HIV-associated Neurocognitive Disorders Research Articles

Decoding HIV-associated neurocognitive disorders: a new perspective from multimodal connectomics

Currently, HIV-associated neurocognitive disorders (HAND) remains one of the major challenges faced by people living with HIV (PLWH). HAND involves the vulnerability of neural circuits caused by synaptic degeneration and abnormal synaptic pruning. In recent years, connectomics has been gradually applied to HAND research as a cutting-edge method for describing the structural and functional connectivity patterns of the brain, to further elucidate the specific mechanisms underlying these neural circuit vulnerabilities. Using multimodal neuroimaging techniques such as diffusion tensor imaging (DTI), structural magnetic resonance imaging (sMRI), and resting-state functional magnetic resonance imaging (rs-fMRI), researchers can detail the connectome network changes in the brains of PLWH. These technologies offer potential biomarkers for the early diagnosis, prognosis, and treatment monitoring of HAND, while also providing new avenues for personalized prediction of cognitive status. Here, we start with the pathogenesis and risk factors of HAND, providing a comprehensive review of the basic concepts of unimodal and multimodal macro connectomics and related graph theory methods, and we review the latest progress in HAND connectomics research. We emphasize the use of connectomics to identify specific disease patterns of HIV-associated neurodegeneration and discuss the potential research directions and challenges in understanding these diseases from a connectomics perspective.

A longitudinal analysis of neurocognitive profiles in South African women with HIV

ABSTRACT HIV and the consequences of HIV-associated neurocognitive disorders (HAND) disproportionally affect South African women. Longitudinal neurocognitive data on women with HIV are limited. We tracked longitudinal neurocognitive profiles of South African women with HIV (baseline n = 140) compared to women without HIV (baseline n = 156). We determined if lifetime and childhood trauma were significantly correlated with global deficit scores (GDS). We assessed neurocognitive performance at baseline, 1-year, and 5-years. We used mixed linear models to determine between-group differences and neurocognitive profiles over time. We used Pearson's correlations to assess correlations with GDS. There were no significant between-group differences in GDS. Both groups showed a significant decline in GDS (i.e., improved cognition) between baseline and 1-year follow-up (p < 0.01). There were significant group differences in learning (p = 0.02) and attention/working memory (p = 0.01) at baseline, with HIV + status associated with higher deficit scores. Childhood neglect was correlated with baseline GDS among women with HIV. Our results support the use of antiretroviral treatment to improve and/or maintain neurocognition in women with HIV. Future research should focus on the specific types of trauma exposure, specifically neglect and its association with HAND.

Transformation of brain myeloid cell populations by SIV in rhesus macaques revealed by multiomics

The primary immune constituents in the brain, microglia and macrophages, are the target for HIV in people and simian immunodeficiency virus (SIV) in nonhuman primates. This infection can lead to neurological dysfunction, known as HIV-associated neurocognitive disorder (HAND). Given the gaps in our knowledge on how these cells respond in vivo to CNS infection, we perform single-cell multiomic sequencing, including gene expression and ATAC-seq, on myeloid cells from the brains of rhesus macaques with SIV-induced encephalitis (SIVE) as well as uninfected controls. We find that SIVE significantly changes the myeloid cell populations. In SIVE, microglia-like cells express high levels of chemoattractants capable of recruiting highly activated CAM-like cells to the site of infection/inflammation. A unique population of microglia-like cells is found in which the chromatin accessibility of genes diverges from their RNA expression. Additionally, we observe a dramatic shift of upstream gene regulators and their targets in brain myeloid cells during SIVE. This study further uncovers the transcriptome, gene regulatory events, and potential roles of different brain myeloid phenotypes in SIVE. This might deepen the understanding of SIVE/HIVE and enlighten the therapeutic development.

α-Synuclein fibrils enhance HIV-1 infection of human T cells, macrophages and microglia

HIV-associated neurocognitive disorders (HAND) and viral reservoirs in the brain remain a significant challenge. Despite their importance, the mechanisms allowing HIV-1 entry and replication in the central nervous system (CNS) are poorly understood. Here, we show that α-synuclein and (to a lesser extent) Aβ fibrils associated with neurological diseases enhance HIV-1 entry and replication in human T cells, macrophages, and microglia. Additionally, an HIV-1 Env-derived amyloidogenic peptide accelerated amyloid formation by α-synuclein and Aβ peptides. Mechanistic studies show that α-synuclein and Aβ fibrils interact with HIV-1 particles and promote virion attachment and fusion with target cells. Despite an overall negative surface charge, these fibrils facilitate interactions between viral and cellular membranes. The enhancing effects of human brain extracts on HIV-1 infection correlated with their binding to Thioflavin T, a dye commonly used to stain amyloids. Our results suggest a detrimental interplay between HIV-1 and brain amyloids that may contribute to the development of neurodegenerative diseases.

MicroRNA in neuroexosome as a potential biomarker for HIV-associated neurocognitive disorders.

HIV-associated neurocognitive disorder (HAND) is a complication of chronic inflammation caused by HIV infection that impairs cognitive and motor functions. HAND can occur at any age, regardless of the duration of infection, even in people living with HIV (PLWH) whose blood viral load is controlled by antiretroviral therapy. The diagnosis of HAND requires a battery of neuropsychological tests, which is time-consuming and burdensome, limiting its effectiveness for screening PLWH. Here, we aimed to identify biomarkers for quantitatively diagnosing and screening for HAND using minimally invasive blood tests. Neuronal-derived exosomes (neuroexosomes) were isolated from the peripheral blood of PLWH, and the transcriptomes of their microRNAs (miRNAs) were analyzed. We identified five upregulated miRNAs (hsa-miR-16-5p, hsa-miR-26a-3p, hsa-92a-3p, hsa-miR-103a-3p, and hsa-miR-185-5p), and two downregulated miRNA (hsa-miR-3613-3p and hsa-miR-4668-5p) in PLWH diagnosed with HAND (HAND PLWH). Functional analysis of five miRNAs whose expression levels increased in HAND PLWH using the database showed that these miRNAs are involved in motor proteins and endocytosis, which are associated with nerve function. The expression levels of hsa-miR-16-5p, hsa-miR-103a-3p, and hsa-miR-185-5p were significantly higher than those in the non-HIV controls and non-HAND PLWH, suggesting that these miRNAs are potential biomarkers for HAND. Since there were no changes in known dementia miRNA biomarkers in HAND PLWH, the miRNAs identified in this study will allow for early differentiation of HAND.

Brain RNA profiling highlights multiple disease pathways in persons with HAND: uncovering determinants of biotype diversity.

To discover microRNA (miRNA)-RNA transcript interactions dysregulated in brains from persons with HIV-associated neurocognitive disorder (HAND), we investigated RNA expression using machine learning tools. Brain-derived host RNA transcript and miRNA expression was examined from persons with or without HAND using bioinformatics platforms. By combining next generation sequencing, droplet digital (dd)PCR quantitation of HIV-1 genomes, with bioinformatics and statistical tools, we investigated differential RNA expression in frontal cortex from persons without HIV (HIV[-]), with HIV without brain disease (HIV[+]), with HIV-associated neurocognitive disorder (HAND), or HAND with encephalitis (HIVE). Expression levels for 147 transcripts and 43 miRNAs showed a minimum 4-fold difference between clinical groups with a predominance of antiviral (Type I interferon) signaling-, neural cell maintenance-, and neurodevelopmental disorder-related genes that was validated by gene ontology and molecular pathway inferences. Scale of signal-to-noise ratio (SSNR) and biweight midcorrelation (bicor) analyses identified 14 miRNAs and 45 RNA transcripts, which were highly correlated and differentially expressed (p ≤ 0.05). Machine learning applications compared regression models predicated on HIV-1 DNA, or RNA viral quantities that disclosed miR-4683 and miR-154-5p were dominant variables associated with differential expression of host RNAs. These miRNAs were also associated with antiviral-, cell maintenance-, and neurodevelopmental disorder-related genes. Antiviral as well as neurodevelopmental disorder-related pathways in brain were associated with HAND, based on correlated RNA transcripts and miRNAs. Integrated molecular methods with machine learning offer insights into disease mechanisms, underpinning brain-related biotypes among persons with HIV that could direct clinical care.

Sex Affects Cognitive Outcomes in HIV-1 Tat Transgenic Mice: Role of CCR5.

People living with HIV (PLWH) experience HIV-associated neurocognitive disorders (HAND), even though combination antiretroviral therapy (cART) suppresses HIV replication. HIV-1 transactivator of transcription (HIV-1 Tat) contributes to the development of HAND through neuroinflammatory and neurotoxic mechanisms. C-C chemokine 5 receptor (CCR5) is important in immune cell targeting and is a co-receptor for HIV viral entry into CD4+ cells. Notably, CCR5 has been implicated in cognition unrelated to HIV infection. Inhibition of CCR5 has been shown to improve learning and memory. To test whether CCR5 is involved in cognitive changes in HAND, we used a non-infectious, transgenic model in which HIV-1 Tat is inducibly expressed. Well-powered cohorts of male and female mice were placed on a diet containing doxycycline to induce Tat expression for 8-wks. Males showed Tat-mediated deficits in the Barnes maze test of spatial learning and memory; females showed no impairments. Deficits in the males were fully reversed by the CCR5 antagonist, maraviroc (MVC). Tat-mediated deficits were not found in novel object recognition or contextual fear conditioning in either sex. Based on earlier work, we hypothesized that MVC might increase brain-derived neurotrophic factor (BDNF), which is essential in maintaining synaptodendritic function. MVC did increase the mBDNF to proBDNF ratio in males, perhaps contributing to improved cognition.

Neurological impact of HIV/AIDS and substance use alters brain function and structure.

Human immunodeficiency virus (HIV) infection is the cause of acquired immunodeficiency syndrome (AIDS). Combination antiretroviral therapy (cART) has successfully controlled AIDS, but HIV-associated neurocognitive disorders (HANDs) remain prevalent among people with HIV. HIV infection is often associated with substance use, which promotes HIV transmission and viral replication and exacerbates HANDs even in the era of cART. Thus, the comorbid effects of substance use exacerbate the neuropathogenesis of HANDs. Unraveling the mechanism(s) of this comorbid exacerbation at the molecular, cell-type, and brain region levels may provide a better understanding of HAND persistence. This review aims to highlight the comorbid effects of HIV and substance use in specific brain regions and cell types involved in the persistence of HANDs. This review includes an overview of post-translational modifications, alterations in microglia-specific biomarkers, and possible mechanistic pathways that may link epigenomic modifications to functional protein alterations in microglia. The impairment of the microglial proteins that are involved in neural circuit function appears to contribute to the breakdown of cellular communication and neurodegeneration in HANDs. The epigenetic modification of N-terminal acetylation is currently understudied, which is discussed in brief to demonstrate the important role of this epigenetic modification in infected microglia within specific brain regions. The discussion also explores whether combined antiretroviral therapy is effective in preventing HIV infection or substance-use-mediated post-translational modifications and protein alterations in the persistence of neuropathogenesis in HANDs.

Bridging brain and blood: a prospective view on neuroimaging-exosome correlations in HIV-associated neurocognitive disorders.

HIV-associated neurocognitive disorder (HAND) is a complex neurological complication resulting from human immunodeficiency virus (HIV) infection, affecting about 50% of individuals with HIV and significantly diminishing their quality of life. HAND includes a variety of cognitive, motor, and behavioral disorders, severely impacting patients' quality of life and social functioning. Although combination antiretroviral therapy (cART) has greatly improved the prognosis for HIV patients, the incidence of HAND remains high, underscoring the urgent need to better understand its pathological mechanisms and develop early diagnostic methods. This review highlights the latest advancements in neuroimaging and exosome biomarkers in HAND research. Neuroimaging, particularly magnetic resonance imaging (MRI), offers a non-invasive and repeatable method to monitor subtle changes in brain structure and function, potentially detecting early signs of HAND. Meanwhile, exosomes are nano-sized vesicles secreted by cells that serve as key mediators of intercellular communication, playing a crucial role in the neuropathology of HIV and potentially acting as a critical bridge between peripheral blood and central nervous system lesions. Thus, combining plasma exosome biomarkers with indicators derived from neuroimaging scans may enhance the early diagnosis of HAND. This review summarizes evidence supporting the role of exosomes as reliable biomarkers for early detection and management of HAND. Furthermore, we emphasize the correlation between neuroimaging biomarkers and exosome biomarkers and explore their potential combined use. This review discusses the technical challenges and methodological limitations of integrating these two types of biomarkers and proposes future research directions. This multidisciplinary integrative approach not only promises to improve the neurocognitive health management of HIV patients but may also offer valuable insights for research into other neurodegenerative diseases.

Mild Neurocognitive Disorder: Clinical Manifestations and Treatment

The decrease in fertility and the increase in the number of older people is a phenomenon that has never been observed before. This has brought with it an increase in chronic degenerative diseases, among which neurocognitive disorders stand out, particularly Mild Cognitive Impairment (MCI). This leads to deterioration in cognition and therefore a progression from mild to more severe levels such as major neurocognitive disorder (TNM). Although it is known that MCI is not synonymous with dementia, we must pay attention, since to a large extent people who suffer from mild cognitive impairment of amnestic time can develop Alzheimer's disease. That is why the purpose of the following article is to review and describe the epidemiology, risk factors, the main symptoms, as well as the treatments that have been developed for mild cognitive impairment such as pharmacological treatments, Cognitive Stimulation (CE). and Transcranial Direct Current Stimulation (tDCS).

Alterations in local activity and whole-brain functional connectivity in human immunodeficiency virus-associated neurocognitive disorders: a resting-state functional magnetic resonance imaging study.

Approximately half of human immunodeficiency virus (HIV) patients experience HIV-associated neurocognitive disorders (HAND); however, the neurophysiological mechanisms underlying HAND remain unclear. This study aimed to evaluate changes in functional brain activity patterns during the early stages of HIV infection by comparing local and global indicators using resting-state functional magnetic resonance imaging (rs-fMRI). A total of 165 people living with HIV (PLWH) but without neurocognitive disorders (PWND), 173 patients with asymptomatic neurocognitive impairment (ANI), and 100 matched healthy controls (HCs) were included in the study. A cross-sectional study of the participants was conducted. The metrics of functional segregation and integration were computed, using graph theory to explore differences across methodologies. Brain functional changes in the PWND and ANI groups were assessed, and correlations between the rs-fMRI metrics, clinical data, and cognitive function were examined. As cognitive function declined, changes reflected by regional homogeneity (ReHo) were primarily observed in the default mode network (DMN). In the DMN and visual network (VIS), amplitude of low-frequency fluctuation (ALFF) decreases were mainly observed in the parieto-occipital lobes, while increases were mainly observed in the limbic network (LIM). Reductions in fractional ALFF (fALFF) were mainly observed in the somatomotor network (SMN) and LIM, while increases were observed in the DMN and LIM. Unlike local indicators, global functional connectivity (FC) significantly decreased in both the PWND and ANI groups compared to the HC group. The ANI group showed partial increases in FC compared to the PWND group, with major changes observed in the DMN, VIS, and LIM. Notably, FC between the right insula and right supramarginal gyrus decreased significantly following HIV infection, while FC between the right caudate nucleus and the left middle frontal gyrus declined further in the ANI group. Graph theory further confirmed the significance of the DMN, and revealed changes in the eigenvector centrality mapping (ECM) values of the frontoparietal network (FPN) and dorsal attention network (DAN). HIV patients exhibit complex changes in both local and global brain activity, regardless of cognitive impairment. Widespread abnormalities primarily involve the DMN, VIS, and LIM. Changes in FC along the fronto-striatal pathway may play a crucial role in the decline of cognitive function in individuals with HAND. Our findings provide new insights that may assist in the early detection of brain damage in the early stages of HIV infection. The use of multiple methodologies may offer a more comprehensive and effective approach, enabling the early detection of brain damage in HIV patients.

HIV-associated neurocognitive disorders (HAND): Optimal diagnosis, antiviral therapy, pharmacological treatment, management, and future scopes

HIV-associated neurocognitive disorders (HAND): Optimal diagnosis, antiviral therapy, pharmacological treatment, management, and future scopes

Clinical practice guidelines for assessment and management of mild neurocognitive disorder

Clinical practice guidelines for assessment and management of mild neurocognitive disorder

Pre-treatment subjective sleep quality as a predictive biomarker of tDCS effects in preclinical Alzheimer's disease patients: Secondary analysis of a randomised clinical trial.

Despite transcranial direct current stimulation (tDCS) has demonstrated encouraging potential for modulating the circadian rhythm, little is known about how well and sustainably tDCS might improve the subjective sleep quality in older adults. This study sought to determine how tDCS affected sleep quality and cognition, as well as how well pre-treatment sleep quality predicted tDCS effects on domain-specific cognitive functions in patients with mild neurocognitive disorder due to Alzheimer's disease (NCD-AD). This clinical trial aimed to compare the effectiveness of tDCS and cognitive training in mild NCD-AD patients (n = 201). Over the course of four weeks, patients were randomized to receive either tDCS plus working memory training, or sham tDCS plus working memory training, or tDCS plus controlled cognitive training. The Pittsburgh Sleep Quality Index (PSQI) was used to measured subjective sleep quality. The Alzheimer's disease assessment scale-cognitive subscale (ADAS-Cog) was used to evaluate domain-specific cognitive functions. Recurrent tDCS treatments enhanced subjective sleep quality and cognition considerably. The poor sleepers (i.e., PSQI > 5) who received tDCS treatment had more cognitive benefits (p = 0.031, Cohen's d = 0.605) and sleep improvements (p < 0.001, Cohen's d = 1.209) in comparison to cognitive training. Pre-treatment subjective sleep quality was linked to tDCS-induced improvement in memory function. During the course of two months, repeated tDCS could considerably enhance subjective sleep quality. For the cognitive benefits of the treatments, the status of pre-treatment subjective sleep quality is crucial. More thorough research is necessary to explore an efficient approach to managing comorbidities for preclinical AD patients.

Neurological Manifestations of HIV-AIDS at Tertiary Care Hospital Quetta

Background: HIV and AIDS continue to pose substantial global health challenges, particularly in resource-constrained settings like Pakistan. This study investigated the prevalence and types of neurological manifestations among HIV-AIDS patients treated at a tertiary care hospital in Quetta. Methodology: A cross-sectional analysis was conducted on 200 HIV-AIDS patients using questionnaires, medical records, and laboratory findings. Results: Neurological manifestations were observed in 70% of the patients, with peripheral neuropathy (40%) being the most common condition, followed by HIV-associated neurocognitive disorders (30%), progressive multifocal leukoencephalopathy (10%), cryptococcal meningitis (7.5%), and cerebral toxoplasmosis (5%). Key risk factors included low CD4 counts (&lt;200), advanced HIV stage (AIDS), and the absence of antiretroviral therapy (ART). Findings: These findings underscore the critical need for early diagnosis and intervention in managing the neurological complications of HIV-AIDS. Peripheral neuropathy and cognitive disorders, in particular, highlight the importance of integrating neurological assessment into routine care for HIV patients. The results call for strengthened ART programs, improved access to healthcare resources, and a holistic approach to treatment. Conclusion: Effective management of HIV-AIDS requires a multidisciplinary strategy to address not only the viral infection but also its neurological and systemic complications. Enhancing healthcare infrastructure and awareness is essential to improve outcomes for patients with HIV-AIDS and to reduce the burden of neurological disorders associated with the disease.

Innate immune memory in chronic HIV and HIV-associated neurocognitive disorders (HAND): potential mechanisms and clinical implications.

Although antiretroviral therapy (ART) has dramatically improved the outlook of the HIV/AIDS pandemic, people living with HIV (PLWH) on suppressive therapy are still at higher risk for a range of comorbidities including cardiovascular disease (CVD) and HIV-associated neurocognitive disorders (HAND), among others. Chronic inflammation and immune activation are thought to be an underlying cause of these comorbidities. Many of the factors thought to drive chronic inflammation and immune activation in HIV overlap with factors known to induce trained immunity. Trained immunity is a form of innate immune memory that metabolically and epigenetically reprograms innate immune cells to mount enhanced inflammatory responses upon secondary encounter with unrelated inflammatory stimuli. While this phenotype has been characterized in a variety of disease states in animals and humans, very little is known about its potential contribution to chronic HIV pathogenesis. In this review, a broad overview of innate immune memory in the periphery and the central nervous system (CNS) is provided and the evidence for trained immunity in the context of HIV is considered. In PLWH on ART, this phenotype could contribute to the chronic inflammation and immune activation associated with HIV comorbidities and could complicate HIV cure strategies due to the potential persistence of the phenotype after eradication of the virus. Further research into this immune state in the context of HIV may open the door for new therapeutics aimed at treating HIV comorbidities like HAND.

P62 Binding to Protein Kinase C Regulates HIV-1 gp120 V3 Loop Induced Microglial Inflammation.

The main pathogenic mechanism of HIV-associated neurocognitive disorders (HAND) is neuronal apoptosis induced by inflammatory mediators, in which microglial inflammation plays a crucial role. However, the exact pathogenic mechanism remains unclear. Previous studies have shown that the HIV-1 gp120 V3 loop can trigger inflammation in CHME-5 microglia. p62 is a post-translational modified multidomain protein that is involved in the regulation of autophagy and is closely related to neuroinflammation. In this study, we found that p62 knockout down-regulated the expression of MCP-1, IL-6 and COX-2, and improved the inflammation of HIV-1 gp120 V3 loop induced microglia, while overexpression of p62 up-regulated the expression of MCP-1, IL-6 and COX-2, and promoted the inflammation of microglia. In addition, protein kinase C (PKC) knockout down-regulated the expression of MCP-1, IL-6 and COX-2 and inhibited the activation of IKK/ NF-κ B pathway, while tumor necrosis factor receptor-associated factor 6 (TRAF6) knockout had no significant effect on the expression of MCP-1, IL-6 and COX-2. Co-immunoprecipitation showed that p62 was bound and interacted with PKC. Inhibition of IKK/ NF-κ B pathway can down-regulate the expression of MCP-1, IL-6 and COX-2, and improve the inflammatory response of microglia. Our research further found that inhibition of IKK/ NF-κ B can decrease the expression of Caspase-3 and reduce the apoptosis of neurons in the co-culture of CHME-5 microglia and primary mouse neurons. The results of this study suggest that HIV-1 gp120 V3 loop induced CHME-5 microglial inflammation may be activated by the direct binding of p62 and PKC through the IKK/ NF-κ B signaling pathway, and these findings provide an important reference for the prevention and treatment of HAND.

Advances in assessment and cognitive neurorehabilitation of HIV-related neurocognitive impairment.

Neurocognitive impairment (NCI) is present in around 40% of people with HIV and substantially affects everyday life, adherence to combined antiretroviral therapy (cART) and overall life expectancy. Suboptimal therapy regimen, opportunistic infections, substance abuse and highly prevalent psychiatric co-morbidities contribute to NCI in people with HIV. In this review, we highlight the need for efficacious treatment of HIV-related NCI through pharmacological approaches and cognitive neurorehabilitation, discussing recent randomized controlled trials in this domain. We also discuss the benefits of a thorough and interdisciplinary diagnostic work-up between specialists in neurology, psychiatry, neuropsychology and infectious diseases, helping to disentangle the various factors contributing to cognitive complaints and deficits in people with HIV. While the advent of cART has contributed to slowing the progression of cognitive deficits in people with HIV and reducing the prevalence of HIV-associated dementia, NCI persists at a significant rate. Adjuvant stimulating or neuroprotective pharmacological agents have shown some potential benefits. Despite promising outcomes, studies on cognitive neurorehabilitation of HIV-related NCI remain sparse and limited in terms of methodological aspects. The access to cognitive neurorehabilitation is also restricted, in particular at the global scale. Novel technology bears a significant potential for restoring cognitive function in people with HIV, affording high degrees of standardization and personalization, along with opportunities for telerehabilitation. Entertaining serious video game environments with immersive graphics can further promote patient motivation, training adherence and impact on everyday life, as indicated by a growing body of evidence, including in seropositive children and older individuals in Africa. Upon validation of technology-assisted cognitive neurorehabilitation for HIV-related NCI in large-scale randomized controlled trials with state-of-the-art methodology, these approaches will promote socio-professional reintegration and quality of life of people with HIV.

Tele-neuropsychological multidomain assessment in Italian people with cognitive disorders: Reliability and user satisfaction.

Tele-neuropsychology has already been employed in neurocognitive disorders, however, in Italy, the evidence of its psychometric quality and satisfaction is still limited. This study aimed to: (1) evaluate the reliability of a standardized battery of neuropsychological screening and domain-specific tests delivered at home via videoconference to a sample of Italian people with cognitive disorders, compared with traditional face-to-face administration; (2) assess the feasibility and satisfaction about remote administration. This crossover study enrolled patients with subjective cognitive disorder, mild neurocognitive disorder, or dementia. All participants performed a brief neuropsychological screening assessment in face-to-face or remote mode. People with milder cognitive disorders (Mini-Mental State Examination ≥ 20) also performed an extended neuropsychological battery. After 15 days, each participant repeated the same assessment in the opposite mode. Finally, participants completed a satisfaction questionnaire. 114 participants were initially enrolled in the study and 100 individuals performed both face-to-face and remote assessments (14 dropouts). All neuropsychological tests showed agreement between the two modes of administration, except for the Digit Span Forward (p = 0.009) and oral-Symbol Digit Modalities Test (p < 0.001). According to Lin's concordance correlation coefficient (LCCCs), tests also showed good or excellent reliability (LCCCs between 0.609 and 0.964); only the Digit Span Backward and the Stroop test showed moderate reliability (LCCCs =0.514-0.441, respectively). Among 100 participants, 65 patients answered the satisfaction questionnaire, declaring high satisfaction for the remote evaluation. Tele-neuropsychology seems to work with in-home assessments among Italian patients with cognitive disorders and seems to be acceptable to them. ClinicalTrials.gov, Identifier: NCT06078332 (October 17, 2023).

Diagnostic accuracy of heart rate variability as a screening tool for mild neurocognitive disorder.

Mild neurocognitive disorder (mNCD) is recognized as an early stage of dementia and is gaining attention as a significant healthcare problem due to current demographic changes and increasing numbers of patients. Timely detection of mNCD provides an opportunity for early interventions that can potentially slow down or prevent cognitive decline. Heart rate variability (HRV) may be a promising measure, as it has been shown to be sensitive to cognitive impairment. However, there is currently no evidence regarding the diagnostic accuracy of HRV measurements in the context of the mNCD population. This study aimed to evaluate the diagnostic accuracy of vagally-mediated HRV (vm-HRV) as a screening tool for mNCD and to investigate the relationship between vm-HRV with executive functioning and depression in older adults who have mNCD. We retrospectively analyzed data from healthy older adults (HOA) and individuals with a clinical diagnosis of mNCD with a biomarker-supported characterization of the etiology of mNCD. Diagnostic accuracy was evaluated using receiver operating characteristic curve analysis based on the area under the curve. Sensitivity and specificity were calculated based on the optimal threshold provided by Youden's Index. Multiple linear regression analyses were conducted to investigate the relationship between vm-HRV and executive functioning and depression. This analysis included 42 HOA and 29 individuals with mNCD. The relative power of high frequency was found to be increased in individuals with mNCD. The greatest AUC calculated was 0.68 (with 95% CI: 0.56, 0.81) for the relative power of high frequency. AUCs for other vm-HRV parameters were between 0.53 and 0.61. No consistent correlations were found between vm-HRV and executive functioning or depression. It appears that vm-HRV parameters alone are insufficient to reliably distinguish between HOA and older adults with mNCD. Additionally, the relationship between vm-HRV and executive functioning remains unclear and requires further investigation. Prospective studies that encompass a broad range of neurocognitive disorders, HRV measurements, neuroimaging, and multimodal approaches that consider a variety of functional domains affected in mNCD are warranted to further investigate the potential of vm-HRV as part of a multimodal screening tool for mNCD. These multimodal measures have the potential to improve the early detection of mNCD in the future.