Mini-Mental State Examination Total Score Research Articles

Relationship of the Japanese Old Stories Cognitive Scale With the Revised Hasegawa Cognitive Scale and Mini-Mental State Examination.

The Revised Hasegawa Dementia Scale (HDS-R) is the most widely used instrument to screen for dementia in Japan and is similar to the Mini-Mental State Examination (MMSE). The development of a quicker and simpler screening tool, the Japanese Old Stories Cognitive Scale (JOSS), was previously reported. A total of 953 new outpatients from 8 memory clinics in Japan completed the JOSS, HDS-R, and MMSE at first visit. We investigated the relationship of JOSS score with both the total and individual domain scores on the HDS-R and MMSE. We found a significant relation between JOSS score and total HDS-R and MMSE scores. In addition, JOSS score was significantly related to scores on 8 of the 9 HDS-R domains and 7 of the 11 MMSE domains. We obtained regression lines for JOSS score versus HDS-R and MMSE scores. JOSS score could be useful for predicting HDS-R and MMSE scores and thus in estimating cognitive functioning.

Attention to the domains of Revised Hasegawa Dementia Scale and Mini-Mental State Examination in patients with Alzheimer's disease dementia.

In Japan, Alzheimer's disease dementia (AD) is the most common cognitive disease, and the most widely used dementia screening tests are the Revised Hasegawa Dementia Scale (HDS-R) and Mini-Mental State Examination (MMSE). This study sought to elucidate the relationships of the individual domains of these tests with age and duration of school education in a large group of patients with AD. Participants were 505 new outpatients diagnosed with AD who completed the HDS-R and MMSE at the first visit. We investigated the relationships of total and individual domains of these tests with age and duration of school education using the least squares method. Next, we plotted regression lines of the individual domain scores against the total test scores. Younger age and longer duration of school education were significantly associated with higher total HDS-R and MMSE scores in AD. Domain-specific results indicated that younger age was significantly associated with a higher immediate memory score on both the HDS-R and MMSE and with a higher orientation (time), repetition score on the MMSE. Longer duration of school education was significantly associated with a higher working memory score on the HDS-R and with higher serial 7, repetition and writing scores on the MMSE. In addition, shorter duration of school education was significantly associated with higher naming score on the MMSE. The regression lines of orientation of time, remote memory, visual memory, and verbal frequency hit the bottom on the HDS-R (4/30, 8/30, 4/30, and 6/30, respectively) and of orientation of time, serial 7, remote memory, and writing also hit the bottom on the MMSE (8/30, 9/30, 11/30, and 8/30, respectively). We should pay attention to age, duration of school education, and the individual domains when using the HDS-R or MMSE to assess patients with AD.

Assessment of Mild Cognitive Impairment Using CogEvo: A Computerized Cognitive Function Assessment Tool.

To assess the utility of the computerized cognitive function assessment tool, CogEvo, as a screening tool for mild cognitive impairment in primary care, we explored the relationship between CogEvo performance, age, and the severity of cognitive dysfunction evaluated by the Mini-Mental State Examination (MMSE). The observational cross-sectional study included 209 individuals' data (mean age 79.4 ± 8.9 years). We conducted a correlation analysis between CogEvo and MMSE scores, compared the performance among the 3 cognitive function groups (MMSE ≥ 28 group; MMSE24-27 group; MMSE ≤ 23 group) using the MMSE cut-off, and evaluated CogEvo's predictive accuracy for cognitive dysfunction through ROC analysis. Both total CogEvo and MMSE scores significantly decreased with age. A significant positive correlation was observed between total CogEvo and MMSE scores, but a ceiling effect was detected in MMSE performance. Significant differences were observed in the total CogEvo score, including orientation and spatial cognitive function scores, among the 3 groups. CogEvo showed no educational bias. ROC analyses indicated moderate discrimination between the MMSE ≥ 28 group and the MMSE24-27 and MMSE ≤ 23 groups. The computer-administered CogEvo has the advantage of not exhibiting ceiling effects or educational bias like the MMSE, and was found to be able to detect age-related cognitive decline and impairment.

Alteration of functional connectivity network in population of objectively-defined subtle cognitive decline.

The objectively-defined subtle cognitive decline individuals had higher progression rates of cognitive decline and pathological deposition than healthy elderly, indicating a higher risk of progressing to Alzheimer's disease. However, little is known about the brain functional alterations during this stage. Thus, we aimed to investigate the functional network patterns in objectively-defined subtle cognitive decline cohort. Forty-two cognitive normal, 29 objectively-defined subtle cognitive decline and 55 mild cognitive impairment subjects were included based on neuropsychological measures from the Alzheimer's disease Neuroimaging Initiative dataset. Thirty cognitive normal, 22 objectively-defined subtle cognitive declines and 48 mild cognitive impairment had longitudinal MRI data. The degree centrality and eigenvector centrality for each participant were calculated by using resting-state functional MRI. For cross-sectional data, analysis of covariance was performed to detect between-group differences in degree centrality and eigenvector centrality after controlling age, sex and education. For longitudinal data, repeated measurement analysis of covariance was used for comparing the alterations during follow-up period among three groups. In order to classify the clinical significance, we correlated degree centrality and eigenvector centrality values to Alzheimer's disease biomarkers and cognitive function. The results of analysis of covariance showed significant between-group differences in eigenvector centrality and degree centrality in left superior temporal gyrus and left precuneus, respectively. Across groups, the eigenvector centrality value of left superior temporal gyrus was positively related to recognition scores in auditory verbal learning test, whereas the degree centrality value of left precuneus was positively associated with mini-mental state examination total score. For longitudinal data, the results of repeated measurement analysis of covariance indicated objectively-defined subtle cognitive decline group had the highest declined rate of both eigenvector centrality and degree centrality values than other groups. Our study showed an increased brain functional connectivity in objectively-defined subtle cognitive decline individuals at both local and global level, which were associated with Alzheimer's disease pathology and neuropsychological assessment. Moreover, we also observed a faster declined rate of functional network matrix in objectively-defined subtle cognitive decline individuals during the follow-ups.

THE MINI-MENTAL STATE EXAMINATION IN A CHINESE POPULATION: RELIABILITY, VALIDITY, AND MEASUREMENT INVARIANCE

Abstract The Mini-Mental State Examination (MMSE) is a widely used screening tool for cognitive impairment and dementia in many cultures and regions. However, the properties of the MMSE in the Chinese context have not been evaluated with large population-representative samples. It is also unclear whether item properties of the MMSE differ across age and education subgroups. We study the psychometric properties of the MMSE using data from 8974 respondents aged 60 years or older in the 2018 Chinese Health and Retirement Longitudinal Study (CHARLS). Using item response theory (IRT) for the ordinal data, we confirm a three-dimensional factor structure for the MMSE in CHARLS in accordance with the underlying theoretical framework and establish acceptable model-data fit (SRMSR = 0.036). Total scores and subscale scores of the MMSE correlated positively with each other and correlated negatively with ADL (r = -0.19), IADL (-0.30), and CESD scores (-0.25). The reliability of the total MMSE scores was estimated at 0.78, indicating moderate measurement precision in the study population. Multiple group IRT analysis found that item characteristics and item functioning of 5 items differed by age group and 14 items differed by educational level. This analysis provided evidence on violations to measurement invariance of MMSE items, pointing to a need to account for item-level differences in measurement properties primarily with respect to education level when using the MMSE in CHARLS and, more generally, in Chinese populations. In addition, revised cognitive measures are advised to be used in CHARLS to improve the precision of measurement.

Aberrant morphometric networks in Alzheimer's disease have hemispheric asymmetry and age dependence.

Alzheimer's disease (AD) is associated with abnormal accumulations of hyperphosphorylated tau and amyloid-β proteins, resulting in unique patterns of atrophy in the brain. We aimed to elucidate some characteristics of the AD's morphometric networks constructed by associating different morphometric features among brain areas and evaluating their relationship to Mini-Mental State Examination total score and age. Three-dimensional T1-weighted (3DT1) image data scanned by the same 1.5T magnetic resonance imaging (MRI) were obtained from 62 AD patients and 41 healthy controls (HCs) and were analysed by using FreeSurfer. The associations of the extracted six morphometric features between regions were estimated by correlation coefficients. The global and local graph theoretical measures for this network were evaluated. Associations between graph theoretical measures and age, sex and cognition were evaluated by multiple regression analysis in each group. Global measures of integration: global efficiency and mean information centrality were significantly higher in AD patients. Local measures of integration: node global efficiency and information centrality were significantly higher in the entorhinal cortex, fusiform gyrus and posterior cingulate cortex of AD patients but only in the left hemisphere. All global measures were correlated with age in AD patients but not in HCs. The information centrality was associated with age in AD's broad brain regions. Our results showed that altered morphometric networks due to AD are left-hemisphere dominant, suggesting that AD pathogenesis has a left-right asymmetry. Ageing has a unique impact on the morphometric networks in AD patients. The information centrality is a sensitive graph theoretical measure to detect this association.

Reliability and validity of the Cognitive Assessment for Stroke Patients (Chinese version) for patients with nonaphasic stroke

This study aimed to preliminarily explore the reliability and validity of the Chinese version of the Cognitive Assessment for Stroke Patients (CASP) in patients with nonaphasic stroke and provide a reliable basis for its clinical application in China. The original French version of the CASP was translated into Mandarin Chinese. The study enrolled 58 patients in the neurological center. Mini-Mental State Examination (MMSE), Montreal Cognitive Assessment (MoCA), and CASP were used to evaluate cognitive function. Content validity, structural validity, and concurrent validity, internal consistency, interrater consistency, and retesting reliability were used to evaluate the results. The Spearman correlation coefficient of each item and the total CASP score was between 0.320 and 0.905 (p < .05), showing good content validity. Two initial factors were extracted using principal component analysis and the orthogonal rotation method, with a cumulative contribution rate of 70.100%. Except for the subitem reproducing a copy of a cube, the factor loading of all subitems was >0.5, indicating good construct validity. The total CASP score significantly correlated with the total MMSE (r = 0.796, p < .001) and total MoCA (r = 0.816, p < .001) scores, indicating good concurrent validity. Cronbach’s α of the CASP was 0.812, showing good internal consistency. The interrater consistency (ICC > 0.85) and retesting reliability (ICC = 0.7–0.951) were good. The Chinese version of the CASP has good reliability and validity and can play a good auxiliary role in evaluating cognitive dysfunction in patients with stroke.

Tangram Puzzles in Patients with Neurocognitive Disorders: A Pilot Study

Objective: The tangram puzzle is a serious math puzzle game used to promote mathematic development in children, which improves visuospatial function and creativity. A game to improve cognitive functions is useful for patients with neurocognitive disorders. This pilot study aimed to determine whether this game could improve cognitive function in patients with neurocognitive disorders. Materials: This study recruited patients with mild Alzheimer’s disease or mild cognitive impairment who were followed longitudinally by the Department of Psychiatry, Juntendo University Hospital, or Juntendo Tokyo Koto Geriatric Medical Center (Tokyo, Japan). Methods: Participants were asked to solve Tangram puzzles 2–3 times weekly, spending 30–40 min/session at home with or without family members for approximately 90 (Study 1) or 180 (Study 2) days. Mini-Mental State Examination (MMSE) in Study 1 as well as a Japanese version of the Montreal Cognitive Assessment and Trail Making Test in Study 2 were performed on the initial and final days. Results: Study 1 comprised eight participants and Study 2 comprised nine participants. Statistically significant improvement was observed in MMSE total score (p = 0.016) and orientation segment (p = 0.026) in Study 1. No statistically significant difference was noted in MMSE total score, orientation segment, or MoCA-J (Japanese version of Montreal Cognitive Assessment) score between the initial and final days in Study 2 (p = 0.764, p = 0.583, and p = 0.401, respectively). Conclusions: Study 1 revealed that Tangram puzzles may ameliorate the progression of cognitive functions in patients with neurocognitive disorders within a short time (3 months); however, Study 2 did not show a consistent result. Thus, randomized controlled trials are warranted to draw a conclusion.

Effects of reminiscence therapy on cognition, agitation, and quality of life in older adults with dementia receiving long-term care.

Dementia is one of the most common neuropsychiatric conditions in older adults. Despite many older adults with dementia receiving long-term care (LTC), few studies have been conducted in Turkey on reminiscence therapy (RT) influencing neuropsychiatric symptoms and quality of life in people with dementia receiving LTC. This study aimed to investigate the effect of RT on cognition, agitation, and quality of life in older adults with dementia receiving LTC in Turkey. The study population consisted of 100 older adults living in a LTC centre in a province. The size of the research group was calculated using the power analysis method, and 54 older adults were included in the study, 27 each in the RT and control (C) groups. Data collection forms Mini-Mental State Examination (MMSE), Cohen-Mansfield Agitation Inventory (CMAI), and the Alzheimer's Disease Quality-of-Life Scale (AD-QOL) were applied to the RT and C groups before RT (T0 ), 1 week after RT (T1 ), 1 month after RT (T2 ), and 3 months after RT (T3 ) to evaluate the effectiveness of the intervention. Mean, standard deviation, ratio, percentile, Fisher's exact test, Pearson Chi-square test, Mann-Whitney U-test, and Friedman test were used in analyzing the data. Older adults in the RT and C groups were similar regarding sociodemographic characteristics, institutional care, and life models (P > 0.05). When comparing the T3 values of MMSE, CMAI, and AD-QOL total scores with the T0 values, a significant difference was observed between the groups, favouring the RT group (P < 0.001). Individual RT may benefit cognition, agitation, and quality of life of older adults with dementia residing in a LTC centre.

Efficacy and Safety of Cilostazol in Mild Cognitive Impairment

Recent evidence indicates the efficacy of β-amyloid immunotherapy for the treatment of Alzheimer disease, highlighting the need to promote β-amyloid removal from the brain. Cilostazol, a selective type 3 phosphodiesterase inhibitor, promotes such clearance by facilitating intramural periarterial drainage. To determine the safety and efficacy of cilostazol in mild cognitive impairment. The COMCID trial (A Trial of Cilostazol for Prevention of Conversion from Mild Cognitive Impairment to Dementia) was an investigator-initiated, double-blind, phase 2 randomized clinical trial. Adult participants were registered between May 25, 2015, and March 31, 2018, and received placebo or cilostazol for up to 96 weeks. Participants were treated in the National Cerebral and Cardiovascular Center and 14 other regional core hospitals in Japan. Patients with mild cognitive impairment with Mini-Mental State Examination (MMSE) scores of 22 to 28 points (on a scale of 0 to 30, with lower scores indicating greater cognitive impairment) and Clinical Dementia Rating scores of 0.5 points (on a scale of 0, 0.5, 1, 2, and 3, with higher scores indicating more severe dementia) were enrolled. The data were analyzed from May 1, 2020, to December 1, 2020. The participants were treated with placebo, 1 tablet twice daily, or cilostazol, 50 mg twice daily, for up to 96 weeks. The primary end point was the change in the total MMSE score from baseline to the final observation. Safety analyses included all adverse events. The full analysis set included 159 patients (66 [41.5%] male; mean [SD] age, 75.6 [5.2] years) who received placebo or cilostazol at least once. There was no statistically significant difference between the placebo and cilostazol groups for the primary outcome. The least-squares mean (SE) changes in the MMSE scores among patients receiving placebo were -0.1 (0.3) at the 24-week visit, -0.8 (0.3) at 48 weeks, -1.2 (0.4) at 72 weeks, and -1.3 (0.4) at 96 weeks. Among those receiving cilostazol, the least-squares mean (SE) changes in MMSE scores were -0.6 (0.3) at 24 weeks, -1.0 (0.3) at 48 weeks, -1.1 (0.4) at 72 weeks, and -1.8 (0.4) at 96 weeks. Two patients (2.5%) in the placebo group and 3 patients (3.8%) in the cilostazol group withdrew owing to adverse effects. There was 1 case of subdural hematoma in the cilostazol group, which may have been related to the cilostazol treatment; the patient was successfully treated surgically. In this randomized clinical trial, cilostazol was well tolerated, although it did not prevent cognitive decline. The efficacy of cilostazol should be tested in future trials. ClinicalTrials.gov Identifier: NCT02491268.

P199: Cluster analysis dissecting cognitive deficits in older adults with major depressive disorder and the association between neurofilament light chain

Objectives:Cognitive impairment is a growing problem with increasing burden in ageing global population. Older adults with major depressive disorder (MDD) have higher risk of dementia during ageing. Neurofilament light chain (NfL) has been proven as a potential biomarker related to dementia. The present study aims to assess the cognitive deficits in older adults with MDD and investigate their association with peripheral blood levels of NfL.Design:We enrolled 39 individuals with MDD and 15 individuals with mild neurocognitive disorder or major neurocognitive disorder, Alzheimer’s type. Both groups were over age 65 and with restricted Mini-Mental State Examination (MMSE) score. Demographic data, clinical variables, and plasma NfL levels were obtained. We used cluster analysis according to their cognitive profile and estimated the correlation between plasma NfL levels and cognitive impairment in each domain.Result:In the MDD group, participants have higher rate of family psychiatry history and higher rate of current alcohol use habit compared with patients with neurocognitive disorders. In the neurocognitive disorders group, participants showed significantly lower score in total MMSE and higher plasma NfL levels. Part of the MDD patients presented cognitive deficits similar to that of neurocognitive disorders (cluster A). In cluster A, the total MMSE score (r=-0.58277, p=0.0287) and the comprehension domain (r=-0.71717, p=0.0039) were negatively correlated to NfL levels after adjusting for age, while the associations had not been observed in the other cluster.Conclusion:We noted the negative correlation between NfL levels and cognitive performance in MDD patients whose cognitive manifestation were more similar to that of degenerative neurocognitive disorders. NfL might be a potential marker to predict patients with MDD to develop cognitive decline especially in domains typically found in Alzheimer’s disease. Further longitudinal studies are required to validate our findings for clinical implications.

Plasma glucose does not influence performance on standard cognitive screening tests in a mixed memory clinic cohort

AbstractBackgroundIt has been shown under experimental conditions that cognitive performance, especially working memory, is impaired in type I and type II diabetes during hyperglycemic and hypoglycemic conditions, perhaps due to altered cerebral glucose metabolism. It is not known if patients with neurodegenerative diseases, who also exhibit pathological cerebral glucose metabolism, are affected in a similar manner by their intrinsic plasma glucose levels. We aimed to test if performance on two standard cognitive screening tests is influenced by intrinsic plasma glucose levels in a memory clinic cohort.MethodIn this retrospective study, we included patients from the Copenhagen Memory Clinic Cohort (CMCC) with an available Mini Mental‐State Examination (MMSE) test score and a plasma glucose measurement performed in conjunction with cognitive testing. Patients were included from the inception of the cohort in 2008 till September 2021. We built linear regression models with MMSE and Addenbrooke’s Cognitive Examination (ACE) test scores as the outcome and plasma glucose as the explaining variable and adjusted models for age, sex and diabetes (plasma glucose measurement &gt; 11.1 mmol/L). We explored non‐linear relationships by adding squared terms to the models and by fitting cubic spline regression models.ResultIn total, 2714 patients had an available MMSE score and a plasma glucose measurement. Patients had a mean age of 71.6 years [range 19‐99] and a baseline plasma glucose level of 5.8 mmol/L [range 2.7‐28.1]. A total of 581 of patients had a plasma glucose level outside normal range (&lt;4.2 or &gt;6.3 mmol/L). A total of 31.2% of the cohort studied had a diagnosis of Alzheimer’s disease (AD). MMSE and ACE total scores were not influenced by plasma glucose in a linear nor in a non‐linear fashion, when we adjusted for age, sex and diabetes. Sub‐group analyses in patients with AD and in patients with cerebrovascular disease showed similar results.ConclusionPlasma glucose levels inside normal range were not shown to influence performance on routinely applied cognitive tests and do not need be taken into consideration when interpreting test results from memory clinic patients.

Association of gait and cognition after surgery in patients with idiopathic normal pressure hydrocephalus

Idiopathic normal pressure hydrocephalus (iNPH) is a treatable disease in older adults. The association between gait and cognition has recently become a topic of interest. Sequential changes in this association were investigated in patients with iNPH using a newly developed statistical method. Data were extracted from the SINPHONI-2 multicenter study on iNPH. Fifty patients who underwent shunt surgery were included in this study. Gait and cognition were assessed using the Timed Up and Go (TUG) and Mini-Mental State Examination (MMSE) tests. In addition to the MMSE total score, changes in the sub-item scores were examined. The ordinal sub-items of the MMSE are usually treated as continuous or categorical; however, both are unsuitable. An ordinal smoothing penalty with a generalized additive model enables precise statistical inference of ordinal and binary predictors. The TUG time improved significantly at 3, 6, and 12 months after surgery. The MMSE total scores increased without statistical significance. Preoperatively, there was no association between TUG time and MMSE sub-items. At 3 months, the “Registration,” ”3-step command,” “Read,” and “Copy” sub-items were statistically significant. The number of significant sub-items increased after 12 months. Thus, the association between gait and cognition gradually increased after surgery in patients with iNPH.

Urinary nicotine metabolites are associated with cognitive impairment among the elderly in southern China.

This study comprehensively assessed the association between eight metabolites of urinary nicotine and cognitive impairment. This cross-sectional study was based on the data of Shenzhen Aging Related Disorder Cohort (SADC), including 51 elderly community data variables such as demographic characteristics, neuropsychological assessment and environmental factors, from July 2017 to November 2018. Participant's cognitive function was assessed by Mini-Mental State Examination (MMSE) scale and urinary nicotine metabolite [including cotinine N-β-D-glucuronide (CotGluc), rac 4-hydroxy-4-(3-pyridyl) butanoic acid dicyclohexylamine salt (HyPyBut), trans-3'-hydroxy cotinine O-β-D-glucuronide (OHCotGluc), and cotinine (Cot), etc.] concentrations were measured by high-performance liquid chromatography-tandem mass spectrometry (LC-MS/MS). Generalized linear models and restricted cubic spline models were used to explore the relationships between the urinary levels of nicotine metabolite and cognitive function. A total of 296 individuals aged >60 years were included. Individuals in the third quartile of CotGluc had a 0.786 point (95% CI: -1.244 - -0.329) decrease or in the highest quartile of OHCotGluc had a 0.804 point (95% CI: -1.330 - -0.278) decreased in attention and calculation compared to those in the lowest quartile (all p for trend <0.05). Compared with those in the lowest quartile, individuals in the highest quartile of CotGluc, HyPyBut, OHCotGluc and Cot, respectively, corresponded to a 1.043 point (95% CI: -2.269-0.182), 1.101 points (95% CI: -2.391-0.188), 2.318 points (95% CI: -3.615 - -1.020), and 1.460 points (95% CI: -2.726 - -0.194) decreased in MMSE total score (all p for trend <0.05). A non-linear dose-response relationship between urinary levels of CotGluc, HyPyBut, OHCotGluc or Cot and cognitive function (all overall p<0.05, non-linear p<0.05). Subgroup analysis showed that urinary levels of CotGluc, OHCotGluc or Cot were significantly negatively associated with cognitive function (all p for trend <0.05) among females and non-smokers. The findings highlight the public health implications of environmental tobacco smoke exposure, and effective interventions need to be performed for vulnerable populations.

Correlation of callosal angle at the splenium with gait and cognition in normal pressure hydrocephalus.

Idiopathic normal pressure hydrocephalus (iNPH) is characterized by ventricular enlargement that deforms the corpus callosum, making the callosal angle (CA) small. The authors aimed to evaluate the clinical usefulness of the CA in different planes in iNPH. Forty patients with iNPH were included in the study. As a control group, 241 patients with other neurological diseases and 50 healthy controls were included. The subjects had been seen at the authors' institutions from 2010 to 2020. The Timed Up and Go (TUG) test total time and Mini-Mental State Examination (MMSE) total score were evaluated. CAs were measured in the axial plane at the splenium and genu and in the coronal plane at the anterior commissure and posterior commissure by using 3-dimensional T1-weighted MR images. As other hydrocephalus parameters, the Evans index, frontal-occipital horn ratio, and third ventricular width were also measured in patients with iNPH. Associations between each CA or hydrocephalus parameter and clinical parameters were evaluated. The classification efficacy of each CA in differentiating between iNPH and other neurological diseases and healthy controls was evaluated. The CA at the splenium, but no other hydrocephalus parameters, was correlated with TUG total time or MMSE total score in patients with iNPH. Receiver operating characteristic analysis showed that a CA of 71.1° at the splenium has 90.0% sensitivity and 89.0% specificity in discriminating iNPH from other neurological diseases and healthy controls. Probabilistic tractography analysis showed that neuronal fibers via the splenium connect the superior parietal lobules, temporal lobes, and occipital lobes. The study results suggest that interhemispheric disconnections at the splenium are, at least in part, responsible for gait and cognitive disturbance in iNPH. The CA at the splenium is a unique morphological feature that correlates with gait and cognition in iNPH, and it is useful for discriminating iNPH from other neurological diseases and healthy controls.

Open RoAD: Design and baseline characteristics of an open‐label rollover study evaluating long‐term safety and tolerability of subcutaneous gantenerumab in participants with early Alzheimer’s disease

AbstractBackgroundGantenerumab, a human monoclonal antibody targeting aggregated beta‐amyloid (Abeta), is a potential disease‐modifying treatment for early (prodromal‐to‐mild) Alzheimer’s disease (AD). SCarlet RoAD (SR) (NCT01224106) and Marguerite RoAD (MR) (NCT02051608) were two Phase III trials which assessed the efficacy and safety of subcutaneous (SC), low‐dose gantenerumab in participants with prodromal and mild AD, respectively, for up to 2 years. Following a gap period gantenerumab treatment was continued with uptitration to a dose of 1,200 mg monthly in open‐label extensions (OLE), which demonstrated substantial Abeta removal by positron emission tomography without new or unexpected safety findings. Here, we describe the study design, present baseline characteristics, and safety data from an additional open‐label, multicenter, rollover study, Open RoAD (OR) (NCT04339413), collecting long‐term safety and tolerability data for gantenerumab in participants who completed the SR OLE or MR OLE.MethodParticipants who completed either OLE study and were treated with doses up to 1,200 mg of gantenerumab for up to 5 years continue to receive the same dose of SC gantenerumab (every 4 weeks [q4w]) for 2 additional years in OR. The primary objective is to evaluate long‐term safety and tolerability by assessing adverse events, including amyloid‐related imaging abnormalities, and injection‐site reactions. Exploratory efficacy objectives include Mini‐Mental State Examination (MMSE) total score. The long‐term effect of gantenerumab on pharmacodynamic measures and biomarkers will also be explored.Result Baseline characteristics Fifty‐nine participants from SR OLE and 56 participants from MR OLE received at least one dose of gantenerumab in OR. The median participant age at baseline was 78 years, and the majority of the participants were female (61%). Sixty‐seven percent of participants were apolipoprotein‐E‐e4 (APOE e4) carriers. The median total MMSE score at baseline was 16. Safety data will be presented. ConclusionThe RoAD studies are among the longest‐duration OLEs of an anti‐amyloid monoclonal antibody. Data from the OR study demonstrate that gantenerumab at doses of 1,200 mg administered SC q4w is well tolerated, with no new or unexpected safety findings in patients with early AD.

Impairment of cognitive functions in patients with chronic thromboembolic pulmonary hypertension before and after surgical treatment

To study cognitive functions in patients with chronic thromboembolic pulmonary hypertension (CTEPH) before and in the long-term after pulmonary thromboendarterectomy and to study factors that negatively affect cognitive status. One hundred and twenty-four patients with CTEPH were examined before and 6 months after surgery with an assessment of cognitive impairment using the Mini-Mental State Examination (MMSE). Multivariate regression analysis was used to identify factors affecting the MMSE indicators before and in the long-term postoperative periods. Initially, patients with CTEPH had a total MMSE score 23.8±1.1. Six months after surgery, the score was 26.1±1.9 (p<0.001). A history of stroke, disability, stress (loss of spouse), and a high Charleson comorbidity index were independent factors affecting MMSE score before surgery. After surgery, the total MMSE score was influenced by a history of stroke, stress (loss of spouse), residual pulmonary hypertension and atrial fibrillation in the early postoperative period. Cognitive impairment in the form of mild dementia was observed in patients with CTEPH before surgery. Six months after the operation, an improvement in cognitive status was revealed, which corresponded to moderate cognitive impairment. At the same time, no complete recovery of cognitive functions was recorded. Patients with CTEPH still experienced the greatest difficulties in the following areas: concentration and counting, memory. A history of stroke, disability, stress (loss of spouse), and a high comorbidity index are associated with a decrease in MMSE scores before surgery. Six months after surgery, MMSE score was affected by a history of stroke, stress (loss of spouse), residual pulmonary hypertension and atrial fibrillation in the early postoperative period.

Assessment of cognitive functioning using the Mini Mental State Examination in men with Alcohol and Crack Cocaine Use Disorder.

The consumption of substances has been associated with cognitive impairment. The Mini Mental State Examination (MMSE) is an easy-to-apply screening used to assess cognitive functions. Our aim was to evaluate the cognitive performance of individuals with alcohol and/or crack cocaine use disorder (AUD, CUD, and polysubstance use) using the MMSE, and to investigate the impact of substance use profile, and the moderation effect of educational level on MMSE performance. Cross-sectional study with 508 inpatient men, diagnosed with substance use disorders (245 with AUD, 85 with CUD and 178 with polysubstance use). Cognitive performance was assessed using the MMSE scale (total and composite scores). Individuals with AUD yielded worse MMSE total score and in the three MMSE components (p < 0.001, oral/written language comprehension, p < 0.001, attention/memory, and p=0.007, motor functions) when compared to individuals with polysubstance use. MMSE scores were positively correlated to education level (p < 0.017), but not associated with age, recent and years of drug use. Education level moderated the impact of substance use on MMSE performance, especially in total score and language comprehension composite score. Individuals with lower education levels (≤ 8 years) had worse performance than those with higher education (≥ 9 years), mainly in individuals with AUD (p < 0.001). Individuals with lower education level and alcohol use are more prone to present cognitive impairment than crack cocaine users, especially involving language aspects. A better-preserved cognitive function could impact treatment adherence and might guide the decision of therapeutic strategies.

Benefits of Cycling Wheelchair Training for Elderly with Physical Disability: A Prospective Cohort Study.

In order to investigate the effect of cycling wheelchair training as an exercise for aged 65+ disabled patients on cognitive function, quality of life, aerobic capacity and physiological parameters. Participants in nursing home performed cycling wheelchair training for 30 min a day, 5 days a week, for a total of 4 weeks. The main outcome measure was the short form 12 survey (SF-12). Other outcome measures included the Mini-Mental State Examination (MMSE), aero bike work rate test, resting blood pressure, and heart rate. In this study, 41 volunteers were recruited and no participants dropped out of the study voluntarily during training, and no serious adverse effect was identified. Physical and mental component summary total scores of SF-12 were significantly higher after training with statistical significance (p = 0.001). 8 subscales also showed significant improvements after training (p = 0.025 ~ <0.001). Total MMSE score has no difference before and after training. Attention/calculation (p = 0.018), short term memory (p = 0.041), and aerobic capacity (p < 0.001) as measured by subscales of MMSE and aero bike test showed marked improvements, while resting systolic blood pressure (p = 0.931) and heart rate (p = 0.793) did not change. Cycling wheelchair is practical for the disabled elderly to exercise, and a 4-week exercise program enhanced their quality of life and aerobic capacity.

Geo‐Cultural Influence on Change in CDR and MMSE Scores

AbstractBackgroundAlzheimer’s disease (AD) clinical trials are increasingly global. Most measures used were validated and standardized with North American, White, English‐speaking populations with limited consideration of cultural nuance. Prior research suggests that both the Clinical Dementia Rating (CDR) and Mini Mental State Examination (MMSE) are not free from cultural and linguistic influence. It is important to understand how geo‐cultural factors influence longitudinal change in scores on these measures, which is often used as the primary endpoint for study efficacy. In this study, we examined whether change in CDR and MMSE scores over one‐year follow‐up varied across geo‐cultural regions.MethodThis study included electronic CDR (eCDR) and electronic MMSE (eMMSE) data from four multi‐national AD clinical trials of subjects with prodromal to mild AD. Data were collected at screening and one‐year follow‐up from seven geo‐cultural regions: East Asia (n = 138); Eastern Europe (n = 170); Western Europe (n = 484); North America (n = 496); South America (n = 55); Middle East/Africa (n = 26); and Oceania (n = 26).ResultThe Kruskal–Wallis test found statistically significant variance in CDR‐Sum of Box (CDR‐SB) scores across geo‐cultural regions (p &lt;0.0001). Results of the Dunn’s test indicated mean change in CDR‐SB scores for South America was significantly lower than those for North America, Eastern Europe, Western Europe, and Mideast/Africa. Additionally, mean change in CDR‐SB scores for East Asia was significantly lower than those for Western and Eastern Europe. Change in MMSE total scores did not vary across geo‐cultural regions.ConclusionOur study found average change in CDR‐SB but not MMSE total scores differed significantly across geo‐cultural regions. CDR‐SB scores were relatively more stable in South America compared to most other regions, and in East Asia compared to Western/Eastern Europe. The CDR may be more susceptible to cultural factors due to its reliance on subjective information from caregivers, in contrast with the MMSE, a standardized, objective measure. Different social norms and expectations for aging, functional independence, and trial participation in these regions may have contributed to the variance. Future studies should examine if specific CDR or MMSE items are more contextually dependent on the local culture.