Shifting from Declines to Improvements: Associations between a Meaningful Walking Speed Change and Cognitive Evolution over Three Years in Older Adults

Background

Although the close relationship between mobility and cognitive declines is well-known, literature has very little questioned whether improvement in walking speed over time could be associated with improvements in cognitive functions. The objective of this study was to examine the associations between a clinically meaningful improvement in walking speed and global and specific cognitive changes in older adults. Design: Prospective cohort study.

Setting

Multidomain Alzheimer Preventive Trial (MAPT) study.

Participants

Three-hundred participants from the control group of the MAPT study (mean age 74.8 ± 4.2; 57% women).

Measurements

The 4-m usual walking speed, global cognition, memory, executive functions, and processing speed measures were collected at baseline, and at 6, 12, 24 and 36 months. Participants were categorized into three groups according to their walking speed change over the three-year study: 1/ Non-Improvers (participants not presenting an increase ≥0.05m/sec on walking speed; n=138); 2/ Improvers (increase ≥0.05m/sec; n=40); Cyclic (≥0.05m/sec improvement at some time points without maintaining it through the whole period; n=122).

Results

Adjusted mixed-effect linear regressions revealed that walking speed improvers did not significantly differ from participants who never or temporarily improved their walking speed on all of global and specific cognitive functions over three years. Nevertheless, a sensitivity analysis (excluding participants with a nonclinical walking speed improvement) indicated specific cognitive trajectories per group associated with better episodic memory scores for Improvers compared to non-improvers (β=2.41, 95% CI=.12 - 4.71; p=.039).

Conclusion

This study found that the overtime trajectories of cognitive functions did not differ as a function of clinically meaningful walking speed changes in older adults. Nevertheless, secondary analyses provided new insights on the relationship between walking speed and specific cognitive functions. The novelty of this approach (switching from declines to improvements) should be considered in future large-scale, observational longitudinal studies.

     

Predictors and Outcomes of Renal Replacement Therapy After Left Ventricular Assist Device Implantation

ObjectiveTo examine the frequency and outcomes of patients requiring renal replacement therapy (RRT) early after left ventricular assist device (LVAD) implantation.Patients and MethodsWe examined use of in-hospital RRT and outcomes in consecutive adults who underwent continuous-flow LVAD implantation from February 15, 2007, through August 8, 2017. Logistic regression was used to examine predictors of RRT. The associations of RRT with outcomes were examined using Cox proportional hazards regression.ResultsOf 354 patients who underwent LVAD implantation, 54 (15%) required in-hospital RRT. Patients receiving RRT had higher preoperative Charlson Comorbidity Index values (median, 5 vs 4; P=.03), Model for End-Stage Liver Disease scores (mean, 19.0 vs 14.5; P<.001), right atrial pressure (mean, 19.1 vs 13.4 mm Hg; P<.001), and estimated 24-hour urine protein levels (median, 357 vs 174 mg; P<.001) and lower preoperative estimated glomerular filtration rate (eGFR) (median, 43 vs 57 mL/min; P<.001) and measured GFR using ¹²⁵I-iothalamate clearance (median, 33 vs 51 mL/min; P=.001) than those who did not require RRT. Approximately 40% of patients with eGFR less than 45 mL/min/1.73 m² and 24-hour urine protein level greater than 400 mg required RRT vs 6% with eGFR greater than45 mL/min/1.73 m² and without significant proteinuria. Lower preoperative eGFR, higher estimated 24-hour urine protein level, higher right atrial pressure, and longer cardiopulmonary bypass time were independent predictors of RRT after LVAD implantation. Of patients requiring in-hospital RRT, 18 (33%) had renal recovery, 18 (33%) required outpatient hemodialysis, and 18 (33%) died before hospital discharge. After median (Q1, Q3) follow-up of 24.3 (8.9, 49.6) months, RRT was associated with increased risk of death (adjusted hazard ratio [HR], 2.86; 95% CI, 1.90-4.33; P<.001) and gastrointestinal bleeding (adjusted HR, 4.47; 95% CI, 2.57-7.75; P<.001).ConclusionIn-hospital RRT is associated with poor prognosis after LVAD. A detailed preoperative assessment of renal function before LVAD may be helpful in risk stratification and patient selection.     

Hyperhomocysteinemia exacerbates the development of intimal hyperplasia in Sprague-Dawley rats: Alleviation by rosiglitazone

The amino acid intermediate homocysteine (Hcy) is formed during the metabolism of methionine to cysteine. Hyperhomocysteinemia (HHcy) is recognized as an independent risk factor for coronary atherosclerosis. The circulating levels of total Hcy (tHcy) can increase due to intake of foods rich in methionine or deficiencies of vitamins such as folate, pyridoxine and cyanocobalamin, which are required for the metabolism of Hcy. In addition, mutations in the genes coding for Hcy metabolizing enzymes can contribute to an increase in tHcy levels. Clinical and epidemiological studies have shown that an elevated level of tHcy measured in serum or plasma is a strong predictor of cardiovascular disease risk, which appears to be greatest in patients who have HHcy following a methionine load. Intimal hyperplasia (IH) (intima/media [I/M] ratio) is the universal response of a vessel to injury and may result in vasoconstriction when left unattended. The effect of dietary HHcy on balloon catheter-injured carotid artery and its modulation (if any) by the peroxisome proliferator-activated receptor agonist gamma rosiglitazone was evaluated in 12-week-old female Sprague-Dawley rats fed either a control diet or a diet containing 1% L-methionine. Once the rats were established on the diet, the group that was fed 1% L-methionine was further subdivided and either given an aqueous preparation of 3 mg/kg/day rosiglitazone or the vehicle via oral gavage for one week. This was followed by surgically injuring the left carotid artery using a Maverick Over-The-Wire catheter (2.0 mm × 20 mm, 3.2F; Boston Scientific, USA). The rats were continued on their respective diets and drug regimen for 21 days postsurgery. On day 22 of the procedure, the rats were sacrificed for collection of blood, the carotid arteries and liver for biochemical and histological evaluation. Compared with controls there was a significant increase in both tHcy levels and I/M ratio in the rats fed 1% L-methionine (5.4±0.28 μM versus 32.8±3.01 μM, P<0.002; and 0.175±0.05 versus 1.05±0.23, P<0.005, respectively). The effect of rosiglitazone in rats fed the control diet was not prominent. On the other hand, administration of rosiglitazone to the rats on the 1% L-methionine diet significantly reduced the levels of serum tHcy (16.6±2.1 μM versus 32.8±3.01 μM, P<0.001); however, the tHcy levels remained significantly elevated compared with animals on the control diet (P<0.002). The group receiving the L-methionine diet plus rosiglitazone had an inhibition in the development of IH compared with those receiving the L-methionine diet alone (I/M of 0.278±0.041 versus 1.05±0.23, P<0.01). Moreover, the development of IH in the group receiving the L-methionine diet plus rosiglitazone treatment was not significantly different from that observed in the group on the control diet without rosiglitazone (0.278±0.041 versus 0.175±0.05, respectively). These findings may have important implications in deciphering the molecular mechanisms involved in the augmentation of IH in HHcy and modulation of this process by rosiglitazone.     

社区医护干预预防产后抑郁症的研究

[目的]调查产后抑郁症患者的现状及需求,探讨预防措施。[方法]定性与定量研究相结合,定性采用专题小组讨论和半结构性访谈,12人参加专题讨论、9人半结构性访谈;定量研究随机抽取本市各社区产后42d的产妇776例行问卷调查。[结果]产妇月子期间常发生头疼、恶心、焦虑、恐惧、失眠以及照顾新生儿困难;半结构性访谈中有1产妇处于产后抑郁症的临界,EPDS量表测定为12分;776例产妇月子里有身心健康问题者692例,求助者91.0%,其中需要社区护理人员帮助的71.7%,实际寻求帮助仅12.7%。[结论]预防产后抑郁症应实行社区医护人员培训与产后访视人员的准入制度,采取社区医护干预的三级预防,同时拓展社区产后保健服务的内涵。     

26万女性队列人群中乳腺癌与人工流产关系的研究（上海）

目的：评估人工流产（指手术流产）对乳腺癌危险性的可能影响。方法：研究在上海267040例妇女的一项乳房自我检查随机试验的队列人群中进行，由队列研究和巢式病例对照研究两部分组成。结果：依据基线调查表采集的资料分析，人工流产不增加乳腺癌危险性。调整潜在的混淆因素后，OR=1．06（95％CI：0．91～1．25）。人工流产次数增加无危险性趋势增加。从更详细的652例乳腺癌病例和694例对照资料分析，得出相似的结果。人工流产发生在首次生育后不增加危险性；少数妇女在首次生育前人工流产以及妊娠13周后人工流产，虽然被观察到危险性有增加，但无显著性统计学意义。结论：在中国，人工流产不是乳腺癌发生的重要原因。     

Contractile leg fatigue after cycle exercise: a factor limiting exercise in patients with chronic obstructive pulmonary disease

We evaluated whether contractile fatigue of the quadriceps occurs after cycling exercise in patients with chronic obstructive pulmonary disease (COPD) and whether it could contribute to exercise limitation. Eighteen COPD patients performed two constant work-rate cycling exercises up to exhaustion. These tests were preceded by nebulization of placebo or 500 microg of ipratropium bromide. Muscle fatigue was defined as a postexercise reduction in quadriceps twitch force of more than 15% of the resting value. There was an increase in endurance time postipratropium compared with placebo nebulization (440 +/- 244 seconds vs. 322 +/- 188 seconds, p = 0.06). Nine patients developed contractile fatigue after placebo exercise. In these patients, ipratropium did not increase the endurance time (394 +/- 220 seconds with placebo vs. 400 +/- 119 seconds with ipratropium) despite an 11% improvement in FEV1. In the nine patients who did not fatigue after placebo exercise, endurance time increased from 249 +/- 124 seconds with placebo to 479 +/- 298 seconds with ipratropium (p < 0.05). There was a significant correlation between the improvement in endurance time with ipratropium and quadriceps twitch force at 10 minutes after placebo exercise (r = 0.59, p = 0.01). The occurrence of contractile fatigue during exercise may explain why bronchodilation fails to improve exercise tolerance in some COPD patients.     

Lipofuscin accumulation in the vastus lateralis muscle in patients with chronic obstructive pulmonary disease

Exercise-induced oxidative stress has been reported in patients with chronic obstructive pulmonary disease (COPD) and may play a role in muscle fatigue. It is speculated that oxidative stress during exercise originates from the contracting muscles but this has not been documented. The accumulation of lipofuscin, a marker of cellular oxidative damage, was evaluated in the vastus lateralis muscle in 17 patients with COPD and 10 healthy subjects of similar age. Each subject performed a stepwise exercise test up to maximal capacity during which oxygen uptake (VO(2)) was measured. Resting and peak exercise blood gases were also obtained. Two indices of lipofuscin accumulation were used: lipofuscin inclusions/fiber ratio (LI/F) and lipofuscin inclusions/fiber cross-sectional area ratio (LI/CSA). These ratios were also determined for each specific fiber-type. LI/F (P < 0.01) and LI/CSA (P < 0.01) were greater in COPD compared to healthy subjects. LI/F and LI/CSA for all fiber types were also greater in COPD (P < 0.001). In both groups, LI/F (P < 0.001) and LI/CSA (P < 0.01) were higher in type I than in type II fibers. LI/F and LI/CSA did not correlate significantly with resting PaO(2) and SaO(2), peak VO(2), and DeltaPaO(2) and DeltaSaO(2) during exercise (P > 0.05). Increased lipofuscin accumulation, a marker of oxidative damage, was found in the vastus lateralis muscle in patients with COPD compared to healthy subjects. Oxidative damage of muscle tissue may thus be involved in skeletal muscle dysfunction and wasting in COPD.     

5-HYDROXYTRYPTAMINE-INDUCED CONTRACTION OF THE MARMOSET AORTA IS MEDIATED BY A 5-HT1-LIKE RECEPTOR

1. 5-Hydroxytryptamine (5-HT) exerts both contractile and relaxant effects in the marmoset isolated aorta, actions that are unaffected by the 5-HT₂ antagonist ketanserin. The aim of the present study was to define the receptors mediating the contractile activity of 5-HT in the marmoset aorta.
2. Contractile responses were elicited in aortic rings that were either: (i) precontracted submaximally with the thromboxane A₂ agonist U44069 in order to amplify the responses; or (ii) exposed to N ^ω-nitro- L -arginine (100 μmol/L) plus LY 53857 (0.1 μmol/L; a 5-HT₂ receptor antagonist shown previously to inhibit relaxation). The effect of 5-HT on adenosine 3',5'-cyclic monophosphate (cAMP) formation was also investigated.
3. The effects of agonists and antagonists comprised: (i) agonist potencies in the order 5-carboxamidotryptamine > 5-HT > sumatriptan > 8-hydroxy-2-(di- n -propylamino)tetralin; (ii) inhibition of contractile action of 5-HT by the 5-HT_1D antagonist GR 127935; (iii) a contractile response to methysergide; (iv) a lack of effect of tropisetron, an antagonist of 5-HT₃ and 5-HT₄ receptors; and (v) inhibition of forskolin-stimulated cAMP formation by 5-HT (in the presence of LY 53857), indicative of negative coupling to adenylate cyclase.
4. The above effects fulfil the criteria for a 5-HT₁-like receptor. In view of the previous finding that this contractile response is insensitive to ketanserin, it is concluded that the contractile effects of 5-HT in the marmoset aorta are mediated exclusively by a 5-HT₁-like receptor.     

Hypoxaemia enhances peripheral muscle oxidative stress in chronic obstructive pulmonary disease

BACKGROUND: Because oxidative stress affects muscle function, the underlying mechanism to explain exercise induced peripheral muscle oxidative stress in patients with chronic obstructive pulmonary disease (COPD) is clinically relevant. This study investigated whether chronic hypoxaemia in COPD worsens peripheral muscle oxidative stress and whether an abnormal muscle inflammatory process is associated with it. METHODS: Nine chronically hypoxaemic and nine non-hypoxaemic patients performed repeated knee extensions until exhaustion. Biopsy specimens were taken from the vastus lateralis muscle before and 48 hours after exercise. Muscle oxidative stress was evaluated by lipid peroxidation (lipofuscin and thiobarbituric acid reactive substances (TBARs)) and oxidised proteins. Inflammation was evaluated by quantifying muscle neutrophil and tumour necrosis factor (TNF)-alpha levels. RESULTS: When both groups were taken together, arterial oxygen pressure was positively correlated with quadriceps endurance time (n = 18, r = 0.57; p < 0.05). At rest, quadriceps lipofuscin inclusions were significantly greater in hypoxaemic patients than in non-hypoxaemic patients (2.9 (0.2) v 2.0 (0.3) inclusions/fibre; p < 0.05). Exercise induced a greater increase in muscle TBARs and oxidised proteins in hypoxaemic patients than in non-hypoxaemic patients (40.6 (9.1)% v 10.1 (5.8)% and 51.2 (11.9)% v 3.7 (12.2)%, respectively, both p = 0.01). Neutrophil levels were significantly higher in hypoxaemic patients than in non-hypoxaemic patients (53.1 (11.6) v 21.5 (11.2) counts per fibre x 10(-3); p < 0.05). Exercise did not alter muscle neutrophil levels in either group. Muscle TNF-alpha was not detected at baseline or after exercise. CONCLUSION: Chronic hypoxaemia was associated with lower quadriceps endurance time and worsened muscle oxidative stress at rest and after exercise. Increased muscle neutrophil levels could be a source of the increased baseline oxidative damage. The involvement of a muscle inflammatory process in the exercise induced oxidative stress of patients with COPD remains to be shown.