Purpose To systematically evaluate and quantify the effects of Tai Chi/Qigong (TCQ) on motor (UPDRS III, balance, falls, Timed-Up-and-Go, and 6-Minute Walk) and non-motor (depression and cognition) function, and quality of life (QOL) in patients with Parkinson’s disease (PD). Methods A systematic search on 7 electronic databases targeted clinical studies evaluating TCQ for individuals with PD published through August 2016. Meta-analysis was used to estimate effect sizes (Hedge’s g) and publication bias for randomized controlled trials (RCTs). Methodological bias in RCTs was assessed by two raters. Results Our search identified 21 studies, 15 of which were RCTs with a total of 755 subjects. For RCTs, comparison groups included no treatment (n=7, 47%) and active interventions (n=8, 53%). Duration of TCQ ranged from 2 to 6 months. Methodological bias was low in 6 studies, moderate in 7, and high in 2. Fixed-effect models showed that TCQ was associated with significant improvement on most motor outcomes (UPDRS III [ES=-0.444, p<.001], balance [ES=0.544, p<.001], Timed-Up-and-Go [ES=−0.341, p=.005], 6MW [ES=−0.293, p=.06]), falls [ES=−.403, p=.004], as well as depression [ES=−0.457, p=.008] and QOL [ES=−0.393, p<.001], but not cognition [ES= −0.225, p=.477]). I2 indicated limited heterogeneity. Funnel plots suggested some degree of publication bias. Conclusion Evidence to date supports a potential benefit of TCQ for improving motor function, depression and QOL for individuals with PD, and validates the need for additional large-scale trials.

Aging is the major risk factor for neurodegenerative diseases such as Alzheimer's disease, but little is known about the processes that lead to age-related decline of brain structures and function. Here we use RNA-seq in combination with high resolution histological analyses to show that aging leads to a significant deterioration of neurovascular structures including basement membrane reduction, pericyte loss, and astrocyte dysfunction. Neurovascular decline was sufficient to cause vascular leakage and correlated strongly with an increase in neuroinflammation including up-regulation of complement component C1QA in microglia/monocytes. Importantly, long-term aerobic exercise from midlife to old age prevented this age-related neurovascular decline, reduced C1QA+ microglia/monocytes, and increased synaptic plasticity and overall behavioral capabilities of aged mice. Concomitant with age-related neurovascular decline and complement activation, astrocytic Apoe dramatically decreased in aged mice, a decrease that was prevented by exercise. Given the role of APOE in maintaining the neurovascular unit and as an anti-inflammatory molecule, this suggests a possible link between astrocytic Apoe, age-related neurovascular dysfunction and microglia/monocyte activation. To test this, Apoe-deficient mice were exercised from midlife to old age and in contrast to wild-type (Apoe-sufficient) mice, exercise had little to no effect on age-related neurovascular decline or microglia/monocyte activation in the absence of APOE. Collectively, our data shows that neurovascular structures decline with age, a process that we propose to be intimately linked to complement activation in microglia/monocytes. Exercise prevents these changes, but not in the absence of APOE, opening up new avenues for understanding the complex interactions between neurovascular and neuroinflammatory responses in aging and neurodegenerative diseases such as Alzheimer’s disease.

Background Environmental factors are critical in the development of age-related cognitive decline and dementia. A western diet (WD) can cause nutrient deficiency and inflammation that could impact cognition directly. It is increasingly recognized that innate immune responses by brain myeloid cells, such as resident microglia, and infiltrating peripheral monocytes/macrophages may represent an essential link between a WD, cognitive decline, and dementia. Our previous data demonstrated that chronic consumption of a WD induced inflammation through brain myeloid cells in aging mice and a mouse model of Alzheimer’s disease (AD). However, the subtypes of myeloid cells that contribute to the WD-induced inflammation remain unclear. Methods C57BL/6J (B6), myeloid cell reporter mice (B6. Ccr2 RFP/+ Cx3cr1 GFP/+ ), and Ccr2 -deficient mice (B6. Ccr2 RFP/RFP ) were fed a WD or a control chow diet (CD) from 2 to 6 or 12 months of age. CD11b+CD45 lo and CD11b+CD45 hi cells from WD- and CD-fed B6 or Ccr2 -deficient mice were characterized using flow cytometry, RNA-sequencing, and immunofluorescence. Results Ccr2 ::RFP expressing myeloid cells were significantly increased in brains of WD- compared to CD-fed mice, but were not elevated in Ccr2 -deficient WD-fed mice. The percent of CD11b+CD45 hi cells was significantly increased in WD- compared to CD-fed mice. Comparison of RNA-sequencing data with immune cell data in ImmGen supports that CD11b+CD45 hi cells from WD-fed mice are enriched for peripheral monocytes and neutrophils. Ingenuity pathway analysis predicted these cells elicit proinflammatory responses that may be damaging to the brain. Using stringent criteria for gene expression levels between CD11b+CD45 hi and CD11b+CD45 lo cells, we identified approximately 70 genes that we predict are uniquely expressed in infiltrating cells, including Itgal , Trem1 , and Spp1 (osteopontin, OPN ) . Finally, we show a significantly greater number of OPN+IBA1– cells in WD- compared to CD-fed mice that we propose are activated neutrophils based on ImmGen data. OPN+IBA1– cells are not significantly increased in Ccr2 -deficient WD-fed mice. Conclusions These data further support the model that peripheral myeloid cells enter the brain in response to diet-induced obesity. Elucidating their contribution to age-related cognitive decline and age-related neurodegenerative diseases should offer new avenues for therapeutic intervention ...

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