The mitochondria-targeted small molecule SS31 delays progression of behavioral deficits by attenuating ß-amyloid plaque formation and mitochondrial/synaptic deterioration in APP/PS1 mice.

Alzheimer's disease (AD) is a common neurodegenerative disorder characterized by progressive cognitive dysfunction and an impaired ability to carry out daily life functions. Mitochondrial dysfunction and ß-amyloid (Aß) deposition are the most common causes of AD. Antioxidants have been shown to delay brain aging and AD development; however, it remains unknown whether the antioxidant peptide SS31 can protect mitochondrial and synaptic function and delay the progression of behavioral deficits in early-stage AD in vivo. Therefore, in this study we compared mitochondrial and synaptic changes, as well as the protective effects of SS31, in APP/PS1 transgenic mice and C57BL/6J control mice. The APP/PS1 transgenic mice exhibited elevated expression of Aß40/Aß42 and mitochondrial fission protein DLP1 and reduced expression of synaptophysin (SYN) and postsynaptic density protein 95 (PSD95) reductions, as well as increased levels of neuronal apoptosis and ROS in the hippocampus, and long-term treatment with SS31 reversed these effects. Furthermore, the cognitive impairments observed in APP/PS1 transgenic mice were reversed by SS31 treatment. Our findings show that SS31 lowers ROS and Aß levels, protecting mitochondrial homeostasis and synaptic integrity, and ultimately improving behavioral deficits in early-stage AD. This suggests that SS31 is a potential pharmacological agent for treating or slowing the progression of AD.

Trends in cognitive function assessed by a battery of neuropsychological tests after mild acute ischemic stroke.

OBJECTIVE: The aim of this study is to investigate the domain-specific trends of cognitive function up to 12 months after mild acute ischemic stroke. METHODS: Enrolment of consecutive cohort of patients with mild acute ischemic stroke with recorded clinical characteristics and extensive neuropsychological assessments, including five cognitive domains. The Montreal cognitive assessment of the Beijing version (MoCA-Bj) was used to assess overall cognition. All patients completed all domain-specific examinations were categorised into three groups according to the time between the stroke onset and neuropsychological profiling, the time duration including less than one month (n = 174), one month to six months (n = 65) and over six months (n = 39). RESULTS: The final cohort consisted of 278 patients. The executive (χ2 = 6.95, P<0.05) and memory dysfunctions (χ2 = 9.6, P<0.01) showed strong improvement, especially in executive function, which prevalence was 48.85% at <1- month group and 25.64% at >6 months group. The prevalence of attention and information processing also had a declining trend, the differences, however, were not statistically significant (χ2 = 0.23 and 2.25, respectively, P>0.05). There was no significant change in language function (χ2 = 0.46, P>0.05) and the MoCA (χ2 = 0.59, P>0.05) at 3-time point groups. In 195 first-ever stroke patients, the results of memory (χ2 = 6.94 P<0.05) and executive dysfunctions (χ2 = 6.25 P<0.05) also showed significant improvement. CONCLUSION: There is varying degree of improvement tendency in executive and memory dysfunctions after mild acute ischemic stroke. Early cognitive assessments after mild acute ischemic stroke do not reflect the cognitive level of stable period.

Assessing executive function following the early stage of mild Ischemic stroke with three brief screening tests.

OBJECTIVE: Executive dysfunction following stroke is well documented, but less is known about whether it occurs in mild stroke patients. The purpose of the study was to investigate executive impairment in this population and explore the correlation between executive function tests and cognitive tests of other domains. METHODS: Cross-sectional study was undertaken to compare 139 mild ischemic stroke patients (National Institute of Health Stroke Scale (NIHSS) ≤ 7) aged 40-80 with 131 normal controls matched age, gender and levels of education. All participants were administered a neuropsychological test battery including three measures of executive functioning: Clock Drawing Test (CDT), Trial Making Test-A and B (TMT-A and B), and Stroop Color Word Test (SCWT). The CDT was evaluated using three quantitative scoring rubrics, with a total score of 3,10,18, respectively and a qualitative scoring method with six types of errors. Spearman's correlations were made to analyze the correlation between executive function tests and other neuropsychological tests. RESULTS: Control group performed better than stroke group on most executive function tests at a statistical significance. Qualitative CDT showed that errors of "graphic difficulties", "conceptual deficits" and "spatial and/or planning deficits" occurred frequently in the early stage of mild stroke. Correlation data clarified that among the executive function tests, time for TMT-B correlated with global cognition most. CONCLUSION: Executive dysfunction is common following even mild strokes, and that relatively brief measures such as CDT, TMT and SCWT can be employed for it before discharge as part of rehabilitation planning.

Chinese version of the auditory verbal learning test: normative study and clinical applications in Chinese-speaking population in Shijiazhuang city.

OBJECTIVE: The purposes were to establish standardized values for the Auditory Verbal Learning Test (AVLT) in the communities of Shijiazhuang city (China), with particular focus on the influences of age, education and sex, and to detect the discriminant validity data of the AVLT in patients with acute ischemic stroke (AIS). METHODS: 406 Chinese-speaking subjects (age: 50-84 years old) from Shijiazhuang city, were brought into this study. Using linear regression analyses, standardized values were developed for three variables of interest, including scores on short-term memory (sum of AVLT trials 1-3), delayed recall (AVLT trial 4), and an index representing recognition memory corrected for false-positive identifications (AVLT trial 5). 177 patients with AIS were included to probe the discriminant validity of the AVLT. RESULTS: The linear regression analysis showed statistically significant effect of age and sex on all trials of the AVLT. Years of education contributed significantly to trial 1-3 and trial 4 but not trial 5. Based on the results obtained, trail 1-3 and trail 4 of AVLT norms were stratified by age (3 strata), education (2 strata), and sex (2 strata). Trail 5 norms were stratified by age (3 strata) and sex (2 strata). Moreover, AIS groups performed significantly worse on most AVLT trials than matched cognitively healthy controls. CONCLUSIONS: Normative data stratified by age, education and sex for the Chinese-speaking community-residents in Shijiazhuang was presented for use in research and clinical settings. The AVLT measures adequately differentiated between the cognitive performance (especially memory decline) of healthy adults and patients with AIS.

The montreal cognitive assessment and mini-mental state examination visuoexecutive subtests in acute ischemic stroke patients and their correlations with demographic and clinical factors.

Visuoexecutive impairment is common among acute ischemic stroke patients. This study aimed to examine the ability of the Montreal Cognitive Assessment (MoCA) and Mini-Mental State Examination (MMSE) visuoexecutive subtests to detect visuoexecutive abnormality in acute ischemic stroke patients and to identify the predictors for their impairments. 336 patients who completed the MMSE and MoCA were enrolled in this study. We compared the proportion of participants with incorrect MoCA visuoexecutive tasks and MMSE pentagon copying. Multivariate logistic regression analysis was used to evaluate the associations between the visuoexecutive dysfunction and demographic and clinical characteristics in the samples. Among all the participants, the MoCA detected more visuoexecutive dysfunction than the MMSE (88.69% vs. 45.83%, respectively; p < 0.001). The predictors identified by the univariate analysis included the factors of gender, age, educational level, smoking, alcohol consumption, Oxfordshire Community Stroke Project (OCSP), previous strokes, initial NIHSS score and number of old lacunar infarctions, while from the multivariate logistic regression analysis, the factors of age, educational level, NIHSS score, previous strokes and number of old lacunar infarctions served as predictive factors for the visuoexecutive impairment in acute stroke patients. In conclusion, visuoexecutive impairment is associated with the factors of the educational level, stroke severity, stroke history and number of old lacunar infarctions. Our findings may guide the clinicians to intervene the risks for the patients at an early stage after stroke and form the basis for good rehabilitation plans.

Clock-drawing test: Normative data of three quantitative scoring methods for Chinese-speaking adults in Shijiazhuang City and clinical utility in patients with acute ischemic stroke.

OBJECTIVE: The clock-drawing test (CDT) is a widely used screening tool for detecting cognitive decline. However, normative data for Chinese individuals are scarce. Our study aimed to provide standardized values for the three quantitative CDT scoring methods that were tailored for Chinese-speaking adults in Shijiazhuang City and explore the discriminant validity of the CDT scores in patients with acute ischemic stroke. METHODS: We conducted the CDT among 418 healthy individuals aged between 35 and 84 years. The CDT was administered and scored by five raters using the method derived from the Montreal Cognitive Assessment (MoCA), Rouleau's, and Babins' scoring systems. The influence of age, education, and sex on the performance in the CDT was analyzed. Furthermore, 336 patients with acute ischemic stroke were enrolled to explore the discriminant validity of CDT scores. RESULTS: In all three scoring systems, CDT scores were significantly correlated with age and years of education but not with sex. Normative data stratified for age and years of education were established. Interrater and intersystem reliability were high in our study. CDT total scores and subscores showed significant differences between stroke patients and healthy individuals. CONCLUSIONS: Our study provides CDT normative data using three quantitative scoring methods for Chinese-speaking adults in Shijiazhuang City. Age and education level were the key factors that affected the CDT scores. CDT total scores and subscores provided good discriminant validity for patients with acute ischemic stroke.