Cumulative Exposure to Lead in Relation to Cognitive Function in Older Women

Background: Recent data indicate that chronic low-level exposure to lead is associated with accelerated declines in cognition in older age, but this has not been examined in women. Objective: We examined biomarkers of lead exposure in relation to performance on a battery of cognitive tests among older women. Methods: Patella and tibia bone lead—measures of cumulative exposure over many years—and blood lead, a measure of recent exposure, were assessed in 587 women 47–74 years of age. We assessed their cognitive function 5 years later using validated telephone interviews. Results: Mean ± SD lead levels in tibia, patella, and blood were 10.5 ± 9.7 μg/g bone, 12.6 ± 11.6 μg/g bone, and 2.9 ± 1.9 μg/dL, respectively, consistent with community-level exposures. In multivariable-adjusted analyses of all cognitive tests combined, levels of all three lead biomarkers were associated with worse cognitive performance. The association between bone lead and letter fluency score differed dramatically from the other bone lead-cognitive score associations, and exclusion of this particular score from the combined analyses strengthened the associations between bone lead and cognitive performance. Results were statistically significant only for tibia lead: one SD increase in tibia lead corresponded to a 0.051-unit lower standardized summary cognitive score (95% confidence interval: −0.099 to −0.003; p = 0.04), similar to the difference in cognitive scores we observed between women who were 3 years apart in age. Conclusions: These findings suggest that cumulative exposure to lead, even at low levels experienced in community settings, may have adverse consequences for women’s cognition in older age

Toward industry 4.0: Efficient and sustainable manufacturing leveraging MAESTRI total efficiency framework

© Springer International Publishing AG 2017.This paper presents an overview of the work under development within MAESTRI EU-funded collaborative project. The MAESTRI Total Efficiency Framework (MTEF) aims to advance the sustainability of manufacturing and process industries by providing a management system in the form of a flexible and scalable platform and methodology. The MTEF is based on four pillars: (a) an effective management system targeted at process continuous improvement; (b) Efficiency assessment tools to support improvements, optimisation strategies and decision support; (c) Industrial Symbiosis paradigm to gain value from waste and energy exchange; (d) an Internet-of-Things infrastructure to support easy integration and data exchange among shop-floor, business systems and tools

Methylphenidate produces selective enhancement of declarative memory consolidation in healthy volunteers

RATIONALE: Methylphenidate inhibits the reuptake of dopamine and noradrenaline and is used to treat children with attention deficit hyperactivity disorder (ADHD). Besides reducing behavioral symptoms, it improves their cognitive function. There are also observations of methylphenidate-induced cognition enhancement in healthy adults, although studies in this area are relatively sparse. We assessed the possible memory-enhancing properties of methylphenidate. OBJECTIVE: In the current study, the possible enhancing effects of three doses of methylphenidate on declarative and working memory, attention, response inhibition and planning were investigated in healthy volunteers. METHODS: In a double blind placebo-controlled crossover study, 19 healthy young male volunteers were tested after a single dose of placebo or 10, 20 or 40 mg of methylphenidate. Cognitive performance testing included a word learning test as a measure of declarative memory, a spatial working memory test, a set-shifting test, a stop signal test and a computerized version of the Tower of London planning test. RESULTS: Declarative memory consolidation was significantly improved relative to placebo after 20 and 40 mg of methylphenidate. Methylphenidate also improved set shifting and stopped signal task performance but did not affect spatial working memory or planning. CONCLUSIONS: To the best of our knowledge, this is the first study reporting enhanced declarative memory consolidation after methylphenidate in a dose-related fashion over a dose range that is presumed to reflect a wide range of dopamine reuptake inhibition

Executive Functioning in Daily Life in Parkinson's Disease: Initiative, Planning and Multi-Task Performance

Impairments in executive functioning are frequently observed in Parkinson's disease (PD). However, executive functioning needed in daily life is difficult to measure. Considering this difficulty the Cognitive Effort Test (CET) was recently developed. In this multi-task test the goals are specified but participants are free in their approach. This study applies the CET in PD patients and investigates whether initiative, planning and multi-tasking are associated with aspects of executive functions and psychomotor speed. Thirty-six PD patients with a mild to moderate disease severity and thirty-four healthy participants were included in this study. PD patients planned and demonstrated more sequential task execution, which was associated with a decreased psychomotor speed. Furthermore, patients with a moderate PD planned to execute fewer tasks at the same time than patients with a mild PD. No differences were found between these groups for multi-tasking. In conclusion, PD patients planned and executed the tasks of the CET sequentially rather than in parallel presumably reflecting a compensation strategy for a decreased psychomotor speed. Furthermore, patients with moderate PD appeared to take their impairments into consideration when planning how to engage the tasks of the test. This compensation could not be detected in patients with mild PD

Intra-Individual Variability in Alzheimer's Disease and Cognitive Aging: Definitions, Context, and Effect Sizes

To explore different definitions of intra-individual variability (IIV) to summarize performance on commonly utilized cognitive tests (Mini Mental State Exam; Clock Drawing Test); compare them and their potential to differentiate clinically-defined populations; and to examine their utility in predicting clinical change in individuals from the Alzheimer's Disease Neuroimaging Initiative (ADNI).) were computed for each of these definitions in 500 simulated replicates using scores on the Mini Mental State Exam and Clock Drawing Test. IIV was computed based on test items separately (‘within test’ IIV) and the two tests together (‘across test’ IIV). The best performing definition was then used to compute IIV for a third test, the Alzheimer's Disease Assessment Scale-Cognitive, and the simulations and effect sizes were again computed. All effect size estimates based on simulated data were compared to those computed based on the total scores in the observed data. Association between total score and IIV summaries of the tests and the Clinician's Dementia Rating were estimated to test the utility of IIV in predicting clinically meaningful changes in the cohorts over 12- and 24-month intervals.ES estimates differed substantially depending on the definition of IIV and the test(s) on which IIV was based. IIV (coefficient of variation) summaries of MMSE and Clock-Drawing performed similarly to their total scores, the ADAS total performed better than its IIV summary.IIV can be computed within (items) or across (totals) items on commonly-utilized cognitive tests, and may provide a useful additional summary measure of neuropsychological test performance

Neuropsychological assessment of attention in children with spina bifida

<p>Abstract</p> <p>Background</p> <p>Children with the severe form of spina bifida (SBM: spina bifida with myelomeningocele with accompanying hydrocephalus) may manifest attention deficits, and have a similar psychological profile to children with hydrocephalus due to other etiologies. It is unclear to what extent tests to assess attention in SBM are confounded by the accompanying cognitive or visual-motor impairments. The aim of this study was to analyse attention functions by administering two different types of attention tests, one with high and the other with low cognitive and motor requirements. This enabled the possible interaction between attention and cognitive and motor impairment to be assessed.</p> <p>Methods</p> <p>The study group comprised 31 children with SBM with shunted hydrocephalus. Twenty children with SB-only formed a closely matched comparison group. Of these, 19 children with SBM and 18 with SB had a full-scale IQ (FSIQ) higher than 70. All had undergone spinal surgery and all children with SBM had been shunted within the first months of life. Between 6 and 15 years of age, the children were assessed on focused and sustained attention, encoding, and distractibility/impulsivity, using both traditional tests and computerized attention tests.</p> <p>Results</p> <p>Compared to the SB group, attention scores of children with SBM were lower on the traditional tests, but when interfering cognitive and visual-motor requirements were eliminated using the computerised tasks, most differences disappeared. Furthermore, in contrast to traditional attention tasks, computerized tests showed no significant correlations with IQ-scores and visual-motor skills.</p> <p>Conclusion</p> <p>Assessment of attention functions in children with SBM by traditional tests may be misleading, because this paediatric population with complex cerebral malformations has difficulty with the cognitive and visual-motor requirements. To control for these interactions, the use of both traditional and computerized attention tests is recommended.</p

Maximum (prior) brain size, not atrophy, correlates with cognition in community-dwelling older people: a cross-sectional neuroimaging study

<p>Abstract</p> <p>Background</p> <p>Brain size is associated with cognitive ability in adulthood (correlation ~ .3), but few studies have investigated the relationship in normal ageing, particularly beyond age 75 years. With age both brain size and fluid-type intelligence decline, and regional atrophy is often suggested as causing decline in specific cognitive abilities. However, an association between brain size and intelligence may be due to the persistence of this relationship from earlier life.</p> <p>Methods</p> <p>We recruited 107 community-dwelling volunteers (29% male) aged 75–81 years for cognitive testing and neuroimaging. We used principal components analysis to derived a 'general cognitive factor' (g) from tests of fluid-type ability. Using semi-automated analysis, we measured whole brain volume, intracranial area (ICA) (an estimate of maximal brain volume), and volume of frontal and temporal lobes, amygdalo-hippocampal complex, and ventricles. Brain atrophy was estimated by correcting WBV for ICA.</p> <p>Results</p> <p>Whole brain volume (WBV) correlated with general cognitive ability (g) (r = .21, P < .05). Statistically significant associations between brain areas and specific cognitive abilities became non-significant when corrected for maximal brain volume (estimated using ICA), i.e. there were no statistically significant associations between atrophy and cognitive ability. The association between WBV and g was largely attenuated (from .21 to .03: i.e. attenuating the variance by 98%) by correcting for ICA. ICA accounted for 6.2% of the variance in g in old age, whereas atrophy accounted for < 1%.</p> <p>Conclusion</p> <p>The association between brain regions and specific cognitive abilities in community dwelling people of older age is due to the life-long association between whole brain size and general cognitive ability, rather than atrophy of specific regions. Researchers and clinicians should therefore be cautious of interpreting global or regional brain atrophy on neuroimaging as contributing to cognitive status in older age without taking into account prior mental ability and brain size.</p

Measurement error adjustment in essential fatty acid intake from a food frequency questionnaire: alternative approaches and methods

<p>Abstract</p> <p>Background</p> <p>We aimed at assessing the degree of measurement error in essential fatty acid intakes from a food frequency questionnaire and the impact of correcting for such an error on precision and bias of odds ratios in logistic models. To assess these impacts, and for illustrative purposes, alternative approaches and methods were used with the binary outcome of cognitive decline in verbal fluency.</p> <p>Methods</p> <p>Using the Atherosclerosis Risk in Communities (ARIC) study, we conducted a sensitivity analysis. The error-prone exposure – visit 1 fatty acid intake (1987–89) – was available for 7,814 subjects 50 years or older at baseline with complete data on cognitive decline between visits 2 (1990–92) and 4 (1996–98). Our binary outcome of interest was clinically significant decline in verbal fluency. Point estimates and 95% confidence intervals were compared between naïve and measurement-error adjusted odds ratios of decline with every SD increase in fatty acid intake as % of energy. Two approaches were explored for adjustment: (A) External validation against biomarkers (plasma fatty acids in cholesteryl esters and phospholipids) and (B) Internal repeat measurements at visits 2 and 3. The main difference between the two is that Approach B makes a stronger assumption regarding lack of error correlations in the structural model. Additionally, we compared results from regression calibration (RCAL) to those from simulation extrapolation (SIMEX). Finally, using structural equations modeling, we estimated attenuation factors associated with each dietary exposure to assess degree of measurement error in a bivariate scenario for regression calibration of logistic regression model.</p> <p>Results and conclusion</p> <p>Attenuation factors for Approach A were smaller than B, suggesting a larger amount of measurement error in the dietary exposure. Replicate measures (Approach B) unlike concentration biomarkers (Approach A) may lead to imprecise odds ratios due to larger standard errors. Using SIMEX rather than RCAL models tends to preserve precision of odds ratios. We found in many cases that bias in naïve odds ratios was towards the null. RCAL tended to correct for a larger amount of effect bias than SIMEX, particularly for Approach A.</p

A feasibility study exploring the role of pre-operative assessment when examining the mechanism of ‘chemo-brain’ in breast cancer patients

Background: Women receiving chemotherapy treatment for breast cancer may experience problems with their memory and attention (cognition), which is distressing and interferes with quality of life. It is unclear what causes or contributes to the problems they report: psychological distress, fatigue, coping style, or specific biological changes for example to pro inflammatory cytokines. Research shows however, that approximately a third of women with breast cancer perform poorly on tests of cognition before commencing chemotherapy. We aimed to examine the acceptability and relevance of pre-surgical assessments (bloods, brain imaging, cognitive tests and self-report questionnaires) when investigating the phenomenon of ‘chemo-brain’ and investigate whether inflammatory markers mediate chemotherapy-induced neuropsychological impairments in women treated for breast cancer. Methods: Women with early stage breast cancer completed neuropsychological and quality of life assessments at T1 (pre-surgery), T2 (post-surgery before chemotherapy) and T3 (6 months later). Blood cytokine levels were measured at the same time points and brain imaging was performed at T1 and T3. Results: In total, 14/58 women participated (8 chemotherapy, 6 non-chemotherapy). Prior to the start of chemotherapy a decline in cognitive performance compared to baseline was observed in one participant. At T3 women who received chemotherapy reported poorer quality of life and greater fatigue. Increases in soluble tumour necrosis factor receptor II (sTNFRII), interleukin-6, interleukin-10 and vascular endothelial growth factor occurred post chemotherapy only. Levels of sTNFRII were inversely correlated with grey matter volume (GMV) of the right posterior insula in both groups. At T3, the chemotherapy group displayed a greater reduction in GMV in the subgenual and dorsal anterior cingulate, and the inferior temporal gyrus. Conclusions: Pre-operative recruitment to the study was challenging; however, the lack of significant changes in blood cytokine levels and neuropsychological tests at T2 implies that post surgery may be a valid baseline assessment, but this needs further investigation in a larger study. The preliminary results support the hypothesis that chemotherapy induced fatigue is mediated by a change in peripheral cytokine levels which could explain some symptoms of ‘chemo brain’ experienced by patients

Double blind randomized placebo-controlled trial on the effects of testosterone supplementation in elderly men with moderate to low testosterone levels: design and baseline characteristics [ISRCTN23688581]

In ageing men testosterone levels decline, while cognitive function, muscle and bone mass, sexual hair growth, libido and sexual activity decline and the risk of cardiovascular diseases increase. We set up a double-blind, randomized placebo-controlled trial to investigate the effects of testosterone supplementation on functional mobility, quality of life, body composition, cognitive function, vascular function and risk factors, and bone mineral density in older hypogonadal men. We recruited 237 men with serum testosterone levels below 13.7 nmol/L and ages 60–80 years. They were randomized to either four capsules of 40 mg testosterone undecanoate (TU) or placebo daily for 26 weeks. Primary endpoints are functional mobility and quality of life. Secondary endpoints are body composition, cognitive function, aortic stiffness and cardiovascular risk factors and bone mineral density. Effects on prostate, liver and hematological parameters will be studied with respect to safety. Measure of effect will be the difference in change from baseline visit to final visit between TU and placebo. We will study whether the effect of TU differs across subgroups of baseline waist girth (< 100 cm vs. ≥ 100 cm; testosterone level (<12 versus ≥ 12 nmol/L), age (< median versus ≥ median), and level of outcome under study (< median versus ≥ median). At baseline, mean age, BMI and testosterone levels were 67 years, 27 kg/m(2 )and 10.72 nmol/L, respectively