Search Results (50)

Introduction: Cognitive dysfunction (“brain fog”) is a common manifestation of post-acute COVID-19 syndrome (PACS) and may persist long after the acute infection. While cross-sectional studies have described cognitive deficits, longitudinal evidence on recovery trajectories remains limited. Methods: We conducted a longitudinal observational study of neurocognitive performance and neuropsychiatric symptoms in patients with PACS. Participants underwent assessment with 20 standardized tests covering five cognitive domains (memory, attention, language, executive functions, psychomotor processing speed); anxiety, depression, and sleep quality were assessed at three time points. Changes were analysed using the Friedman test. Results: Forty-two patients were included (median age 57 years; 35.7% female) from a predominantly hospitalized cohort (81% hospitalised; 66.7% requiring respiratory support). Patients who completed all three assessments (completers, n = 42) were compared with those who attended the first evaluation but did not complete follow-up (non-completers, n = 544); completers were more severely ill during the acute phase rather than healthier or more motivated. At the group level, statistically significant improvements over time were observed across the whole sample in verbal short-term learning, visuospatial memory, working memory, constructional praxis, phonological verbal fluency, and psychomotor processing speed (all p ≤ 0.05); after Benjamini–Hochberg adjustment across the twenty cognitive outcomes, visuospatial span forward and backward and psychomotor processing speed remained significant (all FDR-adjusted p ≤ 0.013), with the change confined to the first six months. Sleep quality also improved (p < 0.0001). Conclusion: In this cohort, group-level performance improved in six of the twenty tests administered, of which three remained significant after correction for multiple comparisons, while 28 of 42 patients (66.7%) still scored in the impaired range on at least one test at 12 months, and 17 (40.5%) on two or more. These findings highlight the importance of long-term neuropsychological monitoring and integrated cognitive-psychiatric evaluation in post-COVID care. Given the small, predominantly hospitalized sample, improvements should be interpreted cautiously and confirmed in larger controlled studies, although the use of alternate forms for part of the battery makes task-specific learning an incomplete explanation. Full article

Background and Objectives: Functional decline is a major determinant of disability, caregiver burden, and loss of independence in behavioral variant frontotemporal dementia (bvFTD). Although bvFTD is characterized by early and rapidly progressive deterioration in everyday functioning, the multimodal contributors associated with longitudinal functional change remain insufficiently understood. The present study aimed to identify the strongest cognitive, behavioral, personality, and neuroimaging correlates of longitudinal functional deterioration in bvFTD using an integrated multimodal framework over a 12-month follow-up period. Methods: Twenty-seven patients diagnosed with bvFTD were recruited from the 2nd Neurology Clinic of the “AHEPA” University Hospital in Thessaloniki, Greece, and underwent comprehensive face-to-face neuropsychological assessment for the evaluation of a wide range of cognitive domains, alongside caregiver-based evaluations of behavioral disturbances, personality changes, and functional abilities, at baseline, 6 months, and 12 months. Brain perfusion single-photon emission computed tomography (SPECT) was acquired only at baseline, with regional cerebral blood flow (rCBF) quantified using a Brodmann area (BA)-based approach. Functional status was assessed using the Disability Assessment for Dementia (DAD) as the primary outcome, while the Frontotemporal Dementia Rating Scale (FRS) served as a secondary measure. Repeated-measures analysis of variance (ANOVA) was used to characterize longitudinal changes across cognitive, behavioral, personality, and functional domains, while linear mixed-effects (LME) models were applied to identify longitudinal correlates of functional decline and sources of inter-individual variability in functional outcomes. Results: Significant progressive decline in functional abilities was observed over the 1-year follow-up period, consistent with an aggressive and rapidly deteriorating clinical course in bvFTD. Reductions in functional performance were evident across both basic and instrumental activities of daily living, with deterioration being more pronounced in instrumental activities. Based on the final LME model, greater apathy-related (negative) behavioral symptoms, global cognitive impairment, attentional and processing speed deficits, and impaired inhibitory control were independently associated with poorer longitudinal functional outcomes (p < 0.001). At the neuroimaging level, reduced baseline perfusion in the right BA 24 within the anterior cingulate cortex was also significantly associated with greater loss of functional independence over time (p < 0.001). Conclusions: Longitudinal functional decline in bvFTD reflects the combined disruption of behavioral regulation, global cognition, executive control, and frontal–cingulate network integrity. The findings provide a preliminary foundation for future research investigating factors associated with accelerated functional decline. Further validation in larger, multicenter longitudinal cohorts is needed to determine the prognostic relevance of these factors and their potential applicability to patient stratification and individualized care planning. Full article

Objective: This study examined the association between glycemic status, indexed by HbA1c, and cognitive functioning in individuals with bipolar disorder (BD), recurrent major depressive disorder (rMDD), schizophrenia (SZ), and healthy controls (HCs). Methods: In this cross-sectional study, 215 participants (45 HCs, 64 BD, 62 rMDD, 44 SZ) were assessed. Cognitive performance was evaluated using a comprehensive neuropsychological battery measuring attention, processing speed, memory, executive functions, and social cognition. Sociodemographic characteristics, chlorpromazine-equivalent antipsychotic doses (CEDA), and metabolic variables (body mass index, waist circumference, lipid profile, fasting glucose, and HbA1c) were collected. Group differences, correlation analyses, and multiple regression models were performed. Results: All patient groups showed significantly poorer cognitive performance compared with HCs. HbA1c levels were highest in the SZ group; however, associations between HbA1c and cognitive performance were strongest in the BD group and less consistent in rMDD. In regression analyses, HbA1c was associated with cognitive performance in BD and HCs, with weaker effects in rMDD. CEDA was associated with HbA1c levels and partially attenuated the relationship between HbA1c and cognitive outcomes. Conclusions: HbA1c levels were associated with cognitive performance in non-diabetic individuals, particularly in BD and rMDD. These findings suggest that subclinical variation in glycemic regulation may be relevant to cognitive functioning in psychiatric disorders. Further longitudinal studies are needed to clarify the influence of metabolic factors and psychotropic medication on cognitive outcomes. Full article

Background/Objectives: Delayed neurological deficits after decompressive craniectomy may improve after cranioplasty, but quantitative imaging markers for postoperative monitoring remain limited. This study evaluated diffusion tensor imaging analysis along the perivascular space (DTI-ALPS) as an exploratory diffusion-based marker of defect-referenced perivascular diffusivity asymmetry and examined its relationship with white matter microstructure. Methods: Forty-three adults undergoing first-time cranioplasty after decompressive craniectomy and thirty-four matched healthy controls underwent diffusion magnetic resonance imaging and neuropsychological assessment before cranioplasty; twenty-five patients were reassessed at 3 months. DTI-ALPS was quantified globally and according to defect laterality. The white matter microstructure was assessed using tract-based spatial statistics and automated fiber quantification. The associations between imaging measures and cognitive performance were also examined. Results: Global DTI-ALPS was significantly lower in patients than in controls both before cranioplasty and at 3-month follow-up, with no significant longitudinal increase. Defect-referenced hemispheric asymmetry persisted, with lower ALPS values on the affected side, and white matter abnormalities were widespread before cranioplasty and remained evident at follow-up. Associations between imaging measures and cognitive performance were not significant after multiple-comparison correction. Conclusions: DTI-ALPS may capture persistent defect-related hemispheric diffusion asymmetry after cranioplasty and provide complementary information to conventional white matter metrics. However, in patients with substantial postoperative anatomical and fiber-orientation changes, ALPS should be interpreted cautiously as an exploratory proxy of perivascular diffusivity rather than as a direct measure of glymphatic function or physiological recovery. Full article

Background/Objectives: Chronic obstructive pulmonary disease (COPD) management increasingly relies on patient self-management; however, medication non-adherence, inhaler misuse, delayed exacerbation recognition, and suboptimal engagement in pulmonary rehabilitation remain highly prevalent across disease stages. Cognitive impairment is increasingly recognised in this population, particularly in moderate-to-severe disease and in those with greater systemic burden, yet it is most often treated as a descriptive comorbidity rather than a determinant of disease control. Methods: This conceptual narrative review synthesises biological, neuropsychological, and clinical evidence to examine the extent to which cognitive impairment contributes to variability in self-management performance and clinical outcomes, and to propose a structured framework linking disease burden, neurocognitive vulnerability, behavioural execution, and downstream outcomes. Results: COPD-related processes—including chronic hypoxaemia, hypercapnia, systemic inflammation, oxidative stress, vascular comorbidity, and recurrent exacerbations—provide biologically plausible pathways to neurocognitive vulnerability. Reported deficits in executive function, attention, working memory, processing speed, and visuomotor integration may affect the execution of cognitively demanding tasks central to disease management, including inhaler technique, medication adherence, symptom appraisal, and sustained participation in pulmonary rehabilitation. Across studies, cognitive impairment is consistently associated with inhaler errors, reduced adherence and independence, rehabilitation dropout, impaired symptom recognition, increased healthcare utilisation, functional decline, and mortality. Conclusions: Collectively, these findings support the interpretation that cognitive vulnerability may act as an intermediary mechanism through which disease burden translates into behavioural instability and adverse outcomes. Although this framework remains hypothesis-generating, it provides a coherent basis for future longitudinal and interventional studies to formally evaluate the mediating role of cognition in disease management and outcome trajectories. Full article

Obstructive sleep apnea (OSA) is the most common sleep-related breathing disorder and is increasingly recognized as a contributor to cognitive decline and a potential risk factor for neurodegeneration. Previous studies have also identified various associated comorbidities such as vascular dysfunction, metabolic alterations, and neuroinflammatory changes. Positive airway pressure (PAP) therapy has been associated with cognitive improvement in some studies, but its long-term effects on cognitive function remain uncertain. This study employs a prospective, observational, longitudinal cohort design to examine longitudinal associations between disease severity, PAP therapy and cognition. Additionally, we aim to examine the relationships between cognitive dysfunction, brain structure and associated OSA-related risk factors. A total of 100 eligible participants with mild to severe OSA will be recruited. All participants will undergo comprehensive assessments at baseline and after 12 months, including neurological, pulmonary, and ear, nose and throat clinical examinations, polysomnography, neuropsychological testing, brain magnetic resonance imaging with volumetry, anthropometric measurements, blood and saliva sampling for the assessment of the selected laboratory parameters, gut microbiome analysis, and evaluation of endothelial function and baroreflex sensitivity. This study may improve understanding of how PAP therapy and OSA-related pathophysiological processes influence cognitive outcomes. Full article

Background/Objectives: Minor neurocognitive disorder (minor NCD) represents a heterogeneous and potentially modifiable stage along the continuum from normal aging to dementia, offering a critical window for targeted health promotion interventions. Early identification of individuals at increased risk of progression is essential for implementing preventive strategies that may delay functional decline. This study developed a transparent machine learning (ML) framework to predict diagnostic change from minor to major NCD at 12 and 24 months using baseline demographic, clinical, and multidomain neuropsychological data. Methods: A retrospective cohort of 162 memory clinic patients was analyzed using a rigorously controlled pipeline incorporating nested stratified cross-validation, SMOTE-based imbalance correction, and sequential forward feature selection. Logistic regression, support vector machines (SVMs), and XGBoost were evaluated, with SHapley Additive exPlanations (SHAPs) applied to ensure interpretability. Results: SVM achieved the most balanced predictive performance at both 12 months (accuracy = 0.90) and 24 months (accuracy = 0.81). Short-term progression was primarily driven by subtle multidomain cognitive inefficiencies, while longer-term risk reflected continued cognitive vulnerability modulated by metabolic factors such as diabetes. Conclusions: These findings highlight the potential of explainable ML as a health promotion tool and suggest that explainable ML can uncover clinically meaningful cognitive risk signatures at the earliest stages of NCD. By identifying modifiable systemic contributors alongside cognitive risk profiles, this framework supports precision-oriented preventive strategies and proactive longitudinal monitoring in minor NCD. Full article

Background: Moyamoya disease (MMD) is a rare, progressive cerebrovascular arteriopathy characterized by stenosis and occlusion of the distal internal carotid arteries with the development of compensatory collateral networks. In children, MMD is a major cause of ischemic stroke; however, neurological morbidity frequently extends beyond cerebrovascular events to include epilepsy, headache, cognitive impairment, and psychiatric manifestations. Data regarding the long-term evolution of these complications in Caucasian pediatric patients remains limited. Case Report: We present the longitudinal case of a Caucasian female diagnosed with advanced MMD after an ischemic stroke at the age of 7 years, followed by indirect surgical revascularization (encephalo-duro-arterio-synangiosis) and chronic antiplatelet therapy. Four years later, she developed recurrent focal aware sensory–motor seizures associated with chronic post-ischemic cortical injury. Despite stable vascular imaging and absence of recurrent infarction, the patient experienced persistent neurological sequelae, including residual spastic hemiparesis, episodic tension-type headaches, and evolving neuropsychological complications. Cognitive assessment initially suggested mild neurocognitive impairment, with subsequent improvement during adolescence. In late follow-up, prominent anxiety symptoms emerged, and psychiatric evaluation confirmed panic disorder requiring psychological and pharmacological support. The patient remained neurologically stable into adulthood under continued multidisciplinary care. This case illustrates the broad spectrum of neurological and psychiatric complications that may accompany pediatric MMD, even in the absence of new ischemic events. The accompanying literature review emphasizes that epilepsy, headache, cognitive dysfunction, and psychiatric disorders represent clinically significant components of the long-term disease burden in children with MMD. Conclusions: Pediatric moyamoya disease should be regarded not only as a cause of childhood stroke, but also as a chronic condition with long-term epileptic, cognitive, and psychiatric sequelae that may evolve independently of recurrent ischemic injury. By providing longitudinal follow-up from childhood into adulthood in a Caucasian patient, this report underscores the importance of integrating neuropsychological and psychiatric surveillance into standard care pathways, alongside vascular and surgical management, to better address the full spectrum of morbidity and improve quality of life. Full article

Introduction: Psychotic symptoms (PS) in Alzheimer’s disease (AD) are associated with unfavorable prognosis, including accelerated functional decline and reduced survival. Multiple neurotransmitter systems have been implicated in the pathophysiology of PS, with the serotonergic system emerging as particularly relevant. Materials and Methods: Between 2010 and 2020, 120 patients with prodromal AD and 26 cognitively healthy controls underwent comprehensive evaluation, including clinical history, neurological and neuropsychological assessment, neuroimaging, and lumbar puncture. All participants underwent longitudinal clinical monitoring for a minimum of five years or until the emergence of PS. In February 2024, baseline cerebrospinal fluid (CSF) serotonin (5-HT) concentrations were quantified using competitive ELISA (FineTest, Wuhan, China). Results: CSF 5-HT levels were significantly elevated (p < 0.003) in patients who subsequently developed psychosis (n = 49) compared with those who remained free of PS during the 8-year follow-up (n = 19). A threshold of 4.89 ng/mL yielded 80% sensitivity for identifying individuals at risk. Baseline Neuropsychiatric Inventory (NPI; p < 0.001) and Unified Parkinson’s Disease Rating Scale part III (UPDRS III; p < 0.009) scores also demonstrated strong discriminative capacity. Conclusions: Measurement of CSF 5-HT and detailed clinical profiling in prodromal AD may provide predictive value for psychosis onset within 8 years of diagnosis. To our knowledge, this is the first study to report CSF 5-HT findings in AD patients. Full article

This study presents Care-MOVE, a smartphone-based application designed for continuous, passive, and unobtrusive monitoring of mobility, environmental exposure, and cognitive status in older adults within a telemedicine framework. The system integrates movement-related data collected through smartphone sensors (GPS, activity recognition, and caloric expenditure estimation) with contextual air quality information and standardized neuropsychological assessments, resulting in a comprehensive multimodal dataset (Care-MOVE Dataset). An exploratory proof-of-concept study was conducted on a subsample of 53 participants aged over 65, each monitored continuously for five days, contributing on average more than 30,000 longitudinal records. To investigate whether daily motor behavior can serve as a digital biomarker of cognitive functioning, several Machine Learning and Deep Learning models were evaluated using a Leave-One-User-Out (LOUO) cross-validation strategy. The comparative analysis included traditional classifiers (Logistic Regression, Random Forest, Gradient Boosting, K-Nearest Neighbors, and Support Vector Machines) as well as temporal deep learning architectures (1D CNN, LSTM, GRU, and Transformer). Among all of the evaluated approaches, the Support Vector Machine with RBF kernel achieved the best performance, reaching an accuracy of 98.1%, a balanced accuracy of 0.988, and an F1-score of 0.981, demonstrating robust generalization across unseen subjects. For this reason, the study was designed and presented as an exploratory proof-of-concept rather than a definitive clinical validation. This integrated approach not only enables the collection of detailed and contextualized data but also opens new perspectives for proactive digital healthcare, focused on risk prevention, improving quality of life, and promoting autonomy in elderly patients. Full article

Background: Research to identify changes in driving behavior that occur with the onset of Pre-MCI and MCI is an emerging area with many gaps still to be addressed. These gaps include limited use of objective, continuous measurement of driver behavior in real-life traffic conditions and comprehensive, biomarker-validated, cognitive evaluation based upon both testing and clinical ratings. Using these strategies, the questions addressed in this exploratory study are whether or not differences in driving behavior are indicative of Pre-MCI/MCI and which behaviors are most predictive of Pre-MCI/MCI. Methods: As part of a naturalistic longitudinal study, older drivers with a Montreal Cognitive Assessment score ≥ 19 had telematic sensors installed in their vehicles and underwent comprehensive cognitive assessment quarterly for three years. Thirty-six participants were classified as Unimpaired (n = 23) or Pre-MCI/MCI (n = 10/3) based upon a neuropsychological battery and diagnostic algorithm. A penalized generalized linear mixed-effects model (GLMM) with a logistic link and LASSO regularization was used to model Pre-MCI/MCI group membership vs. unimpaired as a function of ten trip-level telematic features (trip distance, hard acceleration, hard braking, hard turns, speed average, maximum speed, RPM average, fuel level, throttle average, and throttle variability) at the end of their first 12 months in the study. Results: Higher RPM, shorter average trips, and greater throttle variability predicted higher odds of Pre-MCI/MCI, while more frequent hard braking, hard turns, higher mean speed, and lower average throttle (steadier pedal control) predicted lower odds of Pre-MCI/MCI. Conclusions: The model clearly distinguished unimpaired older drivers from those with MCI or Pre-MCI, suggesting that distinct patterns of driver behavior may be related to levels of cognitive function. Full article

Background: Obstructive sleep apnea (OSA) is highly prevalent in the early stages of Alzheimer’s disease (AD), and its hallmark, sleep fragmentation, may accelerate cognitive decline. Continuous positive airway pressure (CPAP) improves OSA-related hypoxia during slow-wave sleep, but its cognitive benefits in AD remain unclear. Methods: We performed a 12-month sub-analysis of a prospective, longitudinal pilot study that enrolled 21 adults (median age = 77 yr; 71% women) with Mild Cognitive Impairment (MCI) with AD confirmed biomarkers and polysomnography-diagnosed OSA. All participants underwent baseline overnight polysomnography (PSG) and neuropsychological testing (Clinical Dementia Rating (CDR), Mini-Mental State Examination (MMSE), Repeatable Battery for the Assessment of Neuropsychological Status (RBANS)) that were repeated after 12 months. Twelve participants were CPAP-compliant (moderate/severe OSA) and nine were non-users (mild OSA/intolerance). Cognitive change scores (Δ = 12 months -baseline) were compared with Generalized Linear Models (GLM) adjusted for baseline cognition and Apnea–Hypopnea Index (AHI); associations between baseline sleep parameters and cognitive trajectories were examined. And the association of sleep variables with the use of CPAP was also evaluated. Results: Compared with non-users, CPAP users showed significantly slower global decline (Δ MMSE: p = 0.016) and improvements in overall cognition (Δ RBANS Total: p = 0.028) and RBANS sub-domains (Δ RBANS FC: p = 0.010; Δ RBANS SF: p = 0.045). Longer baseline non-rapid eye movement (NREM) stage 3 and rapid eye movement (REM) sleep, greater total sleep time and sleep efficiency, and right-side sleeping were each linked to better cognitive outcomes, whereas extended NREM stage 2, wakefulness, and supine sleeping were associated with poorer trajectories. Conclusions: Twelve months of CPAP use was associated with attenuated cognitive decline and domain-specific gains in AD-related MCI with OSA. Sleep architecture and body position during sleep predicted cognitive outcomes, underscoring the therapeutic relevance of optimizing breathing and sleep quality. Larger, longer-term trials are warranted to confirm CPAP’s disease-modifying potential and to clarify the mechanistic role of sleep in AD progression. Full article

The COVID-19 pandemic has left millions worldwide with persistent cognitive difficulties, making long-term studies essential to understand their trajectory and inform rehabilitation strategies. This research is presented within the context of Long COVID, emphasizing that cognitive symptoms (including deficits in attention, memory, and executive functions) are reported even in non-hospitalized individuals, yet longitudinal evidence beyond two years remains scarce. An observational, cross-sectional, and retrospective design was applied to a sample of 297 adults with their cognition assessed, divided into mild, moderate, and severe COVID-19 groups, and evaluated using standardized cognitive tests. Findings showed that cognitive performance declined with increasing severity of COVID-19 symptoms, particularly in divided attention, working memory, executive control, verbal fluency, recognition memory, and general intelligence. Age consistently predicted lower scores across cognitive domains, especially in moderate and severe groups, whereas education level did not exert a significant protective effect. The study shows that cognitive deficits can persist at least three years after infection, affecting older adults and those with the more severe symptoms. These results highlight the need for long-term neuropsychological monitoring and individualized rehabilitation strategies to mitigate impacts on autonomy and quality of life. Full article

Background: HIV-associated neurocognitive disorders (HANDs) continue to be a significant concern, despite the advancements in prognosis achieved through Combination Antiretroviral Therapy (cART). Neuropsychological assessment, recommended by international guidelines for HANDs diagnosis, can be resource-intensive. Brief screening tools, like the International HIV Dementia Scale (IHDS) and the Montreal Cognitive Assessment (MoCA), are crucial in facilitating initial evaluations. This study aims to assess the Italian IHDS (IHDS-IT) and evaluate its sensitivity and specificity in detecting cognitive impairment in HIV patients. Methods: This cross-sectional study involved 294 patients aged ≥30 years, evaluated at the Immunology Unit of the University of Cagliari. Cognitive function was assessed using the MoCA and IHDS. Laboratory parameters, such as CD4 nadir, current CD4 count, and HIV-RNA levels, were also collected. Statistical analyses included Spearman’s correlation, Receiver Operating Characteristic analysis, and the Youden J statistic to identify the optimal IHDS-IT cut-off for cognitive impairment detection. Results: The IHDS and MoCA scores showed a moderate positive correlation (Spearman’s rho = 0.411, p < 0.0001). ROC analysis identified an IHDS-IT cut-off of ≤9, yielding an Area Under the Curve (AUC) of 0.76, sensitivity of 71.7%, and specificity of 67.2%. At this threshold, 73.1% of patients with MoCA scores below 23 also presented abnormal IHDS scores, highlighting the complementary utility of both cognitive assessment instruments. Conclusions: The IHDS-IT exhibited fair diagnostic accuracy for intercepting cognitive impairment, with a lower optimal cut-off than previously reported. The observed differences may reflect this study cohort’s demographic and clinical characteristics, including advanced age and long-lasting HIV infection. Further, longitudinal studies are necessary to validate these findings and to confirm the proposed IHDS cut-off over extended periods. Full article

Background/Objectives: Gender differences influence the clinical manifestations, progression, and treatment response in obstructive sleep apnea (OSA) syndrome, suggesting the existence of distinct gender-related phenotypes potentially driven by anatomical, physiological, and hormonal factors. However, the impact of gender on OSA-related cognitive profiles remains unknown. This study aimed to investigate the neuropsychological and polysomnographic (PSG) differences between OSA females and males in order to detect the impact of gender on clinical manifestation and PSG features. Methods: Data were collected from 28 OSA patients (14 females and 14 males matched for age, education, and disease severity). All patients performed a complete neuropsychological evaluation, Epworth sleepiness scale, and whole-night PSG. To evaluate the relationship between specific sleep profiles and cognitive performance, PSG parameters were correlated to scores obtained on neuropsychological tests. Results: Both male and female groups performed within the normal range across all administered neuropsychological tests, according to Italian normative values. Compared with OSA males, female patients showed significantly lower values on the Rey–Osterrieth Complex Figure (ROCF) Recall Test. By contrast, no significant statistical clinical difference emerged between the two OSA groups in terms of clinical manifestation and sleep parameters. Conclusions: This study improves the knowledge on gender-related cognitive impairment in OSA patients. Our preliminary findings demonstrate that the ROCF Recall Test may be altered in OSA females, but not in males. Further longitudinal studies are needed to investigate whether OSA female patients will develop a frank dementia over time. Full article