Neuropsychological measures of post-COVID-19 cognitive status.

Background: COVID-19 may result in persistent symptoms in the post-acute phase, including cognitive and neurological ones. The aim of this study is to investigate the cognitive and neurological features of patients with a confirmed diagnosis of COVID-19 evaluated in the post-acute phase through a direct neuropsychological evaluation. Methods: Individuals recovering from COVID-19 were assessed in an out-patient practice with a complete neurological evaluation and neuropsychological tests (Mini-Mental State Examination; Rey Auditory Verbal Test, Multiple Feature Target Cancellation Test, Trial Making Test, Digit Span Forward and Backward, and Frontal Assessment Battery). Pre- and post-COVID-19 global and mental health status was assessed along with the history of the acute phase of infection. Post-COVID-19 cognitive status was modeled by combining persistent self-reported COVID-related cognitive symptoms and pathologic neuropsychological tests. Results: A total of 406 individuals (average age 54.5 ± 15.1 years, 45.1% women) were assessed on average at 97.8 ± 48.0 days since symptom onset. Persistent self-reported neurological symptoms were found in the areas of sleep (32%), attention (31%), and memory (22%). The MMSE mean score was 28.6. In total, 84 subjects (20.7%) achieved pathologic neuropsychological test results. A high prevalence of failed tests was found in digit span backward (18.7%), trail making (26.6%), and frontal assessment battery (10.9%). Cognitive status was associated with a number of factors including cardiovascular disease history, persistent fatigue, female sex, age, anxiety, and mental health stress. Conclusion: COVID-19 is capable of eliciting persistent measurable neurocognitive alterations particularly relevant in the areas of attention and working memory. These neurocognitive disorders have been associated with some potentially treatable factors and others that may stratify risk at an early stage.

Sensing red blood cell nano-mechanics: Toward a novel blood biomarker for Alzheimer's disease.

Red blood cells (RBCs) are characterized by a remarkable elasticity, which allows them to undergo very large deformation when passing through small vessels and capillaries. This extreme deformability is altered in various clinical conditions, suggesting that the analysis of red blood cell (RBC) mechanics has potential applications in the search for non-invasive and cost-effective blood biomarkers. Here, we provide a comparative study of the mechanical response of RBCs in patients with Alzheimer's disease (AD) and healthy subjects. For this purpose, RBC viscoelastic response was investigated using atomic force microscopy (AFM) in the force spectroscopy mode. Two types of analyses were performed: (i) a conventional analysis of AFM force-distance (FD) curves, which allowed us to retrieve the apparent Young's modulus, E; and (ii) a more in-depth analysis of time-dependent relaxation curves in the framework of the standard linear solid (SLS) model, which allowed us to estimate cell viscosity and elasticity, independently. Our data demonstrate that, while conventional analysis of AFM FD curves fails in distinguishing the two groups, the mechanical parameters obtained with the SLS model show a very good classification ability. The diagnostic performance of mechanical parameters was assessed using receiving operator characteristic (ROC) curves, showing very large areas under the curves (AUC) for selected biomarkers (AUC > 0.9). Taken all together, the data presented here demonstrate that RBC mechanics are significantly altered in AD, also highlighting the key role played by viscous forces. These RBC abnormalities in AD, which include both a modified elasticity and viscosity, could be considered a potential source of plasmatic biomarkers in the field of liquid biopsy to be used in combination with more established indicators of the pathology.

Neuropsychological Measures of Long COVID-19 Fog in Older Subjects.

Coronavirus disease 2019 is known to impact older people more severely and to cause persistent symptoms during the recovery phase, including cognitive and neurologic ones. We investigated the cognitive and neurologic features of 100 elderly patients with confirmed diagnosis of coronavirus disease 2019 evaluated in the postacute phase through a direct neuropsychological evaluation consisting on Mini Mental State Examination and 8 neuropsychological tests. Overall, a total of 33 participants were found to perform at a level considered to be pathologic; more specifically, 33%, 23%, and 20% failed on Trial Making, Digit Span Backwards, and Frontal Evaluation Battery tests, respectively.

COVID-19 atypical Parsonage-Turner syndrome: a case report.

BACKGROUND: Neurological manifestations of Sars-CoV-2 infection have been described since March 2020 and include both central and peripheral nervous system manifestations. Neurological symptoms, such as headache or persistent loss of smell and taste, have also been documented in COVID-19 long-haulers. Moreover, long lasting fatigue, mild cognitive impairment and sleep disorders appear to be frequent long term neurological manifestations after hospitalization due to COVID-19. Less is known in relation to peripheral nerve injury related to Sars-CoV-2 infection. CASE PRESENTATION: We report the case of a 47-year-old female presenting with a unilateral chest pain radiating to the left arm lasting for more than two months after recovery from Sars-CoV-2 infection. After referral to our post-acute outpatient service for COVID-19 long haulers, she was diagnosed with a unilateral, atypical, pure sensory brachial plexus neuritis potentially related to COVID-19, which occurred during the acute phase of a mild Sars-CoV-2 infection and persisted for months after resolution of the infection. CONCLUSIONS: We presented a case of atypical Parsonage-Turner syndrome potentially triggered by Sars-CoV-2 infection, with symptoms and repercussion lasting after viral clearance. A direct involvement of the virus remains uncertain, and the physiopathology is unclear. The treatment of COVID-19 and its long-term consequences represents a relatively new challenge for clinicians and health care providers. A multidisciplinary approach to following-up COVID-19 survivors is strongly advised.

Corrigendum: Top-Down Proteomics of Human Saliva Highlights Anti-inflammatory, Antioxidant, and Antimicrobial Defense Responses in Alzheimer Disease.

[This corrects the article DOI: 10.3389/fnins.2021.668852.].

Top-Down Proteomics of Human Saliva Highlights Anti-inflammatory, Antioxidant, and Antimicrobial Defense Responses in Alzheimer Disease.

Alzheimer disease (AD) is the most prevalent neurodegenerative disease in the elderly, characterized by accumulation in the brain of misfolded proteins, inflammation, and oxidative damage leading to neuronal cell death. By considering the viewpoint that AD onset and worsening may be influenced by environmental factors causing infection, oxidative stress, and inflammatory reaction, we investigated the changes of the salivary proteome in a population of patients with respect to that in healthy controls (HCs). Indeed, the possible use of saliva as a diagnostic tool has been explored in several oral and systemic diseases. Moreover, the oral cavity continuously established adaptative and protective processes toward exogenous stimuli. In the present study, qualitative/quantitative variations of 56 salivary proteoforms, including post-translationally modified derivatives, have been analyzed by RP-HPLC-ESI-IT-MS and MS/MS analyses, and immunological methods were applied to validate MS results. The salivary protein profile of AD patients was characterized by significantly higher levels of some multifaceted proteins and peptides that were either specific to the oral cavity or also expressed in other body districts: (i) peptides involved in the homeostasis of the oral cavity; (ii) proteins acting as ROS/RNS scavengers and with a neuroprotective role, such as S100A8, S100A9, and their glutathionylated and nitrosylated proteoforms; cystatin B and glutathionylated and dimeric derivatives; (iii) proteins with antimicrobial activity, such as α-defensins, cystatins A and B, histatin 1, statherin, and thymosin ß4, this last with a neuroprotective role at the level of microglia. These results suggested that, in response to injured conditions, Alzheimer patients established defensive mechanisms detectable at the oral level. Data are available via ProteomeXchange with identifier PXD021538.

Intraexaminer and interexaminer reliability of pressure biofeedback unit for assessing lumbopelvic stability during 6 lower limb movement tests.

OBJECTIVE: The purpose of this study was to assess examiners' intrarater and interrater reliability to use a pressure biofeedback unit (PBU) during 6 lower limb movement tests based on Movement System Impairment classification model for low back pain (LBP) in people with nonspecific LBP. METHODS: Thirty subjects (13 men and 17 women) with chronic nonspecific LPB were assessed during 6 lower limb movement tests based on Movement System Impairment classification using a PBU. Each test was performed twice by 2 assessors with a 48-hour interval between test sessions. Reliability indices of PBU measures (intraclass correlation coefficient [ICC]) were calculated. RESULTS: Intrarater reliability for hip and knee movement tests was good to excellent (ICC(3,3), 0-.60-0.95). Interrater reliability for hip and knee movement tests was fair to excellent (ICC(2,3), 0.40-0.86). Standard error of the measurement and smallest detectable change for the movement tests ranged from 1.4 to 11.3 mm Hg and from 3.9 to 31.3 mm Hg, respectively. CONCLUSIONS: The results of this study indicate that trained examiners can reliably perform PBU measures for patients with chronic LBP.

EPA and DHA differentially affect in vitro inflammatory cytokine release by peripheral blood mononuclear cells from Alzheimer's patients.

It has been hypothesized that pro-inflammatory cytokines may play a pathogenic role in Alzheimer's disease (AD), and that n-3 polyunsaturated fatty acids may be protective against the development and progression of this disease. A reduced release of inflammatory cytokines by lipopolysaccharide (LPS)-stimulated peripheral blood mononuclear cells (PBMCs) from AD patients dietary supplemented with a mixture of eicosapentaenoic (EPA) and docosahexaenoic acid (DHA) was recently reported. On this basis, we investigated the possible differential effects of the two purified fatty acids on inflammatory cytokine release, a subject still not explored, even though of great pharmacological interest. We treated in vitro phytohaemagglutinin (PHA)- or LPS-stimulated PBMCs from AD patients and age-matched healthy controls (HCs) with purified EPA or DHA. Higher pro- to anti-inflammatory cytokine ratios, indicative of a pro-inflammatory profile, were observed in PHA-stimulated PBMCs from AD patients in basal conditions. The addition of both EPA and DHA markedly reduced the cytokine release, with DHA showing always a more prominent effect than EPA. However, whereas DHA reduced only the high IL-1ß/IL-10 ratio, EPA was able to reduce also the IL-6/IL-10 ratio. In stimulated PMBCs from HCs the reducing effect on cytokine release was not always observed, or observed at a lower degree. In conclusion, whereas DHA appeared more powerful in inhibiting each single inflammatory cytokine, the proinflammatory profile of the AD patients' cells was better reverted by EPA to a profile more similar to that found in HCs. A combination of both the fatty acids, seems to be still the best solution.

Survival in Alzheimer's disease is shorter in women carrying heterozygosity at codon 129 of the PRNP gene and no APOE epsilon 4 allele.

We assessed the role of the APOE genotype and prion protein polymorphism at codon 129 in predicting the clinical duration of 92 neuropathologically confirmed sporadic Alzheimer's disease patients. Analyses of survival showed that the absence of the APOE epsilon 4 allele in heterozygous codon 129 PRNP carriers is a negative predictor of survival. When this subgroup of patients was stratified by sex, the effect of APOE was observed in women, but not in men.