[Acute methotrexate-related neurotoxicity and pseudo-stroke syndrome]. / Neurotoxicité aiguë secondaire au méthotrexate et « pseudo-stroke ¼ syndrome.

Treatment of acute lymphoblastic leukemia requires high-dose systemic and/or intrathecal methotrexate to prevent and/or treat central nervous system disorders. Acute neurotoxicity of methotrexate, of unknown etiopathogenesis, is characterized by the polymorphism of clinical manifestations, responsible for a potentially harmful diagnostic delay in these immunosuppressed patients. We describe five episodes of transient acute leukoencephalopathy mimicking a stroke, reported in the literature as "pseudo-stroke syndrome". Neurologic symptoms occurred 3-10 days after IV or IT methotrexate and manifested as aphasia and alternating sensorimotor deficit. The fluctuating symptomatology regressed completely within a few days. Brain MRI, which is essential for diagnosis, demonstrated early white matter diffusion restriction in the affected cerebral area. These anomalies disappeared in one week, while hyperintense T2 FLAIR signals developed in the corresponding brain areas. The long-term progression of these pseudo-stroke patients was favorable, without any therapeutic modification. Nevertheless, the involvement of transient acute leukoencephalopathy episodes in the progressive onset of neuro-cognitive disorders is discussed.

Dietary recommendations for the prevention of depression.

BACKGROUND: Major depressive disorder is a common, chronic condition that imposes a substantial burden of disability globally. As current treatments are estimated to address only one-third of the disease burden of depressive disorders, there is a need for new approaches to prevent depression or to delay its progression. While in its early stages, converging evidence from laboratory, population research, and clinical trials now suggests that dietary patterns and specific dietary factors may influence the risk for depression. However, largely as a result of the recency of the nutritional psychiatry field, there are currently no dietary recommendations for depression. AIM: The aim of this paper is to provide a set of practical dietary recommendations for the prevention of depression, based on the best available current evidence, in order to inform public health and clinical recommendations. RESULTS: Five key dietary recommendations for the prevention of depression emerged from current published evidence. These comprise: (1) follow 'traditional' dietary patterns, such as the Mediterranean, Norwegian, or Japanese diet; (2) increase consumption of fruits, vegetables, legumes, wholegrain cereals, nuts, and seeds; (3) include a high consumption of foods rich in omega-3 polyunsaturated fatty acids; (4) replace unhealthy foods with wholesome nutritious foods; (5) limit your intake of processed-foods, 'fast' foods, commercial bakery goods, and sweets. CONCLUSION: Although there are a number of gaps in the scientific literature to date, existing evidence suggests that a combination of healthful dietary practices may reduce the risk of developing depression. It is imperative to remain mindful of any protective effects that are likely to come from the cumulative and synergic effect of nutrients that comprise the whole-diet, rather than from the effects of individual nutrients or single foods. As the body of evidence grows from controlled intervention studies on dietary patterns and depression, these recommendations should be modified accordingly.

Interleukin-6 as a predictor of symptom resolution in psychological distress: a cohort study.

BACKGROUND: Elevated levels of interleukin-6 (IL-6) have been associated with the development of common mental disorders, such as depression, but its role in symptom resolution is unclear. METHOD: We examined the association between IL-6 and symptom resolution in a non-clinical sample of participants with psychological distress. RESULTS: Relative to high IL-6 levels, low levels at baseline were associated with symptom resolution at follow-up [age- and sex-adjusted risk ratio (RR) = 1.15, 95% confidence interval (CI) 1.06-1.25]. Further adjustment for covariates had little effect on the association. Symptomatic participants with repeated low IL-6 were more likely to be symptom-free at follow-up compared with those with repeated high IL-6 (RR = 1.21, 95% CI 1.03-1.41). Among the symptomatic participants with elevated IL-6 at baseline, IL-6 decreased along with symptom resolution. CONCLUSIONS: IL-6 is potentially related to the mechanisms underlying recovery from symptoms of mental ill health. Further studies are needed to examine these mechanisms and to confirm the findings in relation to clinical depression.

Measuring cognitive change in subjects with prodromal Alzheimer's disease.

OBJECTIVE: To investigate the sensitivity of a large set of neuropsychological tests to detect cognitive changes due to prodromal Alzheimer's disease(AD); to compare their metrological properties in order to select a restricted number of these tests for the longitudinal follow-up of subjects with prodromal AD. PARTICIPANTS: 212 patients with mild cognitive impairment were tested at baseline by a standardised neuropsychological battery, which included: the Free and Cued Selective Reminding test (FCSRT), the Benton Visual Retention test, the Deno100, verbal fluency, a serial digit learning test, the double task of Baddeley, the Wechsler Adult Intelligence Scale (WAIS) similarities, the Trail-Making Test and the WAIS digit symbol test. Patients were monitored every 6 months for up to 3 years in order to identify those who converted to AD (retrospectively classified as prodromal AD). Statistical analyses were performed using a nonlinear multivariate mixed model involving a latent process. This model assumes that the psychometric tests are nonlinear transformations of a common latent cognitive process, and it captures the metrological properties of tests. RESULTS: 57 patients converted to AD. The most sensitive tests in the detection of cognitive changes due to prodromal AD were the FCSRT, the semantic verbal fluency and the Deno100. Some tests exhibited a higher sensitivity to cognitive changes for subjects with high levels of cognition, such as the free recall, delayed free recall scores of the FCSRT and the semantic verbal fluency, whereas others showed a higher sensitivity at low levels of cognition, such as the total recall score of the FCSRT. CONCLUSIONS: Tests used for the follow-up of prodromal AD subjects should be chosen among those that actually decline in this stage of the disease and should be selected according to the subject's initial scores.

Physical activity patterns over 10 years in relation to body mass index and waist circumference: the Whitehall II cohort study.

OBJECTIVE: Physical activity patterns over 10-years in relation to changes in body mass index (BMI) and waist circumference (WC) were examined. DESIGN AND METHODS: Participants (4,880, mean age 49.3 years at baseline) from the Whitehall II cohort study were included. Self-reported physical activity and anthropometric data were collected at baseline (1991) and twice during follow-up (1997 and 2002). RESULTS: At baseline, meeting established guidelines for physical activity, particularly through vigorous activity, was associated with lower WC (multivariable adjusted B compared to not meeting the guidelines -2.08 cm, 95% CI, -1.39, -0.75) and BMI (-0.34 kg/m(2) , -0.10, -0.59). Based on repeat data, "high adherence" to the guidelines compared to "rare adherence" over follow-up was associated with lower BMI (adjusted difference, -0.43 kg/m(2) , 95% CI, -0.79, -0.08) and WC (-2.50 cm, 95% CI, -3.46, -1.54) at follow-up. Compared to participants that remained stable between 1997 and 2002 (change of <2.5 h/week), those that reported an increase in moderate-vigorous physical activity of at least 2.5 h/week displayed lower BMI (-0.40 kg/m(2) , 95% CI, -0.71, -0.08) and WC (-1.10 cm, 95% CI, -1.95, -0.75). CONCLUSION: Regular physical activity, confirmed by repeated assessments, is associated with relatively favorable levels of adiposity markers after 10 years follow-up.

Gender differences in copper, zinc and selenium status in diabetic-free metabolic syndrome European population - the IMMIDIET study.

BACKGROUND AND AIMS: The European 'IMMIDIET' study was designed to evaluate the effect of genetic and dietary habit interactions on cardiovascular disease risk factors in non-diabetic subjects. Copper, zinc and selenium are involved in redox balance and modifications of their homeostasis could be associated with metabolic syndrome. Because few studies have dealt with trace element status in metabolic syndrome with conflicting results, we aimed at investigating the relationships between plasma copper, zinc and selenium concentrations and metabolic syndrome in the IMMIDIET population. METHODS AND RESULTS: Male-female couples born and living in Abruzzo, Italy (n = 271); Limburg, Belgium (n = 267), southwest part of London, England (n = 263) and 205 Italian-Belgian mixed couples living in Belgium were enrolled. Data on medical history, hypertension and blood lipid profile, medication use, smoking and alcohol habits, physical activity and socioeconomic status were collected using a standardised questionnaire. Anthropometric, blood pressure, glucose, insulin, lipid profile and copper, zinc and selenium measurements were performed. Participants were classified in two groups according to the presence of metabolic syndrome (Yes/No). Comparison between these two groups, performed separately in men and women, indicated no association in men whereas, in women, metabolic syndrome was associated with higher plasma selenium concentrations (odds ratio (OR) = 1.55(1.28-1.89)); this association remained significant after adjustment for age, group, social status, physical activity, energy intake, alcohol consumption, smoking and hormonal status (OR = 1.33 (1.06-1.67)). CONCLUSION: Our results indicate gender differences in the association between plasma selenium concentration and metabolic syndrome without diabetes and may suggest a sub-clinical deleterious effect of high selenium status in women.

Selenium status and blood lipids: the cardiovascular risk in Young Finns study.

BACKGROUND: Concern has been recently raised about possible adverse cardio-metabolic effects of high selenium status, such as increased risks of diabetes and hyperlipidaemia. However, most of the evidence comes from selenium-replete populations such as that of the United States. OBJECTIVES: To examine cross-sectional and longitudinal associations of serum selenium with cardiovascular risk factors in Finland where selenium levels were amongst the lowest in the world until the early 1980s before the implementation of a nationwide selenium fertilization programme. METHODS: Serum selenium was measured in 1235 young Finns aged 3-18 years at baseline in 1980 (prefertilization) and in a subgroup (N = 262) at the 6-year follow-up (1986, postfertilization). During the 27-year follow-up, serum lipids, blood pressure, body mass index and smoking were assessed five times (1980, 1983, 1986, 2001 and 2007). RESULTS: Mean (±SD) serum selenium concentrations were 74.3 ± 14.0 ng mL(-1) in 1980 and 106.6 ± 12.5 ng mL(-1) in 1986 (average increase 32.3 ng mL(-1); 95% CI: 30.3 to 34.3, P < 0.0001). In univariate and multivariable cross-sectional models in 1980 and 1986, increased serum selenium levels were consistently associated with increased total, HDL and Low-density lipoprotein (LDL) cholesterol. However, the average longitudinal changes in lipids were -0.20 mmol L(-1) (95% CI: -0.30 to -0.10, P < 0.0001) for total cholesterol, 0.06 mmol L(-1) (95% CI: 0.03 to 0.10, P < 0.0001) for HDL cholesterol, and -0.23 mmol L(-1) (95% CI: -0.31 to -0.14, P < 0.0001) for LDL cholesterol. Selenium measured in 1986 was not associated with lipids assessed in 2001 and 2007. CONCLUSIONS: Cross-sectional findings from the Young Finns study corroborate positive associations of selenium status with serum lipids. However, longitudinal evidence does not support the causality of this link.

Metabolic syndrome and cognitive decline in French elders: the Three-City Study.

OBJECTIVE: To examine associations between metabolic syndrome (MetS) and its individual components with risk of cognitive decline on specific cognitive functions. METHODS: Participants were 4,323 women and 2,764 men aged 65 and over enrolled in the longitudinal Three-City Study. Cognitive decline, defined as being in the worst quintile of the distribution of the difference between baseline score and either 2- or 4-year follow-up, was assessed by the Mini-Mental State Examination (MMSE, global cognitive function), the Isaacs Set Test (IST, verbal fluency), and the Benton Visual Retention Test (BVRT, visual working memory). MetS was defined by National Cholesterol Education Program-Adult Treatment Panel III criteria (at least 3 of 5 cardio-metabolic abnormalities: hypertension, high waist circumference, hypertriglyceridemia, low high-density lipoprotein [HDL] cholesterol, hyperglycemia). Proportional hazards models were adjusted for age, gender, educational level, center, baseline cognitive score, APOE4 genotype, and other potential confounders. RESULTS: MetS at baseline was associated with an increased risk of cognitive decline on MMSE (hazard ratio [HR] = 1.22 [1.08-1.37]; p = 0.001) and BVRT (HR = 1.13 [1.01-1.26]; p = 0.03) but not on IST (HR = 1.11 [0.95-1.29]; p = 0.18). Among MetS components, hypertriglyceridemia and low HDL cholesterol were significantly associated with higher decline on MMSE; diabetes, but not elevated fasting glycemia, was significantly associated with higher decline on BVRT and IST. CONCLUSIONS: MetS as a whole and several of its components had a negative impact on global cognitive decline and specific cognitive functions in older persons.

Changes in C-reactive protein levels before type 2 diabetes and cardiovascular death: the Whitehall II study.

OBJECTIVE: Prospective studies show that high C-reactive protein (CRP) levels predict diabetes and cardiovascular disease (CVD), but changes in this marker preceding disease onset are not well characterized. This study describes CRP trajectories prior to type 2 diabetes onset and fatal CVD. METHODS: In a prospective cohort of 7350 British civil servants (70% male, mean age 51 years), 558 incident type 2 diabetes cases (75-g oral glucose tolerance test, doctor's diagnosis, or self-report) and 125 certified fatal cardiovascular events were observed during a median follow-up of >14 years. Trajectories of logarithmically transformed CRP levels prior to incident diabetes or fatal cardiovascular event (cases), or the end of follow-up (controls) were calculated using multilevel modeling. RESULTS: Baseline CRP levels were higher among participants who developed diabetes (median (interquartile range) 1.44 (2.39) vs 0.78 (1.21) mg/l) or fatal CVD (1.49 (2.47) vs 0.84 (1.30) mg/l) compared with controls (both P<0.0001). In models adjusted for age, sex, body mass index, ethnicity, and employment grade, CRP levels increased with time among both incident diabetes cases and controls (P<0.0001), but this increase was less steep for cases group (P<0.05). CRP levels followed increasing linear trajectories in fatal cardiovascular cases and controls (P<0.0001) with no slope difference between the groups. CONCLUSIONS: CRP levels were higher among those who subsequently developed diabetes or died from CVD. For type 2 diabetes, age-related increase in CRP levels was less steep in the cases group than in controls, whereas for fatal CVD these trajectories were parallel.

Work disability following major organisational change: the Whitehall II study.

BACKGROUND: Privatisation and private sector practices have been increasingly applied to the public sector in many industrialised countries. Over the same period, long-term work disability has risen substantially. We examined whether a major organisational change--the transfer of public sector work to executive agencies run on private sector lines--was associated with an increased risk of work disability. METHODS: The study uses self-reported data from the prospective Whitehall II cohort study. Associations between transfer to an executive agency assessed at baseline (1991-1994) and work disability ascertained over a period of approximately 8 years at three follow-up surveys (1995-1996, 1997-1999 and 2001) were examined using Cox proportional hazard models. RESULTS: In age- and sex-adjusted models, risk of work disability was higher among the 1263 employees who were transferred to an executive agency (HR 1.90, 95% CI 1.46 to 2.48) compared with the 3419 employees whose job was not transferred. These findings were robust to additional adjustment for physical and mental health and health behaviours at baseline. CONCLUSIONS: Increased work disability was observed among employees exposed to the transfer of public sector work to executive agencies run on private sector lines. This may highlight an unintentional cost for employees, employers and society.

The association of cognitive performance with mental health and physical functioning strengthens with age: the Whitehall II cohort study.

BACKGROUND: Cognitive performance has been associated with mental and physical health, but it is unknown whether the strength of these associations changes with ageing and with age-related social transitions, such as retirement. We examined whether cognitive performance predicted mental and physical health from midlife to early old age. METHOD: Participants were 5414 men and 2278 women from the Whitehall II cohort study followed for 15 years between 1991 and 2006. The age range included over the follow-up was from 40 to 75 years. Mental health and physical functioning were measured six times using SF-36 subscales. Cognitive performance was assessed three times using five cognitive tests assessing verbal and numerical reasoning, verbal memory, and phonemic and semantic fluency. Socio-economic status (SES) and retirement were included as covariates. RESULTS: High cognitive performance was associated with better mental health and physical functioning. Mental health differences associated with cognitive performance widened with age from 39 to 76 years of age, whereas physical functioning differences widened only between 39 and 60 years and not after 60 years of age. SES explained part of the widening differences in mental health and physical functioning before age 60. Cognitive performance was more strongly associated with mental health in retired than non-retired participants, which contributed to the widening differences after 60 years of age. CONCLUSIONS: The strength of cognitive performance in predicting mental and physical health may increase from midlife to early old age, and these changes may be related to SES and age-related transitions, such as retirement.

Leisure activities and the risk of dementia in the elderly: results from the Three-City Study.

OBJECTIVE: There is accumulating evidence that involvement in leisure activities may be related to risk of dementia; however, there is no consensus concerning the underlying mechanism of this association. Hypothesizing that leisure activities may contribute to cognitive reserve (CR), we examined the association between leisure activities and risk of incident dementia and its subtypes within a general population sample, categorizing leisure activity as stimulating, passive, physical, and social. The possibility that these associations may be driven by other proxies of CR was also examined. METHODS: Analyses were carried out on 5,698 dementia-free participants aged 65 and over included in the Three-City cohort study in Dijon and Montpellier (France) in 1999-2001. Hazard ratios (HR) were calculated for incident dementia and its subtypes (mixed/vascular dementia and Alzheimer disease) in relation to category of leisure activity. RESULTS: Stimulating leisure activities were found to be significantly associated with a reduced risk of dementia (n = 161, HR = 0.49, 95% confidence interval [CI]: 0.31; 0.79) and Alzheimer disease (n = 105, HR = 0.39, 95% CI: 0.21; 0.71) over the 4-year follow-up 1) independently of other proxies of CR, 2) after adjusting for vascular risk factors, depressive symptoms, and physical functioning, and 3) independently of other leisure activities. Furthermore, no significant association was found with other leisure activities and dementia after controlling for the potential confounders. CONCLUSION: Our findings support the hypothesis that cognitively stimulating leisure activities may delay the onset of dementia in community-dwelling elders.

Increased selenium intake in elderly high fish consumers may account for health benefits previously ascribed to omega-3 fatty acids.

OBJECTIVE: To examine relationships between fish consumption and plasma selenium (Se) and red blood-cell fatty acid (RBC FA) profile in aged subjects. We hypothesised that the importance of Se has been underestimated when interpreting the beneficial effect of fish consumption on health. DESIGN: Cross-sectional analysis of data from a prospective cohort study. SETTING: The EVA study in Nantes, France (1991-2002). SUBJECTS: 200 subjects aged > or = 69 y with information on RBC FAs, plasma Se and completed food frequency questionnaires. METHODS: We examined correlations between the most abundant FAs, Se and number of fish meals per week. Linear regression models were used. RESULTS: Plasma Se was negatively correlated with RBC omega6 poly-unsaturated FA (PUFAs) and positively with omega3 PUFAs. Plasma Se, RBC omega3 PUFAs, docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) increased with fish consumption. Conversely, levels of omega6 PUFAs were lower in the highest fish consumption group. All associations between plasma Se and fish consumption remained significant when adjusting for omega6 PUFAs alone or additionally for age, sex, education, diabetes, hypertension, dyslipidemia, cardiovascular diseases, and broad food categories (meat, eggs, dairy products, cereals, fruit and vegetable). Associations between omega3 PUFAs and fish also remained significant in the same model independently of Se. In linear regression models adjusted for demographic indicators, fish consumption explained only 2.6% of the variance in RBC omega3 FAs (6.2% for omega6) but as much as 15% of the variance in plasma selenium. CONCLUSIONS: The observed health benefits of fish consumption in the elderly could be related not only to the increase in omega3 FA intake but also to other nutrients such as selenium. It is important to consider this observation when interpreting associations between fish consumption and health status in the elderly, particularly with regard to brain function.