Emilie Vierron

Design effect in multicenter studies: gain or loss of power?

BackgroundIn a multicenter trial, responses for subjects belonging to a common center are correlated. Such a clustering is usually assessed through the design effect, defined as a ratio of two variances. The aim of this work was to describe and understand situations where the design effect involves a gain or a loss of power.MethodsWe developed a design effect formula for a multicenter study aimed at testing the effect of a binary factor (which thus defines two groups) on a continuous outcome, and explored this design effect for several designs (from individually stratified randomized trials to cluster randomized trials, and for other designs such as matched pair designs or observational multicenter studies).ResultsThe design effect depends on the intraclass correlation coefficient (ICC) (which assesses the correlation between data for two subjects from the same center) but also on a statistic S, which quantifies the heterogeneity of the group distributions among centers (thus the level of association between the binary factor and the center) and on the degree of global imbalance (the number of subjects are then different) between the two groups. This design effect may induce either a loss or a gain in power, depending on whether the S statistic is respectively higher or lower than 1.ConclusionWe provided a global design effect formula applying for any multicenter study and allowing identifying factors – the ICC and the distribution of the group proportions among centers – that are associated with a gain or a loss of power in such studies.

Precuneus and Cingulate Cortex Atrophy and Hypometabolism in Patients with Alzheimer’s Disease and Mild Cognitive Impairment: MRI and 18F-FDG PET Quantitative Analysis Using FreeSurfer

Objective. The objective of this study was to compare glucose metabolism and atrophy, in the precuneus and cingulate cortex, in patients with Alzheimers disease (AD) and mild cognitive impairment (MCI), using FreeSurfer. Methods. 47 individuals (17 patients with AD, 17 patients with amnestic MCI, and 13 healthy controls (HC)) were included. MRI and PET images using 18F-FDG (mean injected dose of 185 MBq) were acquired and analyzed using FreeSurfer to define regions of interest in the hippocampus, amygdala, precuneus, and anterior and posterior cingulate cortex. Regional volumes were generated. PET images were registered to the T1-weighted MRI images and regional uptake normalized by cerebellum uptake (SUVr) was measured. Results. Mean posterior cingulate volume was reduced in MCI and AD. SUVr were different between the three groups: mean precuneus SUVr was 1.02 for AD, 1.09 for MCI, and 1.26 for controls (p < 0.05); mean posterior cingulate SUVr was 0.96, 1.06, and 1.22 for AD, MCI, and controls, respectively (p < 0.05). Conclusion. We found graduated hypometabolism in the posterior cingulate cortex and the precuneus in prodromal AD (MCI) and AD, whereas atrophy was not significant. This suggests that the use of 18F-FDG in these two regions could be a neurodegenerative biomarker.

Conversion from nonischemic to ischemic retinal vein occlusion: prediction by venous velocity on color Doppler imaging

Purpose To identify color Doppler imaging (CDI) parameters and other prognostic factors of a conversion from nonischemic to ischemic retinal vein occlusion (RVO) in a large population with a long follow-up. Methods This was a retrospective observational study. Data were collected for patients who had been admitted to the ophthalmologic department of the Hospital of Tours because of nonischemic central RVO (CRVO) or branch RVO (BRVO). We analyzed the relation between time until conversion into ischemic RVO and several prognostic factors of conversion, mainly vein velocities as measured by CDI. Results Analyses involved 162 patients. One year after inclusion, conversion into ischemic RVO occurred in 25.0% of the 113 CRVO and in 28.6% of the 49 BRVO cases. For CRVO, an increase of the minimal central retinal venous velocity (CRV), measured by CDI before and after treatment by hemodilution, diminished the risk of conversion into an ischemic form (p=0.048). For BRVO, an elevated maximal CRV on diagnosis was a protector (p=0.004). Age was associated with a high risk of ischemic evolution for CRVO (p=0.023) but not BRVO. Initial visual acuity was not associated with the conversion, for BRVO or CRVO. Increased retinal hemorrhages highly increased the risk of conversion both for CRVO (p<0.0001) and BRVO (p=0.010). Conclusions Risk of ischemic evolution for BRVO and CRVO treated by isovolemic hemodilution was associated with central venous velocities. CDI might be useful for identifying risk of ischemic conversion and individualizing the follow-up of patients.

Center Effect on Ankle–Brachial Index Measurement When Using the Reference Method (Doppler and Manometer): Results From a Large Cohort Study

BACKGROUND The ankle-brachial index (ABI) is a simple and noninvasive tool used to detect peripheral arterial disease (PAD). We aimed to assess, in a French multicenter cohort, the center effect associated with arterial pressure (AP) and ABI measurements using the reference method and using a semiautomatic device. METHODS This study included baseline and 9-year follow-up data from 3,664 volunteers of 10 health examination centers of the DESIR (Data from an Epidemiological Study on the Insulin Resistance) syndrome French cohort. Ankle and brachial AP were measured at inclusion by the reference method (a mercury sphygmomanometer coupled with a Doppler probe for ankle measurements) and at 9 years by a semiautomatic device (Omron HEM-705CP). The center effect was assessed by the intraclass correlation coefficient (ICC), ratio of the between-center variance to the total variance of the measurement. RESULTS At inclusion, the sample mean age was 47.5 (s.d. 9.9) years; 49.3% were men. Although ICCs were smaller than 0.05 for brachial AP measurements, they were close to 0.18 and 0.20 for ankle systolic AP (SAP) and ABI measurements, respectively, when the reference method was used. No center effect for measures other than ankle SAP was detected. With the semiautomatic device method, all ICCs, including those for ankle SAP and ABI measurements, were between 0.005 and 0.04. CONCLUSIONS We found an important center effect on ABI measured with a sphygmomanometer and a Doppler probe but not a semiautomatic device. A center effect should be taken into account when planning any multicenter study on ABI measurement.

Brain Tissue Pulsatility is Increased in Midlife Depression: a Comparative Study Using Ultrasound Tissue Pulsatility Imaging

Cerebrovascular disease (CVD) is consistently associated with late-life depression but poorly documented in midlife depression. It can be hypothesized that the relatively low sensitivity of conventional neuroimaging techniques does not allow the detection of subtle CVD in midlife depression. We used tissue pulsatility imaging (TPI), a novel ultrasound (US) neuroimaging technique that has demonstrated good sensitivity to detect changes in the pulsatility of small brain volumes, to identify early and subtle changes in brain vascular function in midlife depression. We compared the maximum and mean brain tissue pulsatility (MaxBTP and MeanBTP), as identified by TPI, between three groups of middle-aged females matched for age: patients with depression (n=25), patients with remitted depression (n=24) and community controls (n=25). MRI arterial spin labeling, white matter hyperintensities (WMHs) and transcranial doppler (TCD) were used as control conventional markers for CVD. We found no difference in the MRI and TCD measures among the three groups. In contrast, depressive patients showed an increased BTP related to the mean global brain pulsatility (MeanBTP) and no change related to large vessels (MaxBTP) in comparison with the remitted and control groups. US neuroimaging is a highly accurate method to detect brain pulsatility changes related to cerebrovascular functioning, and TPI identified an increased BTP in midlife depressed patients, suggesting early and subtle vascular impairments in this population at risk for CVD such as stroke or WMHs. Because high pulsatility could represent prodromal cerebrovascular changes that damage the brain over time, this paper provides a potential target for blocking the progression of CVD.

Total Protein Level in Cerebrospinal Fluid is Stable in Elderly Adults

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The Pattern of Brain Amyloid Load in Posterior Cortical Atrophy Using (18)F-AV45: Is Amyloid the Principal Actor in the Disease?

Background: Posterior cortical atrophy (PCA) is characterized by progressive higher-order visuoperceptual dysfunction and praxis declines. This syndrome is related to a number of underlying diseases, including, in most cases, Alzheimers disease (AD). The aim of this study was to compare the amyloid load with 18F-AV45 positron emission tomography (PET) between PCA and AD subjects. Methods: We performed 18F-AV45 PET, cerebrospinal fluid (CSF) biomarker analysis and a neuropsychological assessment in 11 PCA patients and 12 AD patients. Results: The global and regional 18F-AV45 uptake was similar in the PCA and AD groups. No significant correlation was observed between global 18F-AV45 uptake and CSF biomarkers or between regional 18F-AV45 uptake and cognitive and affective symptoms. Conclusion: This 18F-AV45 PET amyloid imaging study showed no specific regional pattern of cortical 18F-AV45 binding in PCA patients. These results confirm that a distinct clinical phenotype in amnestic AD and PCA is not related to amyloid distribution.