Recent evidence demonstrates that age and disease-related decline in cognition depends not only upon degeneration in brain structure and function, but also on dietary intake and nutritional status. Memory, a potential preclinical marker of Alzheimer’s disease, is supported by white matter integrity in the brain and dietary patterns high in omega-3 and omega-6 polyunsaturated fatty acids. However, the extent to which memory is supported by specific omega-3 and omega-6 polyunsaturated fatty acids, and the degree to which this relationship is reliant upon microstructure of particular white matter regions is not known. This study therefore examined the cross-sectional relationship between empirically-derived patterns of omega-3 and omega-6 polyunsaturated fatty acids (represented by nutrient biomarker patterns), memory, and regional white matter microstructure in healthy, older adults. We measured thirteen plasma phospholipid omega-3 and omega-6 polyunsaturated fatty acids, memory, and regional white matter microstructure in 94 cognitively intact older adults (65 to 75 years old). A three-step mediation analysis was implemented using multivariate linear regressions, adjusted for age, gender, education, income, depression status, and body mass index. The mediation analysis revealed that a mixture of plasma phospholipid omega-3 and omega-6 polyunsaturated fatty acids is linked to memory and that white matter microstructure of the fornix fully mediates the relationship between this pattern of plasma phospholipid polyunsaturated fatty acids and memory. These results suggest that memory may be optimally supported by a balance of plasma phospholipid omega-3 and omega-6 polyunsaturated fatty acids through the preservation of fornix white matter microstructure in cognitively intact older adults. This report provides novel evidence for the benefits of plasma phospholipid omega-3 and omega-6 polyunsaturated fatty acid balance on memory and underlying white matter microstructure.

Superficial temporal artery-middle cerebral artery (STA-MCA) has been used for the treatment of occlusive cerebrovascular disease including moyamoya disease. The effect of STA-MCA bypass depends not only on the patency of anastomosis, but also on integrity and functional capacity of the donor artery. In the present prospective study, we investigated the effect of extensive stripping STA adventitia and fasciae on hemodynamic function in STA-MCA bypass of moyamoya disease patients. Twenty patients (n=8 in control group, n=12 in stripping group) of moyamoya disease were subjected to STA-MCA end-to-side direct anastomosis. Perfusion unit (PU) values of the cortex were measured and recorded using a Laser Doppler flowmetry (LDF) for 5 days. Computed tomography perfusion was performed to determine blood flow before and after bypass. No patient experienced significant neurologic deficits associated with neurosurgical complications. LDF demonstrated that adventitial stripping group had higher cerebral blood flow increase than control group. The adventitia stripping group tends to have higher rate of increased cerebral perfusion after bypass than non-stripping group. Furthermore, the ultrasound examination at 3 days after bypass demonstrated that the adventitial stripping group has a tendency of bigger STA and higher peak systolic velocity than control group. Our result suggests that stripping adventitia of STA improves hemodynamics of STA-MCA bypass in moyamoya disease.

Limb Remote ischemic conditioning (LRIC) has been proved to be a promising neuroprotective method in white matter lesions after ischemia; however, its mechanism underlying protection after chronic cerebral hypoperfusion remains largely unknown. Here, we investigated whether LRIC promoted myelin growth by activating PI3K/Akt/mTOR signal pathway in a rat chronic hypoperfusion model. Thirty adult male Sprague Dawley underwent permanent double carotid artery (2VO), and limb remote ischemic conditioning was applied for 3 days after the 2VO surgery. Cognitive function, oligodendrocyte counts, myelin density, apoptosis and proliferation activity, as well as PTEN/Akt/mTOR signaling activity were determined 4 weeks after treatment. We found that LRIC significantly inhibited oligodendrocytes apoptosis (p<0.05), promoted myelination (p<0.01) in the corpus callosum and improved spatial learning impairment (p<0.05) at 4 weeks after chronic cerebral hypoperfusion. Oligodendrocytes proliferation, along with demyelination, in corpus callosum were not obviously affected by LRIC (p>0.05). Western blot analysis indicated that LRIC upregulated PTEN/Akt/mTOR signaling activities in corpus callosum (p<0.05). Our results suggest that LRIC exerts neuroprotective effect on white matter injuries through activating PTEN/Akt/mTOR signaling pathway after chronic cerebral hypoperfusion.

Early readmission following hip fracture (HFx) is associated with high morbidity and mortality. We conducted a survival analysis of patients with readmission within 1 year after HFx to elucidate the trend and predictors for readmission. We used Taiwan National Health Insurance Database to recruit HFx patients who underwent operations between 2000 and 2009. Patients < 60 years; with pathological fractures; involved in major traffic accidents; with previous pelvis, femur, and hip operations; or who died during the index admission were excluded. We used the Chi-square test, logistic regression, Kaplan-Meier method, and Cox proportional hazards model to analyze variables, including age, gender, hospital stay duration, index admission time, and comorbidity on readmission. 5,442 subjects (61.2% female) met the criteria with mean age of 78.8 years. Approximately 15% and 43% HFx patients were readmitted within 30 days (early) and between 30 days and 1 year (late) after discharge, respectively. Highest readmission incidence was observed within the first 30 days. Most common causes of readmission in early and late groups were respiratory system diseases and injuries, respectively. Cox model showed male, old age, hospital stay > 9 days, Charlson Comorbidity Index ≥ 1, index admission during 2000–2003, and internal fixation of HFx were independent predictors of readmission. One-year mortality of the early and the late readmission groups was 44.9% and 32.3%, much higher than overall mortality which was 16.8%. Predictive factors for readmission within 1 year included male, old age, comorbidities, and longer hospital stay. One-year mortality in readmitted patients was significantly higher. HFx patients with these factors need careful follow-up, especially within 30 days after discharge.

Erythropoietin (EPO) promotes oligodendrogenesis and attenuates white matter injury in neonatal rats. However, it is unknown whether this effect extends to adult mice and whether EPO regulate microglia polarization after ischemic stroke. Male adult C57BL/6 mice (25–30g) were subjected to 45 min of middle cerebral artery occlusion (MCAO). EPO (5000 IU/kg) or saline was injected intraperitoneally every other day after reperfusion. Neurological function was evaluated using the rotarod test at 1, 3, 7 and 14 days after MCAO. Brain tissue loss volume was determined by hematoxylin-eosin staining. Immunofluorescence staining and Western blot were also used to assess the severity of white matter injury and phenotypic changes in microglia/macrophages. Bromodeoxyuridine (BrdU) was injected intraperitoneally daily for 1 week to analyze the number of newly proliferating glia cells (oligodendrocytes, microglia, and astrocytes). We found that EPO significantly reduced Brain tissue loss volume, ameliorated white matter injury, and improved neurobehavioral outcomes at 14 days after MCAO (P<0.05). In addition, EPO also increased the number of newly generated oligodendrocytes and attenuated the rapid hypertrophy and hyperplasia of microglia and astrocytes after ischemic stroke (P<0.05). Furthermore, EPO reduced M1 microglia and increased M2 microglia (P<0.05). Taken together, our results suggest that EPO treatment improves white matter integrity after cerebral ischemia, which could be attributed to EPO attenuating gliosis and facilitating the microglial polarization toward the beneficial M2 phenotype to promote oligodendrogenesis.

Elderly pneumonia patients have various underlying diseases and social backgrounds, and it is difficult to predict their mortality using the current severity assessment tools. However, aspiration is a risk factor for mortality in pneumonia patients. In the evaluation of aspiration, endoscopic and video fluoroscopic methods are reliable but cannot be performed in all pneumonia patients. We evaluated the significance of the Mann Assessment of Swallowing Ability (MASA) in these patients. This study was prospectively performed between December 2014 and June 2015, and all adult hospitalized patients with pneumonia were consecutively enrolled. The MASA score was evaluated soon after admission. The outcome measures were in-hospital mortality, a recurrence of pneumonia within 30 days, 6-month mortality, and the detection of antibiotic-resistant bacteria. A total of 153 patients were ultimately included. The proportion of in-hospital mortality was greater among the severe MASA score patients than normal score patients (p < 0.01), as was the proportion of recurrence of pneumonia (p < 0.01) and 6-month mortality (p < 0.01). In addition, patients with a moderate MASA score more often experienced recurrence of pneumonia than normal score patients (p < 0.05). Furthermore, patients with a mild MASA score more often experienced recurrence of pneumonia (p < 0.01) and 6-month mortality (p < 0.05) than normal score patients. The areas under the curve were 0.74 (95% confidence interval [CI], 0.67-0.82) for in-hospital mortality, 0.75 (95% CI, 0.68-0.82) for recurrence of pneumonia, 0.72 (95% Cl, 0.64-0.81) for 6-month mortality, and 0.60 (95% CI, 0.46-0.73) for detection of antibiotic-resistant bacteria. A multivariate analysis showed an abnormal MASA score to be an independent risk factor for the recurrence of pneumonia (p = 0.001) and 6-month mortality (p = 0.005). The MASA is useful for predicting the mortality and recurrence of pneumonia in elderly patients.

Heart failure (HF) is one of the most frequent cause of hospitalization in elderly and often coexists with concurrent geriatric syndromes, like cognitive disturbances; various pathophysiological mechanisms are shared by HF and cognitive decline, notably a substrate of low-grade inflammation. We investigated whether SNPs in the purinergic receptor (P2X₇R) and apolipoprotein (APO) E genes, both involved in a series of inflammatory responses, are associated to HF or cognitive impairment and are able to predict post-discharge mortality in the elderly. We prospectively analyzed 198 patients (age 85 ± 8 years, predominantly females) admitted to a Geriatric unit for acute HF, whose diagnosis was based on clinical signs, brain natriuretic peptide (BNP) values and ecocardiography in uncertain diagnosis (BNP values between 100 and 400 pg/mL); cognitive performance was assesed by Short Portable Mental Status Questionnaire (SPMSQ). In all the participants, SNPs rs208294 and rs3751143 for P2X₇R gene and rs429558 and rs7412 for APOE gene were assessed. Information on all-cause mortality was adjudicated by medical records review 36 months after discharge. We found no relationship between P2X₇R and APOE polymorphisms and 36-month post-discharge mortality; a better outcome for overall survival was observed in patients with BNP values below the median (281 pg/mL) (p=0.002) persisting after adjustment for renal function and age, and in those with cognitive impairment (p<0.001). Patients harboring APOE-ε4 genotype showed higher BNP concentrations than noncarriers (1289.9 ± 226.9 vs 580.5 ± 90.2 pg/mL respectively,p=0.004), whereas none of the studied SNPs were associated to impairment in cognitive performance. In conclusion, neither P2X₇R or APOE genotype seem to predict long-term mortality in elderly patients. Interestingly, APOE-ε4 genotype was associated to higher BNP values, suggesting a putative interaction between genetic and biochemical markers in identifying people at risk for HF.

Minimal hepatic encephalopathy (MHE) is induced by elevated intracranial dopamine (DA). The relationship of the Shh pathway with memory loss in MHE, however, is elusive. In the current study, rats with MHE induced with DA displayed downregulation of the Shh pathway. Additionally, injection of Shh into MHE/DA-treated rats reversed downregulation of BDNF/NT3, whereas administration of cyclopamine (Cyc) enhanced the inhibition of expression of BDNF/NT3. Furthermore, naringin (Nrg) substantially prevented cognitive impairment in MHE/DA-treated rats and upregulated the Shh pathway, paralleling the elevated expression of BDNF/NT3. Overall, our results indicate that the Shh pathway can induce the expression of BDNF/NT3, and DA causes memory loss by inactivation of Shh pathway signaling to BDNF/NT3 in MHE rats, which is reversed by Nrg. Our study may provide new theory basis of pathogenesis and therapeutic target of MHE.

Oxidative stress and iron accumulation are tightly associated with neurodegenerative diseases. Mitochondrial ferritin (FtMt) is identified as an iron-storage protein located in the mitochondria, and its role in regulation of iron hemeostasis in neurodegenerative diseases has been reported. However, the role of FtMt in hydrogen peroxide (H₂O₂)-induced oxidative stress and iron accumulation in neuronal cells has not been studied. Here, we overexpressed FtMt in neuroblastoma SH-SY5Y cells and induced oxidative stress by treating with extracellular H₂O₂. We found that overexpression of FtMt significantly prevented cell death induced by H₂O₂, particularly the apoptosis-dependent cell death. The protective effects involved inhibiting the generation of cellular reactive oxygen species, sustaining mitochondrial membrane potential, maintaining the level of anti-apoptotic protein Bcl-2, and inhibiting the activation of pro-apoptotic protein caspase 3. We further explored the mechanism of these protective effects and found that FtMt expression markedly altered iron homeostasis of the H₂O₂ treated cells as compared to that of controls. The FtMt overexpression significantly reduced cellular labile iron pool (LIP) and protected H₂O₂-induced elevation on LIP. While in H₂O₂ treated SH-SY5Y cells, the increased iron uptake and reduced iron release, in correlation with levels of DMT1(-IRE) and ferroportin 1, resulted in heavy iron accumulation, the FtMt overexpressing cells didn’t show any significant changes in levels of iron transport proteins and in the level of LIP. These results implicate a neuroprotective role of FtMt on H₂O₂-induced oxidative stress, which may provide insights into the treatment of iron accumulation associated neurodegenerative diseases.

The lack of data on lung function decline in the aging process as well as the lack of gold standards to define obstructive and restrictive respiratory disease in older people point out the need for a multidimensional assessment and interpretation of the aging airways. By integrating clinical data together with morphologic and morphometric findings clinicians can assess the airways with a more comprehensive perspective, helpful in the interpretation of the “grey zone” between normal aging and disease. This review focuses on the value of a multidimensional approach in the study of the aging airways, including clinical findings, respiratory function tests, and imaging as parts of a whole. Nowadays this multidimensional diagnostic approach can be used in daily clinical practice. In next future, it can be implemented by the analysis of exhaled gases, post-processing imaging techniques, and genetic analysis, that will hopefully reduce the gaps in knowledge of normal aging and airway disease in older people.

As with many age-related diseases including vascular dysfunction, age is considered an independent and crucial risk factor. Complicated alterations of structure and function in the vasculature are linked with aging hence, understanding the underlying mechanisms of age-induced vascular pathophysiological changes holds possibilities for developing clinical diagnostic methods and new therapeutic strategies. Here, we discuss the underlying molecular mediators that could be involved in vascular aging, e.g., the renin-angiotensin system and pro-inflammatory factors, metalloproteinases, calpain-1, monocyte chemoattractant protein-1 (MCP-1) and TGFβ-1 as well as the potential roles of testosterone and estrogen. We then relate all of these to clinical manifestations such as vascular dementia and stroke in addition to reviewing the existing clinical measurements and potential interventions for age-related vascular dysfunction.

Neurodegenerative diseases are a heterogeneous, mostly age-associated group of disorders characterized by progressive neuronal loss, the most prevalent being Alzheimer disease. It is anticipated that, with continuously increasing life expectancy, these diseases will pose a serious social and health problem in the near feature. Meanwhile, however, their etiology remains largely obscure even though all possible novel clues are being thoroughly examined. In this regard, a concept has been proposed that p53, as a transcription factor controlling many vital cellular pathways including apoptosis, may contribute to neuronal death common to all neurodegenerative disorders. In this work, we review the research devoted to the possible role of p53 in the pathogenesis of these diseases. We not only describe aberrant changes in p53 level/activity observed in CNS regions affected by particular diseases but, most importantly, put special attention to the complicated reciprocal regulatory ties existing between p53 and proteins commonly regarded as pathological hallmarks of these diseases, with the ultimate goal to identify the primary element of their pathogenesis.