Panagiotis Alexopoulos

Background: Direct comparisons of different scoring methods of the Clock Drawing Test (CDT) and the copy trial of the Rey Complex Figure Test (RCFT) remain limited. Objective: The study aimed to compare the effectiveness of four- and two scoring systems of the CDT and the RCFT, respectively, in detecting mild neurocognitive disorder (MildND) due to Alzheimer's disease (AD) and major neurocognitive disorder (MajorND) due to AD. Methods: The study included 141 cognitively unimpaired individuals, 209 people with MildND and 76 with MajorND due to AD. The 3-point CDT scoring method (CDT3), the Gestalt-, Freund-, and Rouleau methods were employed, while the RCFT Copy trial was scored with the 36-point Taylor system and the RCFT central-items (RCFTci) method. Statistical analyses included comparison analyses and proportional odds logistic regression (POLR) models, while stratified bootstrap resampling was used to repeatedly partition the sample into training and validation sets (70/30 ratio). Results: The Rouleau CDT scoring method achieved the highest classification performance (F1 = 0.67; 95% CI: 0.59–0.74), followed by the Gestalt method (F1 = 0.65; 95% CI: 0.57–0.72), the Freund method (F1 = 0.64; 95% CI: 0.56–0.72), and the CDT3 (F1 = 0.63; 95% CI: 0.55–0.71). The CDT Rouleau method and the RCFT Copy trial showed similar performance (F1 = 0.67; 95% CI: 0.59–0.74), while RCFTci was less effective (F1 = 0.62; 95% CI: 0.54–0.70). Conclusions: The CDT and RCFT Copy trial demonstrated comparable diagnostic accuracy, yet their distinct characteristics (administration time, scoring complexity) may guide test selection across healthcare settings.

Background:Despite their negative effects on cognitive function and cognitive decline risk, drugs with anticholinergic properties are commonly prescribed, particularly in older individuals. In this observational study we aimed to shed light on the relationships between anticholinergic burden (ACB) and depressive symptoms and cognitive and functional performance in a real-world clinical setting. Methods:The study included individuals seeking care at the old-age psychiatry outpatient clinic of Patras University Mental Health Services. Depressive symptoms were assessed using the 15-item Geriatric Depression Scale; cognitive function was tapped using the Cognitive Telephone Screening Instrument, the Montreal Cognitive Assessment, and the Mini-Mental State Examination; and functional performance was assessed using the Bristol Activities of Daily Living Scale. Differences in demographic and clinical variables across the four diagnostic groups were analyzed. Regression analyses were performed to examine the associations between ACB, cognitive and non-cognitive symptoms, and demographic variables. In addition, clustering analyses were conducted to identify distinct, naturally occurring examinee subgroups and to assess if ACB differed across them. Results:The study sample consisted of individuals without cognitive impairment (N = 301), people with mild neurocognitive disorder (MiND, N = 264), major neurocognitive disorder caused by Alzheimer’s disease (ADMaND, N = 114), or other diseases (nonADMaND, N = 63). Significant associations were detected between ACB and depressive symptoms (0.72, p < 0.001), short-term memory (–0.11, p = 0.017), long-term memory (–0.24, p < 0.001), working memory (–0.24, p = 0.001), attention/concentration (–0.13, p = 0.004), verbal fluency (–0.57, p = 0.003), inductive reasoning (–0.17, p = 0.002), basic activities of daily living (0.29, p = 0.001), and instrumental activities of daily living (0.58, p < 0.001). The clustering analyses indicated that in the cluster including individuals with more advanced cognitive decline, poorer functional status, and more severe depressive symptoms, ACB was higher compared with the second group identified by the analyses (p < 0.001). Conclusions:ACB is related to different aspects of the clinical phenotype of cognitive decline. Despite the lack of solid evidence regarding causal relationships and need for further research, minimizing ACB in clinical settings may embody a potential pragmatic strategy in managing cognitive decline in ageing.

Psychological stress has been linked to the onset and course of autoimmune diseases. However, limited data exist regarding the relationship between pre-diagnosis stress exposure and subsequent disease course in systemic lupus erythematosus (SLE). We evaluated the association between psychological stress prior to SLE diagnosis and subsequent disease characteristics. We conducted a cross-sectional study of adults with SLE treated at a tertiary hospital between November 2019 and December 2022. Stress exposure during the two years preceding SLE diagnosis was assessed using the Holmes-Rahe Social Readjustment Rating Scale (life change units, LCU), and categorized as low (< 150), intermediate (150–299), or high (≥ 300). Data on clinical manifestations, comorbidities, disease activity patterns, patient-reported outcomes, and organ damage were collected. Associations between stress levels and outcomes were analyzed using logistic regression models. A total of 140 patients were included (90.7% female; median age at diagnosis 35.5 years). Moderate-to-high stress exposure (LCU ≥ 150) was reported by 46% of patients. Compared with low stress exposure (< 150 LCU), high stress exposure (≥ 300 LCU) was associated with significantly higher rates of depression (62.5% vs. 28.0%; p = 0.002), hypertension (54.2% vs. 24.0%, p = 0.006), and obesity (12.5% vs. 0.0%, p = 0.013), as well as greater fatigue burden (median 68.7 vs. 46.9, p = 0.005). High stress exposure was associated with antiphospholipid syndrome (OR 6.3, 95% CI 1.4–28.8), depression (OR 4.3, 95% CI 1.6–11.3), and a lower likelihood of long quiescent disease course (OR 0.22, 95% CI 0.07–0.7). Patients with higher stress exposure more frequently believed that stress contributed to both disease onset (100% vs. 71.7%, p = 0.006) and flares (100% vs. 69%, p = 0.006). Elevated stress levels preceding SLE diagnosis are associated with comorbidities and less favorable disease patterns. These findings underscore the clinical relevance of psychological stress in SLE and support the need for prospective studies examining its relationship with disease course.

Introduction: Brain health is a multidimensional construct encompassing cognitive, mental, motor, and sensory functioning, influenced by multiple determinants across the lifespan. Evidence of children’s perceptions of brain health remain limited, particularly in the Greek context. Objective(s): This study aimed to explore primary school students’ knowledge, attitudes, and perceptions regarding brain health and its determinants. Methods: A cross-sectional study was conducted among 346 fifth-grade students from 22 public primary schools in Patras, Greece. Data were collected using a Greek-translated and age-adapted version of the Global Brain Health Questionnaire (GBHSQ-C). Internal consistency was assessed using Cronbach’s alpha, while group comparisons were conducted using Mann–Whitney and Independent Median tests (p < 0.05). Results: Most participants (96.2%) reported general knowledge about the brain, and 21.4% indicated having a family member with a brain disease. The scale assessing determinants of brain health demonstrated acceptable internal consistency (Cronbach’s α = 0.693); education and sleeping habits were rated as the most influential factors, whereas smoking was considered the least. Childhood and adolescence were perceived as the most critical stages for maintaining brain health (Cronbach’s α = 0.680). Knowledge of brain diseases was limited and demonstrated poor internal consistency (Cronbach’s α = 0.580). No significant differences were observed across most demographic variables (all p > 0.05); however, family status was significantly associated with knowledge of brain diseases (p = 0.044), with differences identified between one-parent and separated-parent families (p = 0.041). Discussion: These findings highlight critical gaps in foundational brain health literacy among primary school students. Enhancing awareness of modifiable determinants of brain health may promote lifelong healthy behaviors and improve brain health outcomes across the lifespan.

Age-related sensory loss is a strong and possibly causal predictor of cognitive decline, and early detection-even via self-report-is feasible and valuable. Auditory loss has a considerable impact on cognition as shown by cross-sectional data deriving from the AD-HEARING study (https://doi.org/10.3389/fpsyt.2025.1494197), as well as from genomic and epidemiological investigations in the Genome-wide association studies database and in communities in China, respectively (https://doi.org/10.3389/fnagi.2024.1380145). In addition, visual dysfunction is likewise implicated in cognitive impairment and impairment of daily living activities in people with MCI (https://doi.org/10.3389/fnagi.2025.1505815). Of note, in older individuals without cognitive impairment, subjective visual impairment complaints are positively related to visual performance, whereas in those carrying the APOE e4 allele such complaints pertain to attention, processing speed and executive function (https://doi.org/10.3389/fnagi.2024.1465812). Thus, it becomes evident that assessment of sensory function embodies a component of the diagnostic workup of cognitive decline in ageing (https://doi.org/10.3389/fnagi.2024.1465812). Pragmatic and effective tools are urgently needed for facilitating the early detection of sensory loss. An ultra-brief screening tool based on demographic data, one item of the Hearing Handicap Inventory for the Elderly (HHIE) and one of the HHIE for the communication partner is here presented. It may help the greater integration of hearing assessment and can complement the cognitive function assessment with simple and quickly administered tests like the ten-words recall test (https://doi.org/10.3389/fpsyt.2024.1429934), in community and primary healthcare settings where the preponderance of older people in fact seek care (Aggeletaki et al., 2024) (https://doi.org/10.3389/fnagi.2025.1504358). Of note, Lei Kei et al unveiled that the combined effect of sensory loss and low physical performance on cognitive function is additive and this effect is mitigated by participation in social activities such as interacting with friends, playing chess or cards and being involved in voluntary or charity work (https://doi.org/10.3389/fnagi.2024.1498354).Mounting evidence points to the protective influence of physical activity, muscle strength, and overall physical performance on cognitive function in ageing.Recreational physical activity of moderate to high intensity is associated with better performance on semantic fluency, executive function and processing speed and this relationship is partly mediated by depressive symptoms (https://doi.org/10.3389/fnagi.2025.1470256). Moreover, in another paper of this research topic, grip strength and performance on the 30-second sit-to-stand test, assessing lower body strength, balance and endurance, were shown to relate with processing speed, sustained attention and general cognition (https://doi.org/10.3389/fnagi.2025.1496725) (Benedict et al., 2017;Hagenaars et al., 2017). Interestingly, EEG markers were shown to reflect both muscle strength and information processing. They provide valuable insights into their potential utility in deciphering the neuropathophysiological interplay between muscle strength and cognitive function. A systematic review and network meta-analysis provide evidence for the optimal dose and type of exercise to improve cognitive function in people with mild neurocognitive disorder, commonly embodying a pre-dementia stage in people with neurodegenerative disorders (Guo et al., 2013) (https://doi.org/10.3389/fpsyt.2024.1436499). In particular, 12-24 week-, multicomponent exercise sessions with 60-85% of maximum heart rate which last 30 minutes and take place 3-4 times per week are beneficial for global cognition, while sessions lasting 30-61 minutes, 3-4 times per week for 25 weeks or longer, show greater effectiveness in enhancing executive function. Nonetheless, no consensus can be reached yet regarding the optimal dose of physical exercise, since in another study, even though individuals with a longer history of exercise were less likely to experience cognitive decline, prolonged exercise duration was found to increase the risk of cognitive decline, since it may overload the body (https://doi.org/10.3389/fnagi.2025.1496677).Physical health and healthy dietary habits are crucial for maintaining cognitive function in ageing. For instance, calf circumference, a screening method for sarcopenia (Piodena-Aportadera et al., 2022), and bone mineral density, a marker of osteoporosis, are both associated with global cognition in women. Notably, in females correlations between both calf circumference and bone mineral density and global cognition and several neuropsychological scores, i.e. executive function, memory, attention, and brain speed were detected (https://doi.org/10.3389/fnagi.2025.1473135; https://doi.org/10.3389/fnagi.2024.1372583). Moreover, previous reports highlight the role of insulin in amyloid β peptide clearance, tau phosphorylation, and the modulation of vascular function, which pertain to cognitive decline and progression to dementia (Kellar and Craft, 2020). In line with that, triglyceride-glucose index, a marker of insulin resistance, was found to be associated with impairment in both basic and complex activities of daily living (https://doi.org/10.3389/fnagi.2025.1488124). Depressive symptoms and sleep disturbances have emerged as consistent risk factors for cognitive decline in ageing, while they even serve as mediators in the relationship between physical/medical factors and cognitive decline. Depression in old adults, which often manifests with physical discomfort and somatic symptoms (https://doi.org/10.3389/fpsyt.2024.1478359), has increasingly attracted attention from researchers (https://doi.org/10.3389/fnagi.2024.1393110). Besides its relation to intrinsic capacity, which refers to the set of all the physical and mental...

Dementia with Lewy bodies (DLB) is a complex neurodegenerative disorder characterized by cognitive fluctuations, visual hallucinations, parkinsonism, mood disturbances and REM sleep behavioural disorder. Despite extensive research into its neuropathology, most notably the deposition of Lewy pathology and widespread neural loss, the mechanistic link between cellular pathology and clinical manifestations remains elusive. In this review, we propose a translational framework that focuses on the disruption of the excitation-inhibition (E/I) balance in large-scale networks, governed by the dysfunction of neuromodulatory systems. The dopaminergic, cholinergic, serotonergic, and noradrenergic systems, each affected in DLB, modulate excitatory and inhibitory signalling, synaptic plasticity, and large-scale neural dynamics. We synthesize evidence from molecular, neuroimaging, and clinical studies to support the notion that neuromodulatory impairment leads to E/I imbalance, contributing to altered brain connectivity and dysfunctional network states. These disruptions underlie key neuropsychiatric symptoms including cognitive deficits, hallucinations, and mood disturbances. Moreover, we discuss current and emerging pharmacologic strategies, targeting neurotransmitter receptors and synaptic excitability, that may restore E/I balance and improve symptom management. Finally, we highlight the role of neuromodulation in regulating brain states and propose that DLB symptoms emerge from dysfunction of network states, reflecting a failure of the neuromodulatory control. We also explore how risk factors, cognitive reserve, and disease progression affect compensatory capacity and the integrity of E/I homeostasis. This integrative model provides a mechanistic basis for understanding symptom emergence in DLB and offers a translational roadmap for novel therapeutic interventions.

Introduction: Delusions are common in Lewy body disease (LBD), significantly impacting quality of life. This study examined clinical factors, characteristics and themes associated with delusions in LBD. Methods: Clinical and demographic factors were compared between 91 individuals attending St. James’s Hospital in Ireland with LBD both with and without delusions. Clinical scales include the Clinical Dementia Rating Scale (CDR), Epworth sleepiness scale (ESS), Addenbrooke’s Cognitive Evaluation (ACE-III), and Neuropsychiatric Inventory-12 (NPI-12). Themes of delusions extracted from clinical descriptions were mapped onto a typology from primary psychiatric populations. Results: Individuals with delusions were older, had higher CDR and ESS scores, lower ACE-III performance, higher scores on the NPI-12, and demonstrated cognitive impairment at the MCI or dementia level. Misidentification delusions were most common, followed by delusions of “being harmed, attacked, or killed” and “residence is not their home”. Conclusion: These findings suggest delusions are related to disease stage, sleep, distinct cognitive and neuropsychiatric patterns, and follow a unique thematic typology.

This chapter discusses innovative integrated, adaptive, and collaborative service models designed to address the growing prevalence of dementia in low- and middle-income countries. These models aim to overcome the challenges of a limited healthcare infrastructure, lack of dementia-specific training for healthcare professionals, and cultural misconceptions about dementia. Three service models are discussed: the hub-and-spoke model in Nepal, telemedicine for dementia care in Nigeria, and the INTRINSIC services in Greece. Each model overcomes spatial barriers through telehealth and/or interlinked networks of healthcare professionals and services, providing cost-effective, culturally sensitive care. They emphasize the importance of early diagnosis, ongoing care, and community engagement to reduce stigma and improve dementia care outcomes. The chapter also highlights the need for such services to be tailored to local contexts and the importance of continuous training and education for healthcare workers to ensure effective dementia care.

The prevalence of neurocognitive disorders is projected to rise substantially, particularly in low-and middle-income countries (LMICs)(Sachdev et al., 2014; Nichols et al., 2022). Interestingly, the development, clinical expression and progression of brain pathologies causing neurodegenerative conditions, are influenced by modifiable risk factors like low cognitive brain reserve, sensory loss and hypertension, which account for approximately 45% of dementia cases(Livingston et al., 2024). The deciphering of this complex interplay triggers a shift from disease-based management strategies to brain health-promoting ones (PMID: 39081987). This collection of papers explores global approaches to brain health promotion and dementia prevention, the impact of neurocognitive disorders on communities at individual and societal levels, and innovative approaches to diagnostic and post diagnostic care services addressing inequities. The rapidly increasing number of people with cognitive decline renders radical changes in the paradigm of care services for neurocognitive disorders inevitable. Three papers in this collection highlight that in low-resource settings memory clinics and old-age mental health services are scarce and primary healthcare providers do not routinely carry out cognitive screening in older people (Ogbuagu et al., 2023). (PMID: 39081987; PMID: 39081985; PMID: 39081604). Collaborative healthcare services, bridging primary healthcare services with secondary or tertiary ones, may pragmatically address the changing and complex healthcare needs of people with neurocognitive disorders (PMID: 39081604; PMID: 39665073; PMID: 39081472), and the needs of their care partners(PMID: 39081614). They are based on multiprofessional teams who are aware of the particularities of the local setting. In this research topic, three living labs (PMID: 39749098) of such collaborative community services are presented, mainly a multiprofessional case management and e-psychoeducation model of services delivered by mobile teams (PMID: 39081604) and two telehealth-based memory clinic models embedded within primary healthcare services in low-resource settings (PMID: 39665073). Considering the significant impact of modifiable risk factors on the development of cognitive decline in aging and the still small effect sizes of potentially disease modifying drugs, dementia prevention remains a priority and was the primary focus of two papers in the collection (PMID: 39830987, PMID: 39081987). Indeed, it has been included as a strategic goal in the National Dementia plans of several European and North American countries, while in LMICs like Pakistan, no such plans have been enacted at all (PMID: 39830987; PMID: 39081985). In both papers the benefits of evidence-based population-wide approaches to dementia prevention over those relying on lifestyle interventions alone are underscored. Nonetheless, even if included in National Dementia plans, prevention actions are commonly depicted in very general terms and their implementation is undermined by staff shortages, lack of interest of healthcare professionals, pervasive stigma pertaining to aging and dementia and widespread misconceptions regarding the nature of age-related cognitive decline (PMID: 39081987). Modifiable cognitive decline risk factors are related to cardiovascular, sensory, mental and physical health, as well as to societal determinants of brain health which makes multiprofessional cooperation essential for implementing dementia prevention strategies(Gorelick and Sorond, 2024). Interestingly, the ties of collaborative community healthcare services to local contexts may facilitate localized approaches to addressing dementia risk factors, brain health promotion and destigmatization of aging and dementia(PMID: 39081987). Indeed, the impact of each dementia risk factor may vary across different contexts, considering for instance the high rates of brain injuries in Pakistan because of lack of road regulations, domestic and sexual violence or the better memory function of older rural-dwellers compared to urban-dwellers in Southern Nevada in the United States, even though rural living commonly poses putative risk for cognitive decline and dementia (PMID: 39081985; PMID: 39081981). This variability warrants in-depth investigation and should inform local awareness raising campaigns, prevention and care. In addition, the central role of primary healthcare professionals in collaborative healthcare services enables a "one-stop-shop" approach to the management of several risk factors of cognitive decline (PMID: 39665073). Collaborative community healthcare services are increasingly based on telemedicine, with technology a key focus of two papers in the collection (PMID: 39665073; PMID: 39081472). E-health tools facilitate communication between collaborating healthcare professionals serving at spatially distant services, between service users and healthcare professionals, distant monitoring of symptoms and behavior of older people living alone, support for their informal care partners and/or assessment and decision-making for people with dementia living in care homes(Schaller et al., 2015; Vuong et al., 2015) (PMID: 39081472). For instance, e-health tools can be used by the staff of care homes to communicate the symptoms of the residents through video consultations, safeguarding appropriate prescribing, advance care planning and reduction of hospitalizations (PMID: 39081472). Although telemedicine contributes to the quality of dementia care, it can also lead to inequities in access and usage (PMID: 39749098). Equity promoting e-health solutions was a recurring theme in this collection of papers. The development of practical guidelines for equitable e-health solutions for dementia care in the UK is depicted (PMID: 39749098), so does a tablet-based, brain health assessment tool which was adapted to the cultural nuances of communities in Southeast Nigeria (PMID: 39081611)....