Accumulating studies have suggested that targeting transcription factor EB (TFEB), an essential regulator of autophagy‐lysosomal pathway (ALP), is promising for the treatment of neurodegenerative disorders, including Alzheimer's disease (AD). However, potent and specific small molecule TFEB activators are not available at present. Previously, we identified a novel TFEB activator named curcumin analog C1 which directly binds to and activates TFEB. In this study, we systematically investigated the efficacy of curcumin analog C1 in three AD animal models that represent beta‐amyloid precursor protein (APP) pathology (5xFAD mice), tauopathy (P301S mice) and the APP/Tau combined pathology (3xTg‐AD mice). We found that C1 efficiently activated TFEB, enhanced autophagy and lysosomal activity, and reduced APP, APP C‐terminal fragments (CTF‐β/α), β‐amyloid peptides and Tau aggregates in these models accompanied by improved synaptic and cognitive function. Knockdown of TFEB and inhibition of lysosomal activity significantly inhibited the effects of C1 on APP and Tau degradation in vitro. In summary, curcumin analog C1 is a potent TFEB activator with promise for the prevention or treatment of AD.

BACKGROUND/OBJECTIVES Mind‐body exercise has positive effects on cognitive performance, according to clinical observation and experts’ recommendations. However, its potential benefits for the cognitive function of aging adults are uncertain and still lack systematic estimations. Therefore, we conducted a systematic review and meta‐analysis to evaluate the overall efficacy and effectiveness of mind‐body exercises for cognitive performance in aging individuals with or without cognitive impairment. DESIGN A systematic review and meta‐analysis. SETTING AND PARTICIPANTS We searched related trials through June 2018 from four databases: Medline, Embase, PsycINFO (all via Ovid), and the Cochrane Library/Central Register of Controlled Trials. MEASUREMENTS Methodological quality was assessed using the Cochrane Risk of Bias Tool. A meta‐analysis of comparative effects was performed using Review Manager v.5.3 software, and publication bias was examined using Egger's test. RESULTS A total of 32 randomized controlled trials with 3624 participants were ultimately included in this meta‐analysis. The results revealed that mind‐body exercises as a whole had benefits in improving global cognition compared with that of the control group (mean difference [MD] = 0.92; 95% confidence interval [CI] = 0.33‐1.51; p = .002) and were more effective than control interventions in promoting cognitive flexibility (MD = −8.80; 95% CI = −15.22 to −2.38; p = .007), working memory (MD = 0.32; 95% CI = 0.01‐0.64; p = .05), verbal fluency (standardized mean difference [SMD] = 0.27; 95% CI = 0.09‐0.45; p = .003), and learning (SMD = 0.24; 95% CI = 0.10‐0.39; p = .001) on cognitively intact or impaired older adults. In dose‐subgroup analysis, only moderate exercise intensity (60‐120 min per week) significantly increased global cognition scores compared with those of the control group (MD = 1.15; 95% CI = 0.34‐1.97; p = .006). CONCLUSION Mind‐body exercises, especially tai chi and dance mind‐body exercise, are beneficial for improving global cognition, cognitive flexibility, working memory, verbal fluency, and learning in cognitively intact or impaired older adults. Moderate intensity is recommended as the optimal dose for older adults. J Am Geriatr Soc 67:749–758, 2019.

Nenggui Xu and colleagues call for more effective evidence dissemination of and research into promising acupuncture therapies

Background The aim of this study was to assess the passive stiffness of the medial and lateral gastrocnemius (MG and LG), Achilles tendon (AT), and plantar fascia (PF) at different ankle and knee positions. Material/Methods Stiffness was assessed using a portable hand-held device (MyotonPRO). In 30 healthy participants (15 males, 15 females) with the knee fully extended or flexed 90°, stiffness of the MG, LG, AT, and PF was measured at 50° plantar flexion, 0° (neutral position), and 25° dorsiflexion (not for AT) of the ankle joint by passive joint rotation. Results With the knee fully extended, passive dorsiflexion caused significant increase in muscle stiffness ( P <0.001), whereas AT and PF stiffness increased with passive ankle dorsiflexion regardless of knee position ( P <0.001). Increased stiffness was observed in MG compared to LG ( P <0.001) and at the 3-cm site of AT compared to the 6-cm site ( P <0.05). Stiffness was greater in LG compared to MG at −50° plantar flexion ( P <0.001) and was greater in MG compared to LG at 25° dorsiflexion ( P <0.05). Stiffness of AT increased in a distal-to-proximal pattern: 0 cm >3 cm >6 cm ( P <0.001). Conclusions Stiffness assessed by use of the MyotonPRO was similar assessments using other techniques, suggesting that the MyotonPRO is capable of detecting the variations in stiffness of MG, LG, AT, and PF at different ankle and knee positions.

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