A Combined Intervention of Aerobic Exercise and Video Game in Older Adults: The Efficacy and Neural Basis on Improving Mnemonic Discrimination.

BACKGROUND: Mnemonic discrimination is very vulnerable to aging. Previous studies have reported that aerobic exercise and enriched cognitive stimulation (e.g., video games) could improve mnemonic discrimination in older adults. The animal model suggested that combining the 2 training methods could result in a larger improvement. However, there is limited evidence on the potential superior efficacy of combined intervention with human participants. Moreover, the neural basis of this potential superior is poorly understood. METHODS: We conducted a 16-week intervention trial with 98 community-dwelling older adults assigned to one of the four groups (combined training, aerobic cycling alone, video game alone, or passive control). Mnemonic discrimination was measured as the primary behavioral outcome, hippocampal volume, and functional connectivity of the default mode network (DMN) were measured as neural indicators. RESULTS: Participants receiving the combined intervention demonstrated the largest effect size of mnemonic discrimination improvement. Magnetic resonance image results indicated aerobic exercising increased left hippocampal volume, while video-game training counteracted the decline of DMN functional connectivity with aging. The synergy of hippocampal structural and functional plasticity observed in the combined training group explained why the largest intervention benefits were obtained by this group. CONCLUSION: Despite the nonrandomized design (i.e., likely self-selection bias), our results provide new evidence that combined intervention of exercise and cognitive training is more effective than single intervention for older adults. Parallel to animal studies, aerobic exercise and the video game with enriched cognitive stimulation could induce hippocampal plasticity through separate structural and functional pathways. CLINICAL TRIALS REGISTRATION NUMBER: ChiCTR1900022702.

Computer Image Analysis Reveals C-Myc as a Potential Biomarker for Discriminating between Keratoacanthoma and Cutaneous Squamous Cell Carcinoma.

The distinction between Keratoacanthoma (KA) and Cutaneous Squamous Cell Carcinoma (cSCC) is critical yet usually challenging to discriminate clinically and histopathologically. One approach to differentiate KA from cSCC is through assessing the immunohistochemical staining patterns of the three indicators, ß-catenin, C-Myc, and CyclinD1, which are critical molecules that play important roles in the Wnt/ß-catenin signaling pathway. Ki-67, as a proliferation biomarker for human tumor cells, was also assessed as an additional potential marker for differentiating KA from cSCC. In this report, these four indicators were analyzed in 42 KA and 30 cSCC cases with the use of the computer automated image analysis system. Computer automated image analysis is a time-based and cost-effective method of determining IHC staining in KA and cSCC samples. We found that C-Myc staining was predominantly localized in the nuclei of basal cells within KA patients, whereas cSCC staining was predominantly localized in the nuclei of diffuse cells. This C-Myc staining pattern has a sensitivity of 78.6% and a specificity of 66.7% for identifying KA. Moreover, positive rates of distinct expression patterns of C-Myc and Ki-67 may also serve as a means to clinically distinguish KA from cSCC. Taken together, our results suggest that these markers, in particular C-Myc, may be useful in differentiating KA from cSCC.

KIBRA polymorphism modulates gray matter volume to influence cognitive ability in the elderly.

Genetic variation in the kidney and brain expressed protein (KIBRA) rs17070145 gene has been linked to episodic memory and cognitive aging; yet, the neural mechanism underlying this association remains to be fully understood. Using the magnetic resonance imaging (MRI) technique, this study investigated the effect of KIBRA polymorphism on gray matter volume in 37 healthy, Chinese adults from the older population. Voxel-based morphometry (VBM) analysis revealed that KIBRA gene selectivity influences the prefrontal cortex and the parahippocampal cortex. The gray matter volume (GMV) in these structures is significantly lower in KIBRA C-allele carriers than in TT carriers. Moreover, multi-voxel pattern correlation analysis revealed that decreased prefrontal GMV could in turn affect individual cognitive function in C-allele carriers; whereas, TT individuals utilized more integrated gray matter volume in whole-brain voxels to achieve relatively better cognitive function. Overall, the findings suggest that the KIBRA rs17070145 polymorphism modulates gray matter volume, which in turn further influences cognitive function in the elderly.

Long-Term Transcranial Direct Current Stimulation Does Not Improve Executive Function in Healthy Older Adults.

Background: Executive function tends to decline as people age. Transcranial direct current stimulation (tDCS) is assumed to have beneficial effects on various cognitive functions. Some prior investigations have shown that repeated sessions of tDCS enhance the executive function performance of healthy elderly people by mediating cognitive training gains. However, studies of the effect of long-term stimulation on executive function without cognitive training are absent. Objective: The purpose of this study was to explore whether the executive function of healthy older adults could be enhanced with long-term tDCS alone applied on the prefrontal cortex. Methods: Sixty-five cognitively normal older adults were enrolled and randomly assigned to two groups: an anodal tDCS group and a sham tDCS group. The participants in the two groups received anodal stimulation or sham stimulation over the left dorsolateral prefrontal lobe, for 30 min per day for 10 consecutive days. Executive function was tested before stimulation, immediately after stimulation and 3 months after stimulation. Three core components of executive function were tested using a two-back task for updating, a flanker task for inhibition, and a switching task for shifting. Results: Across the three tasks, we failed to discover any differences between the anodal and sham stimulation. Moreover, we found no statistically significant stimulation effect in the follow-up session. Conclusion: Our study does not support the assumption that multiple sessions of tDCS that are independent of cognitive training have a beneficial effect on executive function in healthy older adults, presumably because the effect of the stimulation lies in its amplification of training gains. It indicates that combining traditional cognitive training methods with brain stimulation may be a better approach to improve older adults' executive function.