Longitudinal changes in global and domain specific cognitive function in the very-old: findings from the Newcastle 85+ Study.

OBJECTIVE: Ageing is associated with changes in cognition in some, but not all domains. In young-old adults, defined as persons aged 65-84 years, baseline cognitive function has been shown to impact on cognitive trajectories. Whether similar patterns occur in the very-old, defined as persons aged 85 years and over, is not known. METHODS: Longitudinal changes (5 years' follow-up) in global and domain specific cognitive function including memory, attention and speed were investigated in participants from the Newcastle 85+ Study (n = 845). At baseline, participants were grouped using Mini-Mental State Examination cut-off scores and dementia status into the following: not impaired, mildly impaired or severely impaired/dementia groups. RESULTS: Only a limited number of cognitive measures showed significant decline in performance over time. Where observed, change generally occurred only in the severely impaired group. In the severely impaired group, small differences in baseline age were associated with poorer performance over time on most measures. Education was not protective against cognitive decline in any group. CONCLUSIONS: There are individuals who maintain a high level of cognitive function or only show mild impairments even into their ninth decade of life. This group of successful cognitive agers may provide insight for identifying predictors of cognitive integrity in later life. In individuals with severe impairment, cognitive performance shows significant decline over time, especially in measures of attention and speed. Further work to identify those individuals at highest risk of cognitive decline is necessary to implement early support and intervention strategies in this rapidly expanding age group. © 2017 The Authors. International Journal of Geriatric Psychiatry published by John Wiley & Sons Ltd.

A longitudinal study of patients with cirrhosis treated with L-ornithine L-aspartate, examined with magnetization transfer, diffusion-weighted imaging and magnetic resonance spectroscopy.

The presence of overt hepatic encephalopathy (HE) is associated with structural, metabolic and functional changes in the brain discernible by use of a variety of magnetic resonance (MR) techniques. The changes in patients with minimal HE are less well documented. Twenty-two patients with well-compensated cirrhosis, seven of whom had minimal HE, were examined with cerebral 3 Tesla MR techniques, including T1- and T2-weighted, magnetization transfer and diffusion-weighted imaging and proton magnetic resonance spectroscopy sequences. Studies were repeated after a 4-week course of oral L-ornithine L-aspartate (LOLA). Results were compared with data obtained from 22 aged-matched healthy controls. There was no difference in mean total brain volume between patients and controls at baseline. Mean cerebral magnetization transfer ratios were significantly reduced in the globus pallidus and thalamus in the patients with cirrhosis irrespective of neuropsychiatric status; the mean ratio was significantly reduced in the frontal white matter in patients with minimal HE compared with healthy controls but not when compared with their unimpaired counterparts. There were no significant differences in either the median apparent diffusion coefficients or the mean fractional anisotropy, calculated from the diffusion-weighted imaging, or in the mean basal ganglia metabolite ratios between patients and controls. Psychometric performance improved in 50 % of patients with minimal HE following LOLA, but no significant changes were observed in brain volumes, cerebral magnetization transfer ratios, the diffusion weighted imaging variables or the cerebral metabolite ratios. MR variables, as applied in this study, do not identify patients with minimal HE, nor do they reflect changes in psychometric performance following LOLA.

Quantitative magnetic resonance imaging in patients with cirrhosis: a cross-sectional study.

Cerebral magnetic resonance imaging was undertaken, at 3 Tesla field strength, employing magnetization transfer (MT) and diffusion-weighted imaging (DWI) sequences, in 26 patients with well-compensated cirrhosis, free of overt hepatic encephalopathy. Results were compared to those from 18 aged-matched healthy volunteers. Cerebral magnetization transfer ratios (MTR) were reduced in the frontal white matter, caudate, putamen and globus pallidus in patients with cirrhosis, compared to healthy controls, while the apparent diffusion coefficients (ADC) on DWI were significantly increased in the genu and body of the corpus callosum. An association between previous excessive alcohol consumption and both MTR and ADCs was noted, but this association was lost when controls were exercised for the severity of liver disease and psychometric impairment on multivariate analysis. Eight (31 %) of the 26 patients had impaired psychometric performance consistent with a diagnosis of minimal hepatic encephalopathy. No statistically significant difference in regional cerebral MTRs or ADCs was found in relation to neuropsychiatric status, although there was a trend towards lower MTRs in patients with impaired psychometric performance. The alterations in MTR and ADC in the patients with functionally compensated cirrhosis are compatible with theories governing the genesis of hepatic encephalopathy, including changes in astrocyte membrane permeability, with subsequent redistribution of macromolecules.

Relationship between cognition, magnetic resonance white matter hyperintensities, and cardiovascular autonomic changes in late-life depression.

OBJECTIVES: To explore the relationship between specific aspects of cognition, white matter hyperintensities (WMHs), and cardiovascular autonomic parameters in late-life depression (LLD). DESIGN: Cross-sectional analysis. SETTING: Secondary care psychiatry. PARTICIPANTS: Forty-one individuals older than 60 years, with current or previous history of major depression, and 32 age-matched comparison subjects. MEASUREMENTS: Cognition was assessed by a standardized computer battery of tasks (Cognitive Drug Research) that measured processing speed, attention, episodic memory, and working memory. Cardiovascular autonomic parameters were estimated by a noninvasive device that calculated blood pressure, heart rate variability, and baroreflex sensitivity (Task Force Monitor). Magnetic resonance imaging was performed on a 3-T magnetic resonance imaging system, and WMH volume was estimated using an automated validated method. RESULTS: As expected, cognitive deficits in all tested domains were present in LLD subjects compared with comparison subjects. In the LLD group, processing speed was correlated with scores on memory and working memory tasks. Attentional deficits were correlated with total and periventricular WMH volume, and episodic memory was associated with heart rate variability. There were no associations between cognitive variables and traditional vascular risk factors or between cognitive variables and any of these parameters in the comparison subjects. CONCLUSIONS: This study suggests that processing speed may be an important factor underlying deficits in LLD, but it also indicates that other factors, including those related to vascular disease, are important and thus provide further support for the vascular depression hypothesis.

Longitudinal investigation of the factor structure of the Parkinson's disease activities of daily living, interference and dependence instrument.

The Parkinson's Disease Activities of Daily Living, Interference, and Dependence Instrument© (PD-AID) is a patient-reported outcome (PRO) instrument, recently developed to assess the clinical benefit of Parkinson's Disease (PD) treatment. The PD-AID consists of morning and evening assessments, administered daily. To benefit from the full set of the repeated observations over time, analytic approaches that account for both within- and between-individual variability are required. The current study aimed to employ the advantages of exploratory Multilevel Factor Analysis (MFA) on data collected from 93 participants with moderate to advanced PD, currently using and responding to Levodopa (L-Dopa), who completed the PD-AID twice daily as part of a prospective, non-intervention, observational study for ~28 days. Average daily completion rates were comparable for the Morning and the Evening PD-AID (78% and 74%, respectively). The intraclass correlation coefficients for the Morning and Evening PD-AID items were in the range of 0.70-0.90, with an average of 0.81 for the Morning PD-AID items and 0.83 for the Evening PD-AID items, suggesting that most variability (81%-83%) in responses was due to between-individual variability. For the Morning PD-AID, one factor (including nine out of 10 Morning PD-AID items) emerged at the between-individual level and four factors (core physical actions, basic self-care activities, feeding, and interference & dependence) at the within-individual level. For the Evening PD-AID, there were four between-individual factors (basic activities of daily living ADLs, life interference, impact on planning, and emotional consequences) and five within-individual factors (basic ADLs, toileting, life interference, medication planning, and emotional impact). The factors had high reliability.

Elevated plasma homocysteine is associated with increased brain atrophy rates in older subjects with mild hypertension.

We determined using serial MR imaging whether raised plasma homocysteine levels are associated with increased brain atrophy, white matter lesion (WML) progression or incidence of silent brain infarcts (SBIs) in older hypertensive subjects. Brain atrophy rates (0.58 ± 0.48% per year, mean ± SD) were significantly correlated with homocysteine (ß = 0.46, p = 0.001 homocysteine; ß = 0.44, p = 0.007 homocysteine/folate/B12 models) but not with folate or B12 levels. Progression of WML (0.08 ± 0.16%) was not associated with homocysteine level (B = 0.01, p = 0.29). New SBIs were uncommon. In older hypertensive individuals, plasma homocysteine levels are associated with increased rates of whole-brain atrophy but not WML progression.

Plasma homocysteine and cognitive decline in older hypertensive subjects.

BACKGROUND: Elevated plasma homocysteine concentrations have been associated with both cognitive impairment and dementia. However, it is unclear whether some cognitive domains are more affected than others, or if this relationship is independent of B12 and folate levels, which can also affect cognition. We examined the relationship between plasma homocysteine and cognitive decline in an older hypertensive population. METHODS: 182 older people (mean age 80 years) with hypertension and without dementia, were studied at one center participating in the Study on COgnition and Prognosis in the Elderly (SCOPE). Annual cognitive assessments were performed using a computerized assessment battery and executive function tests, over a 3-5 year period (mean 44 months). Individual rates of decline on five cognitive domains were calculated for each patient. End of study plasma homocysteine, folate and B12 concentrations were measured. The relationship between homocysteine levels and cognitive decline was studied using multivariate regression models, and by comparing high versus low homocysteine quartile groups. RESULTS: Higher homocysteine showed an independent association with greater cognitive decline in three domains: speed of cognition (ß = -27.33, p = 0.001), episodic memory (ß = -1.25, p = 0.02) and executive function (ß = -0.05, p = 0.04). The association with executive function was no longer significant after inclusion of folate in the regression model (ß = -0.032, p = 0.22). Change in working memory and attention were not associated with plasma homocysteine, folate or B12. High homocysteine was associated with greater decline with a Cohen's d effect size of approximately 0.7 compared to low homocysteine. CONCLUSIONS: In a population of older hypertensive patients, higher plasma homocysteine was associated with cognitive decline.

Homocysteine is associated with hippocampal and white matter atrophy in older subjects with mild hypertension.

BACKGROUND: Plasma homocysteine has been associated with reduced brain volumes in cross-sectional studies. We aimed to investigate if homocysteine is associated with ongoing atrophy, and if so, if this is localized to gray or white matter. METHODS: In a group of 80 hypertensive subjects aged 70-90 years (from the SCOPE study) MRI images were obtained at two time points two years apart. Rates of gray and white matter and hippocampal atrophy were determined by calculating the difference in segmentation probability maps using SPM5. Plasma homocysteine, folate, B12 and creatinine were measured at study end. RESULTS: Homocysteine levels correlated with white matter atrophy rate (p = 0.006) hippocampal baseline volume (p = 0.011) and hippocampal atrophy rate (p = 0.004) but not global gray matter atrophy or baseline gray or white matter volumes. The correlations remained significant (p < 0.05) after controlling for subject age, blood pressure, folate levels and white matter lesion volume. CONCLUSION: In older hypertensives, plasma homocysteine levels are associated with increased rates of progressive white matter and hippocampal atrophy.

Computerized psychometric testing in minimal encephalopathy and modulation by nitrogen challenge and liver transplant.

BACKGROUND & AIMS: A lack of standardized tests was cited by hepatologists for not testing for minimal hepatic encephalopathy. We therefore compared paper and pencil neuropsychologic tests with a comprehensive computerized assessment (Cognitive Drug Research [CDR], Goring-on-Thames, United Kingdom) of cognitive function. METHODS: Eighty-nine cirrhotic patients were studied. Composite scores were calculated from the CDR subtests to reflect 5 cognitive domains, and results were validated by comparison with those from 6 standard paper and pencil tests. Level of impairment was defined using the sum of the standard deviations by which each CDR domain (CDR factor score [CDRS]) and each paper and pencil test score (PHES) differed from age-matched norms. CDRS and PHES were repeated in 21 patients after liver transplantation and CDRS in 24 patients after a 108-g amino acid challenge. RESULTS: There was a high correlation between the 2 assessment methods (r = 0.748; P = .001). Using multiple regression, Model of End-Stage Liver Disease score (P = .011) correlated with PHES. In contrast, the CDR domains Continuity of Attention and Quality of Episodic Memory were significantly related to venous blood ammonia levels (adjusted R(2) = 0.200; F(6,76) = 4.41; P = .001). There were marked deteriorations in the CDR composite scores representing Accuracy of Working (P = .005) and Episodic Memory (P = .001) after amino acid challenge when blood ammonia increased from 63 +/- 36 to 126 +/- 62 micromol/L (P = .001). Both PHES and CDRS returned to the control range after liver transplantation (PHES: pretransplantation, -6; posttransplantation, 0; P < .001; CDRS: pretransplantation, -6; posttransplantation, -2; P = .003). CONCLUSIONS: CDRS is valuable for the recognition of minimal hepatic encephalopathy.

Poststroke urinary incontinence: one-year outcome and relationships with measures of attentiveness.

OBJECTIVES: To investigate the prognostic effect of poststroke urinary incontinence (UI) on 1-year outcome in relation to measurements of attention and mental processing speed. DESIGN: Prospective observational study. SETTING: Geriatric department (stroke and rehabilitation unit) in a university hospital. PARTICIPANTS: Two hundred thirty-five previously continent patients (median age 78) with an acute stroke. MEASUREMENTS: Clinical stroke syndromes, subtypes of UI, pre- and poststroke cognitive function and activities of daily living, computerized assessment of attention and processing speed for 110 of the participants, mortality and accommodation at 1 year. RESULTS: One hundred seventy patients remained continent, and 65 developed UI (27 with urge UI, 38 with UI with impaired awareness of the need to void (IA-UI). Patients with urge UI had poorer power of attention and speed of memory than continent patients but similar continuity of attention (P<.001, .001, and .07, respectively). Patients with IA-UI performed poorer in all categories than continent and patients with urge UI (all P<.01). In regression analyses, IA-UI was the strongest predictor of mortality and nursing home residence after 1 year (odds ratio=15.7, 95% confidence interval=3.6-69.7). When deaths were excluded, IA-UI and continuity of attention remained independent risk factors. CONCLUSION: Patients with poststroke UI are less attentive than continent patients. Those with IA-UI perform poorest. Sustained attention seems important for outcome and should be taken more into account in the rehabilitation process. In patients who recognize their incontinence, attention-focused training might be the most effective measure of reestablishing bladder control.

A comparison of computerized and pencil-and-paper tasks in assessing cognitive function in community-dwelling older people in the Newcastle 85+ Pilot Study.

OBJECTIVES: To compare the acceptability and feasibility of computerized and pencil-and-paper tests of cognitive function in 85-year-old people. DESIGN: Group comparison of participants randomly allocated to pencil-and-paper (Wechsler Adult Intelligence and Memory Scales) or computerized (Cognitive Drug Research) tests of verbal memory and attention. SETTING: The Newcastle 85+ Pilot Study was the precursor to the Newcastle 85+ Study a United Kingdom Medical Research Council/Biotechnology and Biological Sciences Research Council cohort study of health and aging in the oldest-old age group. PARTICIPANTS: Eighty-one community-dwelling individuals aged 85. MEASUREMENTS: Participant and researcher acceptability, completion rates, time taken, validity as cognitive measures, and psychometric utility. RESULTS: Participants randomized to computerized tests were less likely to rate the cognitive function tests as difficult (odds ratio (OR)=0.16, 95% confidence interval (CI)=0.07-0.39), stressful (OR=0.18, 95% CI=0.07-0.45), or unacceptable (OR=0.18, 95% CI=0.08-0.48) than those randomized to pencil-and-paper tests. Researchers were also less likely to rate participants as being distressed in the computer test group (OR=0.19, 95% CI=0.07-0.46). Pencil-and-paper tasks took participants less time to complete (mean+/-standard deviation 18+/-4 minutes vs 26+/-4 minutes) but had fewer participants who could complete all tasks (91% vs 100%). Both types of task were equally good measures of cognitive function. CONCLUSION: Computerized and pencil-and-paper tests are both feasible and useful means of assessing cognitive function in the oldest-old age group. Computerized tests are more acceptable to participants and administrators.

Brain atrophy and white matter hyperintensity change in older adults and relationship to blood pressure. Brain atrophy, WMH change and blood pressure.

Hypertension is a major risk factor for stroke and dementia and is associated with white matter hyperintensities (WMH) and reduced brain volumes. We measured the increase in WMH volume, and rate of cerebral atrophy over two years, in hypertensive subjects participating in the Study on COgnition and Prognosis in the Elderly (SCOPE), receiving candesartan or placebo, and normotensive controls. We recruited 163 subjects who had MRI (FLAIR and volumetric T1) at 2 and 4 years after baseline assessment. From these two scans, volumetric change in WMH (n = 133) and brain atrophy rates (n = 95) were determined. Total WMH fraction increased in both normotensive and treated hypertensive groups (p < 0.01) median change: 0.05% of brain volume [range: -0.45% to 1.51%]. Deep WMH increased in hypertensive (p = 0.001) but not the normotensive group. The number of subjects with an increase of total WMH in the 5(th) quintile differed between the treatment groups (chi square p = 0.006), being greatest in the placebo group (32%), then candesartan (20%) then normotensive (5%). Regression analysis found significant predictors of change in WMH to be blood pressure and initial deep WMH, but not treatment group. Increased atrophy rate was predicted by baseline systolic blood pressure (p = 0.02) but was not associated with measures of WMH. Similar to WMH, there was a trend with treatment, with atrophy in normotensive < Candesartan < Placebo (Spearman's rho = 0.23, p = 0.026). Hypertension in older people is associated with increased rates of progressive whole brain atrophy and an increase in WMH. These changes are independent. Successful hypertension treatment was associated with reduced risk of WMH progression and possibly brain atrophy.

Regulation of attention and response to therapy in dementia by butyrylcholinesterase.

OBJECTIVES: To determine the response of patients with different butyrylcholinesterase genotypes to therapy, and the influence of butyrylcholinesterase on cognition. Acetylcholine plays a key role in attention and memory and reduced cortical acetylcholine is associated with the severity of dementia. Inhibitors of the enzyme acetylcholinesterase are an effective dementia treatment, though the role of the related enzyme butyrylcholinesterase is less well understood. METHODS: We examined the response of a cohort of dementia patients enrolled in a trial of a cholinesterase inhibitor who had been genotyped at the butyrylcholinesterase locus. Additionally a prospectively assessed cohort of dementia patients was genotyped and rate of cognitive decline examined, along with baseline cognitive performance in a group of elderly non-demented individuals. We identified that the presence of reduced-activity butyrylcholinesterase variants correlates with preserved attentional performance and reduced rate of cognitive decline. During cholinesterase inhibitor therapy, patients with normal butyrylcholinesterase show improved attention, though patients carrying reduced-activity enzyme do not, possibly due to being at ceiling performance. Butyrylcholinesterase did not however affect attentional performance in non-demented individuals with mild cognitive impairment. CONCLUSIONS: These findings indicate that the butyrylcholinesterase enzyme is a major regulator of attention especially in cholinergic deficiency states through its ability to hydrolyse acetylcholine. Pharmacologic manipulation of this enzyme may be a viable strategy in dementia treatment and, with butyrylcholinesterase genotyping, may provide pharmacogenomic treatment of dementia.

Effects of hypertension on attention, memory, and executive function in older adults.

Hypertension is associated with impairments in cognitive function in older adults, but the nature and extent of these deficits are unclear. Brief cognitive measures lack sensitivity, whereas comprehensive assessments produce numerous variables that are difficult to interpret. The authors performed a principal-components analysis using a computerized cognitive assessment battery and neuropsychological measures of executive function in 506 hypertensive and normotensive older participants. Composite factor scores were used to reanalyze data from 223 untreated participants without vascular complications. The hypertensive group had deficits in Speed of Cognition, Episodic and Working Memory, and Executive Function but not Continuity of Attention. Using composite scores simplified data interpretation and suggested differential effects of hypertension on cognitive performance not clearly evident in individual test results.

Modulation of neural activation following treatment of hepatic encephalopathy.

OBJECTIVE: To measure changes in psychometric state, neural activation, brain volume (BV), and cerebral metabolite concentrations during treatment of minimal hepatic encephalopathy. METHODS: As proof of principle, 22 patients with well-compensated, biopsy-proven cirrhosis of differing etiology and previous minimal hepatic encephalopathy were treated with oral l-ornithine l-aspartate for 4 weeks. Baseline and 4-week clinical review, blood chemistry, and psychometric evaluation (Psychometric Hepatic Encephalopathy Score and Cognitive Drug Research Score) were performed. Whole-brain volumetric and functional MRI was conducted using a highly simplistic visuomotor task, together with proton magnetic resonance spectroscopy of the basal ganglia. Treatment-related changes in regional BV and neural activation change (blood oxygenation level dependent) were assessed. RESULTS: Although there was no change in clinical, biochemical state, basal ganglia magnetic resonance spectroscopy, or in regional BV, there were significant improvements in Cognitive Drug Research Score (+1.2, p = 0.003) and Psychometric Hepatic Encephalopathy Score (+1.5, p = 0.003) with treatment. This cognitive amelioration was accompanied by changes in blood oxygenation level-dependent activation in the posterior cingulate and ventral medial prefrontal cortex, 2 regions that form part of the brain's structural and metabolic core. In addition, there was evidence of greater visual cortex activation. CONCLUSIONS: These structurally interconnected regions all showed increased function after successful encephalopathy treatment. Because no regional change in BV was observed, this implies that mechanisms unrelated to astrocyte volume regulation were involved in the significant improvement in cognitive performance.

Optimised anaesthesia to reduce post operative cognitive decline (POCD) in older patients undergoing elective surgery, a randomised controlled trial.

BACKGROUND: The study determined the one year incidence of post operative cognitive decline (POCD) and evaluated the effectiveness of an intra-operative anaesthetic intervention in reducing post-operative cognitive impairment in older adults (over 60 years of age) undergoing elective orthopaedic or abdominal surgery. METHODS AND TRIAL DESIGN: The design was a prospective cohort study with a nested randomised, controlled intervention trial, using intra-operative BiSpectral index and cerebral oxygen saturation monitoring to enable optimisation of anaesthesia depth and cerebral oxygen saturation in older adults undergoing surgery. RESULTS: In the 52 week prospective cohort study (192 surgical patients and 138 controls), mild (χ(2) = 17.9 p<0.0001), moderate (χ(2) = 7.8 p = 0.005) and severe (χ(2) = 5.1 p = 0.02) POCD were all significantly higher after 52 weeks in the surgical patients than among the age matched controls. In the nested RCT, 81 patients were randomized, 73 contributing to the data analysis (34 intervention, 39 control). In the intervention group mild POCD was significantly reduced at 1, 12 and 52 weeks (Fisher's Exact Test p = 0.018, χ(2) = 5.1 p = 0.02 and χ(2) = 5.9 p = 0.015), and moderate POCD was reduced at 1 and 52 weeks (χ(2) = 4.4 p = 0·037 and χ(2) = 5.4 p = 0.02). In addition there was significant improvement in reaction time at all time-points (Vigilance Reaction Time MWU Z = -2.1 p = 0.03, MWU Z = -2.7 p = 0.004, MWU Z = -3.0 p = 0.005), in MMSE at one and 52 weeks (MWU Z = -2.9 p = 0.003, MWU Z = -3.3 p = 0.001), and in executive function at 12 and 52 weeks (Trail Making MWU Z = -2.4 p = .0.018, MWU Z = -2.4 p = 0.019). CONCLUSION: POCD is common and persistent in older adults following surgery. The results of the nested RCT indicate the potential benefits of intra-operative monitoring of anaesthetic depth and cerebral oxygenation as a pragmatic intervention to reduce post-operative cognitive impairment. TRIAL REGISTRATION: Controlled-Trials.com ISRCTN39503939.

Testosterone and mood dysfunction in women with polycystic ovarian syndrome compared to subfertile controls.

Women with polycystic ovarian syndrome (PCOS) have been found to suffer from fertility problems and mood dysfunction. To control for any effect of fertility problems, the present study compared mood dysfunction in women with PCOS to non-PCOS women with fertility problems. Seventy-six women with PCOS and 49 subfertile controls reported their anxiety, depression and aggression levels, and the relationship between mood and testosterone (T) was assessed. Controlling for age and BMI using MANCOVA, women with PCOS were significantly more neurotic (had difficulty coping with stress) than controls, had more anger symptoms, were significantly more likely to withhold feelings of anger and had more quality of life problems related to the symptoms of their condition (acne, hirsutism, menstrual problems and emotions). In a subgroup of 30 women matched on age, BMI and ethnicity, it was found that women with PCOS were significantly more anxious and depressed than controls. T was not generally correlated with mood states. This is the first study to identify problems with neuroticism and withholding anger in women with PCOS. These mood problems appear to be mainly attributable to PCOS symptoms, though other factors, such as hypoglycaemia, cannot be ruled out.

Measurement issues when assessing quality of life outcomes for different types of hernia mesh repair.

INTRODUCTION: The NHS is required to collect data from patient reported outcome measures (PROMs) for inguinal hernia surgery. We explored the use of one such measure, the Carolinas Comfort Scale(®) (CCS), to compare long-term outcomes for patients who received two different types of mesh. The CCS questionnaire asks about mesh sensation, pain and movement limitations, and combines the answers into a total score. PATIENTS AND METHODS: A total of 684 patients were treated between January 2007 and August 2008 and were followed up in November 2009. RESULTS: Data on 215 patients who met the inclusion criteria were available (96 patients who received Surgipro™ mesh and 119 who received Parietene™ Progrip™ mesh). Recurrence rates were similar in the Surgipro™ group (2/96, 2.1%) and Progrip™ group (3/118, 2.5%) (Fisher's exact test = 1.0). Chronic pain occurred less frequently in the Surgipro™ group (11/95, 11.6%) than in the Progrip™ group (22/118, 18.6%) (p<0.157). Overall, 90% of CCS total scores indicated a good outcome (scores of 10 or less out of 115). A principal component analysis of the CCS found that responses clustered into two subscales: 'mesh sensation' and 'pain+movement limitations'. The Progrip™ group had a slightly higher mesh sensation score (p<0.051) and similar pain+movement limitations scores (p<0.120). CONCLUSIONS: In this study of quality of life outcomes related to different mesh types, the CCS subscales were more sensitive to differences in outcome than the total CCS score for the whole questionnaire. Future research should consider using the CCS subscales rather than the CCS total score.

A high-fat diet impairs cardiac high-energy phosphate metabolism and cognitive function in healthy human subjects.

BACKGROUND: High-fat, low-carbohydrate diets are widely used for weight reduction, but they may also have detrimental effects via increased circulating free fatty acid concentrations. OBJECTIVE: We tested whether raising plasma free fatty acids by using a high-fat, low-carbohydrate diet results in alterations in heart and brain in healthy subjects. DESIGN: Men (n = 16) aged 22 ± 1 y (mean ± SE) were randomly assigned to 5 d of a high-fat, low-carbohydrate diet containing 75 ± 1% of calorie intake through fat consumption or to an isocaloric standard diet providing 23 ± 1% of calorie intake as fat. In a crossover design, subjects undertook the alternate diet after a 2-wk washout period, with results compared after the diet periods. Cardiac (31)P magnetic resonance (MR) spectroscopy and MR imaging, echocardiography, and computerized cognitive tests were used to assess cardiac phosphocreatine (PCr)/ATP, cardiac function, and cognitive function, respectively. RESULTS: Compared with the standard diet, subjects who consumed the high-fat, low-carbohydrate diet had 44% higher plasma free fatty acids (P < 0.05), 9% lower cardiac PCr/ATP (P < 0.01), and no change in cardiac function. Cognitive tests showed impaired attention (P < 0.01), speed (P < 0.001), and mood (P < 0.01) after the high-fat, low-carbohydrate diet. CONCLUSION: Raising plasma free fatty acids decreased myocardial PCr/ATP and reduced cognition, which suggests that a high-fat diet is detrimental to heart and brain in healthy subjects.

The effect of passive heating and head cooling on perception, cardiovascular function and cognitive performance in the heat.

The present study examined the effects of raising both skin temperature and core temperature, separately and in combination, on perceptions of heat-related fatigue (alertness, contentment, calmness and thermal comfort), cardiovascular function and on objective measures of cognitive performance (reaction time and accuracy). Ten (six males) subjects had cognitive performance assessed in three conditions; at low skin and low core temperature (LL), at high skin and low core temperature (HL) and at high skin and high core temperatures (HH). In one trial, subjects had their head and neck cooled (HC); the other trial was a control (CON). Raising skin temperature increased heart rate and decreased perception of thermal comfort (P < 0.05), whereas raising both skin and core temperature decreased perception of heat-related fatigue (P < 0.05) and increased cardiovascular strain (P < 0.05) resulting in decrements in cognitive performance shown by faster reaction times (P < 0.05) and a loss of accuracy (P < 0.05). At high skin and core temperatures, cooling the head and neck improved feelings of heat-related fatigue (P < 0.05) and cardiovascular strain (P < 0.05), but had no effect on cognitive performance. In conclusion, the results of this study suggest that feelings of heat-related fatigue and cardiovascular strain can be attributed to a combination of elevated skin and core body temperature, whereas decrements in cognitive performance can be attributed to an elevated core temperature.