Eleni Poptsi

The early identification of cognitive decline is crucial for well-timed intervention and diagnosis, particularly in the context of preclinical Alzheimer’s disease (AD). In this study, we investigated the complex interplay between trait affect, objective cognitive performance, and subjective memory estimations in a sample of 105 older adults. Using path analysis, we aimed to determine whether trait affect and objective cognitive control abilities predict individuals’ subjective perceptions of their own memory abilities. The results revealed that both positive and negative trait affect significantly predicted subjective memory estimations, while objective cognitive control performance did not significantly predict these estimations. These findings highlight a crucial dissociation between objective and subjective cognitive measures. Therefore, the present results underscore the critical importance of complementing self-reported cognitive estimations, which can be biased by stable emotional dispositions, with objective cognitive tools like the R4Alz-pc (preclinical) index. This approach enables a more accurate evaluation of cognitive health in advancing age, especially for the early detection of subtle dysfunction in preclinical AD.

Background/Objectives: Early identification of preclinical Alzheimer’s disease (AD) is critically important. This study investigates whether early cognitive decline in preclinical AD can be detected through the executive functioning index R4Alz-pc by predicting memory-related worry and negative affect. Methods: A sample of 105 cognitively healthy, community-dwelling older adults (M = 59.25 years) completed the Multifactorial Memory Questionnaire (MMQ) and the R4Alz-pc index battery. Results: Lower performance on the R4Alz-pc index was significantly associated with increased negative affect related to memory. Mediation analysis indicated that memory-related worry mediated the relationship between executive dysfunction and negative affect. Conclusions: This study highlights the importance of early, objective cognitive assessment using easy-to-administer and non-invasive tools like the R4Alz-pc, enabling timely detection and intervention for preclinical AD. Such methods may reduce reliance on costly biomarker-based diagnostics.

Background/Objectives: Behavioral variant frontotemporal dementia (bvFTD), the most prevalent clinical subtype within the frontotemporal lobar degeneration spectrum disorders, is characterized by early and prominent changes that significantly disrupt everyday functioning. This study aims to identify the key correlates of functional status in bvFTD, by investigating the relative contributions of cognitive deficits, behavioral disturbances, personality changes, and brain perfusion abnormalities. Additionally, it seeks to develop a theoretical framework to elucidate how these factors may interconnect and shape unique functional profiles. Methods: A total of 26 individuals diagnosed with bvFTD were recruited from the 2nd Neurology Clinic of “AHEPA” University Hospital in Thessaloniki, Greece, and underwent a comprehensive neuropsychological assessment to evaluate their cognitive functions. Behavioral disturbances, personality traits, and functional status were rated using informant-based measures. Regional cerebral blood flow was assessed using Single Photon Emission Computed Tomography (SPECT) imaging to evaluate brain perfusion patterns. Penalized Least Absolute Shrinkage and Selection Operator (LASSO) regression analysis was performed to identify the most robust correlates of functional impairment, followed by path analyses using structural equation modeling to explore how these factors may interrelate and contribute to functional disability. Results: The severity of negative behavioral symptoms (e.g., apathy), conscientiousness levels, and performance on neuropsychological measures of semantic verbal fluency, visual attention, visuomotor speed, and global cognition were identified as the strongest correlates of performance in activities of daily living. Neuroimaging analysis revealed hypoperfusion in right prefrontal (Brodmann area 8) and inferior parietal (Brodmann area 40) cortices as major neural correlates of functional impairment in bvFTD. Path analyses showed that brain hypoperfusion contributed to attentional and processing speed deficits, which subsequently exacerbated negative behavioral symptoms, leading to declines in global cognition and conscientiousness, ultimately compromising daily functioning. Conclusions: Hypoperfusion in key prefrontal and parietal regions, along with the subsequent cognitive and neuropsychiatric manifestations, underlies the pronounced functional limitations observed in individuals with bvFTD, even in early stages. Understanding the key determinants of the disease can inform the development of more targeted, personalized treatment strategies, aimed at mitigating functional deterioration and enhancing the quality of life for affected individuals.

Background: The Dementia Attitude Scale (DAS) is a validated instrument used to capture the affective, behavioural, and cognitive components of attitudes toward people living with dementia (PLwD). This study conducts confirmatory and exploratory factor analyses (CFA and EFA) of the DAS assessed by caregivers of PLwD and BPSD enrolled in the RECage multicentre clinical trial. Methods: The baseline questionnaire was completed by 485 caregivers (29.7% male, 70.3% female), from six European countries, reflecting diverse cultural contexts. CFA tested the two-factor structure of the original model, while EFA thoroughly explored the factor structure. Results: The CFA results showed a poor model fit, with significant deviations from ideal values for RMSEA (0.0861), SRMSR (0.0781), and CFI (0.7117), showcasing an inadequate representation of the data. EFA revealed a three-factor structure, explaining the 45.2% variance for social comfort, 28.8% for social discomfort, and 25.9% for dementia knowledge. The social comfort items reflected positive caregiver attitudes toward PLwD, while social discomfort captured feelings of discomfort and uncertainty about caregiving. Dementia knowledge included items related to understanding dementia’s symptoms and needs. Conclusions: The three-factor model highlights the importance of emotional comfort, knowledge of dementia, and social discomfort as key dimensions in caregiver attitudes.

The accurate diagnosis of aging-related neurocognitive disorders as early as possible, even in a phase that is characterized by the absence of clinical symptoms, is nowadays the holy grail of the neurosciences. R4Alz-R is a novel cognitive tool designed to objectively detect the subtle cognitive changes that emerge as the very first result of the aging processes and could be developed and broadened in a continuum from healthy aging to subjective cognitive impairment (SCI) and mild cognitive impairment (MCI), before reaching some type of dementia. The goal of the present study was to examine whether the R4Alz-R battery has the potential to detect these subtle changes. The study sample comprised 184 people divided into (a) cognitively healthy young adults (HCya), (b) cognitively healthy older adults (HCoa), (c) people diagnosed with SCI, and (d) people diagnosed with MCI. The R4Alz-R comprises tests examining short-term memory storage, information processing, and updating of working memory, attention in different types of it, and main dimensions of executive functioning such as set-shifting, inhibitory control, and cognitive flexibility, as well as episodic memory. The flexibility and attention score showed an excellent potential to discriminate HCya from SCI (AUC 0.936, sensitivity 89.7%, specificity 88.4%). The executive functioning score almost excellently discriminated HCoa from SCI (AUC 0.898, sensitivity 87%, specificity 76.5%), while the fluid intelligence score had also an excellent potential to discriminate HCoa from MCI (AUC 0.953, sensitivity 85.7%, specificity 94.1%). The findings show that cognitive impairment in aging may start from the frontal lobe and prefrontal cortex, areas more closely related to cognitive control rather than memory. The lack of significant differences between HCya and HCoa proves that healthy older adults can keep their cognition at almost the same level as younger adults, a finding consistent with the new theoretical models regarding aging. The R4Alz-R battery is an innovative, free-of-demographic effect, valid, and reliable tool that can provide a highly accurate diagnosis of aging-related cognitive decline in its beginnings when it could still be possible to be reversed.

The importance of night sleep for maintaining good physical and cognitive health is well documented as well as its negative changes during aging. Since Mild Cognitive Impairment (MCI) patients bear additional disturbances in their sleep, this study aimed at examining whether there are potential mixed effects of sleep and afternoon time of day (ToD) on the storage, processing, and updating components of working memory (WM) capacity in older adults with MCI. In particular, the study compared patients’ performance in the three working memory components, in two-time conditions: “early in the morning and after night sleep”, and “in the afternoon and after many hours since night sleep”. The Working Memory Capacity & Updating Task from the R4Alz battery was administered twice to 50 older adults diagnosed with MCI. The repeated measures analysis showed statistically significant higher performance in the morning condition for the working memory updating component (p < 0.001). Based on the findings, it seems that the afternoon ToD condition negatively affects tasks with high cognitive demands such as the WM updating task in MCI patients. These findings could determine the optimal timing for cognitive rehabilitation programs for MCI patients and the necessary sleep duration when they are engaged in cognitively demanding daily activities.

R4Alz is utilized for the early detection of minor neurocognitive disorders. It was designed to assess three main dimensions of cognitive-control abilities: working-memory capacity, attentional control, and executive functioning. Objectives: To reveal the cognitive-control dimensions that can differentiate between adults and older adults with healthy cognition, people with subjective cognitive impairment, and people diagnosed with mild cognitive impairment by examining the factorial structure of the R4Alz tool. Methods: The study comprised 404 participants: (a) healthy adults (n = 192), (b) healthy older adults (n = 29), (c) people with SCI (n = 74), and (d) people diagnosed with MCI (n = 109). The R4Alz battery was administered to all participants, including tests that assess short-term memory storage, information processing, information updating in working memory, and selective, sustained and divided attention), task/rule-switching, inhibitory control, and cognitive flexibility. Results: A two-factorial structural model was confirmed for R4Alz, with the first factor representing “fluid intelligence (FI)” and the second factor reflecting “executive functions (EF)”. Both FI and EFs discriminate among all groups. Conclusions: The R4Alz battery presents sound construct validity, evaluating abilities in FI and EF. Both abilities can differentiate very early cognitive impairment (SCI) from healthy cognitive aging and MCI.

Mild cognitive impairment (MCI) is associated with deficits in decision-making, which is of utmost importance for daily functioning. Despite evidence of declined decision-making abilities, research on decision-making interventions for MCI is scarce. As metacognition seems to play an important role in decision-making, the present study’s aim was to examine whether a metacognitive strategy training can improve MCI patients’ decision-making abilities. Older adults—patients of a day care center, diagnosed with amnestic MCI (n = 55) were randomly allocated in two groups, which were matched in gender, age and educational level. Τhe experimental group (n = 27, 18 women, mean age = 70.63, mean years of education = 13.44) received the metacognitive strategy training in parallel with the cognitive and physical training programs of the day care center, and the active control group (n = 28, 21 women, mean age = 70.86, mean years of education = 13.71) received only the cognitive and physical training of the center. The metacognitive strategy training included three online meeting sessions that took place once per week. The basis of the intervention was using analytical thinking, by answering four metacognitive-strategic questions, to make decisions about everyday situations. To examine the efficacy of the training, the ability to make decisions about everyday decision-making situations and the ability to apply decision rules were measured. Both groups participated in a pre-test session and a post-test session, while the experimental group also participated in a follow-up session, one month after the post-test session. The results showed that the experimental group improved its ability to decide, based on analytical thinking, about economic and healthcare-related everyday decision-making situations after they received the metacognitive strategy training. This improvement was maintained one month later. However, the ability to apply decision rules, which requires high cognitive effort, did not improve. In conclusion, it is important that some aspects of the analytical decision-making ability of amnestic MCI patients were improved due to the present metacognitive intervention.

Background: One of the most widely used instruments for assessing agitation in dementia patients is the Cohen-Mansfield Agitation Inventory (CMAI), nevertheless no global score has been proposed. The aim of this study is: (a) to conduct a confirmatory (CFA) and exploratory factor analysis (EFA) of CMAI on people with dementia and Psychological and Behavioral Symptoms (BPSD), and (b) to propose an alternative structure, based on clinical criteria including all CMAI items. Methods: Confirmatory and exploratory factor analyses were carried out on the CMAI 29 items administered at baseline to 505 patients with dementia (PwD) and BPSD enrolled in the international observational RECage study. Results: The three-factor structure has not been confirmed by the CFA, whilst the EFA was carried out respectively on 25 items disregarding 4 items with a prevalence ≤5% and then on 20 items disregarding 9 items with a prevalence ≤10%. The four-factor structure explaining 56% of the variance comprised Physically Aggressive behavior, Verbally Aggressive behavior, Physically non-aggressive behavior, and Physically and verbally aggressive behavior. Conclusions: A new grouping of all items according to a clinical criterion is proposed, allowing for a more sensible evaluation of the symptoms leading to better differentiation.

Background: The diagnosis of the minor neurocognitive diseases in the clinical course of dementia before the clinical symptoms’ appearance is the holy grail of neuropsychological research. The R4Alz battery is a novel and valid tool that was designed to assess cognitive control in people with minor cognitive disorders. The aim of the current study is the R4Alz battery’s extension (namely R4Alz-R), enhanced by the design and administration of extra episodic memory tasks, as well as extra cognitive control tasks, towards improving the overall R4Alz discriminant validity. Methods: The study comprised 80 people: (a) 20 Healthy adults (HC), (b) 29 people with Subjective Cognitive Decline (SCD), and (c) 31 people with Mild Cognitive Impairment (MCI). The groups differed in age and educational level. Results: Updating, inhibition, attention switching, and cognitive flexibility tasks discriminated SCD from HC (p ≤ 0.003). Updating, switching, cognitive flexibility, and episodic memory tasks discriminated SCD from MCI (p ≤ 0.001). All the R4Alz-R’s tasks discriminated HC from MCI (p ≤ 0.001). The R4Alz-R was free of age and educational level effects. The battery discriminated perfectly SCD from HC and HC from MCI (100% sensitivity—95% specificity and 100% sensitivity—90% specificity, respectively), whilst it discriminated excellently SCD from MCI (90.3% sensitivity—82.8% specificity). Conclusion: SCD seems to be stage a of neurodegeneration since it can be objectively evaluated via the R4Alz-R battery, which seems to be a useful tool for early diagnosis.