of elderly volunteers and dementia patients. We used spatial homogeneity within white matter (WM) and gray matter (GM) and scan-rescan measures as quality metrics.RESULTSNAVcor and PMC reduced artifacts and improved the homogeneity and reproducibility of parameter maps. In elderly participants, NAVcor improved scan-rescan reproducibility of parameter maps (coefficient of variation decreased by 14.7% and 11.9% within WM and GM respectively). Spurious inhomogeneities within WM were reduced more in the elderly than in the young cohort (by 9% vs 2%). PMC increased regional GM/WM contrast and was especially important in the elderly cohort, which moved twice as much as the young cohort. We did not find a significant interaction between the two corrections.CONCLUSIONNavigator correction and PMC significantly improved the quality of PD, R1 and R2* maps, particularly in less compliant elderly volunteers and dementia patients.