Gait variability at fast-pace walking speed: A biomarker of mild cognitive impairment?

The interpretation of the increase in stride-to-stride variability of stride time (STV) regarding the evolution of cognitive deficits across the dementia spectrum is matter of debate.The aim of this study was to compare STV at usual and fast-pace walking speeds of MCI patients with that of cognitively healthy individuals (CHI) and Alzheimer\u27s disease (AD) patients with mild dementia, while considering the effects of potential confounders. STV while walking at usual and fast-pace walking speeds was recorded with the GAITRiteA (R) system from 116 older adults (mean age 75.6 +/- 6.5 years; 55.2% female) divided into 3 groups according to their cognitive status (44 CHI, 39 MCI patients and 33 AD patients with mild dementia). The full adjusted multiple linear regression models showed that high STV was associated with slow gait speed at usual-pace walking speed (P=0.002) and with the MCI status at fast-pace walking speed (P=0.015). High STV at fast-pace walking speed was a specific gait disturbance of MCI patients in the sample of studied participants, and thus could be used in the future as a specific biomarker of MCI patients

Effectiveness of the Combination of Memantine Plus Vitamin D on Cognition in Patients With Alzheimer Disease: A Pre-Post Pilot Study

Objective: To determine whether treatment with memantine plus vitamin D is more effective than memantine or vitamin D alone in improving cognition among patients with Alzheimer disease (AD). Methods: We studied 43 white outpatients (mean 84.7±6.3 years; 65.1% women) with a new diagnosis of AD, who had not taken anti-dementia drugs or vitamin D supplements. We prescribed memantine alone (n=18), vitamin D alone (n=17), or memantine plus vitamin D (n=8) for an average of 6 months. We assessed cognitive change with the Mini-Mental State Examination (MMSE). We used age, sex, pre-treatment MMSE score, and duration of treatment as covariables. Results: Before treatment, the 3 groups had comparable MMSE scores. At 6 months, participants taking memantine plus vitamin D increased their MMSE score by 4.0±3.7 points (P=0.034), while participants taking memantine alone remained stable (change of 0.0±1.8 points; P=0.891), as did those taking vitamin D alone (−0.6±3.1 points; P=0.504). Treatment with memantine plus vitamin D was associated with improvement in the MMSE score compared to memantine or vitamin D alone after adjustment for covariables (P<0.01). Mixed regression analysis showed that the visit by combined treatments (memantine plus vitamin D) interaction was significant (P=0.001), while memantine or vitamin D alone showed no effect. Conclusions: Patients with AD who took memantine plus vitamin D for 6 months had a statistically and clinically relevant gain in cognition, underlining possible synergistic and potentiating benefits of the combination

Peripheral stimulation affects subthreshold Triple Stimulation Technique.

Compared to conventional transcranial magnetic stimulation (TMS), the triple stimulation technique (TST) strongly decrease the effects of desynchronization of descending discharges and accompanying phase cancellation that follow TMS and offers a more sensitive method to quantify motor evoked potentials (MEPs). Using the TST, we explored as to whether sub-threshold TMS evokes peripheral motor neuron discharges (MNs). We compared the number of MEPs elicited by TMS and by TST in fifteen healthy participants. We used the subthreshold intensity of 80 % resting motor threshold. To control the TST assessment of the corticospinal tract, we included a peripheral stimulation control condition, which consisted of peripheral stimulation alone, in a subgroup of five volunteers. Compared to TMS, TST at sub-threshold intensities did not detect significantly more responses unequivocally attributable to the cortical stimulation. In contrast, the peripheral supra-maximal stimuli produced confounding effects in the TST condition that were, in part, indistinguishable from cortical responses. At subthreshold TMS intensities, the TST does not detect more discharges of spinal MNs than conventional TMS and, in addition, it is confounded by effects from peripheral stimulation. The TST can be useful in assessing the integrity of the MN pool and of the corticospinal tract. However, if used at near threshold intensity, the confounding effects of peripheral stimulation need to be considered; for instance, in paired-pulse stimulation paradigms assessing the cortical physiology

Higher vitamin D dietary intake is associated with lower risk of alzheimer's disease: a 7-year follow-up

BACKGROUND: Hypovitaminosis D is associated with cognitive decline among older adults. The relationship between vitamin D intakes and cognitive decline is not well understood. Our objective was to determine whether the dietary intake of vitamin D was an independent predictor of the onset of dementia within 7 years among women aged 75 years and older.METHODS: Four hundred and ninety-eight community-dwelling women (mean, 79.8 3.8 years) free of vitamin D supplements from the EPIDemiology of OSteoporosis Toulouse cohort study were divided into three groups according to the onset of dementia within 7 years (ie, no dementia, Alzheimer\u27s disease [AD], or other dementias). Baseline vitamin D dietary intakes were estimated from self-administered food frequency questionnaire. Age, body mass index, initial cognitive performance, education level, physical activity, sun exposure, disability, number of chronic diseases, hypertension, depression, use of psychoactive drugs, and baseline season were considered as potential confounders. RESULTS: Women who developed AD (n = 70) had lower baseline vitamin D intakes (mean, 50.3 19.3 mug/wk) than nondemented (n = 361; mean intake = 59.0 29.9 mug/wk, p = .027) or those who developed other dementias (n = 67; mean intake = 63.6 38.1 mug/wk, p = .010). There was no difference between other dementias and no dementia (p = .247). Baseline vitamin D dietary intakes were associated with the onset of AD (adjusted odds ratio = 0.99 [95% confidence interval = 0.98-0.99], p = .041) but not with other dementias (p = .071). Being in the highest quintile of vitamin D dietary intakes was associated with a lower risk of AD compared with the lower 4 quintiles combined (adjusted odds ratio = 0.23 [95% confidence interval = 0.08-0.67], p = .007). CONCLUSIONS: Higher vitamin D dietary intake was associated with a lower risk of developing AD among older women

Derivation and validation of a Short Form of the Mini-Mental State Examination for the screening of dementia in older adults with a memory complaint

BACKGROUND AND PURPOSE: To validate a Short Form of the Mini-Mental State Examination (SMMSE) as a screening test for dementia in older ambulatory individuals followed in a memory clinic for a memory complaint. METHODS: A total of 202 cognitively healthy individuals, 100 individuals with a mild cognitive impairment and 304 demented individuals sent for a memory complaint by their primary care physician to a memory clinic were prospectively included in this cross-sectional study. They were randomized into derivation (n = 303) and validation (n = 303) groups. The SMMSE score was built from six memory items of MMSE, with a score ranging from 0 to 6 (i.e. best performance). RESULTS: The receiver operating characteristic curve showed an area under the curve of 0.98 for the derivation group and 0.97 for the validation group without differences between curves (P = 0.254). The cut-off between the sensitivity and the specificity of the SMMSE score for clinically diagnosed dementia wa

The Vitamin A Derivative All-Trans Retinoic Acid Repairs Amyloid-β-Induced Double-Strand Breaks in Neural Cells and in the Murine Neocortex.

The amyloid-β peptide or Aβ is the key player in the amyloid-cascade hypothesis of Alzheimer's disease. Aβ appears to trigger cell death but also production of double-strand breaks (DSBs) in aging and Alzheimer's disease. All-trans retinoic acid (RA), a derivative of vitamin A, was already known for its neuroprotective effects against the amyloid cascade. It diminishes, for instance, the production of Aβ peptides and their oligomerisation. In the present work we investigated the possible implication of RA receptor (RAR) in repair of Aβ-induced DSBs. We demonstrated that RA, as well as RAR agonist Am80, but not AGN 193109 antagonist, repair Aβ-induced DSBs in SH-SY5Y cells and an astrocytic cell line as well as in the murine cortical tissue of young and aged mice. The nonhomologous end joining pathway and the Ataxia Telangiectasia Mutated kinase were shown to be involved in RA-mediated DSBs repair in the SH-SY5Y cells. Our data suggest that RA, besides increasing cell viability in the cortex of young and even of aged mice, might also result in targeted DNA repair of genes important for cell or synaptic maintenance. This phenomenon would remain functional up to a point when Aβ increase and RA decrease probably lead to a pathological state

Source Dimensions in Ultrarelativistic Heavy Ion Collisions

Recent experiments on pion correlations, interpreted as interferometric measurements of the collision zone, are compared with models that distinguish a prehadronic phase and a hadronic phase. The models include prehadronic longitudinal expansion, conversion to hadrons in local kinetic equilibrium, and rescattering of the produced hadrons. We find that the longitudinal and outward radii are surprisingly sensitive to the algorithm used for two-body collisions. The longitudinal radius measured in collisions of 200 GeV/u sulfur nuclei on a heavy target requires the existence of a prehadronic phase which converts to the hadronic phase at densities around 0.8-1.0 GeV/fm$^3$. The transverse radii cannot be reproduced without introducing more complex dynamics into the transverse expansion.Comment: RevTeX 3.0, 28 pages, 6 figures, not included, revised version, major change is an additional discussion of the classical two-body collision algorithm, a (compressed) postscript file of the complete paper including figures can be obtained from Authors or via anonymous ftp at ftp://ftp_int.phys.washington.edu/pub/herrmann/pisource.ps.

Relations between lipoprotein(a) concentrations, LPA genetic variants, and the risk of mortality in patients with established coronary heart disease: a molecular and genetic association study

Background: Lipoprotein(a) concentrations in plasma are associated with cardiovascular risk in the general population. Whether lipoprotein(a) concentrations or LPA genetic variants predict long-term mortality in patients with established coronary heart disease remains less clear. Methods: We obtained data from 3313 patients with established coronary heart disease in the Ludwigshafen Risk and Cardiovascular Health (LURIC) study. We tested associations of tertiles of lipoprotein(a) concentration in plasma and two LPA single-nucleotide polymorphisms ([SNPs] rs10455872 and rs3798220) with all-cause mortality and cardiovascular mortality by Cox regression analysis and with severity of disease by generalised linear modelling, with and without adjustment for age, sex, diabetes diagnosis, systolic blood pressure, BMI, smoking status, estimated glomerular filtration rate, LDL-cholesterol concentration, and use of lipid-lowering therapy. Results for plasma lipoprotein(a) concentrations were validated in five independent studies involving 10 195 patients with established coronary heart disease. Results for genetic associations were replicated through large-scale collaborative analysis in the GENIUS-CHD consortium, comprising 106 353 patients with established coronary heart disease and 19 332 deaths in 22 studies or cohorts. Findings: The median follow-up was 9·9 years. Increased severity of coronary heart disease was associated with lipoprotein(a) concentrations in plasma in the highest tertile (adjusted hazard radio [HR] 1·44, 95% CI 1·14–1·83) and the presence of either LPA SNP (1·88, 1·40–2·53). No associations were found in LURIC with all-cause mortality (highest tertile of lipoprotein(a) concentration in plasma 0·95, 0·81–1·11 and either LPA SNP 1·10, 0·92–1·31) or cardiovascular mortality (0·99, 0·81–1·2 and 1·13, 0·90–1·40, respectively) or in the validation studies. Interpretation: In patients with prevalent coronary heart disease, lipoprotein(a) concentrations and genetic variants showed no associations with mortality. We conclude that these variables are not useful risk factors to measure to predict progression to death after coronary heart disease is established. Funding: Seventh Framework Programme for Research and Technical Development (AtheroRemo and RiskyCAD), INTERREG IV Oberrhein Programme, Deutsche Nierenstiftung, Else-Kroener Fresenius Foundation, Deutsche Stiftung für Herzforschung, Deutsche Forschungsgemeinschaft, Saarland University, German Federal Ministry of Education and Research, Willy Robert Pitzer Foundation, and Waldburg-Zeil Clinics Isny

Global surveillance of cancer survival 1995-2009: analysis of individual data for 25,676,887 patients from 279 population-based registries in 67 countries (CONCORD-2)

BACKGROUND: Worldwide data for cancer survival are scarce. We aimed to initiate worldwide surveillance of cancer survival by central analysis of population-based registry data, as a metric of the effectiveness of health systems, and to inform global policy on cancer control. METHODS: Individual tumour records were submitted by 279 population-based cancer registries in 67 countries for 25·7 million adults (age 15-99 years) and 75,000 children (age 0-14 years) diagnosed with cancer during 1995-2009 and followed up to Dec 31, 2009, or later. We looked at cancers of the stomach, colon, rectum, liver, lung, breast (women), cervix, ovary, and prostate in adults, and adult and childhood leukaemia. Standardised quality control procedures were applied; errors were corrected by the registry concerned. We estimated 5-year net survival, adjusted for background mortality in every country or region by age (single year), sex, and calendar year, and by race or ethnic origin in some countries. Estimates were age-standardised with the International Cancer Survival Standard weights. FINDINGS: 5-year survival from colon, rectal, and breast cancers has increased steadily in most developed countries. For patients diagnosed during 2005-09, survival for colon and rectal cancer reached 60% or more in 22 countries around the world; for breast cancer, 5-year survival rose to 85% or higher in 17 countries worldwide. Liver and lung cancer remain lethal in all nations: for both cancers, 5-year survival is below 20% everywhere in Europe, in the range 15-19% in North America, and as low as 7-9% in Mongolia and Thailand. Striking rises in 5-year survival from prostate cancer have occurred in many countries: survival rose by 10-20% between 1995-99 and 2005-09 in 22 countries in South America, Asia, and Europe, but survival still varies widely around the world, from less than 60% in Bulgaria and Thailand to 95% or more in Brazil, Puerto Rico, and the USA. For cervical cancer, national estimates of 5-year survival range from less than 50% to more than 70%; regional variations are much wider, and improvements between 1995-99 and 2005-09 have generally been slight. For women diagnosed with ovarian cancer in 2005-09, 5-year survival was 40% or higher only in Ecuador, the USA, and 17 countries in Asia and Europe. 5-year survival for stomach cancer in 2005-09 was high (54-58%) in Japan and South Korea, compared with less than 40% in other countries. By contrast, 5-year survival from adult leukaemia in Japan and South Korea (18-23%) is lower than in most other countries. 5-year survival from childhood acute lymphoblastic leukaemia is less than 60% in several countries, but as high as 90% in Canada and four European countries, which suggests major deficiencies in the management of a largely curable disease. INTERPRETATION: International comparison of survival trends reveals very wide differences that are likely to be attributable to differences in access to early diagnosis and optimum treatment. Continuous worldwide surveillance of cancer survival should become an indispensable source of information for cancer patients and researchers and a stimulus for politicians to improve health policy and health-care systems