Screening for cognitive sequelae of SARS-CoV-2 infection: a comparison between the Mini-Mental State Examination (MMSE) and the Montreal Cognitive Assessment (MoCA).

BACKGROUND: Due to SARS-CoV-2-related encephalopathic features, COVID-19 patients may show cognitive sequelae that negatively affect functional outcomes. However, although cognitive screening has been recommended in recovered individuals, little is known about which instruments are suitable to this scope by also accounting for clinical status. This study thus aimed at comparatively assessing the Mini-Mental State Examination (MMSE) and the Montreal Cognitive Assessment (MoCA) in detecting cognitive deficits in post-COVID-19 patients premorbidly/contextually being or not at risk for cognitive deficits (RCD + ; RCD-). METHODS: Data from N = 100 COVID-19-recovered individuals having been administered both the MMSE and the MoCA were retrospectively analyzed separately for each group. RCD ± classification was performed by taking into consideration both previous and disease-related conditions. Equivalent scores (ESs) were adopted to examine classification performances of the two screeners. RESULTS: The two groups were comparable as for most background and cognitive measures. MMSE or MoCA adjusted scores were mostly unrelated to disease-related features. The two screeners yielded similar estimates of below-cut-off performances-RCD + : MMSE: 20%, MoCA: 23.6%; RCD-: MMSE: 2.2%, MoCA: 4.4%. However, agreement rates dropped when also addressing borderline, "low-end" normal, and normal ability categories-with the MoCA attributing lower levels than the MMSE (RCD + : Cohen's k = .47; RCD-: Cohen's k = .17). DISCUSSION: Although both the MMSE and the MoCA proved to be equally able to detect severe cognitive sequelae of SARS-CoV-2 infection in both RCD + and RCD- patients, the MoCA appeared to be able to reveal sub-clinical defects and more sharply discriminate between different levels of ability.

Episodic long-term memory in post-infectious SARS-CoV-2 patients.

BACKGROUND: Episodic long-term memory (LTM) difficulties/deficits are frequent in COVID-19-recovered patients and negatively impact on prognosis and outcome. However, little is known about their semiology and prevalence, also being still debated whether they arise from primary amnesic features or are secondary to dysexecutive/inattentive processes and disease-related/premorbid status. Hence, this study aimed at (1) assessing LTM functioning in post-infectious SARS-CoV-2 patients by accounting for premorbid and disease-related confounders and (2) exploring its cognitive etiology. METHODS: Measures of global cognition (Mini-Mental State Examination (MMSE) and Montreal Cognitive Assessment (MoCA)) and LTM (Babcock Memory Test (BMT)) of fifty-four COVID-19-recovered patients were retrospectively collected. Patients were subdivided into those being already at risk or not for cognitive decline (RCD + ; RCD -). Cognitive measures were converted into equivalent scores (ESs). RESULTS: LTM sub-clinical/clinical deficits (ESs = 0/1) were mildly-to-moderately prevalent in both RCD + (MoCA-Memory, 31.8%; BMT, 31.8%) and RCD - (MoCA-Memory, 28.6%; BMT, 39.3%) patients. MMSE and MoCA total scores, but not the MoCA-Attention subtest, were associated with the BMT. RCD + asymptomatic patients performed better on the BMT (p = .033) than those requiring O2 therapy (but not ventilation). DISCUSSION: COVID-19-recovered individuals might show LTM deficits of both primary and secondary etiology and should be thus screened for them, especially those having suffered mid-to-moderate COVID-19 and those already being at risk for cognitive decline. Both I- and II-level measures of verbal LTM can be adopted, although the former might be more sensitive.

Dissecting the Puzzling Roles of FAM46C: A Multifaceted Pan-Cancer Tumour Suppressor with Increasing Clinical Relevance.

FAM46C is a well-established tumour suppressor with a role that is not completely defined or universally accepted. Although FAM46C expression is down-modulated in several tumours, significant mutations in the FAM46C gene are only found in multiple myeloma (MM). Consequently, its tumour suppressor activity has primarily been studied in the MM context. However, emerging evidence suggests that FAM46C is involved also in other cancer types, namely colorectal, prostate and gastric cancer and squamous cell and hepatocellular carcinoma, where FAM46C expression was found to be significantly reduced in tumoural versus non-tumoural tissues and where FAM46C was shown to possess anti-proliferative properties. Accordingly, FAM46C was recently proposed to function as a pan-cancer prognostic marker, bringing FAM46C under the spotlight and attracting growing interest from the scientific community in the pathways modulated by FAM46C and in its mechanistic activity. Here, we will provide the first comprehensive review regarding FAM46C by covering (1) the intracellular pathways regulated by FAM46C, namely the MAPK/ERK, PI3K/AKT, ß-catenin and TGF-ß/SMAD pathways; (2) the models regarding its mode of action, specifically the poly(A) polymerase, intracellular trafficking modulator and inhibitor of centriole duplication models, focusing on connections and interdependencies; (3) the regulation of FAM46C expression in different environments by interferons, IL-4, TLR engagement or transcriptional modulators; and, lastly, (4) how FAM46C expression levels associate with increased/decreased tumour cell sensitivity to anticancer agents, such as bortezomib, dexamethasone, lenalidomide, pomalidomide, doxorubicin, melphalan, SK1-I, docetaxel and norcantharidin.

Cognitive Stimulation with Music in Older Adults with Cognitive Impairment: A Scoping Review.

BACKGROUND: The use of music in cognitive interventions represents a possibility with potential worthy of further investigation in the field of aging, both in terms of prevention from dementia, in the phase of mild cognitive impairment, and in the treatment of overt dementia. OBJECTIVES: Currently, the types of music-based interventions proposed in the literature are characterized by wide heterogeneity, which is why it is necessary to clarify which interventions present more evidence of effectiveness in stimulating different cognitive domains. METHOD: The study was conducted in accordance with PRISMA guidelines for scoping reviews. By searching two different databases, PubMed and the Web of Science, all studies evaluating the cognitive effects of music-based interventions on people at early stages of cognitive decline (MCI or mild-to-moderate dementia) were selected. RESULTS: The study selection included a total of 28 studies involving n = 1612 participants (mean age ranged from 69.45 to 85.3 years old). Most of the studies analyzed agree with the observation of an improvement, or at least maintenance, of global cognitive conditions (mainly represented by the results of the MMSE test) following music-based interventions, together with a series of other positive effects on verbal fluency, memory, and executive processes. CONCLUSIONS: The results of this review suggest the introduction of music-based interventions as complementary approaches to usual cognitive treatments. Also, the use of standardized and well-defined protocols, in addition to strong methodological research approaches, is suggested. Music-based interventions are recommended in the early stages of dementia, in MCI, and in a preventive sense in healthy older adults.

Multidimensional screening and intervention program for neurocognitive disorder in vascular and multimorbid outpatients: Study protocol for a randomized clinical trial.

BACKGROUND: The heightened risk of dementia resulting from multiple comorbid conditions calls for innovative strategies. Engaging in physical and cognitive activities emerges as a protective measure against cognitive decline. This protocol aims to discuss a multidomain intervention targeting individuals with dementias secondary to cerebrovascular or other medical diseases, emphasizing an often underrepresented demographic. METHODS: This study primary objectives are: a) to identify patients affected by Neurocognitive disorder due to vascular disease or multiple etiologies (screening and diagnostic phase) and b) to evaluate the effectiveness of distinct rehabilitation protocols (intervention phase): motor training alone, paper-based cognitive rehabilitation combined with motor training, digital-based cognitive rehabilitation coupled with motor training. DISCUSSION: Identifying cognitive impairment beyond rigid neurological contexts can facilitate timely and targeted interventions. This protocol strives to address the complex interplay of cognitive decline and comorbidities through a multidimensional approach, providing insights that can shape future interventions and enhancing overall well-being in this vulnerable population. TRIAL REGISTRATION: The study has been registered on July 13, 2023 with the ClinicalTrials.gov NCT05954741 registration number (https://classic.clinicaltrials.gov/ct2/show/NCT05954741).

FAM46C Is an Interferon-Stimulated Gene That Inhibits Lentiviral Particle Production by Modulating Autophagy.

FAM46C is a multiple myeloma (MM) tumor suppressor whose function is only starting to be elucidated. We recently showed that in MM cells FAM46C triggers apoptosis by inhibiting autophagy and altering intracellular trafficking and protein secretion. To date, both a physiological characterization of FAM46C role and an assessment of FAM46C-induced phenotypes outside of MM are lacking. Preliminary reports suggested an involvement of FAM46C with regulation of viral replication, but this was never confirmed. Here, we show that FAM46C is an interferon-stimulated gene and that the expression of wild-type FAM46C in HEK-293T cells, but not of its most frequently found mutant variants, inhibits the production of both HIV-1-derived and HIV-1 lentiviruses. We demonstrate that this effect does not require transcriptional regulation and does not depend on inhibition of either global or virus-specific translation but rather mostly relies on FAM46C-induced deregulation of autophagy, a pathway that we show to be required for efficient lentiviral particle production. These studies not only provide new insights on the physiological role of the FAM46C protein but also could help in implementing more efficient antiviral strategies on one side and lentiviral particle production approaches on the other. IMPORTANCE FAM46C role has been thoroughly investigated in MM, but studies characterizing its role outside of the tumoral environment are still lacking. Despite the success of antiretroviral therapy in suppressing HIV load to undetectable levels, there is currently no HIV cure, and treatment is lifelong. Indeed, HIV continues to be a major global public health issue. Here, we show that FAM46C expression in HEK-293T cells inhibits the production of both HIV and HIV-derived lentiviruses. We also demonstrate that such inhibitory effect relies, at least in part, on the well-established regulatory role that FAM46C exerts on autophagy. Deciphering the molecular mechanism underlying this regulation will not only facilitate the understanding of FAM46C physiological role but also give new insights on the interplay between HIV and the cellular environment.

Perceived risk, illness perception and dispositional optimism related to COVID-19 among oncologic outpatients undergoing in-hospital treatments and healthy controls.

OBJECTIVE: This study aimed to explore risk estimations (perceived risk, dispositional optimism) related to COVID-19 perception and distress in oncologic outpatients undergoing active hospital treatments compared to the general population. DESIGN AND MAIN OUTCOME MEASURES: Data were collected during the Italian lockdown on 150 oncologic outpatients and a sample of 150 healthy subjects. They completed a battery of questionnaires including the Perceived Risk scale, the Brief Illness Perception Questionnaire, the Life Orientation Test- Revised and the Patient Health Questionnaire-4. Descriptive statistics, correlation analysis, and a moderated mediation model were performed to test the study hypotheses. RESULTS: The moderated mediation model attested significant conditional indirect associations of both clinical status and dispositional optimism with distress through the mediation of COVID-19 perceived risk. Healthy individuals and less optimistic people were more likely than others to report higher psychological distress only when they showed neutral or negative COVID-19-related illness perception. CONCLUSIONS: Cancer patients manifest a lower risk perception and a more positive illness representation related to COVID-19 compared to control subjects; the distress level is not associated with the clinical status, but it is moderated by illness perception. Adequate protective behaviors in cancer patients may avoid a dangerous underestimation of objective risks.

Psychiatric symptoms subsequent to COVID-19 and their association with clinical features: A retrospective investigation.

This study explores the association between psychiatric symptoms following COVID-19 and demographic, disease-related and premorbid clinical confounders. Global cognition, depression, anxiety and PTSD features were assessed in 152 post-COVID-19 patients, subdivided into being at risk for brain disorders or not. In both groups, clinically meaningful depression, anxiety and PTSD symptoms were mildly-to-moderately frequent (4-45%). No demographic or clinical variables predicted psychiatric measures (except for lower age predicting higher anxiety levels). Depression, anxiety and PTSD measures were associated among each other. Hence, depression-, anxiety- and PTSD-spectrum disturbances in COVID-19 survivors are likely to be unassociated with disease-related and premorbid features.