Search Results (29)

Background: As survival improves in transfusion-dependent β-thalassemia, long-term adult morbidity, including cognitive dysfunction, has become increasingly relevant. Adult data remain limited, particularly in Eastern Europe, and many studies rely on single screening tools with limited control for confounding. Methods: We conducted a single-center case–control study (2024–2025) at the Congenital Hemolytic Anemia Treatment Center, University Hospital “Sv. Georgi” Plovdiv, Bulgaria. Fifty adults with transfusion-dependent β-thalassemia (86% thalassemia major; 14% transfusion-dependent intermedia) and 30 frequency-matched healthy controls completed a multi-domain cognitive battery: Montreal Cognitive Assessment (MoCA), Mini-Mental State Examination (MMSE), Clock Drawing Test (CDT), Trail Making Test (TMT-A/B), and timed verbal fluency. Associations between thalassemia status and cognitive outcomes were estimated using three prespecified models: unadjusted, adjusted for age and sex, and a doubly robust model combining covariate balancing propensity score inverse probability weighting (balancing BMI, smoking, education, and comorbidity) with age/sex regression adjustment. Results: Patients performed worse than controls on global cognition and executive/visuospatial measures. MoCA scores were lower in patients (−2.26 unadjusted, p = 0.016; −2.83 doubly robust, p = 0.001), as were MMSE scores (−1.64, p = 0.015; −1.87, p = 0.002). CDT performance was consistently poorer (OR ≈ 0.28–0.30 across models). Patients were slower on TMT-B (time ratio 1.35 unadjusted, p = 0.003; 1.42 doubly robust, p < 0.001); TMT-A reached significance only after weighting (ratio 1.32, p = 0.001). Verbal fluency was modestly lower with borderline significance (p ≈ 0.05–0.06). Conclusions: Transfusion-dependent β-thalassemia in adults is associated with poorer cognitive performance, particularly in global cognition and executive/visuospatial domains, with results robust across adjustment strategies. Routine multi-domain cognitive screening may be warranted in adult thalassemia care. Full article

Alzheimer’s disease (AD) is the most common cause of neurocognitive disorder, and the integration of cognitive assessment with biological markers remains essential for clinical characterization. The Clock Drawing Test (CDT) is a brief and widely used screening tool assessing visuospatial and executive functions, which may reflect underlying neurodegenerative processes. This study investigated the diagnostic performance of the CDT and its association with cerebrospinal fluid (CSF) biomarkers within the A/T/(N) research framework. Ninety-seven patients with mild or major neurocognitive disorder were classified as AD or non-AD according to CSF amyloid-β, phosphorylated tau, and total tau profiles, and compared with 36 healthy participants. All subjects underwent a comprehensive neuropsychological evaluation, including the CDT scored using the quantitative–qualitative method proposed by Rouleau et al. Group comparisons, ROC analyses, and regression models adjusted for age, sex, and education were performed. CDT scores effectively distinguished patients from healthy participants, showing large effect sizes, and modestly differentiated AD from non-AD profiles, particularly on the Hands subscale. Diagnostic accuracy was fair, with adjusted AUC values ranging from 0.65 to 0.75. Lower CDT performance was significantly associated with higher CSF total tau levels, while associations with amyloid-β and phosphorylated tau were not robust after correction. These findings suggest that the CDT is sensitive to cognitive impairment severity and shows limited but meaningful relationships with neurodegenerative biomarkers, supporting its role as a practical complementary tool alongside biological assessment. Full article

Objective: The non-verbal nature of the Clock Drawing Test (CDT) suggests it is a suitable cognitive screening instrument for populations with lower educational levels and/or language barriers. This study evaluates whether the CDT is a valid screening instrument for low-educated patients and includes a qualitative analysis of CDT errors. Method: A total of 503 participants were included, divided into four groups (dementia, MCI, no cognitive impairment, and other diagnosis), based on a clinical diagnosis by a geriatrician. Educational levels were categorized into four groups: no education and low, middle, and high education. CDT scores were assessed using the seven-point scoring system (Freedman), and two cutoff points were evaluated. Results: Results showed that in all education categories, the dementia group scored significantly lower on the CDT compared to the non-dementia group. The difference was smallest in participants with no education. Two cut-off points were assessed: <4 and <3. A cut-off of <4 showed better sensitivity versus <3, particularly for low-educated groups. A cut-off of <3 provided better specificity versus <4. Error analysis showed that errors made by low-educated participants without dementia were similar to those of patients with dementia. Conclusions: These findings show that the CDT (both total score and qualitative error analysis) has limited value in dementia case-finding in low-educated groups. The CDT is recommended primarily for middle- and high-educated groups. Full article

Brain-derived neurotrophic factor (BDNF) plays a crucial role in cognitive functions and dementia. In individuals with mild cognitive impairment (MCI) and dementia, we have investigated BDNF Val66Met genotype distribution, peripheral BDNF DNA methylation, mRNA and protein levels, and cognitive performance using the Mini-Mental State Examination (MMSE) and Clock Drawing Test (CDT). Lower BDNF_IV1 methylation had predictive value for dementia. Patients with mild-to-moderate dementia had lower levels of BDNF_IV2 methylation, whereas patients with severe dementia had higher levels than the MCI group, while BDNF_IV2 methylation positively correlated with CDT scores. An insignificant decline in BDNF mRNA levels in dementia patients positively correlated with significantly lower BDNF plasma levels, especially pronounced in severe dementia patients. BDNF mRNA and protein levels were positively correlated with CDT and MMSE scores, respectively. BDNF Val66Met polymorphism was associated with methylation of the BDNF_IX amplicon, but not with methylation in BDNF promoters I and IV, peripheral BDNF gene and protein expression, MMSE and CDT scores, or dementia. Methylation at the BDNF Val66Met site was positively correlated with overall BDNF_IX methylation and methylation at 5 BDNF_IX CpG loci but negatively correlated with methylation of BDNF_IV1, BDNF_IV3, and BDNF_I1 amplicons. Further studies should evaluate the translational potential of these peripheral BDNF-based biomarkers for dementia. Full article

Background: Physical exercise has been linked to improvements in motor and cognitive functions as well as to the modulation of neurotrophic and inflammatory factors, particularly in older adults. This aim of this study was to investigate the effects of a 12-week multimodal exercise program on cognitive function, motor performance, and plasma levels of brain-derived neurotrophic factor (BDNF) and cytokines in elderly individuals with Alzheimer’s disease (AD). Methods: A non-randomized controlled trial design was employed, involving 23 participants aged 62 to 85 years diagnosed with mild to moderate AD. The intervention group (n = 7) attended 60-minute sessions three times per week, incorporating aerobic, strength, flexibility, and motor coordination exercises, while the control group (n = 8) maintained usual activities. Methods: A non-randomized controlled trial design was used, involving 23 participants aged 62 to 85 years. Of these, 15 had a clinical diagnosis of mild to moderate AD and were allocated to either an intervention group (n = 7) or and AD control group (n = 8). The remaining eight participants were cognitively healthy and formed a control group matched for age and sex, used exclusively for baseline comparisons. The intervention group participated in 60-minute sessions three times per week, including aerobic, strength, flexibility, and motor coordination exercises. The AD control group (n = 8) maintained their usual daily routines. Results: Compared to baseline, the intervention group demonstrated significant improvements in executive and attentional functions, as measured by the Frontal Assessment Battery (FAB) and Clock Drawing Test (CDT); mobility, balance, gait speed, and lower limb strength also improved (p < 0.05). Additionally, plasma BDNF levels increased significantly, and interleukin-2 (IL-2) levels decreased. Conclusions: In conclusion, the multimodal exercise program resulted in cognitive and motor benefits and positively modulated biomarkers related to neuroplasticity and inflammation, supporting its potential as a complementary intervention in elderly individuals with AD. Full article

Background: Depressive symptoms and cognitive decline are common in older adults. The aims of this study were (i) to assess the frequency of depressive symptoms and cognitive impairment in users of municipal home care services and (ii) to explore factors that may pertain to seeking in-depth neuropsychiatric diagnostic workup, if recommended. Methods: The study was mainly conducted in low-resource areas of south-western Greece. The Geriatric Depression Scale (GDS-15), the Mini-Mental State Examination (MMSE) and the Clock Drawing Test (CDT) were employed. The study included the tracking of whether participants sought medical consultation within 12 months after receiving the recommendation for further neuropsychiatric diagnostic workup. Results: The study encompassed 406 individuals. Cognitive deficits were detected in 312 (76.84%) study participants, of whom only 82 (26.28%) had received the diagnosis of a mental or neurological disorder. Depressive symptoms were detected in 236 (58.27%) individuals, of whom only 18 (4%) had received the diagnosis of a mental or neurological disorder. Only just over a third of individuals consulted physicians. Reluctance towards in-depth neuropsychiatric workup mainly derived from a lack of insight and fears related to COVID-19. Previously diagnosed neuropsychiatric disorders slightly correlated with the decision to consult a physician. Conclusions: Developing pragmatic cognitive and mental healthcare services to address the needs of older people with disabling chronic disorders who live in low-resource settings is urgently needed. Full article

The evolving understanding of asthma and COPD pathomechanisms led to this study examining chronic obstructive lung diseases’ impact on cognitive decline—a growing concern in aging populations. We explored whether subunits of key inflammatory regulators NF-κB, c-Rel (neuroprotective), and p65 (neurodegenerative), are linked to cognitive impairment. A pilot study with an explorative design across three groups (asthma, COPD, and control) included 78 patients. Participants underwent assessments via 16 questionnaires (covering demographics, quality of life, disease control, and cognitive and psychiatric evaluations), spirometry, and blood sampling to measure c-Rel and p65 mRNA expression. While both c-Rel and p65 are NF-κB subunits, their expression levels differ independently. Median c-Rel expression was highest, and p65 lowest, in the group with the best cognitive function (control). The most notable correlations for both markers with PKA, CREB, MMSE, and HAM-D were in COPD. The significant association between p65 and the Clock-Drawing Test, without a corresponding link to MMSE, may indicate that a future correlation between p65 and cognitive decline, as assessed by CDT, is likely to emerge. Full article

Background/Objectives: Glaucoma and Alzheimer’s disease (AD) are neurodegenerative conditions with vascular underpinnings. This study aimed to explore the relationship between blood pressure parameters such as mean arterial pressure (MAP), pulse pressure (PP), and cerebral perfusion pressure (CPP) and cognitive performance in patients with AD, normal-tension glaucoma (NTG), and healthy controls. We hypothesized that NTG patients, like those with mild cognitive impairment (MCI), may experience subtle cognitive changes related to vascular dysregulation. Methods: Ninety-eight participants (35 NTG, 17 AD, 46 controls) were assessed for CPP, MAP, OPP, and cognitive performance. Statistical analyses compared groups and examined correlations. Results: AD patients showed lower CPP and MAP (p < 0.001), indicating systemic vascular dysfunction, while NTG patients had higher ocular perfusion pressure (OPP) (p = 0.008), suggesting compensatory mechanisms. CPP correlated with visuospatial abilities in AD (r = 0.492, p = 0.045). MAP correlated with the Clock drawing test (CDT) scores in the NTG group (r = 0.378, p = 0.025). PP negatively correlated with cognition in AD (r = −0.527, p = 0.016 for CDT scores) and controls (r = −0.440, p = 0.002 for verbal fluency and r = −0.348, p = 0.019 for total ACE scores). Conclusions: The study highlights distinct hemodynamic profiles: systemic dysfunction in AD and localized dysregulation in NTG. These findings emphasize the role of vascular dysregulation in neurodegeneration, with implications for personalized treatment approaches targeting vascular health in neurodegenerative conditions. Full article

Ensemble learning (EL), a machine learning technique that combines the results of multiple learning algorithms to obtain predicted values, aims to achieve better predictive performance than a single learning algorithm alone. Machine learning techniques, including EL, have been applied in the field of medicine to assist in the clinical interpretation of specific diseases. Although neurodegenerative diseases, especially Alzheimer’s disease (AD), are of interest to clinicians and researchers due to their rapid increase in clinical cases, the application of EL in AD diagnosis has been relatively less attempted. In this research, we demonstrate that three machine learning algorithms, trained on an ensemble of electroencephalogram (EEG) and clock drawing test (CDT) feature data for an AD classification task, show improved AD detection accuracy compared to when either the EEG or CDT dataset is used independently. We also explore which feature contributes most to decision-making in AD and healthy control (HC) classification. In conclusion, the current study suggests that EL can be a novel clinical application of machine learning (ML) in the automated AD screening process. Full article

Background: In search of indicators for dementia, this study investigated the association of cerebrospinal fluid (CSF) biomarkers and neuropsychological test results with disease stage in patients with early manifestations of dementia. Methods: In 190 consecutive patients with symptoms of dementia, the CSF parameters amyloid-β 1-42 (Aβ1-42), phosphorylated tau protein (pTau), total tau protein (tTau), neuron-specific enolase (NSE), protein S100B (S100B), and Aβ (1-42)/(1-40) ratio (Aβ ratio), as well as the results of the CERAD-Plus test battery supplemented by the Clock Drawing Test (CDT), were analysed. Patients were divided into two groups based on the median duration of reported symptom onset. Results: Most prominent in the early phase of the disease were the relationships between Aβ1-42 and neuropsychological memory subtests, which were absent in the later phase. Less pronounced relationships to memory function were detectable for Aβ ratio and pTau. Conclusions: The results substantiate the relevance of Aβ1-42 for memory deficits and support the amyloid cascade hypothesis for Alzheimer’s dementia (AD). Our data suggest other pathomechanisms for visuospatial impairments in AD. Full article

Background: Post-operative delirium is a dreaded complication after surgery in older patients. The identification of risk factors for delirium and comprehensive geriatric assessment is an extensive part of recent research. However, the preoperative assessment of risk factors, such as impaired cognition, is frequently not standardized. Methods: A comprehensive preoperative assessment was performed in 421 surgical patients to investigate the impact of preoperative cognitive impairment (PCI) on the risk of delirium and to evaluate appropriate screening tools (Six-item screener (SIS) and clock-drawing test (CDT)). Results: Both screening tools showed a significantly increased risk of delirium with p < 0.001 (OR 12.5, 95% [6.42; 24.4]) in SIS and p = 0.042 (OR 2.02, 95%CI [1.02; 4.03]) in CDT for existing cognitive impairment. A higher level of care (p < 0.001) and statutory care (p < 0.001, OR 5.42, 95%CI [2.34; 12.6]) also proved to be significant risk factors. The ROC curves of the two tests show AUC values of 0.741 (SIS) and 0.630 (CDT). The COP values for the SIS are 4 points with a Youden index of 0.447; for the CDT, the COP is 2 (Youden index = 0.177). Conclusions: The recording of PCI should be a central component of the preoperative geriatric assessment. The tools used are simple yet effective and can be easily implemented in routine clinical practice. By reliably identifying patients at risk, the available resources can be personalized and used in a targeted approach. Full article

Background/Objectives: Hypomagnesemia and hypocalcemia are common conditions among older adults that may contribute to cognitive decline. However, most of the existing research has focused primarily on dietary intake rather than the actual serum levels of these nutrients or examined them separately. This study aims to investigate the relationship between hypomagnesemia, hypocalcemia, and the concurrent presence of both deficiencies in relation to cognitive performance among seniors. Methods: A total of 1220 hospitalized patients aged 60 and older were included in the analysis. The participants were categorized into four groups: those with normal serum levels of magnesium and calcium, those with hypomagnesemia, those with hypocalcemia, and those with both serum magnesium and calcium deficiencies. To evaluate the potential influence of age, sex, common comorbidities, and disturbances in magnesium and calcium levels on cognitive performance, two general linear models were employed, using the Mini-Mental State Examination (MMSE) and Clock-Drawing Test (CDT) as dependent variables. Results: After adjusting for age, sex, body mass index, and comorbidities, the mean values for the MMSE and CDT were 23.33 (95%CI: 22.89–23.79) and 5.56 (95%CI: 5.29–5.83) for the group with normomagnesemia and normocalcemia, 22.59 (95%CI: 21.94–23.24) and 5.16 (95%CI: 4.77–5.54) for the group with hypomagnesemia, 19.53 (95%CI: 18.36–20.70) and 4.52 (95%CI: 3.83–5.21) for the group with hypocalcemia, and 21.14 (95%CI 19.99–22.29) and 4.28 (95%CI 3.61–4.95) for the group with both hypomagnesemia and hypocalcemia, respectively. Magnesium and calcium deficiencies contributed to MMSE and CDT variance in the general linear models. Conclusions: Our findings indicate that in addition to age, body mass index, and chronic heart failure, both hypomagnesemia and hypocalcemia are associated with reduced cognitive performance. Full article

Background: This study investigates changes in cognitive function in patients with severe carotid stenosis who underwent carotid endarterectomy (CEA) and carotid stenting (CAS) over two decades. Methods: We compared cognitive function within 30 days after the procedure in 267 patients (first 100 each for CEA and CAS in two periods: 2008–2012 and 2018–2022) in a single institution. Assessments used Adenbrooke’s Cognitive Examination–Revised (ACE-R), the Mini-Mental State Examination (MMSE), Speech Fluency Test (SFT), and Clock Drawing Test (CDT), conducted before and 30 ± 2 days after surgery. Results: Patients (mean age 67.2 years, 70%+ carotid stenosis) exhibited different cognitive changes over periods. In 2008–2012, significant declines in MMSE (CEA, p = 0.049) and CDT (CAS, p = 0.015) were observed among asymptomatic patients. On the contrary, in 2018–2022, improvements were observed in ACE-R and MMSE for symptomatic and asymptomatic patients undergoing CEA and CAS. Conclusion: Over a decade, advances in interventional techniques and patient management have reduced risks of cognitive decline in patients with asymptomatic carotid stenosis and also have improved cognitive functions in both symptomatic and asymptomatic individuals. Full article

Introduction. The purpose of this study is to determine the usefulness of the CTMT (Comprehensive Trail Making Test) in diagnosing mild cognitive impairment in older patients. The test is used to assess executive functions, of which impairment is already observed in the early stages of the neurodegenerative process. Materials and Methods. The study includes 98 patients of a geriatric ward assigned to 2 groups of 49 patients each: patients diagnosed with a mild cognitive impairment and patients without a cognitive impairment, constituting the control group (group K). A set of screening tests was used in the initial study: the MMSE (Mini-Mental State Examination), MoCA (Montreal Cognitive Assessment), and CDT (Clock Drawing Test), GDS (Geriatric Depression Scale). The second study included the performance of the CTMT; the performance indicator was the time of performance. Results. Statistically significant differences are obtained between patients with mild cognitive impairments and those in cognitive normality in the performance of the CTMT test (p < 0.01). Patients with MCIs took longer to complete all trails of the test. To identify cognitive impairment, cutoff points were proposed for the CTMT total score and the other test trails. The CTMT overall score and CTMT 5 scored the highest AUCs (CTMT overall score = 0.77, CTMT Trail 5 = 0.80). Conclusions. The Comprehensive Trail Making Test may be useful in diagnosing mild cognitive impairment as a complementary screening tool. Full article

Anemia causes hypo-oxygenation in the brain, which could lead to cognitive disorders. We examined dietary iron intake as well as anemia markers (i.e., hemoglobin, hematocrit, mean corpuscular volume) and diabetes coexistence in relation to neuropsychological function and quality of life. In this study, 6117 community-dwelling adults aged 55–75 years (men) and 60–75 years (women) with overweight/obesity and metabolic syndrome were involved. We performed the Mini-Mental State Examination (MMSE), the Trail Making Test parts A and B (TMT-A/B), Semantic Verbal Fluency of animals (VFT-a), Phonological Verbal Fluency of letter P (VFT-p), Digit Span Test (DST), the Clock Drawing Test (CDT), and the Short Form-36 Health Survey (SF36-HRQL test). Dietary iron intake did not influence neuropsychological function or quality of life. However, anemia and lower levels of anemia markers were associated with worse scores in all neurophysiological and SF36-HRQL tests overall, but were especially clear in the MMSE, TMT-B (cognitive flexibility), and the physical component of the SF36-HRQL test. The relationships between anemia and diminished performance in the TMT-A/B and VFT tasks were notably pronounced and statistically significant solely among participants with diabetes. In brief, anemia and reduced levels of anemia markers were linked to inferior cognitive function, worse scores in different domains of executive function, as well as a poorer physical, but not mental, component of quality of life. It was also suggested that the coexistence of diabetes in anemic patients may exacerbate this negative impact on cognition. Nevertheless, dietary iron intake showed no correlation with any of the outcomes. To make conclusive recommendations for clinical practice, our findings need to be thoroughly tested through methodologically rigorous studies that minimize the risk of reverse causality. Full article