A cognitive function test utilizing eye tracking technology in virtual reality

The medial temporal lobe, especially the hippocampus, is important for normal cognitive function. especially for memory, and is the region with the earliest and most extensive pathological changes in Alzheimer's disease (AD). We investigated the atrophic changes of the hippocampus over a 5-year period and its relation to cognitive screening test performances in normal elderly subjects, those with very mild AD, and patients with AD. Fifty-seven elderly subjects without a moderate or greater degree of cerebrovascular disease as shown by MRI were randomly selected from the town of Tajiri. Thirty-three subjects with a clinical dementia rating (CDR) of 0 (normal), 18 CDR-0.5 (very mild AD) subjects, and six CDR-1&2 (AD) subjects underwent MRI and the Mini Mental State Examination (MMSE) twice during the period. Retrospective changes in the hippocampal width and the MMSE scores were evaluated. There were significant CDR group effects for the changes in the mean bilateral hippocampal widths and the MMSE scores. Normal subjects did not show cognitive decline, although there was a slight tendency for hippocampal atrophy. A significant and meaningful Spearman's correlation was noted between left hippocampal atrophy and the MMSE scores over the 5-year period for the CDR-0.5 group. These CDR-0.5 subjects met the MCI (mild cognitive impairment) criteria as proposed by the consensus paper. Findings suggested that normal elderly subjects maintain a high level of cognitive functions for at least 5 years, although hippocampal atrophy might occur. Atrophic change of the left hippocampus might be a good marker of the very early stage of AD.

The value of informant reports for assessment and prediction of dementia.

Objective To investigate the characteristics of cognitive impairment and psychotic symptoms in general paresis of insane (GPI) before and after penicillin therapy, and explore factors that may predict the clinical outcomes. Methods Thirty patients with GPI were recruited. All GPI patients underwent a comprehensive neuropsychological assessment before receiving penicillin therapy, and returned for follow-up visits after 7 months. The severity of dementia was determined by Clinical Dementia Rating Scale (CDR), cognitive functions were assessed by Mini Mental State Examination (MMSE) and Alzheimer's Disease Assessment Scale-cognitive subscale (ADAS-Cog), ability of daily living was assessed by Instrumental Activities of Daily Living Scale (IALD) and Physical Self maintenance Scale(PSMS), behavioral and psychological symptoms were assessed by Neuropsychiatric Inventory (NPI). Aqueous crystalline penicillin G 24 million units per day was administered as continuous infusion for 14 days, followed by benzathine penicillin 2.4 million units IM once per week for 3 weeks. Patients returned for follow-up visits after 7 months. Clinical outcomes were determined by the improvement of neuropsychological test scores at the end of the treatment. Grouped by CDR scores, changes in neuropsychological tests scores among different GPI groups were used to explore the correlation between severity of dementia and clinical outcomes. Univariate analysis and multivariate linear regression analysis were used to identify factors that may predict the clinical outcomes. Results (1)After penicillin therapy, GPI patients' MMSE scores (14.4±6.9 vs.17.1±9.1) and IADL scores (4.0 (2.0, 5.0) vs.6.0 (2.0, 7.3) ) both improved significantly (t=5.820, Z=3.710, P 1,significant change was found only in total scores of NPI (t=-3.772,P<0.05) . (3) Univariate analysis and multivariate linear regression analysis showed that improvement of MMSE scores after the treatment was significantly correlated with IADL scores and MMSE scores at baseline (β=0.541, P=0.004; β=0.364, P=0.044) . Conclusions After penicillin treatment, GPI patients may improve in both cognitive function and psychotic symptoms but not in all the domains. Symptoms of anxiety, sleep/nigh-time behavior change, and apathy, as well as moderate to severe GPI patients may not benefit much from the treatment. Key words: Neurosyphilis; Cognition disorders; Neurobehavioral manifestations; Therapy; Prognosis

The progression of Alzheimer’s disease (AD) and its interaction with COVID-19-induced social isolation remains poorly understood. This study investigated the longitudinal trajectories of AD severity on cognitive function, functional ability, and neuropsychiatric symptoms, and examined the impact of COVID-19 lockdown on AD patients in South Korea. In this retrospective longitudinal study, data from 253 adults (aged ≥ 55) diagnosed with mild cognitive impairment (MCI) or AD were analyzed, collected between 2018 and 2022. Participants were classified into four groups based on clinical dementia rating (CDR) scores: MCI, AD-CDR0.5, AD-CDR1, and AD-CDR2. Cognitive function, functional abilities, neuropsychiatric symptoms, depressive symptoms, and overall dementia severity were assessed. Linear mixed-effects models, along with mediation and moderation analyses were employed to analyze the data. Significant trajectories of decline in cognitive function and functional abilities were observed over time, with more pronounced declines in higher AD severity groups. The COVID-19 lockdown exacerbated cognitive decline and impairment in activities of daily living (ADL) specifically in the most severe AD group (AD-CDR2). Instrumental activities of daily living (IADL) mediated the relationship between mini-mental state examination (MMSE) scores and CDR sum of boxes (CDR-SB) in the MCI, AD-CDR0.5, and AD-CDR1 groups. A significant interaction between MMSE scores and neuropsychiatric symptoms was observed in the moderate AD group (AD-CDR1), indicating that worsening neuropsychiatric symptoms intensified cognitive decline. Neuropsychiatric Inventory (NPI) scores increased over time, indicating worsening neuropsychiatric symptoms, whereas depressive symptoms, measured by the short geriatric depression scale (SGDS), remained stable over the study period. This study highlights the impact of AD severity on cognitive and functional decline, further exacerbated by the COVID-19 lockdown. The mediating role of IADL suggests that maintaining complex daily activities may be crucial in slowing disease progression in AD patients. Additionally, the worsening of neuropsychiatric symptoms underscores the need for targeted mental health support, especially during periods of social isolation, to mitigate adverse effects on patients and caregivers.

Objective To evaluate the changes of resting-state network connection of leukoaraiosis (LA) patients with or without mild cognitive impairment (MCI) by using functional magnetic resonance imaging (fMRI) and to explore the value of resting-state fMRI in the early diagnosis of LA. Methods A total of 49 LA patients were divided into 2 groups: LA with MCI (LA-MCI, N = 34) and LA with non-MCI (LA-NMCI, N = 15) based on Clinical Dementia Rating Scale (CDR). Mini-Mental State Examination (MMSE), Montreal Cognitive Assessment (MoCA), Hamilton Depression Rating Scale-17 Items (HAMD-17) and Hamilton Anxiety Rating Scale-14 Items (HAMA-14) were used to evaluate cognitive function, depression and anxiety symptoms of all patients and 33 normal controls. Resting-state fMRI was used to explore the brain network functional connection. Results The age of LA-MCI patients were significantly older than that of normal controls ( P = 0.003). The MMSE ( P = 0.001, 0.000) and MoCA ( P = 0.001, 0.000) scores in LA-MCI group were significantly higher than those in LA-NMCI group and control group. There was decreased functional connection of nuclei within the salience network in LA-MCI group compared with normal control group. Besides, the connection between salience network and default mode network (DMN) was enhanced, while connection between salience network and central executive network (CEN) was weakened. In LA-NMCI group, there was decreased functional connection of nuclei within the salience network compared with normal control group. Besides, the connection between salience network and DMN was enhanced, while the connection between salience network and CEN was weakened. Conclusions There was significant difference in resting-state fMRI brain network functional connection between normal controls and LA patients with or without MCI. Presumably it could account for the pathophysiological mechanism of LA-related cognitive impairment to some extent. DOI: 10.3969/j.issn.1672-6731.2016.05.004

Introduction: An alteration of cognitive function in geriatrics often occurred after a surgery procedure. To do a surgery, patients would go through the process with anesthesia, whether it is general or regional anesthesia. We aimed to identify the effect of general and regional anesthesia in increasing the risk of alteration in cognitive function from geriatrics who underwent elective surgery followed by other risks. Material and Method: This observational analytic study has a total sample of 60 patients who aged 60 years or more, and half of the total sample underwent an elective surgery with general anesthesia, whereas the other half with regional anesthesia at Gedung Bedah Pusat Terpadu Dr. Soetomo General Hospital in a range of October – November 2016. The cognitive function of patients was assessed with MMSE which is done in approximately 10 – 15 minutes. Result and Discussion: There was a statistically significant correlation between age and both preoperative MMSE score also the alteration of MMSE score after 3 days in patients with regional anesthesia (P-value = 0.032; 0.044). Also, the correlation between educational status and preoperative MMSE score (P-value = 0.001). There was also a statistically significant difference in alteration of the MMSE score after 3 days between patients with general and regional anesthesia which went through the hypotension phase (P-value = 0.022; 0.003). We identified that both general and regional anesthesia could lead to alteration of MMSE score (P-value = 0.001; 0.02) and there was a statistically significant difference between both of them (P-value = 0.001). Conclusion: Both general and regional anesthesia could lower the cognitive function of geriatrics, especially general anesthesia which happened to have a higher risk to occur. Other factors such as age, educational status, and hemodynamic condition during surgery, had their impacts toward lowering cognitive function in geriatrics.

The aim of the research was to investigate the factors contributing to cognitive dysfunction in type 2 diabetic patients, to distinguish the complex relationship between diabetic retinopathy (DR) and different cognitive status. Two hundred and ninety-seven type 2 diabetes mellitus (T2DM) patients were enrolled in our study. We adopted the Clinical Dementia Rating (CDR), Mini-mental State Examination (MMSE) and Montreal Cognitive Assessment (MOCA) to evaluate the cognitive function. Firstly, cognition status was classified into dementia and non-dementia according to MMSE and CDR. Patients with non-dementia were further classified into mild cognitive impairment (MCI) and normal cognition status based on MOCA. The factors contributing to cognitive dysfunction were analyzed. Among the 297 T2DM subjects, 47 were enrolled in the dementia group and 174 in the MCI group according to a battery of cognitive function tests, presenting a prevalence of 15.8% and 58.6% respectively. After adjustment for age, sex, and education level, waist circumference and DR were risk factors for dementia (OR: 1.057, P=0.011; OR: 2.197, P=0.040). Low-density lipoprotein cholesterol (LDL-C) was a risk factor for MCI (OR: 1.635, P=0.047), while age at T2DM onset and moderate drinking were protective factors for MCI (OR: 0.936, P=0.044; OR: 0.289, P=0.004). MCI is common in T2DM patients. Waist circumference and DR are risk factors of dementia, LDL-C is a risk factor for MCI, and moderate drinking and age at T2DM onset are protective factors for MCI. DR is unrelated to MCI in T2DM.

Objective To identify the differences inneuropsychological characteristics between amnestic(AMCI)and vascular mild cognitive impairment(VMCI). Methods Totally 297 old community residents with mild cognitive impairment(MCI)were divided into amnestic MCI(AMCI)and vascular MCI(VMCI)subgroup from Guangzhou MCI prevalence survey.The elderly with MCI were interviewed and tested with the Chinese version of Montreal Cognitive Assessment(MoCA), the Mini-Mental state examination(MMSE), Auditory Verbal Learning Test(AVLT), the Clinical Dementia Rating scale(CDR), Functional Activity Questionnaire(FAQ), the Modified Hachinski Ischemic Scale(M-HIS), Center for Epidemiologic Studies(CES-DC)to evaluate neuropsychological characteristics. Results AMCI versus VMCI group showed that the total scores of MoCA were(9.63±5.17 vs.9.98±6.02), total scores of MMSE were(16.90±4.84 vs.16.90±6.19), AVLT immediate memory was(2.35±1.39 vs.2.91±1.84), AVLT delayed recall was(2.23±2.09 vs.2.47±2.20), AVLT delayed recognition was(7.33±3.98 vs.6.85±4.02)and total scores of CDR(0.5 vs.0.5), with no differences between the 2 groups(all P>0.05). Based on MoCA survey, AMCI versus VMCI group showed statistically significant differences(all P<0.05)in parameters of visual space and execution(0.71±1.02 vs.0.92±1.26), language function(0.34±0.56 vs.0.50±0.80)and abstract thinking(0.25±0.49 vs.0.15±0.43), but based on MMSE survey, no difference was found in the various cognitive domains between the two groups.The AMCI versus VMCI group showed statistically significant differences(all P<0.05)in parameters of CES-DC scale(1.75±4.27 vs.2.76±6.72), FAQ scale(4.42±4.66 vs.8.71±7.03), M-HIS scale(0.40±0.64 vs.7.59±3.53). Conclusions There is no significant difference in general cognitive impairment between AMCI and VMCI, but the visual space and execution, language function are more impaired in AMCI than VMCI, and the abstract thinking, social function are more impaired with more depressive symptoms in VMCI than in AMCI. Key words: Cognition disorders; Neuropsychological tests; Amnesia; Blood vessels

Objective: This study aimed to prospectively investigate the pharmaco-biological optimization of Alzheimer’s disease (AD) treatments in terms of psychocognitive and metabo-inflammatory aspects via multivariate correlation analyses. Methods: A 24-week pre-and-post-treatment follow-up study was conducted prospectively on AD patients. The effects of each pharmacological modality on psycho-cognitive (categorical and numeric)(Mini-Mental Status Examination (MMSE), Clinical Dementia Rating Scale (CDR)), Metabo-inflammatory, and hematologic indexes were analyzed. Results: The mild cognitive impairment (MCI) stage was lower in the standardized Ginkgo biloba extract (EGB-761) (median[Interquartile Range(IQR)]=1[4.0](χ2=15.610)) group compared to the other modalities in CDR analyses, whereas it was higher in the donepezil-memantine (9[36.0](χ2=11.469)). In MMSE analyses (categorical data), MCI patients were dominant (MMSE:21-26) in the donepezil group (median(IQR(17[68.0](χ2=7.946)), while moderate stage (MMSE score:11-20) was in memantine (18[69.2](χ2=9.489)) and donepezil-memantine (16[64.0](χ2=10.545)). The memantine group showed apparent anti-inflammatory effects in hematological and inflammatory indices. Metabolic disturbance regarding thyroid dysfunction was observed in the EGB 761 group. A positive correlation was detected between psycho-cognitive tests and platelet count (20.9% for CDR and 22.3% for MMSE). Conclusion: Donepezil showed superior performance in terms of cognitive improvement, and the combination of donepezil-memantine offers significant advantages, especially in cognitive-functional enhancement. Memantine showed significantly superior results in terms of anti-inflammatory effects; despite the need for careful monitoring of metabolic imbalances, it was demonstrated that EGB-761 can be considered as a monotherapy option in the treatment of MCI. The platelet indices can have an important place in both future research and clinical applications as advanced psychocognitive laboratory markers.

The assessment of daily living activities could provide information about daily functions and participation restrictions to develop intervention strategies. The purposes of this study were to assess the scores of the Barthel Index (BI) and Lawton Instrumental Activities of Daily Living (IADL) scale in older adults with cognitive impairment and to explore the different effects that levels of cognitive functions have on changes in IADL functions. We recruited 31 participants with dementia, 36 with mild cognitive impairment (MCI), and 35 normal controls (NCs) from the neurology outpatient department of a regional hospital. The results of the demographic and clinical characteristics through the Lawton IADL scale, BI, Quick Mild Cognitive Impairment (Qmci) screen, Montreal Cognitive Assessment (MoCA), and Mini-Mental State Examination (MMSE), were collected on the same day and compared with the Kruskal–Wallis test, Wilcoxon rank-sum test, Fisher’s exact test, and a multiple linear regression analysis, as appropriate. In the BI, bathing was the most discriminating activity to differentiate patients with MCI and dementia; in the Lawton IADL scale, medication responsibility and shopping were the most discriminating activities to differentiate NCs and patients with MCI, and patients with MCI and dementia, respectively. In addition, the predictors of changes in Lawton IADL scale scores were the problem-solving score of the Clinical Dementia Rating scale, a Qmci score of > 20.4 and an age of ≤ 81.2 years, a MoCA score of < 9.4 and an age of > 81.2 years, and the MMSE score and an age of > 81.2 years. This study adds to the evidence that the description of basic and instrumental daily activities is integrated in older adults with cognitive impairment. Notably, the Qmci is the most significant predictor of changes in IADL function for “young” older adults, as are the MoCA and MMSE for “old” older adults.

Mild cognitive impairment (MCI) represents a transitional state between normal aging and dementia. However, there is inconsistent opinion as to the validity of subjective memory complaints as a criterion for diagnosis. This study aimed to examine the potential significance of applying a short memory questionnaire in the assessment of Chinese subjects with MCI and early dementia. Three hundred and six ambulatory Chinese subjects were recruited. Each participant completed a short memory questionnaire. They were also assessed with the Chinese versions of the mini-mental state examination (CMMSE), Alzheimer's disease assessment scale-cognitive subscale (ADAS-Cog), category verbal fluency test (CVFT) and span tests. Severity of cognitive impairment was evaluated using the Clinical Dementia Rating (CDR); subjects with CDR 0.5 were further classified into MCI not demented (MCIND) and MCI possible incipient dementia (MCIID) depending on the subscale scores of CDR. An increasing frequency of memory complaints with increasing CDR was observed (Kruskal Wallis test, chi square = 21.29, df 3, p < 0.001). With a cutoff of 3 or more memory complaints, the memory questionnaire demonstrated a sensitivity of 65.3% and 70.4% in identifying subjects with incipient and early dementia respectively. Significant associations between memory complaints and most cognitive test performance were found (Spearman's correlations, p < 0.01). Logistic regression analysis revealed that educational level, the memory questionnaire, ADAS-Cog total and delayed recall scores were significant predictors of MCIID status. The findings suggested that a short memory questionnaire is useful in the screening of MCI, particularly in subjects who already present with subtle functioning disturbances. Subjective memory complaints were significant correlated with objective performance of memory functions, reflecting the usefulness of memory complaints in the assessment of MCI.

Total tau (t-tau) and phosphorylated tau (p-tau) protein elevations in cerebrospinal fluid (CFS) are well-established hallmarks of Alzheimer’s disease (AD), while the associations of serum t-tau and p-tau levels with AD have been inconsistent across studies. To identify more accessible non-invasive AD biomarkers, we measured serum tau proteins and associations with cognitive function in age-matched controls (AMC, n = 26), mild cognitive impairment group (MCI, n = 30), and mild-AD group (n = 20) according to the Mini-mental State Examination (MMSE), Clinical Dementia Rating (CDR), and Global Deterioration Scale (GDS) scores. Serum t-tau, but not p-tau, was significantly higher in the mild-AD group than AMC subjects (p < 0.05), and there were significant correlations of serum t-tau with MMSE and GDS scores. Receiver operating characteristic (ROC) analysis distinguished mild-AD from AMC subjects with moderate sensitivity and specificity (AUC = 0.675). We speculated that tau proteins in neuronal cell-derived exosomes (NEX) isolated from serum would be more strongly associated with brain tau levels and disease characteristics, as these exosomes can penetrate the blood-brain barrier. Indeed, ELISA and Western blotting indicated that both NEX t-tau and p-tau (S202) were significantly higher in the mild-AD group compared to AMC (p < 0.05) and MCI groups (p < 0.01). In contrast, serum amyloid β (Aβ1–42) was lower in the mild-AD group compared to MCI groups (p < 0.001). During the 4-year follow-up, NEX t-tau and p-tau (S202) levels were correlated with the changes in GDS and MMSE scores. In JNPL3 transgenic (Tg) mice expressing a human tau mutation, t-tau and p-tau expression levels in NEX increased with neuropathological progression, and NEX tau was correlated with tau in brain tissue exosomes (tEX), suggesting that tau proteins reach the circulation via exosomes. Taken together, our data suggest that serum tau proteins, especially NEX tau proteins, are useful biomarkers for monitoring AD progression.

Mapping correlations between ventricular expansion and CSF amyloid and tau biomarkers in 240 subjects with Alzheimer's disease, mild cognitive impairment and elderly controls

The Necker cube is usually used for evaluating the visuoconstructional ability of patients with mild cognitive impairment (MCI) and dementia. However, the Necker cube is often considered a drawing with a visual illusionary perspective. The purpose of this study was to investigate whether Necker cube copying could detect participants with MCI due to dementia. We retrospectively analyzed the database of the 1998 prevalence study that was part of the Tajiri Project (n = 599). Pencil drawings of the Necker cube on A4-sized white paper by non-demented people (Clinical Dementia Rating (CDR) 0 and 0.5, n = 256) were classified into two patterns: non-three-dimension (3-D) and 3-D. Two neuropsychologists assessed Necker cube copying according to the criteria of the classification. After the classification, the database of the 2003 incidence study was used according to the subjects' conversion to dementia. In the prevalence study, among those who made a non-3-D drawing of the Necker cube, there were significantly fewer people in the CDR 0 group than in the CDR 0.5 and CDR 1+ groups; similarly, there were significantly fewer people in the CDR 0.5 group than in the CDR 1 + group (χ(2) = 32.6, P < 0.001; post-hoc tests using χ(2) tests, CDR 0 > CDR 0.5 > CDR 1+, P < 0.001). In the incidence study, among those who made a non-3-D drawing of the Necker cube, there were significantly fewer people in the non-converter group than in the converter group (χ(2) = 19.9, P < 0.001). However, there was no significant difference between the non-converter group (n = 21) and the converter group (n = 21) when age, sex, educational levels, and Mini-Mental State Examination scores were controlled (χ(2) = 0.0, P = 1.000). Our results suggested that Necker cube copying may evaluate visual illusion as well as visuoconstructional ability. The Necker cube may not be an appropriate test to detect participants with MCI due to dementia.

Decreased EEG synchronization and its correlation with symptom severity in Alzheimer's disease