Vascular Burden Predicts Gait, Mood, and Executive Function Disturbances in Older Adults with Mild Cognitive Impairment: Results from the Gait and Brain Study

International audienc

Motor cortex and gait in mild cognitive impairment: a magnetic resonance spectroscopy and volumetric imaging study

Gait disorders are common in the course of dementia, even at the stage of mild cognitive impairment, owing to probable changes in higher levels of motor control. Since motor control message is ultimately supported in the brain by the primary motor cortex and since cortical lesions are frequent in the dementia process, we hypothesized that impairments of the primary motor cortex may explain the early gait disorders observed in mild cognitive impairment. Our purpose was to determine whether the neurochemistry of the primary motor cortex measured with proton magnetic resonance spectroscopy, and its volume, were associated with gait performance while single and dual-tasking in mild cognitive impairment. Twenty community dwellers with mild cognitive impairment, aged 76 years (11) [median (interquartile range)] (30% female) from the \u27Gait and Brain Study\u27 were included in this analysis. Gait velocity and stride time variability were measured while single (i.e. walking alone) and dual tasking (i.e. walking while counting backwards by seven) using an electronic walkway (GAITRite System). Ratios of N-acetyl aspartate to creatine and choline to creatine and cortical volume were calculated in the primary motor cortex. Participants were categorized according to median N-acetyl aspartate to creatine and choline to creatine ratios. Age, gender, body mass index, cognition, education level and subcortical vascular burden were used as potential confounders. Participants with low N-acetyl aspartate to creatine (n = 10) had higher (worse) stride time variability while dual tasking than those with high N-acetyl aspartate to creatine (P = 0.007). Those with high choline to creatine had slower (worse) gait velocity while single (P = 0.015) and dual tasking (P = 0.002). Low N-acetyl aspartate to creatine was associated with increased stride time variability while dual tasking (adjusted beta = 5.51, P = 0.031). High choline to creatine was associated with slower gait velocity while single (adjusted beta = -26.56, P = 0.009) and dual tasking (adjusted beta = -41.92, P = 0.022). Cortical volume correlated with faster gait velocity while single (P = 0.029) and dual tasking (P = 0.037), and with decreased stride time variability while single tasking (P = 0.034). Finally, the probability of exhibiting abnormal metabolite ratios in the primary motor cortex was 63% higher among participants with major gait disturbances in dual task. Those with compromised gait velocity in dual task had a 2.05-fold greater risk of having a smaller cortical volume. In conclusion, the neurochemistry and volume of the primary motor cortex were associated with gait performance while single and dual tasking. Stride time variability was mainly sensitive to neuronal function (N-acetyl aspartate to creatine), whereas gait velocity was more affected by inflammatory damage (choline to creatine) and volumetric changes. These findings may contribute to a better understanding of the higher risks of mobility decline and falls in subjects with mild cognitive impairment

Vitamin D concentration and lateral cerebral ventricle volume in older adults

Scope Vitamin D deficiency is associated with an enlargement of the lateral cerebral ventricles in rodents. The effect of low serum 25-hydroxyvitamin D (25OHD) on lateral cerebral ventricle volume has not been studied yet in humans. The purpose of this cross-sectional study was to determine whether vitamin D deficiency was associated with greater lateral cerebral ventricle volume in older adults. Methods and results Ninety-two Caucasian community-dwellers with no clinical hydrocephalus (mean, 72.2 +/- 6.2 years; 46.7% female) were divided into two groups according to serum 25OHD concentration (deficiency <= 50 nmol/L; normal > 50 nmol/L). Cerebral ventricular volume was quantified using semi-automated software from three-dimensional T1-weighted MRI. Age, gender, body mass index, blood pressure, education level, Mini-Mental State Examination, white matter lesions, and serum calcium concentrations were used as covariates. There was an inverse linear association between 25OHD concentration and ventricular volume (p = 0.049). Compared to individuals with normal 25OHD, those with 25OHD deficiency (n = 33) had 28% larger lateral ventricles (46.9 +/- 26.8 mL versus 36.6 +/- 16.4 mL, p = 0.026). Vitamin D deficiency was associated with an increase in ventricular volume (adjusted beta = 16.55, p = 0.023). The ventricular enlargement involved ventricle bodies (p = 0.025) but not temporal horns (p = 0.112). Conclusion Serum 25OHD deficiency was associated with larger lateral cerebral ventricles. These findings provide a scientific base for vitamin D replacement trials

Cost-effectiveness of cerebrospinal biomarkers for the diagnosis of Alzheimer’s disease

Background: Accurate and timely diagnosis of Alzheimer’s disease (AD) is important for prompt initiation of treatment in patients with AD and to avoid inappropriate treatment of patients with false-positive diagnoses. Methods: Using a Markov model, we estimated the lifetime costs and quality-adjusted life-years (QALYs) of cerebrospinal fluid biomarker analysis in a cohort of patients referred to a neurologist or memory clinic with suspected AD who remained without a definitive diagnosis of AD or another condition after neuroimaging. Parametric values were estimated from previous health economic models and the medical literature. Extensive deterministic and probabilistic sensitivity analyses were performed to evaluate the robustness of the results. Results: At a 12.7% pretest probability of AD, biomarker analysis after normal neuroimaging findings has an incremental cost-effectiveness ratio (ICER) of $11,032 per QALY gained. Results were sensitive to the pretest prevalence of AD, and the ICER increased to over$50,000 per QALY when the prevalence of AD fell below 9%. Results were also sensitive to patient age (biomarkers are less cost-effective in older cohorts), treatment uptake and adherence, biomarker test characteristics, and the degree to which patients with suspected AD who do not have AD benefit from AD treatment when they are falsely diagnosed. Conclusions: The cost-effectiveness of biomarker analysis depends critically on the prevalence of AD in the tested population. In general practice, where the prevalence of AD after clinical assessment and normal neuroimaging findings may be low, biomarker analysis is unlikely to be cost-effective at a willingness-to-pay threshold of $50,000 per QALY gained. However, when at least 1 in 11 patients has AD after normal neuroimaging findings, biomarker analysis is likely cost-effective. Specifically, for patients referred to memory clinics with memory impairment who do not present neuroimaging evidence of medial temporal lobe atrophy, pretest prevalence of AD may exceed 15%. Biomarker analysis is a potentially cost-saving diagnostic method and should be considered for adoption in high-prevalence centers

Loss of high-level perceptual knowledge of object structure in DAT

Peer reviewe

What’s in a name? The challenge of describing interventions in systematic reviews: analysis of a random sample of reviews of non-pharmacological stroke interventions

Objective: To assess, in a sample of systematic reviews of non-pharmacological interventions, the completeness of intervention reporting, identify the most frequently missing elements, and assess review authors’ use of and beliefs about providing intervention information. Design: Analysis of a random sample of systematic reviews of non-pharmacological stroke interventions; online survey of review authors. Data sources and study selection: The Cochrane Library and PubMed were searched for potentially eligible systematic reviews and a random sample of these assessed for eligibility until 60 (30 Cochrane, 30 non-Cochrane) eligible reviews were identified. Data collection: In each review, the completeness of the intervention description in each eligible trial (n=568) was assessed by 2 independent raters using the Template for Intervention Description and Replication (TIDieR) checklist. All review authors (n=46) were invited to complete a survey. Results: Most reviews were missing intervention information for the majority of items. The most incompletely described items were: modifications, fidelity, materials, procedure and tailoring (missing from all interventions in 97%, 90%, 88%, 83% and 83% of reviews, respectively). Items that scored better, but were still incomplete for the majority of reviews, were: ‘when and how much’ (in 31% of reviews, adequate for all trials; in 57% of reviews, adequate for some trials); intervention mode (in 22% of reviews, adequate for all trials; in 38%, adequate for some trials); and location (in 19% of reviews, adequate for all trials). Of the 33 (71%) authors who responded, 58% reported having further intervention information but not including it, and 70% tried to obtain information. Conclusions: Most focus on intervention reporting has been directed at trials. Poor intervention reporting in stroke systematic reviews is prevalent, compounded by poor trial reporting. Without adequate intervention descriptions, the conduct, usability and interpretation of reviews are restricted and therefore, require action by trialists, systematic reviewers, peer reviewers and editors

Memory is not enough: the neurobiological substrates of dynamic cognitive reserve

Changes in the residual memory variance are considered as a dynamic aspect of cognitive reserve (d-CR). We aimed to investigate for the first time the neural substrate associated with changes in the residual memory variance overtime in patients with amnestic mild cognitive impairment (aMCI). Thirty-four aMCI patients followed-up for 36 months and 48 healthy elderly individuals (HE) were recruited. All participants underwent 3T MRI, collecting T1-weighted images for voxel-based morphometry (VBM). They underwent an extensive neuropsychological battery, including six episodic memory tests. In patients and controls, factor analyses were used on the episodic memory scores to obtain a composite memory score (C-MS). Partial Least Square analyses were used to decompose the variance of C-MS in latent variables (LT scores), accounting for demographic variables and for the general cognitive efficiency level; linear regressions were applied on LT scores, striping off any contribution of general cognitive abilities, to obtain the residual value of memory variance, considered as an index of d-CR. LT scores and d-CR were used in discriminant analysis, in patients only. Finally, LT scores and d-CR were used as variable of interest in VBM analysis. The d-CR score was not able to correctly classify patients. In both aMCI patients and HE, LT1st and d-CR scores showed correlations with grey matter volumes in common and in specific brain areas. Using CR measures limited to assess memory function is likely less sensitive to detect the cognitive decline and predict the evolution of Alzheimer's disease. In conclusion, d-CR needs a measure of general cognition to identify conversion to Alzheimer's disease efficiently