Background: post-COVID cognitive impairment is an important medical and social problem. Many studies focus on the analysis of the characteristics of cognitive impairment after infection, but neurorehabilitation issues are rarely considered. The aim was to study the effectiveness of combined use of neuropsychological correction and rhythmic magnetic stimulation (rTMS) in the rehabilitation of patients with post-COVID cognitive impairment. Patients and Methods: two groups of 20 people with postCOVID cognitive impairment were compared: group 1 underwent rehabilitation using a multimodal method, group 2 — according to the standard program. The areas of rTMS stimulation were selected based on high-quality neuropsychological diagnostics, which made it possible to identify and form the patient’s neuropsychological profile. The correction program was based on the identified neuropsychological profile and developed individually for each patient. The Montreal Cognitive Assessment, Frontal Area Dysfunction Battery, Clock Drawing Test, Semantic Verbal Fluency Test, 10-Word Learning, Symbolic-Digit Coding Test, Subjective Asthenia Inventory (MFI-20), and Hospital Anxiety and Depression Scale (HADS) were used to assess the state of higher mental functions. Results: after correction, significant differences were found in the MoCA, 10-Word Learning, Symbolic-Digit Coding, and MFI-20 scales, with higher scores in group 1. Comparative analysis showed significant differences in score dynamics between the groups, with group 1 demonstrating better results. Conclusions: multimodal neuropsychological rehabilitation in combination with rTMS demonstrates significantly higher results compared to standard rehabilitation protocols established in the order of the Ministry of Health of the Russian Federation dated July 31, 2020 No. 788n “On approval of the Procedure for organizing medical rehabilitation of adults” [1], as well as with clinical recommendations presented on the website of the Union of Rehabilitation Specialists of Russia [2–4].

AimUric acid to high density lipoprotein cholesterol ratio (UA/HDL-c) related to nutrient metabolism disorder is associated with the onset of diabetic complications including mild cognitive impairment (MCI). However, the relationship between UA/HDL-c and MCI in type 2 diabetes mellitus (T2DM) patients with different gender remains unclear. Therefore, this study aims to explore the association between UA/HDL-c and MCI in female and male patients with T2DM.MethodsA total of 223 patients were stratified into either the control or the MCI group based on the presence or absence of MCI. Comparative analyses of clinical parameters were conducted, and the associations between UA/HDL-c and cognitive function were assessed across all patients as well as within female and male subgroups. Binary logistic regression was employed to identify independent risk factors for MCI in female and male patients with T2DM.ResultsCompared to the 137 participants without MCI, the 86 individuals with MCI exhibited significantly higher levels of UA/HDL-c. Higher UA/HDL-c levels were associated with lower scores on the Montreal Cognitive Assessment, which reflects global cognitive function, as well as with poorer performance on the Verbal Fluency Test and the Clock Drawing Test, which reflect executive and visuospatial functions in female patients, respectively. These associations were not observed in male patients. Furthermore, binary logistic regression analysis indicated that elevated UA/HDL-c levels were a risk factor for MCI in women, regardless of adjustments for age, duration of diabetes mellitus, and duration of hypertension.ConclusionElevated UA/HDL-c levels are not only associated with overall cognitive function in female patients with T2DM, but also specifically linked to impairments in executive function and visuospatial abilities. However, this association is not observed in male patients. Among women with T2DM, elevated UA/HDL-c levels serve as an independent risk factor for the development of MCI. These findings suggest a sex-specific relationship between UA/HDL-c levels and cognitive dysfunction.

BackgroundThe prevalence of type 2 diabetes mellitus (T2DM) is steadily increasing, with central nervous system complications commonly manifesting as mild cognitive impairment and dementia. However, the neuropathophysiological mechanisms underlying T2DM-related cognitive dysfunction remain poorly understood.MethodThis study used voxel-based morphometry (VBM) and seed-to-voxel structural covariance network (SCN) analyses to investigate alterations in cerebellar gray matter volume (GMV) and SCNs in T2DM, as well as their associations with cognitive performance. Intergroup differences were assessed using two-sample t-tests with Gaussian random field correction.ResultsVBM analysis revealed significant GMV reductions in the bilateral cerebellar crus I, left lobules I–IV, left crus II, left lobule IX, and right lobule VIIb in T2DM participants. Seed-to-voxel SCN analysis further demonstrated decreased covariance between the left crus I and the left middle temporal gyrus, middle occipital gyrus, and angular gyrus, along with increased covariance between the left lobules I–IV and the right caudate nucleus. Correlation analysis revealed that GMV of the left crus I was positively associated with Clock Drawing Test scores, while GMV of the right crus I was positively correlated with Auditory Verbal Learning Test (AVLT) scores. In addition, GMV of the right lobule VIIb was positively associated with both AVLT and Grooved Pegboard Test (GPT) scores, and GMV of the left lobule IX was positively correlated with GPT scores. With respect to network integrity, reduced SCN connectivity between the left crus I and the default mode network (DMN) was negatively correlated with AVLT and the color word test performance, whereas enhanced SCN connectivity between the left lobules I–IV and the right caudate nucleus was negatively correlated with AVLT scores and was positively correlated with Trail Making Test-A performance.ConclusionBy integrating VBM and SCN approaches, this study demonstrated that cerebellar GMV atrophy and abnormal structural covariance in T2DM were closely associated with cognitive dysfunction. These findings highlight the role of disrupted cerebro-cerebellar connectivity in the pathophysiology of T2DM-related cognitive impairment.

Extensive research has examined the direct effect of APOE alleles on cognitive decline. However, there is limited investigation into the effect of APOE that is explained or mediated through molecular pathways, such as lipids. In this study, we performed a causal mediation analysis to estimate both the direct effect of APOE2 and its indirect effect through 24 lipid species on cognitive function, measured from the digital Clock Drawing Test (CDT) in 1228 Long Life Family Study (LLFS) participants. Results showed that APOE2 carriers completed the CDT significantly faster compared to common APOE3 carriers. Primary analysis identified two lipids (CE 18:3 and TG 56:5) protectively mediated the effect of APOE2 on cognitive function, resulting in shorter CDT think-time, ink-time, and total-time; conversely, TG 56:4 deleteriously mediated the effect of APOE2, resulting in increased ink-time. Secondary analysis yielded consistent results and identified four additional significant lipid pathways (DG 38:5, TG 51:3, TG 56:1, TG 56:2) that mediated the effect of APOE2. The combined indirect effect in the primary analysis contributed 15%-30% mediated proportion on CDT times, though such mediated proportion did not reach statistical significance. Overall, our analysis identified seven lipid species that significantly mediate the effect of APOE2 on cognitive performance. These lipids represent distinct lipid pathways, including both protective and deleterious mediation effects. Our findings offer insights for new therapeutics targeting those lipids to enhance the protective effects of APOE2 on cognition.

Automatic motor and visuospatial cognition screening with ensemble learning: A computerised clock drawing test approach.

Plain Language SummaryMemory and thinking problems, such as dementia, can be found using different tests. Depending on culture, language, and education, different tests are better than others at finding memory and thinking problems. We compared two tests, the Kimberley Indigenous Cognitive Assessment – Cognitive component (KICA-Cog) and the Clock Drawing Test (CDT), in older Aboriginal and Torres Strait Islander people across Australia. Our results show that the KICA-Cog was better than the CDT at finding dementia.

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.

Introduction: Falls are a critical public health issue, with executive function (EF) impairment being a contributing factor. However, whether apolipoprotein E4 (ApoE4) influences the relationship between EF and falls is unclear. This study investigated the potential moderating effect of ApoE4 on the EF and falls relationship in older adults with unimpaired cognition, mild cognitive impairment (MCI), and Alzheimer’s disease (AD) dementia. Methods: We analyzed cross-sectional data from 486 participants in the Brain and Body Donation Program of the Arizona Study of Aging and Neurodegenerative Disorders database. EF was assessed through a composite latent variable using the Trail Making Test, Stroop Interference, Digit Span, Clock Drawing test, and verbal fluency tests. ApoE genotypes were categorized as carriers and noncarriers of ApoE4. Logistic regression was used with fall history and future falls as outcomes. Results: ApoE4 did not moderate the EF and falls relationship (p ≥ 0.05). A significant interaction effect revealed that EF is associated with fall history for individuals with unimpaired cognition and MCI but not with AD dementia (OR = 1.658, p = 0.032). Significantly associated covariates with fall history included elements from the Unified Parkinson’s Disease Rating Scale, medical conditions, and depression (p < 0.05), while medical conditions and fall history were significantly associated with future falls (p < 0.05). Conclusion: ApoE4 did not significantly moderate the relationship between EF and falls. However, EF’s impact on falls varied by cognitive status.

ObjectiveThis study aimed to investigate the effects of computer-assisted cognitive training (CACT) on cognitive function and activities of daily living in patients with post-stroke cognitive impairment. Additionally, it aimed to explore the changes in specific cognitive domains before and after treatment.DesignThe study was a double-blind, randomized, controlled trial.SettingIt took place in rehabilitation wards or outpatient clinics.ParticipantsSixty patients with post-stroke cognitive impairment took part in the study.InterventionsParticipants were randomly assigned to either the control (n = 30) or the intervention group (n = 30). Both groups received conventional rehabilitation and cognitive training, and the intervention group additionally received CACT.Main outcome measuresThe primary outcome measures included the Mini-Mental State Examination (MMSE) and event-related potential (ERP) P300 for cognitive function, as well as the modified Barthel Index (MBI) for activities of daily living. Secondary outcomes were the Trail Making Test (TMT), the Symbol-Digit Modalities Test (SDMT), the Auditory Verb Learning Test-Huashan version (AVLT-H), the Boston Naming Test (BNT), and the Clock Drawing Test (CDT), which assessed cognitive function across specific domains.ResultsBoth groups showed significant improvements in MMSE, MBI, amplitude of P300, and latency of P300, with the intervention group demonstrating more pronounced improvements compared to the control group. In terms of specific cognitive domains, the intervention group exhibited greater improvements than the control group in TMT-A, TMT-B, and AVLT-H. Both groups showed improvements in SDMT and BNT, but the differences between the groups were not statistically significant. Additionally, there was no significant improvement in the CDT for either group before and after treatment.ConclusionCACT was found to improve patients’ cognitive function, especially in areas of attention, executive function, and memory. It also effectively improved activities of daily living.

The clock drawing test is one of the most common screening instruments for dementia. It is easy and fast to administer and provides a straightforward way to assess a range of cognitive domains. In this article, we divide its interpretation into three main errors, allowing readers to become familiar with its key findings and their meanings.

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.

Profiling the metabolome of older adults who live with overweight/obesity and undiagnosed cognitive impairment.

Postoperative cognitive dysfunction (POCD) following noncardiac surgery in the elderly is a growing concern. This study evaluates the relationship between carotid intima-media thickness (cIMT), a measure of subclinical atherosclerosis, and POCD. In this prospective study, elderly patients (≥60 years) undergoing elective noncardiac surgery were divided into two groups based on cIMT. Cognitive assessments were conducted preoperatively and postoperatively using the mini-mental state examination, clock-drawing, digit span, trail-making, and Stroop tests. The study included 36 patients, with no significant differences in cognitive test outcomes between those with cIMT ≤0.9mmand >0.9mm. The overall incidence of POCD was 2.8%. Increased cIMT was not associated with a higher risk of POCD. Larger studies are necessary to confirm these findings.

Introduction: Cognitive function is key to aging and independence. Our aim was to evaluate the associations of domain-specific cognitive performance with disability and frailty. Understanding these associations can improve clinical decision-making and patient outcomes in aging populations. Methods: This retrospective study was conducted at the Geriatric Outpatient Clinic at a tertiary hospital. Domains of the Standardized Mini-Mental State Examination and the clock drawing test were used for cognitive assessment. Clinical frailty scale (CFS), mini nutritional assessment short form (MNA), geriatric depression scale short form (GDS), activities of daily living (ADL), and instrumental activities of daily living (IADL) were used for geriatric assessment. Results: Of the 274 patients, 65.3% (179) were women, and the mean age of patients was 77.9 (±7.3). While 32.8% of patients were frail according to CFS, 44.9% had IADL disability. The orientation and calculation-attention domains were associated with frailty and IADL disability, regardless of age, sex, education level, number of medications, number of diseases, MNA score, and GDS. On the other hand, the recall and executive function domains were not found to be associated with frailty or IADL disability While language domain was associated with both ADL and IADL scores in linear regression, it was only associated with ADL disability in binary regression analysis in all models. Conclusion: Routine screening of language, orientation, and calculation-attention domains may help identify older adults at risk for frailty and disability, allowing for timely interventions.

Postoperative delirium (POD) is a frequent neuropsychiatric disorder characterized by sudden onset, particularly in elderly patients. The aim of this study is to assess the relationship between cognitive function, depression status, and the risk of POD in geriatric patients undergoing major abdominal surgery. This prospective cohort study included 100 patients aged 65 years and older who underwent major abdominal surgery. Preoperatively and postoperatively, patients underwent cognitive assessments using the mini-mental state examination (MMSE), geriatric depression scale (GDS), three-word recall test, and clock drawing test. Demographic data and test results were subsequently analyzed statistically. The mean age of the participants was 70.8 ± 5.9 years. POD occurred in 18% of patients. Statistically significant differences were observed between preoperative and postoperative values for MMSE, GDS, and clock drawing test (P < .001). Postoperative GDS results showed a significantly lower rate of normal results in the delirium group (16.7%) compared to the non-delirium group (52.4%) (P = .021). Each 1-unit decrease in preoperative MMSE score was associated with an approximately 10-fold increase in the risk of delirium (OR: 9.7; 95% CI: 1.3–71.4). In conclusion, major abdominal surgery can increase depression and impair cognitive function in elderly individuals. POD is a common complication in the elderly, with significant health consequences. The MMSE may be a useful tool for predicting the risk of postoperative delirium.

BackgroundSchizophrenia (SCZ) and bipolar disorder with psychotic features (BDP) are psychiatric disorders with significant impact on affected individuals. However, research comparing cognitive impairments between these groups is limited. This study aimed to evaluate the changes in cognitive function based on the Clock Drawing Test (CDT) among hospitalized SCZ and BDP patients and its association with positive and negative symptoms.MethodsThis cross-sectional study enrolled 84 Iranian patients (42 SCZ, 42 BDP, 51 male and 33 female) aged 42.85 (±11.51), ranging from 20 to 65 years old, from two psychiatric hospitals in Iran. The Positive and Negative Syndrome Scale (PANSS), Clinical Global Impression (CGI) scale and CDT were administered during the admission and discharge of patients. Within-group and between-group changes were analyzed using paired t-tests for pre-post comparisons and multiple regression was used to assess predictive factors of changes in cognitive and symptom changes.ResultsBoth groups showed cognitive and clinical improvements at discharge, but changes were more pronounced in the BDP group for CDT, PANSS-positive symptoms, and CGI. However, PANSS-negative symptoms improved more in SCZ patients. No correlations existed between changes in CDT and positive and negative symptoms in either of the groups.ConclusionWhile both groups exhibited cognitive and clinical improvements following hospitalization, patients with SCZ showed relatively less improvement in the CDT compared to those with BDP. These findings suggest that cognitive recovery may follow a different trajectory in SCZ, independent of changes in positive and negative symptoms but related to the initial cognitive profile. However, given that the CDT is a screening tool rather than a comprehensive cognitive assessment, these results should be interpreted with caution. Future research should incorporate broader neurocognitive assessments to better understand the cognitive trajectories of these populations.

Background. Cognitive decline (CD) during the recovery period of ischemic strokes in patients with atrial fibrillation (AF) is associated with left ventricular ejection fraction (LVEF) ≤ 48 %. Objective: to investigate cognitive changes during the recovery period of ischemic strokes in patients with AF and LVEF ≤ 48 % who took sacubitril/valsartan. Materials and methods. Patients with nonvalvular AF and LVEF ≤ 48 % who had an ische­mic non-lacunar stroke within the last 6 months were examined. Thirty-nine people in the control group received protocol treatment, and 14 patients additionally took sacubitril/valsartan 100 mg twice daily for 6 months. Cognitive and echocardiographic para­meters were assessed at the first examination and after 6 months. CD was diagnosed when the cognitive scores decreased by ≥ 1 point. Results. Both groups of patients at the time of inclusion did not differ significantly in cognitive functioning, socio-demographic, clinical, psycho-emotional characteristics, and echocardiographic parameters. Six-month administration of sacubitril/valsartan was associated with a significant reduction in the relative risk of CD on all used cognitive scales compared to the control group: by 3.18 times (95% confidence interval (CI) 1.42–7.16) on the Montreal Cognitive Assessment, by 2.79 times (95% CI 1.29–6.00) on the Clock Drawing Test and by 2.48 times (95% CI 1.19–5.14) on the Mini-Mental State Examination and the Frontal Assessment Battery. In addition, the sacubitril/valsartan intake was associated with a reliable increase in LVEF compared to baseline (40.3 (38.1–42.4) vs. 40.1 (39.4–42.5) %); in contrast, in the control group, no such pattern was observed. Conclusions. In patients with AF and LVEF ≤ 48 %, sacubitril/valsartan administration in the recovery period of ischemic non-lacunar stroke is associated with a significant improvement in cognitive functioning.

In patients with cerebral infarction (CI) and sleep apnea syndrome (SAS), neurocognitive disorders are a common symptom, which underscores the relevance of improving their early diagnosis and treatment. A prospective dynamic study was conducted on disorders of visual-constructive and executive skills (VCES) in 74 patients with SAS (main group) and 36 patients without SAS (comparison group) during the acute period of CI using route-building tests (RBT), cube copying tests (CCT), and clock drawing tests (CDT). It was found that patients with SAS exhibited more severe VCES disorders within the fi rst 72 hours of CI, primarily due to impaired performance on the CDT, and worse recovery after one month compared to patients without SAS (p &lt; 0.05). The CDT showed good indicators for the early diagnosis of VCES disorders in patients with SAS and CI (AUC — 0.926 (95% CI 0.86–0.97; p &lt; 0.0001), sensitivity — 100.0% (95% CI 84.6–100.0), specifi city — 85.23% (95% CI 76.1–91.90). In patients with severe SAS, the lowest scores for VCES, RBT, and CDT were established (p &lt; 0.05), and moderate negative correlations were identifi ed between the CDT scores and the apnea-hypopnea index and desaturation index (p &lt; 0.001). Among 20 patients receiving CPAP therapy, a positive dynamics in VCES scores was noted (p &lt; 0.05), which was not observed in the subgroup without similar treatment, suggesting a positive eff ect of CPAP therapy on recovery in this cognitive domain

Normative data of neuropsychological tests in the Vietnamese population is considerably lacking. We aim to evaluate the effects of age, education, and sex on the performance of common neuropsychological tests, and to generate normative data for these tests in cognitively normal Vietnamese adults. Participants were recruited from two hospitals in Ho Chi Minh City, with inclusion criteria as follows: age ≥ 40 years, normal cognition and function, and Mini-Mental State Examination (MMSE) scores ≥ 26. Neuropsychological tests were administered in a paper-and-pencil format, including the CERAD Word List, Trail Making Tests, Digit Span, Animal Naming, and Clock Drawing Test. Effects of age, education, and sex on test performance were evaluated using multiple linear regression analyses. Normed scores were reported as regression-based and discrete norms tables. Participants included 385 cognitively normal Vietnamese, with age 61.4 ± 10.9 years (range 40 - 89), female 56%, who were relatively highly educated (42% attended college and beyond, 36% attended high school or equivalent institutions, 22% had less than high school education), and had MMSE scores 27.8 ± 1.0. Trail Making Test Part B was completed within 300 s by only 204/385 (53%) participants. Regression analyses demonstrated significant associations between age and education with performance on all or most tests, and between sex and all CERAD Word List measures and Clock Drawing Test. The present work provides the first known normative data for a relatively comprehensive neuropsychological battery in Vietnamese adults. Performance on all tests was significantly influenced by age and education.

Background: Androgen deprivation therapy (ADT) remains foundational in managing advanced prostate cancer. Although quite successful at managing the progression of tumors, its impact on cognitive functioning over a prolonged period is concerning. This study sought to examine the association between ADT duration and cognitive performance among prostate cancer patients. Methods: A cross-sectional study was carried out between January 2023 and December 2024 with 71 prostate cancer patients on ADT. Participants were categorized into two groups based on duration of therapy: less than 2 years, and 2 years or more. Cognitive domains were assessed using MMSE, MoCA, HVLT, Trail Making B Test and Clock Drawing test. Other Depressive symptoms, fatigue, and quality of life were also measured. ‘Data analysis was conducted with SPSS v25 with significance set at p &lt; 0.05’. Results: Patients on long-term ADT exhibited significantly lower scores in global cognition, memory, executive functioning, and visuospatial tasks compared to those on short-term therapy. Mean MMSE and MoCA scores were lower in the long-term group (26.4 vs. 27.9 and 22.1 vs. 24.2, respectively). Depression scores and fatigue levels were higher, while quality of life was significantly reduced in patients receiving ADT for two years or more. Conclusion: Prolonged ADT use in prostate cancer patients is associated with a decline in cognitive performance and psychosocial well-being. These findings support the need for cognitive monitoring and multidisciplinary support during long-term hormone therapy.