Precisely defining the delay in onset of dementia is a particular challenge for early diagnosis. Brain [18F] fluoro-2-deoxy-2-D-glucose (18F-FDG) Positron Emission Tomography (PET) is a particularly interesting tool for the early diagnosis of neurodegenerative diseases, through the measurement of the cerebral glucose metabolic rate. There is currently a lack of longitudinal studies under real-life conditions, with sufficient patients, to accurately evaluate the predictive values of brain 18F-FDG PET scans. Here, we aimed to estimate the value of brain 18F-FDG PET for predicting the risk of dementia conversion and the risk of occurrence of a neurodegenerative pathology. Longitudinal data for a cohort of patients with no diagnosis of dementia at the time of recruitment referred by a tertiary memory clinic for brain 18F-FDG PET were matched with (Prince M, Wimo A, Guerchet Maëlenn, Ali G-C, Wu Y-T et al. World Alzheimer Report 2015. The Global Impact of Dementia: An analysis of prevalence, incidence, cost and trends. [Research Report] Alzheimer’s Disease International. 2015. 2015.) data from the French National Health Data System (NHDS), (Jack CR, Bennett DA, Blennow K, Carrillo MC, Dunn B, Haeberlein SB, et al. NIA-AA Research Framework: Toward a biological definition of Alzheimer’s disease. Alzheimers Dement. 2018;14(4):535–62.) data from the National Alzheimer Bank (NAB), and (Davis M, O`Connell T, Johnson S, Cline S, Merikle E, Martenyi F, et al. Estimating Alzheimer’s Disease Progression Rates from Normal Cognition Through Mild Cognitive Impairment and Stages of Dementia. CAR. 2018;15(8):777–88.) lumbar puncture (LP) biomarker data. The criteria for dementia conversion were the designation, within the three years after the brain 18F-FDG PET scan, of a long-term condition for dementia in the NHDS and a dementia stage of cognitive impairment in the NAB. The criterion for the identification of a neurodegenerative disease in the medical records was the determination of LP biomarker levels. Among the 403 patients (69.9 ± 11.4 years old, 177 women) from the initial cohort with data matched with the NHDS data, 137 were matched with the NAB data, and 61 were matched with LP biomarker data. Within three years of the scan, a 18F-FDG PET had negative predictive values of 85

BACKGROUND Cardiovascular (CV) mortality remains high despite the improvement of kidney function after kidney transplantation. In heart failure (HF), high concentrations of biomarkers of fibrosis, related to cardiac and/or vascular impairment, are associated with CV outcomes, but their significance in kidney transplantation is still unclear. Our aim was to investigate the association of procollagen type I C-terminal pro-peptide (PICP) and galectin-3 (Gal-3), markers of fibrosis, with arterial stiffness measured by pulse wave velocity (PWV) and CV morbi-mortality in kidney transplantation recipients from the prospective monocenter TRANSARTE study (Transplantation and Arteries), which compared the evolution of arterial stiffness in transplanted patients and patients remained on dialysis. MATERIAL AND METHODS PICP and Gal-3 were measured at 2 years after transplantation in 44 kidney transplantation patients. Spearman's rank-order correlation analysis was conducted to assess the relationship between biomarkers and PWV. Association of biomarkers with CV morbi-mortality was evaluated using Cox regression analysis adjusted for age, renal function, and PWV. RESULTS There was no significant correlation between PWV and PICP (r=-0.16, P=0.3) or Gal-3 (r=0.03, P=0.85). Gal-3, after adjusting for key prognostic factors, including PWV, was significantly associated with CV morbi-mortality [HR (95% CI)=4.30 (1.01-18.22), P=0.048], whereas PICP was not significantly associated with outcome. CONCLUSIONS In multivariable adjusted analysis, elevated Gal-3 concentrations were associated with CV morbi-mortality in kidney transplantation patients, whereas PICP was not. As Gal-3 was not related to PWV, other sources of fibrosis (eg, cardiac fibrosis) may be underlying the prognostic value of Gal-3 in kidney transplantation.

(1) Background: Increased arterial stiffness is associated with cardiovascular (CV) diseases in end-stage renal disease (ESRD) patients, and CV mortality remains higher in kidney transplantation (KT) recipients compared to in the general population. KT is associated with an improvement in arterial stiffness in the early post-transplant period, followed by a potential re-worsening in the late period. In a cohort of KT patients, we evaluated the associations of pulse-wave velocity (PWV) measured at different time-points (pre-transplant, and early and late post-transplant periods) with CV morbi-mortality, as well as the evolution between these measurements with CV morbi-mortality. (2) Methods: Forty KT recipients with a 10-year follow-up were included. The association of PWV with CV events was assessed with multivariable cox analysis. Backward linear regressions were conducted to identify the determinants of PWV at 1 year and those of the long-term evolution of PWV after KT (delta PWV at 1 year—latest PWV). (3) Results: The absence of arterial stiffening during the long-term follow-up after KT is associated with a lower CV outcome rate (HR for the delta PWV = 0.76 (0.58–0.98), p = 0.036). Age at KT is associated with the worsening of arterial stiffness in the late post-transplantation period (β for the delta PWV = −0.104, p = 0.031). A high PWV at 1 year was associated with a potential for recovery during follow-up (β = 0.744, p < 0.0001). (4) Conclusions: The absence of PWV worsening in the late post-transplantation period was significantly associated with a lower risk of CV events, whereas early changes in PWV were not. Finding an intervention capable of reducing long-term PWV could improve the prognosis of KT recipients.

Background: The stiffening of large elastic arteries is currently estimated in research and clinical practice by propagative and non-propagative models, as well as parameters derived from aortic pulse waveform analysis. Methods: Common carotid compliance and distensibility were measured by simultaneously recording the diameter and pressure changes during the cardiac cycle. The aortic and upper arm arterial distensibility was estimated by measuring carotid–femoral and carotid–radial pulse wave velocity (PWV), respectively. The augmentation index and blood pressure amplification were derived from the analysis of central pulse waveforms, recorded by applanation tonometry directly from the common carotid artery. Results: 75 volunteers were enrolled in this study (50 females, average age 53.5 years). A significant inverse correlation was found between carotid distensibility and carotid–femoral PWV (r = −0.75; p < 0.001), augmentation index (r = −0.63; p < 0.001) and central pulse pressure (r = −0.59; p < 0.001). A strong correlation was found also between the total slope of the diameter/pressure rate carotid curves and aortic distensibility, quantified from the inverse of the square of carotid–femoral PWV (r = 0.67). No correlation was found between carotid distensibility and carotid–radial PWV. Conclusions: This study showed a close correlation between carotid–femoral PWV, evaluating aortic stiffness by using the propagative method, and local carotid cross-sectional distensibility.

Background: Hippocampal atrophy is associated with cognitive decline. Determining the clinical features associated with hippocampal volume (HV)/atrophy may help in tailoring preventive strategies. Objective: This study was aimed to investigate the association between HV (at visit 2) and vascular status (both at visit 1 and visit 2) in a cohort of individuals aged 60+ with hypertension and without overt cognitive impairment at visit 1 (visit 1 and visit 2 were separated by approximately 8 years). Methods: Hippocampal volume was estimated in brain MRIs as HV both clinically with the Scheltens' Medial Temporal Atrophy score, and automatically with the Free Surfer Software application. A detailed medical history, somatometric measurements, cognitive tests, leukoaraiosis severity (Fazekas score), vascular parameters including pulse wave velocity, central blood pressure, and carotid artery plaques, as well as several biochemical parameters were also measured. Results: 113 hypertensive patients, 47% male, aged 75.1 f 5.6 years, participated in both visit 1 and visit 2 of the ADE-LAHYDE study. Age (beta = -0.30) and hypertension duration (beta = -0.20) at visit 1 were independently associated with smaller HV at visit 2 (p < 0.05 for all). In addition to these variables, low body mass index (beta = 0.18), high MRI Fazekas score (beta = -0.20), and low Grober-Buschke total recall (beta = 0.27) were associated with smaller HV at visit 2 (p < 0.05 for all). Conclusion: In a cohort of older individuals without cognitive impairment at baseline, we described several factors associated with lower HV, of which hypertension duration can potentially be modified.

Background/Objective:The aim of this study was to assess, in routine, the rates with which an amyloid deposition was documented by 18F-florbetaben PET in patients with suspected Alzheimer’s disease (AD) but with isolated increases in cerebrospinal fluid (CSF) tau-protein concentrations, and the sub sequent impact of these PET results on medical management. Methods:This prospective study included 34 patients with mild neurocognitive disorders (MND) and suspected AD (73±9 years, 16 women) and with abnormal CSF concentrations in total-tau (T-tau) and/or phosphorylated-tau (P-tau) proteins but normal Aβ42 concentration and Aβ42/Aβ40 ratio. These patients were referred to 8F-florbetaben PET from which the PET-related changes in the confidence for AD diagnosis (low, intermediate, or high) and treatments were reported. Results:The PET examinations were positive for amyloid deposition (brain amyloid plaque load, BAPL score >1) in none of the 9 patients with an increase in only T-tau proteins and in 8 among the 25 (32%) with an increase in P-tau proteins (one BAPL score of 2 and seven BAPL scores of 3). Knowledge of the PET results was associated with subsequent changes in diagnostic confidence in 44% of patients (15/34) and in the intention-to-treat with a cholinesterase inhibitor drug in 18% (6/34). Conclusion:In patients with suspected AD and isolated increase in CSF tau protein concentrations, an amyloid deposition is documented by 18F-florbetaben PET in as much as one third of cases when the concentration of P-tau is abnormal, and PET results are associated with significant further changes in medical management.

Mild cognitive impairment and Alzheimer's dementia involve a grey matter disease, quantifiable by F-18-Fluorodeoxyglucose positron emission tomography (FDG-PET), but also white matter damage, evidenced by diffusion tensor magnetic resonance imaging (DTI), which may play an additional pathogenic role. This study aimed to determine whether such DTI and PET variations are also interrelated in a high-risk population of older hypertensive patients with only subjective memory complaints (SMC). Sixty older hypertensive patients (75 +/- 5 years) with SMC were referred to DTI and FDG-PET brain imaging, executive and memory tests, as well as peripheral and central blood pressure (BP) measurements. Mean apparent diffusion coefficient (ADCmean) was determined in overall white matter and correlated with the grey matter distribution of the metabolic rate of glucose (CMRGlc) using whole-brain voxel-based analyses of FDG-PET images. ADCmean was variable between individuals, ranging from 0.82 to 1.01.10(-3) mm(2) sec(-1), and mainly in relation with CMRGlc of areas involved in Alzheimer's disease such as internal temporal areas, posterior associative junctions, posterior cingulum but also insulo-opercular areas (global correlation coefficient: -0.577, p < 0.001). Both the ADCmean and CMRGlc of the interrelated grey matter areas were additionally and concordantly linked to the results of executive and memory tests and to systolic central BP (all p < 0.05). Altogether, our findings show that cross-sectional variations in overall white brain matter are linked to the metabolism of Alzheimer-like cortical areas and to cognitive performance in older hypertensive patients with only subjective memory complaints. Additional relationships with central BP strengthen the hypothesis of a contributing pathogenic role of hypertension.

Objectives: The longitudinal ADELAHYDE-2 study aims to identify the factors associated with cognitive impairment/decline and white matter hyperintensities burden.Methods: Longitudinal single-center study comprising two visits separated by approximately 7 years. A total of 131 patients completed the two visits. The primary outcome was global memory composite scale, while the secondary outcome was white matter hyperintensities (WMH/Fazekas scale) load.Results: Global memory at visit 2 (V2) was largely influenced by age, smoking status, glycated hemoglobin, and history of stroke already present at visit 1 (V1). These variables accounted for similar to 51% of the memory alterations at V2. WMH at V2 was likely influenced by age, left ventricular hypertrophy, diabetes mellitus, carotid intima-media thickness, and body mass index at V1. These findings accounted for similar to 37% of the WMH changes at V2. Increase in pulse wave velocity from V1 to V2 showed a trend for association with memory deterioration (adjusted estimates = 0.06; P =.067), whereas smoking and increase in systolic blood pressure (trend) were associated with an increment in WMH (adjusted estimates = 0.49; P =.047 and adjusted estimates = 0.01; P =.08, respectively). On the other hand, angiotensin-converting enzyme inhibitor/angiotensin receptor blockers and statins (trend) were likely to be protective (adjusted estimates for angiotensin-converting enzyme inhibitor/angiotensin receptor blockers = 0.49; P =.049, and adjusted estimates for statins = -0.46; P =.055).Conclusions: Several readily identifiable factors are associated with memory deterioration and WMH, many of which are potentially modifiable. Interventions aimed to control these risk factors need to be tested prospectively in order to assess their cognitive protective value. (C) 2017 AMDA - The Society for Post-Acute and Long-Term Care Medicine.

Background: Short leukocyte telomere length (LTL) is associated with atherosclerosis. The prevailing view is this association exists since LTL is a biomarker of cumulative inflammation and oxidative stress during adult life. However recent studies show that LTL in adults is defined mainly by LTL at birth and attrition during childhood. Therefore we can suggest that short LTL might precede clinical expression of atherosclerosis. Objectives: To examine the directionality in the relation between carotid atheroma and LTL dynamics. Methods: LTL was measured by TRF in samples donated 9 years apart on average by 257 men and women aged 41 to 80 at the inclusion. Results: LTL attrition during follow-up (FU) period was 25±17 bp/year. No relation was observed between LTL attrition and presence of carotid atherosclerotic plaques (PCAP). Baseline (BL)-LTL was highly correlated (r=0.96, p<0.0001) with FU-LTL. In 87.9%of the subjects LTL ranking by deciles was the same 1 decile at BL and FU. BL- and FU-LTL were inversely associated with PCAP (p<0.01). After adjusting for age and gender, BL-LTL was 6.50±0.04 Kb in subjects without PCAP 6.46±0.06 in those with PCAP only at the FU visit and 6.27±0.06 in those with PCAP in both BL and FU visits (p=0.027). LTL attrition was the same in these groups. Conclusions: LTL attrition in adulthood is not influenced by PCAP and does not play a significant role in LTL ranking. By contrast, patients with shorter telomeres present CAP earlier in life. Telomere length could be considered as a bio-determinant for atherosclerosis.

The metabolic signature associated with subclinical diastolic left ventricular (LV) dysfunction in the general population is unknown. This population study aimed at identifying a specific profile of circulating me-tabolites associated with asymptomatic diastolic LV dysfunction. In 711 randomly recruited Flemish (50.8

Short leukocyte telomere length (LTL) is associated with atherosclerosis in adults and diminished survival in the elderly. The prevailing view is that LTL is associated with accelerated aging since it serves as a biomarker of the cumulative burden of inflammation and oxidative stress during adult life. LTL dynamics are defined by LTL at birth, which is highly variable, and its age-dependent attrition thereafter, which is rapid during the first 20 years of life. We examined whether age-dependent LTL attrition during old age can substantially affect individuals’ LTL ranking (e.g., longer or shorter LTL) in relation to their peers and which clinical, lifestyle or genetic factors can predict it. We measured LTL by Telomeric Restriction Fragment Southern Blot (TRF) in samples donated 8 years apart on average by 76 participants of the ADELAHYDE study. Participants were men and women aged 60 to 85 years with a history of hypertension at the inclusion. We observed a mean LTL attrition of 27 bp per year which is consistent with previous data on telomere attrition in adults. No clinical, lifestyle or genetic factors seem to exert significant effect or can predict LTL attrition in elderly people. We observed a close relationship (r=0.88, figure left panel) between baseline and follow-up LTL values. Ranking individuals by quintiles revealed that 98.6% showed no rank change (59.7%) or one quintile change (38.9%) over time (figure right panel). We conclude that in elderly people, LTL is virtually anchored to a given rank with the passage of time. Accordingly, the links of LTL with atherosclerosis and longevity appear to be established early in life. It is therefore unlikely that lifestyle and its modification during old age exert a major impact on LTL ranking.

Incidence and prevalence of abdominal obesity (AO) are growing exponentially. Subjects with AO are at higher risk of developing heart failure. The purpose of the study was to investigate early changes in cardiac and arterial structure and function and extracellular matrix biomarkers in normotensive healthy subjects with AO. Subjects with AO and age- and sex-matched controls underwent echocardiography, MRI (cardiac remodeling index), carotid intima–media thickness, pulse wave velocity, and blood fibrosis biomarkers measurements. We enrolled 87 subjects with AO and 53 controls. Although normotensive, subjects with AO had higher systolic blood pressure (BP; 122±11 versus 116±11 mm Hg; P =0.003), left ventricular mass (94±24 versus 84±21 g; P =0.034), and cardiac remodeling index (0.67±0.16 versus 0.60±0.10 g/mL; P =0.026) but unchanged carotid intima–media thickness and pulse wave velocity. Diastolic dysfunction (E′ <10 cm/s) could be detected in 38% of subjects with AO (4% in controls). Left ventricular remodeling, as assessed by cardiac remodeling index, was positively and independently associated with higher BP (systolic BP and mean arterial pressure but not diastolic BP) and AO. Higher BP, AO, and procollagen-III-N-terminal peptide (≥2.4 ng/mL) concentrations (odds ratio, 4.15 [1.42–12.2]; P =0.01) were positively associated with diastolic dysfunction. Early cardiac structural remodeling, fibrosis, and diastolic dysfunction were detectable in healthy subjects with AO. Higher BP, procollagen-III-N-terminal peptide, and AO were independently associated with early cardiac structural and functional changes. It is to be investigated whether in subjects with AO, an early BP reduction, even if normotensive, combined with weight loss may avoid adverse cardiac remodeling and protect against progression to heart failure.

The major challenge of vascular tissue engineering is to develop a small calibre vascular graft with a high patency rate. In native vessels, the thrombosis is prevented by the endothelium located at the luminal site of the vessel. The aim of this study was to develop a resistant endothelial lining on the inner surface of vascular graft using a polyelectrolyte multilayers (PEM) film. Umbilical arteries were de-endothelialized, coated with 3.5 bilayers of poly(styrene sulfonate) (PSS)/poly(allylamine hydrochloride) (PAH) and then cellularized with endothelial cells. The grafts were cultured for a week in static condition and preconditioned by exposure to a shear stress of at 1 Pa for three hours before implantation on the rabbit carotid site. Histological and confocal microscopy in vitro investigations showed that PEMs films improve cell adhesion and retention on the luminal surface after shear stress preconditioning. In vivo Doppler data showed that graft preconditioning is a crucial factor for graft patency. Indeed, preconditioned grafts remained over the whole experimental period, whereas unpreconditioned grafts were obstructed after only one week of implantation. These results open the route toward the development of a new generation of vascular substitutes having a long term patency.

Objectives:Several studies have shown lower carotid-femoral pulse wave velocity (cfPWV) levels in women compared to men, a difference that could partially explain the increased longevity in women. However, these studies have been performed in industrial countries while few data are available in emerging populations. We studied arterial stiffness, as evaluated by cfPWV, in elderly Algerian men and women.Methods:cfPWV was studied in 321 Algerian men (81.25.3 years) and women (81.14.4 years). An age-matched and sex-matched cohort of European individuals (n=321) was used as a control group.Results:Comparatively to men, Algerian women exhibited higher BMI and heart rate (HR), higher prevalence of hypertension, and were more frequently treated for hypertension. cfPWV was not different between Algerian men (14.8 +/- 3.3m/s) and women (14.9 +/- 3.4m/s). By contrast, in Europeans, women had lower cfPWV (12.7 +/- 2.7m/s) than men (14.0 +/- 3.3m/s; P<0.001). Comparatively to European women, Algerian women had a higher cfPWV (P<0.01). In both ethnic groups, multivariate analyses revealed that age, mean blood pressure (BP), HR, and diabetes were positively associated with cfPWV, whereas female sex was associated with lower cfPWV only in Europeans.Conclusion:Elderly Algerian women exhibit arterial stiffness similar to men, whereas European women display lower arterial stiffness than men. This loss of arterial sex advantage' in Algerians may be explained by higher BP, HR, and a worse metabolic profile in Algerian women. Interventions in emerging populations, especially in women, should be a priority in order to address these risk factors by acting on current lifestyle.

OBJECTIVES:To determine, using a comprehensive MRI investigation, prevalence and vascular correlates of early left-ventricular concentric remodeling in middle-aged patients with abdominal obesity. Left-ventricular and vascular remodeling are commonly associated with hypertension, but little is known for abdominal obesity patients, a population with definite increase in cardiovascular risk and high rates of further developments of hypertension and of the metabolic syndrome. METHODS:Seventy middle-aged abdominal obesity patients (56 ± 5 years, 49% women, 69% with body mass index > 30 kg/m), who had no additional cardiovascular risk factor except for untreated stage 1 hypertension (16%), and 40 controls underwent MRI for detecting concentric remodeling (increase in left-ventricular mass/end-diastolic volume ratio) and identifying potential determinants, including arterial compliance indexes [aortic pulse wave velocity and total arterial compliance (TAC)] and total peripheral vascular resistances (TPVRs). RESULTS:Twenty abdominal obesity patients (29%) had concentric remodeling (concentric remodeling+), whereas 50 did not (concentric remodeling-). Concentric remodeling+ patients were mostly men (85%), they frequently had stage 1 hypertension (45%) and few had left-ventricular hypertrophy (20%). When adjusted for sex, there was a step-by-step decline in TAC between controls (mean ± SEM: 2.10 ± 0.06 ml/mmHg), concentric remodeling- (1.82 ± 0.06 ml/mmHg) and concentric remodeling+ (1.42 ± 0.09 ml/mmHg, P < 0.005 for inter-group comparisons) and TPVRs were lower than controls for concentric remodeling- (14.7 ± 0.5 vs. 16.8 ± 0.5 ml/mmHg, P = 0.005) but not for concentric remodeling+ (17.5 ± 0.7 mmHg/min per l). CONCLUSIONS:Concentric remodeling is frequently documented by MRI in the middle-aged men with abdominal obesity and in association with a decrease in TAC no longer counter-balanced by a decrease in TPVR, suggesting a remodeling from proximal to peripheral vasculature.

BACKGROUNDIncreased arterial stiffness (AS) is a major determinant of cardiovascular complications in end-stage renal disease (ESRD) patients. Little is known about AS evolution after kidney transplantation. The aim of the study was to characterize the evolution of AS after kidney transplantation in a population of ESRD patients, in comparison to those remaining in dialysis.METHODSEighty-eight patients (age between 35 and 65) were recruited from the waiting list for kidney transplantation of the University Hospital of Nancy. Two vascular evaluations were performed at a 1-year interval. During this interval, 39 patients were transplanted and 49 remained in dialysis.RESULTSAt inclusion, median pulse-wave velocity (PWV) was similar in transplanted patients and transplantation-pending patients, respectively, 9.2 (7.9-11.9) and 9.8 (7.7-12.1) m/s. No difference between the two groups was found at the 1-year interval. Median of time after transplantation was 6.3 (3.8-10.1) months. Median of blood pressure (MBP) decreased only in the transplanted patients [99 (93-112) versus 96 (90-101) mmHg, P < 0.01] Multivariate analysis showed that PWV changes depend on changes in MBP and baseline PWV.CONCLUSIONAlthough no difference in the 1-year PWV evolution was found, the low MBP value in transplanted patients allow to expect a better long-term evolution of AS and a better cardiovascular prognosis after kidney transplantation than in transplantation-pending patients.