Diagnosis of Mild Cognitive Impairment Revisited after One Year Preliminary Results of a Prospective Study

Background/Aims: The diagnostic stability of mild cognitive impairment (MCI) on short-term follow- up is a key issue in the characterization of this clinical syndrome. We aim to determine the cognitive outcome after 1 year of follow- up in a cohort of older adults. Methods: Baseline clinical and neuropsychological assessments were carried out in older subjects recruited at a tertiary memory clinic. The subjects were reassessed after 1 year of follow- up with the same clinical and neuropsychological protocol. Results: A total of 115 older adults, including MCI (n = 54) and controls (n = 61), underwent baseline and follow- up evaluation. Ten subjects classified as MCI at baseline (23%) resumed normal cognitive function and 13 controls (21%) progressed to MCI upon follow-up (chi(2) = 0.015, d.f. = 1, p = 0.90). The subjects diagnosed as having MCI on both assessments were older (p = 0.002) and had a worse global cognitive performance according to the Cambridge Cognitive Test (p = 0.014). Conclusion: The subjects who maintain the MCI status are older and have a worse baseline cognitive performance as well as multiple cognitive deficits. Copyright (C) 2009 S. Karger AG, Basel

Executive dysfunction correlates with impaired functional status in older adults with varying degrees of cognitive impairment

Background: Previous studies have reported an association between executive dysfunction and the ability to perform activities of daily living (ADL)s among older adults. This study aims to examine the association between executive functions and functional status in a cross-section of older adults with varying degrees of cognitive impairment. Methods: 89 individuals (mean age 73.8 years) were recruited at a memory clinic in Sao Paulo, Brazil. Subjects underwent evaluation, and were allocated into three diagnostic groups according to cognitive status: normal controls (NC, n = 32), mild cognitive impairment (MCI, n = 3 1) and mild Alzheimer`s disease (AD, n=26). Executive functions were assessed with the 25-item Executive Interview (EXIT25), and functional status was measured with the Direct Assessment of Functional Status test (DAFS-R). Results: Significantly different total DAFS-R scores were observed across the three diagnostic groups. Patients with AD performed significantly worse in EXIT25 compared with subjects without dementia, and no significant differences were detected between NC and MCI patients. We found a robust negative correlation between the DAFS-R and the EXIT25 scores (r=-0.872, p < 0.001). Linear regression analyses suggested a significant influence of the EXIT-25 and the CAMCOG on the DAFS-R scores. Conclusion: Executive dysfunction and decline in general measures of cognitive functioning are associated with a lower ability to undertake instrumental ADLs. MCI patients showed worse functional status than NC subjects. MCI patients may show subtle changes in functional status that may only be captured by objective measures of ADLs.

Aerobic exercise training improves the role of high-density lipoprotein antioxidant and reduces plasma lipid peroxidation in type 2 diabetes mellitus

In this study, we analyzed the effect of aerobic exercise training (AET) and of a single bout of exercise on plasma oxidative stress and on antioxidant defenses in type 2 diabetes mellitus (DM) and in healthy control subjects (C). DM and C did not differ regarding triglycerides, high-density lipoprotein cholesterol (HDL-c), insulin, and HOMA index at baseline and after AET. To measure the lag time for low-density lipoprotein (LDL) oxidation (LAG) and the maximal rate of conjugated diene formation (MCD), participants` plasma HDL(2) and HDL(3) were incubated with LDL from pooled healthy donors` plasma. In the presence of HDL(3), both LAG and MCD were similar in C and DM, but only in DM did AET improve LAG and reduce MCD. In the presence of HDL(2), the lower baseline LAG in DM equaled C after AET. MCD was unchanged in DM after AET, but was lower than C only after AET. Furthermore, after AET plasma thiobarbituric acid-reactive substances were reduced only in DM subjects. Despite not modifying the total plasma antioxidant status and serum paraoxonase-1 activity in both groups, AET lowered the plasma lipid peroxides, corrected the HDL(2), and improved the HDL(3) antioxidant efficiency in DM independent of the changes in blood glucose, insulin, and plasma HDL concentration and composition.

CAMCOG as a screening tool for diagnosis of Mild Cognitive Impairment and Dementia in a Brazilian clinical sample of moderate to high education

Background The CAMCOG is a brief neuropsychological battery designed to assess global cognitive function and ascertain the impairments that are required for the diagnosis of dementia. To date, the cut-off scores for mild cognitive impairment (MCI) have not been determined. Given the need for an earlier diagnosis of mild dementia, new cut-off values are also necessary, taking into account cultural and educational effects. Methods One hundred and fifty-seven older adults (mean age: 69.6 +/- 7.4 years) with 8 or more years of formal education (mean years of schooling 14.2 +/- 3.8) attending a memory clinic at the Institute of Psychiatry University of Sao Paulo were included. Subjects were divided into three groups according to their cognitive status, established through clinical and neuropsychological assessment: normal controls, n = 62; MCI, n = 65; and mild or moderate dementia, n = 30. ROC curve analyses were performed for dementia vs controls, MCI vs controls and MCI vs dementia. Results The cut-off values were: 92/93 for dementia is controls (AUC = 0.99: sensitivity: 100%, specificity: 95%); 95/96 for MCI vs controls (AUC = 0.83, sensitivity: 64%, specificity: 88%), and 85/86 for MCI vs dementia (AUC = 0.91, sensitivity: 81%, specificity: 88%). The total CAMCOG score was more accurate than its subtests Mini-mental State Examination, Verbal Fluency Test and Clock Drawing Test when used separately. Conclusions The CAMCOG discriminated controls and MCI from demented patients, but was less accurate to discriminate MCI from controls. The best cut-off value to differentiate controls and demented was higher than suggested in the original publication, probably because only cases of mild to moderate dementia were included. This is important given the need for a diagnostic at earlier stages of Alzheimer`s disease. Copyright (C) 2008 John Wiley & Sons, Ltd.

Exercise Training Reduces Sympathetic Modulation on Cardiovascular System and Cardiac Oxidative Stress in Spontaneously Hypertensive Rats

BACKGROUND Spontaneously hypertensive rats (SHRs) show increased cardiac sympathetic activity, which could stimulate cardiomyocyte hypertrophy, cardiac damage, and apoptosis. Norepinephrine (NE)induced cardiac oxidative stress seems to be involved in SHR cardiac hypertrophy development. Because exercise training (ET) decreases sympathetic activation and oxidative stress, it may alter cardiac hypertrophy in SHR. The aim of this study was to determine, in vivo, whether ET alters cardiac sympathetic modulation on cardiovascular system and whether a correlation exists between cardiac oxidative stress and hypertrophy. METHODS Male SHRs (15-weeks old) were divided into sedentary hypertensive (SHR, n = 7) and exercise-trained hypertensive rats (SHR-T, n = 7). Moderate ET was performed on a treadmill (5 days/week, 60 min, 10 weeks). After ET, cardiopulmonary reflex responses were assessed by bolus injections of 5-HT. Autoregressive spectral estimation was performed for systolic arterial pressure (SAP) with oscillatory components quantified as low (LF: 0.2-0.75 Hz) and high (HF:0.75-4.0 Hz) frequency ranges. Cardiac NE concentration, lipid peroxidation, antioxidant enzymes activities, and total nitrates/nitrites were determined. RESULTS ET reduced mean arterial pressure, SAP variability (SAP var), LIF of SAP, and cardiac hypertrophy and increased cardiopulmonary reflex responses. Cardiac lipid peroxidation was decreased in trained SHRs and positively correlated with NE concentrations (r= 0.89, P < 0.01) and heart weight/body weight ratio (r= 0.72, P < 0.01), and inversely correlated with total nitrates/nitrites (r= -0.79, P < 0.01). Moreover, in trained SHR, cardiac total nitrates/nitrites were inversely correlated with NE concentrations (r= -0.82, P < 0.01). CONCLUSIONS ET attenuates cardiac sympathetic modulation and cardiac hypertrophy, which were associated with reduced oxidative stress and increased nitric oxide (NO) bioavailability. Am J Hypertens 2008;21:1138-1193 (C) 2008 American Journal of Hypertension, Ltd.

Exercise training prevents beta-adrenergic hyperactivity-induced myocardial hypertrophy and lesions

Background: Sustained beta-adrenoreceptor activation promotes cardiac hypertrophy and cellular injury. Aims: To evaluate the cardioprotective effect of exercise on damage induced by beta-adrenergic hyperactivity. Methods: Male Wistar rats were randomised into four groups (n=8 per group): sedentary non-treated control (C), sedentary treated with isoproterenol 0.3 mg/kg/day administered subcutaneously for 8 days (1), exercised non-treated (E) and exercised plus isoproterenol administered during the last eight days of exercise (IE). Exercised animals ran on a treadmill for 1 h daily 6 times a week for 13 weeks. Results: Isoproterenol caused increases in left ventricle (LV) wet and dry weight/body weight ratio, LV water content and cardiomyocyte transverse diameter. Additionally, isoproterenol induced severe cellular lesions, necrosis, and apoptosis, increased collagen content and reduced capillary and fibre fractional areas. Notably, all of these abnormalities were completely prevented by exercise. Conclusion: Our data have demonstrated that complete cardioprotection is possible through exercise training; by preventing p-adrenergic hyperactivity-induced cardiac hypertrophy and structural injury. (c) 2008 European Society of Cardiology. Published by Elsevier B.V. All rights reserved.

HDL atheroprotection by aerobic exercise training in type 2 diabetes mellitus

Purpose: In this study we analyzed the role played by aerobic exercise training in the plasma lipoprotein profile, prebeta 1-HDL concentration, and in the in vitro HDL3 ability to remove cholesterol from macrophages and inhibit LDL oxidation in type 2 diabetes mellitus (DM) patients and control subjects, in the fasting and postprandial states. Methods: Healthy controls (HTC, N = 11; 1 M/10 F) and subjects with type 2 diabetes mellitus (DMT, N = 11; 3M/ 8F) were engaged in a 4-month aerobic training program, and compared with a group of sedentary subjects with type 2 diabetes mellitus (DMS, N = 10; 4 M/6 F). All groups were submitted to an oral fat load test to analyze all parameters, both at the beginning of the investigation protocol (basal) and at the end of the study period (final). Results: Exercising did not modify body weight, BMI, plasma concentrations of total cholesterol, LDL cholesterol, HDL cholesterol, triglycerides (TG), glucose, insulin, or HOMA-IR, but it reduced the waist circumference. The HDL3 Composition did not change, and its ability to remove cell cholesterol was unaltered by aerobic training. In DMT but not in HTC, aerobic training improved 15% the HDL3 protective effect against LDL maximal oxidation rate in the fasting state, and reduced 24% the plasma prebeta 1-HDL concentration in the postprandial state, suggesting an enhanced prebeta 1-HDL conversion into larger, more mature HDL particles. In this regard, regular aerobic exercise enriched HDL2 with TG in the fasting and postprandial states in HTC and in the fasting phase in DMT. Conclusion: Our results show that aerobic exercise training in diabetes mellitus improves the HDL efficiency against LDL oxidation and favors HDL maturation. These findings were independent of changes in insulin resistance and of the rise of plasma HDL cholesterol concentration.

Prevalence of cognitive and functional impairment in a community sample from Sao Paulo, Brazil

Aims: To present the prevalence of cognitive and functional impairment (CFI) in community-dwelling elderly subjects from the city of Sao Paulo. Methods: The population was aged 60 years and older (n = 1,563; 68.7% women and 31.3% men) and lived in different socioeconomic areas. The following instruments were administered to the elderly: the Mini Mental State Examination and the Fuld Object Memory Evaluation. The Informant Questionnaire on Cognitive Decline in the Elderly and the Bayer-Activities of Daily Living scale were administered to an informant. Results: The prevalence of CFI (n = 250) was 16% (95% confidence interval, CI: 14.2-17.8%) or 15.8% (95% CI: 13.8-17.8%). In regression models, the increase in the odds ratio (OR) of CFI was associated with age, for elderly individuals aged 75 years or older, illiterates or with 1-4 years of schooling, and with a history of stroke and diabetes mellitus. On the other hand, for subjects with a tumor history, the OR of CFI was significantly reduced. Conclusion: CFI was high and increased at older ages and in subjects with low education. Potentially changeable factors were identified (stroke and diabetes), and the possible `protective effect` of tumor/cancer against CFI should be further investigated by longitudinal studies. Copyright (C) 2007 S. Karger AG, Basel.

Proton spectroscopy in Alzheimer`s disease and cognitive impairment no dementia: A community-based study

Objective: To describe the findings of proton magnetic resonance spectroscopy (H-1-MRS) in Alzheimer`s disease (AD) and cognitive impairment, no dementia (CIND) elderly from a community-based sample. Methods: Thirteen patients with AD, 12 with CIND and 15 normal individuals were evaluated. The H-1-MRS was performed in the right temporal, left parietal and medial occipital regions studying the metabolites N-acetylaspartate (NAA), creatine (Cr), choline (Cho) and myoinositol (ml). The clinical diagnosis was based on standardized cognitive tests - MMSE and CAMDEX - and the results correlated with the H-1-MRS. Results: Parietal Cho was higher in control individuals and lower in CIND subjects. AD and control groups were better identified by temporal and parietal ml combined with the temporal NAA/Cr ratio. CIND was better identified by parietal Cho. Conclusion: The H-1-MRS findings confirmed the hypothesis that metabolic alterations are present since the first symptoms of cognitively impaired elderly subjects. These results suggest that combining MRS from different cerebral regions can help in the diagnosis and follow-up of community elderly individuals with memory complaints and AD. Copyright (C) 2008 S. Karger AG, Basel.

Disease-modifying properties of long-term lithium treatment for amnestic mild cognitive impairment: randomised controlled trial

Background Two recent clinical studies support the feasibility of trials to evaluate the disease-modifying properties of lithium in Alzheimer`s disease, although no benefits were obtained from short-term treatment. Aims To evaluate the effect of long-term lithium treatment on cognitive and biological outcomes in people with amnestic mild cognitive impairment (aMCI). Method Forty-five participants with aMCI were randomised to receive lithium (0.25-0.5mmol/l) (n=24) or placebo (n = 21) in a 12-month, double-blind trial. Primary outcome measures were the modification of cognitive and functional test scores, and concentrations of cerebrospinal fluid (CSF) biomarkers (amyloid-beta peptide (A beta(42)), total tau (T-tau), phosphorylated-tau) (P-tau). Trial registration: NCT01055392. Results Lithium treatment was associated with a significant decrease in CSF concentrations of P-tau (P=0.03) and better perform-ance on the cognitive subscale of the Alzheimer`s Disease Assessment Scale and in attention tasks. Overall tolerability of lithium was good and the adherence rate was 91%. Conclusions The present data support the notion that lithium has disease-modifying properties with potential clinical implications in the prevention of Alzheimer`s disease.

Effects of low level laser therapy (808 nm) on physical strength training in humans

Recent studies have investigated whether low level laser therapy (LLLT) can optimize human muscle performance in physical exercise. This study tested the effect of LLLT on muscle performance in physical strength training in humans compared with strength training only. The study involved 36 men (20.8 +/- 2.2 years old), clinically healthy, with a beginner and/or moderate physical activity training pattern. The subjects were randomly distributed into three groups: TLG (training with LLLT), TG (training only) and CG (control). The training for TG and TLG subjects involved the leg-press exercise with a load equal to 80% of one repetition maximum (1RM) in the leg-press test over 12 consecutive weeks. The LLLT was applied to the quadriceps muscle of both lower limbs of the TLG subjects immediately after the end of each training session. Using an infrared laser device (808 nm) with six diodes of 60 mW each a total energy of 50.4 J of LLLT was administered over 140 s. Muscle strength was assessed using the 1RM leg-press test and the isokinetic dynamometer test. The muscle volume of the thigh of the dominant limb was assessed by thigh perimetry. The TLG subjects showed an increase of 55% in the 1RM leg-press test, which was significantly higher than the increases in the TG subjects (26%, P = 0.033) and in the CG subjects (0.27%, P < 0.001). The TLG was the only group to show an increase in muscle performance in the isokinetic dynamometry test compared with baseline. The increases in thigh perimeter in the TLG subjects and TG subjects were not significantly different (4.52% and 2.75%, respectively; P = 0.775). Strength training associated with LLLT can increase muscle performance compared with strength training only.

Adjuncts to Physical Training of Patients With Severe COPD: Oxygen or Noninvasive Ventilation?

BACKGROUND: Previous studies have shown positive effects from noninvasive ventilation (NIV) or supplemental oxygen on exercise capacity in patients with COPD. However, the best adjunct for promoting physiologic adaptations to physical training in patients with severe COPD remains to be investigated. METHODS: Twenty-eight patients (mean +/- SD age 68 +/- 7 y) with stable COPD (FEV(1) 34 +/- 9% of predicted) undergoing an exercise training program were randomized to either NIV (n = 14) or supplemental oxygen (n = 14) during group training to maintain peripheral oxygen saturation (S(pO2)) >= 90%. Physical training consisted of treadmill walking (at 70% of maximal speed) 3 times a week, for 6 weeks. Patients were assessed at baseline and after 6 weeks. Assessments included physiological adaptations during incremental exercise testing (ratio of lactate concentration to walk speed, oxygen uptake [(V) over dot(O2)], and dyspnea), exercise tolerance during 6-min walk test, leg fatigue, maximum inspiratory pressure, and health-related quality of life. RESULTS: Two patients in each group dropped out due to COPD exacerbations and lack of exercise program adherence, and 24 completed the training program. Both groups improved 6-min walk distance, symptoms, and health-related quality of life. However, there were significant differences between the NIV and supplemental-oxygen groups in lactate/speed ratio (33% vs -4%), maximum inspiratory pressure (80% vs 23%), 6-min walk distance (122 m vs 47 m), and leg fatigue (25% vs 11%). In addition, changes in S(pO2)/speed, (V) over dot(O2), and dyspnea were greater with NIV than with supplemental-oxygen. CONCLUSIONS: NIV alone is better than supplemental oxygen alone in promoting beneficial physiologic adaptations to physical exercise in patients with severe COPD.

Effects of progressive resistance strength training on knee biomechanics during single leg step-up in persons with mild knee osteoarthritis

Background: The goal of this study was to determine if increasing strength in primary knee extensors and flexors would directly affect net knee joint moments during a common functional task in persons with knee osteoarthritis. Methods: An exploratory single sample clinical trial with pre-post treatment measures was used to study volunteers with clinical diagnosis of mild knee osteoarthritis (OA) in one knee. Subjects participated in an individually supervised training program 3 times a week for eight weeks consisting of progressive resistive exercises for knee extensors and knee flexors. Pre and post training outcome assessments included: 1. Net internal knee joint moments, 2. Electromyography of primary knee extensors and flexors, and 3. Self-report measures of knee pain and function. The distribution of lower extremity joint moments as a percent of the total support moment was also investigated. Findings: Pain, symptoms, activities of daily life, quality of life, stiffness, and function scores showed significant improvement following strength training. Knee internal valgus and hip internal rotation moments showed increasing but non-statistically significant changes post-training. There were no significant differences in muscle co-contraction activation of the Quadriceps and Hamstrings. Interpretation: While exercise continues to be an important element of OA management, the results of this study suggest improvements in function, pain, and other symptoms, as a result of strength training may not be causally related to specific biomechanical changes in net joint moments. (C) 2011 Elsevier Ltd. All rights reserved.

Effect of the duration of daily aerobic physical training on cardiac autonomic adaptations

The present study has investigated in conscious rats the influence of the duration of physical training sessions on cardiac autonomic adaptations by using different approaches; 1) double blockade with methylatropine and propranolol; 2) the baroreflex sensitivity evaluated by alternating bolus injections of phenylephrine and sodium nitroprusside; and 3) the autonomic modulation of HRV in the frequency domain by means of spectral analysis. The animals were divided into four groups: one sedentary group and three training groups submitted to physical exercise (swimming) for 15, 30, and 60 min a day during 10 weeks. All training groups showed similar reduction in intrinsic heart rate (IHR) after double blockade with methylatropine and propranolol. However, only 30-min and 60-min physical training presented an increase in the vagal autonomic component for determination of basal heart rate (HR) in relation to group sedentary. Spectral analysis of HR showed that the 30-min and 60-min physical training presented the reduction in low-frequency oscillations (LF = 0.20-0.75 Hz) and the increase in high-frequency oscillations (HF = 0.75-2.5 Hz) in normalized units. These both groups only showed an increased baroreflex sensitivity to tachycardiac responses in relation to group sedentary, however when compared, the physical training of 30-min exhibited a greater gain. In conclusion, cardiac autonomic adaptations, characterised by the increased predominance of the vagal autonomic component, were not proportional to the duration of daily physical training sessions. In fact, 30-minute training sessions provided similar cardiac autonomic adaptations, or even more enhanced ones, as in the case of baroreflex sensitivity compared to 60-minute training sessions. (C) 2010 Elsevier B.V. All rights reserved.

Muscle mass gain observed in patients with short bowel syndrome subjected to resistance training

Few studies are available about the evaluation of resistance training in patients with protein-energy malnutrition. To assess the effects of resistance training on the recovery of nutritional status of patients with short bowel syndrome, with a small bowel remnant of less than 100 cm, 9 patients of both sexes with protein-energy malnutrition after extensive resection of the small bowel were submitted to resistance training of progressive intensity consisting of concentric and eccentric work exercises for the upper limbs, trunk, and lower limbs, with the individuality and limitations of each patients being respected. Food consumption was monitored by 24-hour food recall performed during the initial phase of the study, before and 7 and 14 weeks after physical training, and by a dietary record for a period of 3 days of oral feeding. The nutrients administered by the enteral and parenteral route were recorded. A significant increase in total arm area (P <= .01) and fat-free mass (P <= .01) was observed as determined by computed tomography. An increase in total energy ingestion and carbohydrate consumption (P <= .01) was also observed. In addition, the activity of the enzyme carnosinase was increased after resistance training (P <= .01). The present results show that resistance training in patients with short bowel syndrome and protein-energy malnutrition can be considered to be a part of the nonmedicamentous treatment of these patients, leading to better nutrient use and to a gain of lean mass. (c) 2008 Elsevier Inc. All rights reserved.