A New Look on Long-COVID Effects: The Functional Brain Fog Syndrome

Epidemiological data and etiopathogenesis of brain fog are very heterogeneous in the literature, preventing adequate diagnosis and treatment. Our study aimed to explore the relationship between brain fog, neuropsychiatric and cognitive symptoms in the general population. A sample of 441 subjects underwent a web-based survey, including the PANAS, the DASS-21, the IES-R, the Beck Cognitive Insight Scale, and a questionnaire investigating demographic information, brain fog, subjective cognitive impairments (Scc) and sleep disorders. ANOVA, ANCOVA, correlation and multiple stepwise regression analyses were performed. In our sample, 33% of participants were defined as Healthy Subjects (HS; no brain fog, no Scc), 27% as Probable Brain Fog (PBF; brain fog or Scc), and 40% as Functional Brain Fog (FBF; brain fog plus Scc). PBF and FBF showed higher levels of neuropsychiatric symptoms than HS, and FBF showed the worst psychological outcome. Moreover, worse cognitive symptoms were related to the female gender, greater neuropsychiatric symptoms, sleep disorders, and rumination/indecision. Being a woman and more severe neuropsychiatric symptoms were predictors of FBF severity. Our data pointed out a high prevalence and various levels of severity and impairments of brain fog, suggesting a classificatory proposal and a multifaceted etiopathogenic model, thus facilitating adequate diagnostic and therapeutic approaches

COVID-19 and Stressful Adjustment to Work: A Long-Term Prospective Study About Homeworking for Bank Employees in Italy

The COVID-19 evolution has forced the massive introduction of homeworking (HW) for most employees in the initial stages of the pandemic and then return to work, mainly due to the vaccination campaign. These multiple abrupt adjustment demands in work may be a source of intense stress for office workers with consequences on wellbeing and the quality of life. This long-term prospective study aimed at investigating the effect of adaptation demands on a broad population of employees of a large Italian banking group in the job-related stress framework. We administered a web-based survey to 1,264 participants in Reopening after the first lockdown, from June to October 2020, at 841 subjects in Second Wave, corresponding to the rise of contagions from November 2020 to January 2021, and to 491 individuals in Vaccination Round, which ranged from February to June 2021. We assessed workaholism by using the Dutch Work Addiction Scale (DUWAS-10), work-family conflicting overlap by using the Work and Family Conflict Scale (WAFCS), and concern for back to work (BW) and for HW by specific questions. Higher WAFCS scores characterized Reopening and Vaccination Round while Second Wave had the highest level of concern for HW. Women and younger individuals showed the highest concern for BW, WAFCS, and DUWAS-10 scores regardless of the pandemic stage. HW days per week were related to more heightened concern for BW and lower concern for HW, DUWAS, and WAFCS scores. The number of children was related to lower Concern for BW and higher WAFCS scores in Reopening and Second Wave. Our data showed that massive adjustment demands in work and family routine represented a significant source of stress for employees, regardless of the different pandemic stages. The highest level of fatigue emerged in women and younger subjects. These results shed light on the need for a road map to promote a gradual and structured adjustment for workers and encourage organizations to consider homeworking as a valid stable alternative

White matter hyperintensities segmentation: a new semi-automated method

White matter hyperintensities (WMH) are brain areas of increased signal on T2-weighted or fluid-attenuated inverse recovery magnetic resonance imaging (MRI) scans. In this study we present a new semi-automated method to measure WMH load that is based on the segmentation of the intensity histogram of fluid-attenuated inversion recovery images. Thirty patients with mild cognitive impairment with variable WMH load were enrolled. The semi-automated WMH segmentation included removal of non-brain tissue, spatial normalization, removal of cerebellum and brain stem, spatial filtering, thresholding to segment probable WMH, manual editing for correction of false positives and negatives, generation of WMH map, and volumetric estimation of the WMH load. Accuracy was quantitatively evaluated by comparing semi-automated and manual WMH segmentations performed by two independent raters. Differences between the two procedures were assessed using Student’s t-tests and similarity was evaluated using linear regression model and Dice similarity coefficient (DSC). The volumes of the manual and semi-automated segmentations did not statistically differ (t-value = -1.79, DF = 29, p = 0.839 for rater 1; t-value = 1.113, DF = 29, p = 0.2749 for rater 2), were highly correlated [R(2) = 0.921, F((1,29)) = 155.54, p < 0.0001 for rater 1; R(2) = 0.935, F((1,29)) = 402.709, p < 0.0001 for rater 2] and showed a very strong spatial similarity (mean DSC = 0.78, for rater 1 and 0.77 for rater 2). In conclusion, our semi-automated method to measure the load of WMH is highly reliable and could represent a good tool that could be easily implemented in routinely neuroimaging analyses to map clinical consequences of WMH

Anti-inflammatory Effects of Homotaurine in Patients With Amnestic Mild Cognitive Impairment

Alzheimer’s disease (AD) is a fatal dementing neurodegenerative disease, currently lacking an efficacious disease-modifying therapy. In the last years, there has been some interest in the use of homotaurine as a potential therapeutic compound for AD, but more work is still needed to prove its efficacy as disease modifier in dementia. Since inflammation is believed to play a key role in AD development, we sought to investigate here the in vivo homotaurine effect on inflammatory response in patients at the earliest stages of AD, i.e., suffering from amnestic mild cognitive impairment (aMCI). Thus, the present study aims to evaluate the effects of homotaurine supplementation on cytokine serum levels and memory performances in MCI patients. Neuropsychological, clinical and cytokine assessment was performed at baseline (T0) and after 1 year (T12) of homotaurine supplementation in 20 patients categorized as carriers (n = 9) or no carriers (n = 11) of the ε4 allele of the apolipoprotein E (APOE) gene, the strongest genetic risk factor for AD. The serum levels of the pro-inflammatory mediators Interleukin (IL) 1β, Tumor necrosis factor-alpha (TNFα), IL-6 and IL-18, contextually with the anti-inflammatory molecules IL-18 binding protein (IL-18BP) and Transforming growth factor-beta (TGFβ), were analyzed to explore significant differences in the inflammatory status between T0 and T12 in the two APOE variant carrier groups. No significant differences over time were observed in patients as for most cytokines, except for IL-18. Following homotaurine supplementation, patients carrying the APOEε4 allele showed a significant decrease in IL-18 (both in its total and IL-18BP unbound forms), in turn associated with improved short-term episodic memory performance as measured by the recency effect of the Rey 15-word list learning test immediate recall. Thus, homotaurine supplementation in individuals with aMCI may have a positive consequence on episodic memory loss due, at least in part, to homotaurine anti-inflammatory effects. This study strongly suggests that future research should focus on exploring the mechanisms by which homotaurine controls brain inflammation during AD progression

Rare coding variants in PLCG2, ABI3, and TREM2 implicate microglial-mediated innate immunity in Alzheimer's disease

We identified rare coding variants associated with Alzheimer’s disease (AD) in a 3-stage case-control study of 85,133 subjects. In stage 1, 34,174 samples were genotyped using a whole-exome microarray. In stage 2, we tested associated variants (P<1×10-4) in 35,962 independent samples using de novo genotyping and imputed genotypes. In stage 3, an additional 14,997 samples were used to test the most significant stage 2 associations (P<5×10-8) using imputed genotypes. We observed 3 novel genome-wide significant (GWS) AD associated non-synonymous variants; a protective variant in PLCG2 (rs72824905/p.P522R, P=5.38×10-10, OR=0.68, MAFcases=0.0059, MAFcontrols=0.0093), a risk variant in ABI3 (rs616338/p.S209F, P=4.56×10-10, OR=1.43, MAFcases=0.011, MAFcontrols=0.008), and a novel GWS variant in TREM2 (rs143332484/p.R62H, P=1.55×10-14, OR=1.67, MAFcases=0.0143, MAFcontrols=0.0089), a known AD susceptibility gene. These protein-coding changes are in genes highly expressed in microglia and highlight an immune-related protein-protein interaction network enriched for previously identified AD risk genes. These genetic findings provide additional evidence that the microglia-mediated innate immune response contributes directly to AD development