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.

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.

Cholinesterase inhibitors and memantine for Parkinson's disease dementia and Lewy body dementia: A meta-analysis.

Recently, several randomized controlled trials on the use of cholinesterase inhibitors or memantine as treatments for cognitive impairment in Parkinson's disease (CIND-PD), Parkinson's disease with dementia (PDD) and dementia with Lewy bodies (DLB) were completed. The present study provided a meta-analysis of these studies to evaluate the efficacy of cholinesterase inhibitors and memantine on CIND-PD, PDD and DLB. The Cochrane Library, Pubmed, Embase and Web of Science databases were searched to retrieve eligible studies. As primary efficacy outcomes, cognitive function, global impression, behavioral symptoms and motor function were selected, while falling and adverse events were regarded as safety outcomes. Of note, domain-specific cognitive function was assessed as a primary efficacy outcome and falling as a safety outcome, which, to the best of our knowledge, has not been studied previously in CIND-PD, PDD and DLB. A total of 15 trials were included in the present meta-analysis. The results revealed that treatment with cholinesterase inhibitors resulted in improvements in cognitive function, the clinician's global impression, behavioral symptoms and motor function, in accordance with the results of previous studies. Furthermore, it was revealed that cholinesterase inhibitors had a significant effect on attention, processing speed, executive functions, memory and language; however, they did not improve visuospatial cognition compared with placebos. Memantine had a significant effect on attention, processing speed and executive functions. In addition, cholinesterase inhibitors and memantine did not significantly reduce falling. It was demonstrated that an increased number of adverse events occurred in the pooled cholinesterase inhibitors and memantine group, compared with that in the placebo group (risk ratio (RR)=1.09; 95% confidence interval (CI): 1.04-1.16; P=0.001); however, in the subgroup analysis, only the rivastigmine group experienced significantly more adverse events than the placebo group (85 vs. 73%; RR=1.18; 95% CI: 1.08-1.29; P=0.0001), but donepezil and memantine did not produce any significant adverse events. In conclusion, cholinesterase inhibitors and memantine have an effect not only on global cognitive function and motor function, but also on attention, processing speed, executive functions, memory and language. However, careful monitoring of the side effects of rivastigmine may be required. Further clinical trials are required to verify these conclusions.