Associations among hypertension, dementia biomarkers, and cognition: The MEMENTO cohort

Introduction Approximately 40% of dementia cases could be delayed or prevented acting on modifiable risk factors including hypertension. However, the mechanisms underlying the hypertension–dementia association are still poorly understood. Methods We conducted a cross-sectional analysis in 2048 patients from the MEMENTO cohort, a French multicenter clinic-based study of outpatients with either isolated cognitive complaints or mild cognitive impairment. Exposure to hypertension was defined as a combination of high blood pressure (BP) status and antihypertensive treatment intake. Pathway associations were examined through structural equation modeling integrating extensive collection of neuroimaging biomarkers and clinical data. Results Participants treated with high BP had significantly lower cognition compared to the others. This association was mediated by higher neurodegeneration and higher white matter hyperintensities load but not by Alzheimer's disease (AD) biomarkers. Discussion These results highlight the importance of controlling hypertension for prevention of cognitive decline and offer new insights on mechanisms underlying the hypertension–dementia association. Highlights Paths of hypertension–cognition association were assessed by structural equation models. The hypertension–cognition association is not mediated by Alzheimer's disease biomarkers. The hypertension–cognition association is mediated by neurodegeneration and leukoaraiosis. Lower cognition was limited to participants treated with uncontrolled blood pressure. Blood pressure control could contribute to promote healthier brain aging.Stopping cognitive decline and dementia by fighting covert cerebral small vessel diseas

Swiss Dent J

Air/water syringe (AWS) tips can be used in any type of dental care. They may be disposable (plastic) or reusable (stainless steel or plastic). We assessed the costs of using both sorts of tips in a French teaching hospital. A systematic use of one AWS tip per dental consultation was considered. Consultations performed with reusable AWS (stainless steel) tips give rise to costs linked to initial purchase of tips, their sterilisation, and replacement. Consultation costs of disposable AWS tips were calculated at their current purchase price. Replacing reusable tips was evaluat-ed in two different situations: annual replacement or replacement in case of visual deterioration. Results showed that the number of consultations must lie beyond a certain threshold in order to make reusable tips more economical in use than disposable counterparts. If the reusable tips are replaced every year, this threshold is higher (e.g.: 1,366consultations at the University of Bordeaux) than under a rule of tip replacement in case of visual deterioration (e.g. at the Bordeaux University: 1,267consultations in case of an annual replacement rate of 10%, or 1,289 with a re-placement rate of 30%). This is the first study regarding the costs of disposable versus reusable AWS tips. We suggest that disposable tips might be more cost-effective than reusable tips, not-ably because of their reduced risk of crosscontamination. The choice of the use of one or an-other AWS tip crucially depends on the number of consultations, as well as on their practical utilisation and on infection control issues

Personalized prediction of progression in pre-dementia patients based on individual biomarker profile: A development and validation study

INTRODUCTION: The prognosis of patients at the pre-dementia stage is difficult to define. The aim of this study is to develop and validate a biomarker-based continuous model for predicting the individual cognitive level at any future moment. In addition to personalized prognosis, such a model could reduce trial sample size requirements by allowing inclusion of a homogenous patient population. METHODS: Disease-progression modeling of longitudinal cognitive scores of pre-dementia patients (baseline Clinical Dementia Rating </= 0.5) was used to derive a biomarker profile that was predictive of patient's cognitive progression along the dementia continuum. The biomarker profile model was developed and validated in the MEMENTO cohort and externally validated in the Alzheimer's Disease Neuroimaging Initiative. RESULTS: Of nine candidate biomarkers in the development analysis, three cerebrospinal fluid and two magnetic resonance imaging measures were selected to form the final biomarker profile. The model-based prognosis of individual future cognitive deficit was shown to significantly improve when incorporating biomarker information on top of cognition and demographic data. In trial power calculations, adjusting the primary analysis for the baseline biomarker profile reduced sample size requirements by approximately 10%. Compared to conventional cognitive cut-offs, inclusion criteria based on biomarker-profile cut-offs resulted in up to 28% reduced sample size requirements due to increased homogeneity in progression patterns. DISCUSSION: The biomarker profile allows prediction of personalized trajectories of future cognitive progression. This enables accurate personalized prognosis in clinical care and better selection of patient populations for clinical trials. A web-based application for prediction of patients' future cognitive progression is available online

How Selection Over Time Contributes to the Inconsistency of the Association between Sex/Gender and Cognitive Decline across Cognitive Aging Cohorts

The sex/gender and aging-related cognitive decline association remains poorly understood due to inconsistencies in findings. Such heterogeneity could be attributable to the cognitive functions studied and study population characteristics, but also to a differential selection by drop-out and death between men and women. This work aims to evaluate the impact of selection by drop-out and death on the association between sex/gender and cognitive decline. We first compared the most frequently used statistical methods for longitudinal data, targeting either population estimands (marginal models estimated by Generalized Estimating Equations) or subject-specific estimands (mixed/joint models estimated by likelihood maximization) on eight aging studies: six population-based (ACTIVE(1996-2009), Paquid(1988-2014), REGARDS(2003-2016), 3-City(1999-2016), WHICAP(1992-2017), Whitehall II(2007-2016)) and two clinic-based (ADNI(2004-2017), MEMENTO(2011-2016)) studies. We illustrated the differences in the estimands of the sex/gender association with cognitive decline in selected examples and highlighted the critical role of differential selection by drop-out and death. By using the same estimand, we then contrasted the sex/gender association across cohorts and cognitive measures suggesting residual differential sex/gender association depending on the targeted cognitive measure (memory or animal fluency) and the initial cohort selection. We recommend focusing on subject-specific estimands in the alive population for assessing sex/gender differences while handling differential selection over time

Associations among hypertension, dementia biomarkers, and cognition: The MEMENTO cohort

International audienceIntroduction: Approximately 40% of dementia cases could be delayed or prevented acting on modifiable risk factors including hypertension. However, the mechanisms underlying the hypertension-dementia association are still poorly understood.Methods: We conducted a cross-sectional analysis in 2048 patients from the MEMENTO cohort, a French multicenter clinic-based study of outpatients with either isolated cognitive complaints or mild cognitive impairment. Exposure to hypertension was defined as a combination of high blood pressure (BP) status and antihypertensive treatment intake. Pathway associations were examined through structural equation modeling integrating extensive collection of neuroimaging biomarkers and clinical data.Results: Participants treated with high BP had significantly lower cognition compared to the others. This association was mediated by higher neurodegeneration and higher white matter hyperintensities load but not by Alzheimer's disease (AD) biomarkers.Discussion: These results highlight the importance of controlling hypertension for prevention of cognitive decline and offer new insights on mechanisms underlying the hypertension-dementia association.Highlights: Paths of hypertension-cognition association were assessed by structural equation models. The hypertension-cognition association is not mediated by Alzheimer's disease biomarkers. The hypertension-cognition association is mediated by neurodegeneration and leukoaraiosis. Lower cognition was limited to participants treated with uncontrolled blood pressure. Blood pressure control could contribute to promote healthier brain aging