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Introduction: The competence assessment to give informed consent in the legal and healthcare settings is often performed merely through clinical judgment. Given the acknowledged limited reliability of clinician-based evaluation in the mental health sector, particularly for the assessment of competence to consent, our objective was to ascertain the dependability of clinical judgment when evaluating the ability of schizophrenia patients to make choices about their health., Methods: The potential convergence between clinical evaluation and scores from a new standardized assessment (the "Evaluation of Informed Consent to Treatment" - "EICT" scale) was therefore tested. The scale assesses four dimensions of competence, specifically how patients normally understand information relating to care (Understanding); how they evaluate the choice of treatment in terms of risk/benefit ratio (Evaluating); how they reason coherently in the decision-making process (Reasoning); and, finally, their ability to make a choice between treatment alternatives (Expressing a choice). Thirty-four outpatients with schizophrenia were evaluated for their competence to consent by five referring clinicians with different backgrounds (psychiatrist, forensic psychiatrist, geriatrician, anesthetist, and medico-legal doctor). Inter-raters variability was tested through correlation analyses between the scores obtained by the clinicians on a modified version of the Global Assessment of Functioning scale (GAF) designed specifically to subjectively assess functioning in each of the four competence dimensions. Two validated competence scales (Mac-CAT-T, SICIATRI-R), and a neuropsychological battery were also administered along with scales for evaluating neuropsychiatric symptoms severity and side effects of medication., Results: Clinical judgments of the individual specialists showed great inter-rater variability. Likewise, only weak/non-significant correlations were found between the EICT subscales and the respective clinicians-rated GAF scales. Conversely, solid correlations were found between the EICT and MacCAT-T subscales. As expected, healthy controls performed better in the ability to give informed consent to treatment, as measured by the three scales (i.e., EICT, MacCAT-T, and SICIATRI-R), and neuropsychological test performance. In the comparisons between patients who, according to the administered EICT, were able or not able to give informed consent to treatment, significant differences emerged for the Phonemic verbal fluency task ( p  = 0.038), Verbal judgments ( p  = 0.048), MacCAT-T subscales, and SICIATRI-R total score. Moreover, EICT exhibited excellent internal consistency (Cronbach's alphas ranging from 0.96 to 0.98 for the four subscales) while the Item Analysis, by measuring the correlation between each item of the EICT and the total score, was excellent for all items of all subscales (alphas ranging from 0.86 to 0.98)., Discussion: In conclusion, our findings highlighted that the assessment of competence exclusively through clinical judgment is not fully reliable and needs the support of standardized tools. The EICT scale could therefore be useful in assessing general competence to consent both in healthcare and legal contexts, where it might be necessary to evaluate the effective competence of patients with psychiatric disorders. Finally, this scale could serve as a valuable tool for decisions regarding whether and to what extent a patient needs support., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision., (Copyright © 2024 Di Fazio, Morena, Piras, Piras, Banaj, Delogu, Damato, Frati, Fineschi, Ferracuti, Sani and Dacquino.)

Amnestic mild cognitive impairment (aMCI) and sporadic Alzheimer's disease (AD) are multifactorial conditions resulting from a complex crosstalk among multiple molecular and biological processes. The present study investigates the association of variants localized in genes and miRNAs with aMCI and AD, which may represent susceptibility, prognostic biomarkers or multi-target treatment options for such conditions. We included 371 patients (217 aMCI and 154 AD) and 503 healthy controls, which were genotyped for a panel of 120 single nucleotide polymorphisms (SNPs) and, subsequently, analyzed by statistical, bioinformatics and machine-learning approaches. As a result, 21 SNPs were associated with aMCI and 13 SNPs with sporadic AD. Interestingly, a set of variants shared between aMCI and AD displayed slightly higher Odd Ratios in AD with respect to aMCI, highlighting a specific risk trajectory linking aMCI to AD. Some of the associated genes and miRNAs were shown to interact within the signaling pathways of APP (Amyloid Precursor Protein), ACE2 (Angiotensin Converting Enzyme 2), miR-155 and PPARG (Peroxisome Proliferator Activated Receptor Gamma), which are known to contribute to neuroinflammation and neurodegeneration. Overall, results of this study increase insights concerning the genetic factors contributing to the neuroinflammatory and neurodegenerative mechanisms underlying aMCI and sporadic AD. They have to be exploited to develop personalized approaches based on the individual genetic make-up and multi-target treatments., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Strafella, Caputo, Termine, Fabrizio, Calvino, Megalizzi, Ruffo, Toppi, Banaj, Bassi, Bossù, Caltagirone, Spalletta, Giardina and Cascella.)

Background: In the first wave of the COVID-19 pandemic in 2020, many countries made changes to the routine management of patients with non-communicable diseases, including neurocognitive disorders. Therefore, many "so-called" non-urgent elective procedures and outpatient appointments have been canceled or postponed, possibly impacting negatively on health and well-being of patients in the short- and long-term. Aim: Here, we aimed at describing numbers and types of outpatient appointments canceled as a result of government's restrictive measures in our memory clinic. Methods: The scheduled appointments at the memory clinic of the Santa Lucia Foundation IRCCS, Rome, Italy, are recorded in a comprehensive dataset under strict administrative control. Here, we compared appointments (first-time and follow-up) that were canceled from January to April 2020 with those of the corresponding months in 2019. Results: We observed a substantial decrease in appointments during 2020. The majority of scheduled appointments were follow-up, and about a quarter were first-time appointments. We estimated that 66.7% and 77.4% of patients missed out respectively their first and follow-up appointments in our memory clinic due to government's restrictive measures in March-April 2020. Conclusions: A large number of patients with neurocognitive disorders missed crucial appointments due to government's restrictive measures, and many experienced a delay in initial diagnosis and initiation of treatment. This has relevant impact on their treatment and consequently has (is still having and potentially will have) an increase on the healthcare service burden of clinics. Furthermore, as a second wave of COVID-19 affects Europe, and with winter approaching, it is a compelling priority to ensure easy and rapid access to appropriate assessment, care and treatment in the event of a new outbreak and potential subsequent lockdowns, with particular attention to the development of specific healthcare technologies customized to older persons with cognitive impairment., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2020 Spalletta, Porcari, Banaj, Ciullo and Palmer.)

Background: During the first wave of the COVID-19 pandemic, many non-urgent outpatient services in Italy were closed due to the Government-enforced lockdown period. So far, little is known about what effect the pandemic, quarantine measures, and reductions in medical services had on people with cognitive impairment and their caregivers. Objectives: To develop two versions (i.e., patients and informants/caregivers) of a survey designed to assess the impact of the COVID-19 pandemic during the first Italian lockdown period (11 March -4 May 2020) on Memory Clinic outpatients with Mild Cognitive Impairment (MCI) or dementia, and their caregivers. Design: Psychiatrists, neuropsychologists, and epidemiologists developed two versions: one for patients with Mild Cognitive Impairment and other cognitive disorders, the other for their relatives and/or caregivers. Each version of the survey includes five sections: (a) socio-demographic information and access to technology devices; (b) individual COVID-19 protection methods; (c) knowledge about COVID-19; (d) the effect of COVID-19 on daily life; and (e) the effect of COVID-19 on emotional state. Conclusion: Until an effective vaccine is developed it is likely that future waves of COVID-19 will result in shielding of vulnerable older adults. We believe that this instrument will be useful as a tool to collect information and help clinicians to promptly respond to changes in patients' cognitive, psychiatric, and somatic health needs, and to help for future planning in possible subsequent quarantine periods., (Copyright © 2020 Porcari, Palmer, Spalletta, Ciullo and Banaj.)

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.

The risk for Alzheimer's disease (AD) is associated with the presence of the 𝜀4 allele of Apolipoprotein E ( APOE ) gene and, recently, with a novel genetic variant of the RNF219 gene. This study aimed at evaluating interactions between APOE -𝜀4 and RNF219 /G variants in the modulation of behavioral and cognitive features of two cohorts of patients suffering from mild cognitive impairment (MCI) or AD. We enrolled a total of 173 female MCI or AD patients (83 MCI; 90 AD). Subjects were screened with a comprehensive set of neuropsychological evaluations and genotyped for the APOE and RNF219 polymorphic variants. Analysis of covariance was performed to assess the main and interaction effects of APOE and RNF219 genotypes on the cognitive and behavioral scores. The analysis revealed that the simultaneous presence of APOE -𝜀4 and RNF219 /G variants results in significant effects on specific neuropsychiatric scores in MCI and AD patients. In MCI patients, RNF219 and APOE variants worked together to impact the levels of anxiety negatively. Similarly, in AD patients, the RNF219 variants were found to be associated with increased anxiety levels. Our data indicate a novel synergistic activity APOE and RNF219 in the modulation of behavioral traits of female MCI and AD patients.