'Selected' Exosomes from Sera of Elderly Severe Obstructive Sleep Apnea Patients and Their Impact on Blood-Brain Barrier Function: A Preliminary Report.

Obstructive sleep apnea syndrome (OSAS) affects a large part of the aging population. It is characterized by chronic intermittent hypoxia and associated with neurocognitive dysfunction. One hypothesis is that the blood-brain barrier (BBB) functions could be altered by exosomes. Exosomes are nanovesicles found in biological fluids. Through the study of exosomes and their content in tau and amyloid beta (Aß), the aim of this study was to show how exosomes could be used as biomarkers of OSAS and of their cognitive disorders. Two groups of 15 volunteers from the PROOF cohort were selected: severe apnea (AHI > 30) and control (AHI < 5). After exosome isolation from blood serum, we characterized and quantified them (CD81, CD9, CD63) by western blot and ELISAs and put them 5 h in contact with an in vitro BBB model. The apparent permeability of the BBB was measured using sodium-fluorescein and TEER. Cell ELISAs were performed on tight junctions (ZO-1, claudin-5, occludin). The amount of tau and Aß proteins found in the exosomes was quantified using ELISAs. Compared to controls, OSAS patients had a greater quantity of exosomes, tau, and Aß proteins in their blood sera, which induced an increase in BBB permeability in the model and was reflected by a loss of tight junction' expression. Elderly patients suffering severe OSAS released more exosomes in serum from the brain compartment than controls. Such exosomes increased BBB permeability. The impact of such alterations on the risk of developing cognitive dysfunction and/or neurodegenerative diseases is questioned.

Normative Data for a Neuropsychological Test Battery in the French Aging Population: 20-Year Follow-Up From the "PROgnostic OF Cardiovascular and Cerebrovascular Events" Study.

OBJECTIVE: The study aimed to present relevant norms for the evaluation of pathological aging in the French population over a 20-year period, utilizing the "PROgnostic OF cardiovascular and cerebrovascular events" test and questionnaire. METHODS: Three neuropsychological evaluations were administered over 20 years with 929 participants at the first cognitive evaluation (62-69 years old), 631 at the second (71-78 years old), and 293 at the third (81-88 years old). The tests and questionnaires were administered in the following order: McNair's Cognitive Complaints Questionnaire, Depression Questionnaire of Pichot, Mini Mental State Examination, Free and Cued Selective Reminding test, Benton Visual Retention Test, Digit-Symbol Substitution Test of the WAIS-III, Trail Making Test, Stroop Test, Verbal Fluency, and the Similarities subtest of the WAIS-III. RESULTS: Normative data were presented at three time points of the repeated evaluation over 20 years (62-69 years, 71-78 years, and 81-88 years) and four educational levels (no diploma, primary school certificate, certificate of professional aptitude, and baccalaureate and above). The data showed a significant effect of educational level in all neuropsychological tests regardless of age. Gender primarily affected memory, Stroop scores, and Similarities scores. CONCLUSION: This study highlights the importance of educational level and gender in the evaluation of the memory and executive function of elderly persons. Furthermore, the presented norms consider the self-report cognitive complaints and depression symptoms over a long period of life.

Brain alterations associated with overweight evaluated by body mass index or body fat index in an elderly population: the PROOF study.

Background/objectives: Obesity is a complex health issue in which the brain plays a role yet to be determined, especially in the elderly. Indeed, in the ageing population, the balance between fat and lean mass is different; thus, the co-influence between the brain and obesity may differ between the elderly and younger subjects. Our main goal is thus to explore the relationship between the brain and obesity using two different approaches to measure obesity: body mass index (BMI) and an index centred on fat mass, the body fat index (BFI). Subjects/methods: Among the 1,011 subjects of the PROOF population, 273 subjects aged 75 years underwent 3D magnetic resonance imaging as well as dual-energy X-ray absorptiometry to assess fat mass. Voxel-based morphometry was used to explore the local differences in brain volume with obesity. Results: Higher BMI and BFI were associated with higher grey matter (GM) volume in the left cerebellum. Higher BMI and BFI were mainly associated with higher white matter volume in the left and right cerebellum and near the right medial orbital gyrus. Higher BMI was also associated with higher GM volume in the brainstem, whereas higher BFI was associated with higher GM volume in the left middle temporal gyrus. No decrease in white matter was associated with BMI or BFI. Conclusion: In the elderly, the relationship between the brain and obesity does not depend on the marker of obesity. Supra-tentorial brain structures seem to be slightly associated with obesity, whereas the cerebellum seems to be one of the key structures related to obesity.

Relationship between moderate-to-vigorous, light intensity physical activity and sedentary behavior in a prospective cohort of older French adults: a 18-year follow-up of mortality and cardiovascular events ─ the PROOF cohort study.

Background: It is well documented that moderate-to-vigorous intensity physical activity (MVPA) is effective in the prevention of major chronic diseases. Even though the current international physical activity (PA) guidelines still mainly focus on MVPA, the topic of the most recent epidemiological studies has shifted from MVPA to light intensity physical activity (LPA), owing to the necessity of promoting all activities vs. sedentary behavior (SB). However, the evidence remains currently limited. Thus, the clarification of the effects of LPA and the close relationship with SB is crucial to promote public health. Method: PA and SB were assessed by a validated self-administered questionnaire (POPAQ) investigating 5 different types of PA during the 7 previous days. PA was measured in metabolic equivalent of task (MET)-h, which refers to the amount of energy (calories) expended per hour of PA. SB was measured in hour/day. Medical histories and examinations were taken during each clinical visit to determine clinical events. All-cause mortality was established using the same procedure and by checking local death registries. The relationships between the intensity of PA (light, moderate to vigorous) and mortality and between the periods of SB and mortality or CV events were analyzed by splines and COX models, adjusted for sex and year of birth. Results: From the 1011 65-year-old subjects initially included in 2001 (60% women), the last 18-year follow-up has been currently completed since 2019. A total of 197 deaths (19.2%, including 77 CV deaths) and 195 CV events (19.3%) were reported. Averages (standard deviation) of MVPA, LPA and SB were, respectively, 1.2 h/d (0.3), 5.8 h/d (1.1), and 6.6 h/d (2.3). For all-cause deaths, as well as CV deaths, the splines were significant for LPA (p = 0.04 and p = 0.01), and MVPA (p < 0.001 and p < 0.001), but not for SB (p = 0.24 and p = 0.90). There was a significant reduction in CV events when SB was decreasing from 10.9 to 3.3 h/d. Conclusion: The PROOF cohort study shows a clear dose-response between the dose of LPA, MVPA, SB and risk of mortality. These findings provide additional evidence to support the inclusion of LPA in future PA guidelines.

Obesity related to metabolic syndrome: comparison of obesity indicators in an older french population.

OBJECTIVES: Metabolic syndrome (MS) represents a cluster of metabolic abnormalities. Insulin resistance is a major component of the syndrome. We analyze in this study the relationship between body fat composition and MS in comparison to usual obesity indicators in an older adult population. DESIGN: The PROgnostic indicator OF cardiovascular and cerebrovascular events (PROOF) study is a prospective longitudinal community cohort study among the inhabitants of Saint-Etienne, France. METHODS: The study is a cohort study of 1011 subjects, mean age 65.6 ± 0.8 years old at inclusion, recruited from the electoral list of the town in 2000. Among them, 806 subjects realized a Dual-energy X-ray absorptiometry (DXA) used to evaluate body fat and lean mass repartition. We evaluate biological metabolic parameters according to usual techniques. The indices of obesity were calculated according to standard formula. MS presence and its components were simultaneously evaluated. RESULTS: All obesity parameters were significantly higher (p < 0.0001) in subjects suffering metabolic syndrome as compared to those without. Body fat index (BFI) presented a stronger correlation to total fat mass, trunk fat mass and body adiposity index (BAI). The correlations between body indices and metabolic components showed that body mass index (BMI) and waist circumference were more strongly associated with BFI as compared to BAI and total fat mass. According to logistic regression analysis, only the waist-hip ratio (WHR) demonstrated a significant association with MS severity (p < 0.0001). CONCLUSIONS: Among the obesity indices, BFI and BAI represented the best indicators to characterize global obesity while WHR only is highly predictive of metabolic syndrome presence and severity. The BAI indicator is an alternative for measuring obesity. Comparison of long-term impact of such markers on cardiovascular morbidity and mortality is now questioned.

Sex-related differences in endothelial function and blood viscosity in the elderly population.

Elderly represents a growing population and cardiovascular diseases (CVD) is one of the leading causes of mortality in this population. Sex differences are involved in CVD with middle-aged males being at higher risk than females. After menopause, females are no longer protected by hormones and the role of sex on cardiovascular parameters involved in CVD, such as endothelial function and blood viscosity, is still unclear. The purpose of this study was to investigate the effect of sex on endothelial function, blood viscosity and CVD in elderly. Clinical investigation and blood analyses were performed on 182 (93 females and 89 males) elderly participants (mean age: 75.83 ± 1.22). Health status of participants were classified. Sex differences in endothelial function, blood viscosity, high density lipoprotein (HDL), hematocrit, and red blood cell (RBC) aggregation were assessed. CVD prevalence was higher in males (27.0%) than in females (5.4%) (p < 0.001). Females had higher vasoreactivity (p = 0.014) and HDL (p < 0.001) level than males. Blood viscosity was higher in males than in females at any shear rate (p < 0.001). Hematocrit was greater in males than in females (p < 0.001) while RBC aggregation did not differ between the two populations. To conclude, females have less CVD than age-matched males that might be due to their greater vascular function and lower blood viscosity.

Targeting autonomic nervous system as a biomarker of well-ageing in the prevention of stroke.

Stroke prediction is a key health issue for preventive medicine. Atrial fibrillation (AF) detection is well established and the importance of obstructive sleep apneas (OSA) has emerged in recent years. Although autonomic nervous system (ANS) appears strongly implicated in stroke occurrence, this factor is more rarely considered. However, the consequences of decreased parasympathetic activity explored in large cohort studies through measurement of ANS activity indicate that an ability to improve its activity level and equilibrium may prevent stroke. In support of these observations, a compensatory neurostimulation has already proved beneficial on endothelium function. The available data on stroke predictions from ANS is based on many long-term stroke cohorts. These data underline the need of repeated ANS evaluation for the general population, in a medical environment, and remotely by emerging telemedicine digital tools. This would help uncovering the reasons behind the ANS imbalance that would need to be medically adjusted to decrease the risk of stroke. This ANS unbalance help to draw attention on clinical or non-clinical evidence, disclosing the vascular risk, as ANS activity integrates the cumulated risk from many factors of which most are modifiable, such as metabolic inadaptation in diabetes and obesity, sleep ventilatory disorders, hypertension, inflammation, and lack of physical activity. Treating these factors may determine ANS recovery through the appropriate management of these conditions. Natural aging also decreases ANS activity. ANS recovery will decrease global circulating inflammation, which will reinforce endothelial function and thus protect the vessels and the associated organs. ANS is the whistle-blower of vascular risk and the actor of vascular health. Such as, ANS should be regularly checked to help draw attention on vascular risk and help follow the improvements in response to our interventions. While today prediction of stroke relies on classical cardiovascular risk factors, adding autonomic biomarkers as HRV parameters may significantly increase the prediction of stroke.

Association between depressive symptoms and long-term heart rate variability in older women: Findings from a population-based cohort.

INTRODUCTION: Cross-sectional studies highlighted changes in autonomic nervous system (ANS) activity in geriatric depression. However, few longitudinal studies assessed this link which remains still debated. We examined the longitudinal association between lifetime depression history, current depressive disorders, and the evolution of ANS activity in older community women. METHODS: The present data stemmed from the PROOF study, a population-based cohort of 1011 community-dwellers followed-up at 2-year intervals for 10 years. Only data from female participants was analyzed (n = 508, mean age 68.5 ± 0.88 years), as very few men had depression in our population. Depressive symptoms and depression history were collected at baseline. Participants were classified in four groups according to presence or absence of history of depression (HD) or current depressive symptomatology (CD): HD+/CD+, HD-/CD+, HD+/CD- and HD-/CD-. ANS activity was assessed during the follow-up through 24-h heart rate variability (HRV). Longitudinal associations between depressive status and HRV indices during the follow-up were investigated using multivariate linear mixed models. RESULTS: Compared to HD-/CD- group, women belonging to HD-/CD+ group had greater baseline parasympathetic tone, as measured by lower LF index and LF/HF balance. The longitudinal analysis exhibited a significant enhancement of LF/HF balance with time, measuring an increase of sympathetic tone in HD-/CD+ group. CONCLUSION: Our findings suggest that late-onset depressive symptoms may be associated with subsequent autonomic dysregulation in older women. These results highlight the importance of detecting and managing depressive symptoms to limit their consequences on ANS functioning, and the risk of cardiovascular events.

Insulin Resistance and Type 2 Diabetes in Asymptomatic Obstructive Sleep Apnea: Results of the PROOF Cohort Study After 7 Years of Follow-Up.

The aim of the study was to assess potential associations between obstructive sleep apnea (OSA) and the occurrence of diabetes mellitus and insulin resistance in the elderly. Nondiabetic volunteers (n = 549) with undiagnosed or untreated asymptomatic OSA (66.2+/-1 years at the inclusion) were evaluated as an ancillary study of the PROOF cohort study (n = 1,011). After 7 years follow-up, 494 subjects underwent assessment of fasting insulin and glucose levels. OSA was defined by an apnea-hypopnea index (AHI) of ≥15/h using polygraphy. Diabetes mellitus was defined by a fasting glucose ≥ 1.26 g/L and/or when requiring pharmacological treatment, while insulin resistance corresponded to HOMA-IR ≥ 2. Asymptomatic OSA subjects (men or women) did not display increased risk of incident diabetes (2.8 vs. 3.9%, p = 0.51). However, there was a greater frequency of insulin resistance in subjects with severe OSA (AHI > 30) [OR 2.21; 95% CI (1.22-4.02); p = 0.009]. Furthermore, multiple logistic regression showed that triglycerides levels [OR 1.61; 95% CI (1.10-2.36); p = 0.01] and fasting glycaemia [OR 4.69; 95% CI (1.12-192.78); p = 0.04], but not AHI or oxyhemoglobin desaturation index were independently associated with higher rate of insulin resistance. The deleterious metabolic effect of asymptomatic OSA in the population may be indirectly mediated via perturbations in lipids, and is particularly likely to become manifest in severe apneic subjects with higher glycemic levels.

Leukoaraiosis and Gray Matter Volume Alteration in Older Adults: The PROOF Study.

Background and Purpose: Leukoaraiosis, also called white matter hyperintensities (WMH), is frequently encountered in the brain of older adults. During aging, gray matter structure is also highly affected. WMH or gray matter defects are commonly associated with a higher prevalence of mild cognitive impairment. However, little is known about the relationship between WMH and gray matter. Our aim was thus to explore the relationship between leukoaraiosis severity and gray matter volume in a cohort of healthy older adults. Methods: Leukoaraiosis was rated in participants from the PROOF cohort using the Fazekas scale. Voxel-based morphometry was performed on brain scans to examine the potential link between WMH and changes of local brain volume. A neuropsychological evaluation including attentional, executive, and memory tests was also performed to explore cognition. Results: Out of 315 75-year-old subjects, 228 had punctuate foci of leukoaraiosis and 62 had begun the confluence of foci. Leukoaraiosis was associated with a decrease of gray matter in the middle temporal gyrus, in the right medial frontal gyrus, and in the left parahippocampal gyrus. It was also associated with decreased performances in memory recall, executive functioning, and depression. Conclusion: In a population of healthy older adults, leukoaraiosis was associated with gray matter defects and reduced cognitive performance. Controlling vascular risk factors and detecting early cerebrovascular disease may prevent, at least in part, dementia onset and progression.

Sera of elderly obstructive sleep apnea patients alter blood-brain barrier integrity in vitro: a pilot study.

Obstructive sleep apnea syndrome (OSAS) is characterized by repeated episodes of hypoxia during the night. The severity of the disorder can be evaluated using an apnea-hypopnea index (AHI). The physiological consequences are mainly cardiovascular and neuronal dysfunctions. One hypothesis to explain such associated neurological disorders is disruption of the blood-brain barrier (BBB), which protects the brain from endovascular cytotoxic compounds. We selected two subgroups of volunteers from the PROOF cohort study (France), a group of patients suffering newly diagnosed severe OSAS (AHI > 30/h) and a group showing no sleep apnea (AHI < 5/h). We exposed a human in vitro BBB model of endothelial cells (HBEC-5i) with sera of patients with and without OSAS. After exposure, we measured the apparent BBB permeability as well as tight junction and ABC transporter expression using whole cell ELISA. We showed that after incubation with sera from OSAS patients, there was a loss of integrity in the human in vitro BBB model; this was reflected by an increase in permeability (43%; p < 0.001) and correlated with a 50% and 40% decrease in tight junction protein expression of ZO-1 and claudin-5, respectively. At the same time, we observed an upregulation in Pgp protein expression (52%) and functionality, and a downregulation in BCRP expression (52%). Our results demonstrated that severe BBB disorder after exposure to sera from OSAS patients was reflected by an opening of the BBB.

Role of Gender and Physical Activity Level on Cardiovascular Risk Factors and Biomarkers of Oxidative Stress in the Elderly.

BACKGROUND: Cardiovascular diseases remain as the leading cause of morbidity and mortality in industrialized countries. Ageing and gender strongly modulate the risk to develop cardiovascular diseases but very few studies have investigated the impact of gender on cardiovascular diseases in the elderly, which represents a growing population. The purpose of this study was to test the impact of gender and physical activity level on several biochemical and clinical markers of cardiovascular risk in elderly individuals. METHODS: Elderly individuals (318 women (75.8 ± 1.2 years-old) and 227 men (75.8 ± 1.1 years-old)) were recruited. Physical activity was measured by a questionnaire. Metabolic syndrome was defined using the National Cholesterol Education Program Expert Panel's definition. Polysomnography and digital tonometry were used to detect obstructive sleep apnea and assess vascular reactivity, respectively. Blood was sampled to measure several oxidative stress markers and adhesion molecules. RESULTS: The frequency of cardiovascular diseases was significantly higher in men (16.4%) than in women (6.1%) (p < 0.001). Body mass index (25.0 ± 4.3 vs. 25.8 ± 3.13 kg.m-2) and glycaemia (94.9 ± 16.5 vs. 101.5 ± 22.6 mg.dL-1) were lower, and High Density Lipoprotein (HDL) (74.6 ± 17.8 vs. 65.0 ± 17.2 mg.dL-1) was higher in women compared to men (p < 0.05). Oxidative stress was lower in women than in men (uric acid: 52.05 ± 13.78 vs. 59.84 ± 13.58, advanced oxidation protein products: 223 ± 94 vs. 246 ± 101 µmol.L-1, malondialdehyde: 22.44 ± 6.81 vs. 23.88 ± 9.74 nmol.L-1). Physical activity was not associated with lower cardiovascular risk factors in both genders. Multivariate analyses showed an independent effect of gender on acid uric (ß = 0.182; p = 0.020), advanced oxidation protein products (ß = 0.257; p < 0.001), and HDL concentration (ß = -0.182; p = 0.026). CONCLUSION: These findings suggest that biochemical cardiovascular risk factors are lower in women than men which could explain the lower cardiovascular disease proportion observed in women in the elderly.

Even a Previous Light-Active Physical Activity at Work Still Reduces Late Myocardial Infarction and Stroke in Retired Adults Aged>65 Years by 32%: The PROOF Cohort Study.

Background: Work may contribute significantly to daily physical activity (PA) and sedentary behavior (SB). Physical inactivity and SB at work might be two major risk factors for premature morbidity. Therefore, the aim of this research was to describe self-reported past PA and SB at work and during leisure time within the PROOF cohort subjects, and to determine consequences of PA and SB on late health of these now retired workers. Material and Methods: The PROOF cohort study was used to prospectively allow assessment of the predictive value of PA and SB at work and during leisure time among a healthy retired French population, with regard to cardiovascular and cerebrovascular events. PA (MET-h/week) and SB (h/d) were assessed using the Population Physical Activity Questionnaire (POPAQ) and the modified Global Physical Activity Questionnaire (GPAQ). Odds ratios (ORs with 95% CIs) for cardiovascular and cerebrovascular events were associated with each level of PA at work: light (<3 METs), moderate (3-5.9 METs), vigorous (≥6 METs) and were compared to SB at work. Results: Out of the 1011 65-year-old subjects initially included, the 15-year follow-up has been currently completed for 688 (68%) subjects; 89 deaths (all-cause mortality, 9%) and 91 fatal and non-fatal cardiovascular and cerebrovascular events (9%), were reported. An active work (light, moderate, or vigorous intensity) was associated with a 21% reduced risk of cardiovascular (myocardial infarction) and cerebrovascular events (stroke) (OR = 0.79, 95% CI: 0.32-0.91, p < 0.02) compared to sedentary work. This relationship was already significant for light intensity work (32%; i.e., OR = 0.68, 95% CI: 0.31-0.87, p < 0.02). Conclusion: There is strong causal evidence linking PA and SB at work with late cardiovascular and cerebrovascular disease. All in all, the risk for onset of myocardial infarction and stroke was lower among those who had a previous active work compared to those with previous sedentary work. Even previous light active work produced substantial health benefits. Clinical Trial Registration: www.ClinicalTrials.gov, identifier: NCT00759304.

Sleep apnoea in the asymptomatic elderly: a real issue for the brain?

The link between sleep apnoea and brain structure is unclear; although dysfunction of the hippocampus, middle temporal gyrus and brainstem/cerebellum have been observed previously. However, this link has been little explored in elderly subjects. The aim of this study was to explore the link between sleep apnoea and the brain in an elderly population.226 asymptomatic elderly subjects (age mean±sd 75.3±0.9 years, range 72.3-77.8 years) from the PROOF (Evaluation of Ageing, Autonomic Nervous System Activity and Cardiovascular Events) cohort study were explored using linear voxel-based or cortical thickness with apnoea/hypopnoea index (AHI; mean±sd 15.9±11.5 events·h-1, range 6-63.6 events·h-1) as a covariate of main interest. The brain volumes of 20 control subjects, 18 apnoeic (AHI >29 events·h-1) treated patients and 20 apnoeic untreated patients from this population were compared using voxel-based morphometry, cortical thickness or surface-based analyses.AHI was not associated with any change in local brain volume, cortical thickness or cortex surface. Control subjects, apnoeic treated and untreated patients were not different in terms of local brain volume, cortical thickness or surface.In a specific population of asymptomatic elderly healthy subjects, sleep apnoea does not seem to be associated with a change in local brain volume or in cortical thickness.

Use of Vitamin K Antagonists and Brain Morphological Changes in Older Adults: An Exposed/Unexposed Voxel-Based Morphometric Study.

BACKGROUND: Vitamin K antagonists (VKAs) are commonly used for their role in haemostasis by interfering with the vitamin K cycle. Since vitamin K also participates in brain physiology, this voxel-based morphometric study aimed to determine whether the duration of exposure to VKAs correlated with focal brain volume reduction in older adults. METHODS: In this exposed/unexposed (1: 2) study nested within the GAIT (Gait and Alzheimer Interactions Tracking) cohort, 18 participants exposed to VKA (mean age 75 ± 5 years; 33.3% female; mean exposure 2,122 ± 1,799 days) and 36 matched participants using no VKA (mean age 75 ± 5 years; 33.3% female) underwent MRI scanning of the brain. Cortical grey and white matter volumes were automatically segmented using statistical parametric mapping. Age, gender, educational level, history of atrial fibrillation, type of MRI, and total intracranial volume were included as covariables. RESULTS: The duration of exposure to VKA correlated inversely across the whole brain with the subvolumes of two clusters in the grey matter (right frontal inferior operculum and right precuneus) and one cluster in the white matter (left middle frontal gyrus). In contrast, the grade of white matter hyperintensities did not differ according to the use of VKA. CONCLUSION: We found focal atrophies in older adults exposed to VKA. These findings provide new insights elucidating the effects of VKAs on brain health and function in older adults.

Elderly Patients with Ongoing Migraine Show Reduced Gray Matter Volume in Second Somatosensory Cortex.

AIMS: To identify structural changes in gray matter in suspected migraine generators (the hypothalamus and/or brainstem nuclei) and pain pathways and to evaluate whether structural changes in migraine are definitive or resolve with age. METHODS: Voxel-based morphometry (VBM) was used to assess differences in gray matter between 39 healthy controls (HC), 25 episodic migraine (EM) subjects, and 37 subjects with a history of migraine (HM). In addition, morphometric changes were specifically investigated in suspected migraine generators and/or pain pathways. For statistical analyses, t tests between the groups were performed, and a correction for multiple comparisons was used. RESULTS: Whole-brain analysis did not reveal any gray or white matter changes. However, when the analysis was limited to the pain matrix, a lower gray matter volume was observed in the left second somatosensory (SII) cortex in EM subjects compared to HC subjects. This volume was significantly reduced in the EM group compared to the HC group and to the HM group, but not in the HM group compared to the HC group. CONCLUSION: Morphometric abnormalities in the SII in subjects with ongoing migraine but not in subjects with a resolved migrainous disease are likely to characterize a migrainous state rather than be a marker of brain susceptibility to migraine.

Serum lipid profile, sleep-disordered breathing and blood pressure in the elderly: a 10-year follow-up of the PROOF-SYNAPSE cohort.

OBJECTIVES: Dyslipidemia, sleep-disordered breathing (SDB) and hypertension are comorbid factors evidenced in adults, but poorly studied in old people. This study aimed to examine the long-term evolution of the serum lipid profile, and its relationships with SDB and blood pressure (BP) in the elderly. METHODS: A ten-year follow-up of the prospective Prognostic Indicator of Cardiovascular and Cerebrovascular Events (PROOF) and the Autonomic Nervous System Activity, Aging and Sleep Apnea/Hypopnea (SYNAPSE) cohort, which initially included 1011 elderly subjects from the general population, and who were untreated by continuous positive airway pressure (CPAP). Serum lipid profile, respiratory polygraphy for SDB and ambulatory blood pressure monitoring were performed. RESULTS: A total of 266 subjects (male/female 150/116; age 66.2 ± 0.8 years) were reassessed after 9.6 ± 0.7 years (age 75.8 ± 1.2 years). The prevalence of high-risk dyslipidemia decreased from 61.3 to 44.4%, and hypertension from 57.9 to 27.4%. The nocturnal oxygen desaturation index increased (mean + 2.3 ± 6.7 events/hour; p < 0.001), while the mean SaO2 and minimal SaO2 decreased. These variations (Δ) of oxygen desaturation worsened whether or not elderly subjects took anti-hypertensive and lipid-lowering treatments, and were not associated with serum lipid variations. The decrease in diurnal diastolic BP was independently associated with aging, and with the lowering of the waist/hip ratio (ΔW/H) and low-density lipoprotein cholesterol (LDL-C)/high-density lipoprotein cholesterol (HDL-C) ratio, while the decrease in diurnal systolic BP only depended on aging and ΔW/H. CONCLUSIONS: The results suggested that the observed worsening of nocturnal oxygen desaturation after 10 years in the elderly was independent of the change in circulating lipids, and not influenced by lipid-lowering treatments. However, the variation in blood pressure remained associated with aging, waist/hip and LDL-C/HDL-C ratios. TRIAL REGISTRY: NCT00759304 and NCT00766584 at clinicaltrials.gov.

Incidental findings on brain magnetic resonance imaging in the elderly:the PROOF study.

To prospectively evaluate the prevalence of incidental findings on standardized brain MRI scans in a cohort of elderly subjects. All participants provided written informed consent to participate in this prospective study, which was approved by the institutional review board and was HIPAA compliant. There were 503 subjects (75.3 ± 0.9 years of age, 58 % women) who received brain MRIs on a 1.5-T scanner using a standard acquisition protocol. All scans were reviewed by an experienced neuroradiologist. Incidental findings were stratified as follows: 1, no incidental findings; 2, incidental findings without clinical significance; 3, incidental findings with clinical significance or requiring clinical follow-up. Incidental findings were identified in 77.9 % of subjects. Among 392 scans that exhibited incidental findings, 494 abnormalities were identified. The most common findings in our study were cysts (45.9 % of subjects) and ear, nose, and throat (ENT) lesions (24.8 %) followed by stroke lesions (6.6 %) and neoplasms (3.8 %). There were 472 incidental findings that lacked clinical significance (group 2), and 22 incidental findings that required follow-up evaluation (group 3). Incidental findings on brain MRIs were commonly observed in this cohort of elderly subjects, but clinical follow-up was rarely indicated.

HRVanalysis: A Free Software for Analyzing Cardiac Autonomic Activity.

Since the pioneering studies of the 1960s, heart rate variability (HRV) has become an increasingly used non-invasive tool for examining cardiac autonomic functions and dysfunctions in various populations and conditions. Many calculation methods have been developed to address these issues, each with their strengths and weaknesses. Although, its interpretation may remain difficult, this technique provides, from a non-invasive approach, reliable physiological information that was previously inaccessible, in many fields including death and health prediction, training and overtraining, cardiac and respiratory rehabilitation, sleep-disordered breathing, large cohort follow-ups, children's autonomic status, anesthesia, or neurophysiological studies. In this context, we developed HRVanalysis, a software to analyse HRV, used and improved for over 20 years and, thus, designed to meet laboratory requirements. The main strength of HRVanalysis is its wide application scope. In addition to standard analysis over short and long periods of RR intervals, the software allows time-frequency analysis using wavelet transform as well as analysis of autonomic nervous system status on surrounding scored events and on preselected labeled areas. Moreover, the interface is designed for easy study of large cohorts, including batch mode signal processing to avoid running repetitive operations. Results are displayed as figures or saved in TXT files directly employable in statistical softwares. Recordings can arise from RR or EKG files of different types such as cardiofrequencemeters, holters EKG, polygraphs, and data acquisition systems. HRVanalysis can be downloaded freely from the Web page at: https://anslabtools.univ-st-etienne.fr HRVanalysis is meticulously maintained and developed for in-house laboratory use. In this article, after a brief description of the context, we present an overall view of HRV analysis and we describe the methodological approach of the different techniques provided by the software.