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.

Hippocampus volume and subjective sleepiness in older people with sleep-disordered breathing: a preliminary report.

UNLABELLED: Sleep-disordered breathing (SDB) is associated with excessive daytime sleepiness (EDS) and explained by sleep fragmentation and hypoxaemia, both contributing to brain morphology abnormalities. Recent data on middle-aged SDB patients suggest a link between hippocampus volume (HV) and EDS. We tested this hypothesis in a group of SDB older subjects. A total of 232 healthy participants aged 75 ± 0.9 years were examined. Subjective EDS was assessed by the Epworth Sleep Questionnaire (ESS), with a mean score of 5.6 ± 3.5. Volumetric segmentation of the right (RHV) and left HV (LHV) were measured using FreeSurfer software. All subjects underwent extensive cognitive testing to exclude neurological disease, as well as ambulatory polygraphy to assess SDB status. Sleepy subjects showed a lower HV. In a correlation analysis, RHV (r = -0.162, P = 0.01) and LHV (r = -170, P = 0.05) were correlated negatively with ESS and not associated with respiratory data. Multiple regression analysis did not reveal any effect of age, gender, SDB severity and hypoxia. ESS was the only factor possibly explaining the lower RHV (P = -0.03) and LHV (P = -0.04). In older people with SDB, the subjective EDS was associated with lower HV. This morphological finding should be considered on the pathogenesis of sleepiness in SDB patients. CLINICAL TRIAL REGISTRATION: NCT 00759304 and NCT 00766584.

Sleep-related autonomic overactivity in a general elderly population and its relationship to cardiovascular regulation.

Alteration in cardiac autonomic activity during sleep is a common feature of sleep disorders. Diurnal sympathetic overactivity is a possible consequence and could contribute to future cardiovascular complications. The aim of this study is to assess the relationship between cardiac autonomic activity during sleep and diurnal autonomic cardiovascular control. In a large cohort (n = 1011) of subjects aged 65 years old (± 0.4) free of cardiac and cerebrovascular events and of sleep-related breathing disorders, we evaluated (cross-sectional study) the prevalence of unexpected alteration in sleep-related autonomic overactivity according to the presence of a cyclical nocturnal heart rate variability [quantified using the relative power spectral density of the very low-frequency band of the heart rate increment (VLFi%) from ECG Holter monitoring]. We tested its relationship with diurnal ambulatory blood pressure and spontaneous baroreflex sensitivity (sBRS). An abnormal cardiac autonomic activity during sleep was retained in 34.4% of this population according to a VLFi% >4. Using multiple logistic regression analysis, the severity of the autonomic alteration was mainly correlated after adjustment with lower sBRS (p = 0.01; OR: 0.94; 95% CI: 0.90-0.98). Diurnal baroreflex control alteration is associated with sleep-related autonomic overactivity elderly. Such alteration may contribute to the increased incidence of cardiovascular complications in sleep disorders.

Metabolic syndrome is associated with poor memory and executive performance in elderly community residents: the PROOF study.

OBJECTIVE: Aging is associated with a loss of cognitive performance and an increasing occurrence of cardiovascular events. Moreover, cardiovascular risk factors are linked to cognitive impairment and dementia. Whereas individual components of metabolic syndrome (Met S) have been reported to be linked to cognitive decline and dementia, there are very few studies on Met S as a whole. The present study aims to assess the relationship between Met S and its components and cognitive functioning in a cohort of elderly non-demented community residents. DESIGN: Population-based cohort study (PROOF study). Cross-sectional analysis. PARTICIPANTS: Dementia-free community-dwellers aged 65. MEASURES: The PROOF participants underwent an extensive neuropsychological battery at baseline. Summary cognitive measures including memory, attention, and executive performance were created by converting the individual test results to Z scores and computing the average scores within each domain. Each of the three cognitive scores was individually compared between groups as a function of Met S. The cognitive scores and the covariates which were significant in univariate analyses were then included in logistic regression models. RESULTS: A significant association was observed between the presence of metabolic syndrome, poor memory, and executive function even after adjusting for confounding factors (memory: odds ratio: 1.77, p = 0.008; executive functions: odds ratio: 1.91, p = 0.002). CONCLUSIONS: Our study showed that in a sample of elderly community dwellers, Met S was associated with poor memory and executive performance. These results underline the importance of detecting and managing metabolic syndrome components to prevent cognitive impairment and dementia.

Higher gait variability is associated with decreased parietal gray matter volume among healthy older adults.

The objectives of this study were to examine the association of stride time variability (STV) with gray and white matter volumes in healthy older adults, and to determine the specific location of any parenchymal loss associated with higher STV. A total of 71 participants (mean age 69.0 ± 0.8 years; 59.7 % female) were included in this study. All participants had a 1.0 Tesla 3D T1-weighted MRI of the brain to measure gray and white matter volumes. STV was measured at steady-state self-selected walking speed using an electronic footswitch system. We found an association between higher STV and lower gray matter volume in the right parietal lobe (e.g., angular gyrus, Brodmann area 39, cluster corrected pFWE = 0.035). There were no significant associations between STV and higher gray matter volume or change in white matter volume. To the best of our knowledge this study is the first to identify a significant association of higher STV with lower right parietal gray matter volume in healthy older adults.

Sleep-related breathing disorders and gait variability: a cross-sectional preliminary study.

BACKGROUND: Sleep-related breathing disorders (SRBDs) provoke cognitive and structural brain disorders. Because these disorders have been associated with unsafe gait characterized by an increase in stride-to-stride variability of stride time (STV), we hypothesised that SRBDs could be associated with an increased STV. The aim of this study was to examine the association between SRBDs and STV in French healthy older community-dwellers. METHODS: A total of 49 participants (mean age 69.6 ± 0.8 years; 65.2% female) were included in this cross-sectional study. All participants, who were free of clinically diagnosed SRBDs before their inclusion, had a nocturnal unattended home-sleep assessment. There were separated in three group based on apnea + hypopnea index (AHI): AHI <15 defining the absence of SRBD, AHI between 15-30 defining mild SRBD, and AHI >30 defining moderate-to-severe SRBD. Coefficient of variation of stride time, which is a measure of STV, was recorded while usual walking using SMTEC® footswitches system. Digit span score was used as a measure of executive performance. Age, gender, body mass index (BMI), number of drugs daily taken, vision, proprioception, history of falls, depression symptoms, global cognitive functioning were also recorded. RESULTS: STV and BMI were higher in participants with mild SRBDs (P = 0.031 and P = 0.020) and moderate-to-severe SRBDs (P = 0.004 and P = 0.002) compared to non-SRBDs. STV positively correlated with AHI (P = 0.036). Lower (i.e., better) STV was associated with the absence of SRBDs (P = 0.021), while greater (i.e., worse) STV was associated with moderate-to-severe SRBD (P < 0.045) but not with mild SRBD (P > 0.06). CONCLUSION: Our results show a positive association between STV and SRBDs, with moderate-to-severe SRBD being associated with greater gait variability. This association opens new perspectives for understanding gait disorders in older adults with SRBDs and opens the door to treatments options since SRBDs are potential treatable factors.

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.

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.

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.

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.

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.

At 68 years, unrecognised sleep apnoea is associated with elevated ambulatory blood pressure.

After the age of 65 yrs the specific impact of unrecognised sleep-related breathing disorders (SRBD) on 24-h blood pressure (BP) levels remains under debate. We tested the cross-sectional relationship between the severity of obstructive sleep apnoea/hypopnoea (OSAH) and the increase of BP using ambulatory BP monitoring (ABPM) in the PROOF (PROgnostic indicator OF cardiovascular and cerebrovascular events study)-SYNAPSE (Autonomic Nervous System Activity, Aging and Sleep Apnea/Hypopnea study) cohort. 470 subjects (aged 68 yrs) neither treated for hypertension nor diagnosed for SRBD were included. All subjects underwent ABPM, and unattended at-home polygraphic studies. OSAH was defined by an apnoea/hypopnoea index (AHI) >15 · h(-1). The severity of the sleep apnoea was also quantified as the index of dips in oxyhaemoglobin saturation >3% (ODI). Results are expressed in per protocol analysis. Severe OSAH (AHI >30 · h(-1), 17% of subjects) was associated with a significant 5 mmHg increase in both diurnal and nocturnal systolic BP (SBP), and with a nocturnal 3 mmHg increase in diastolic BP (DBP). Systolic (mean SBP >135 mmHg) or diastolic (mean DBP >80 mmHg) hypertension were more frequently encountered in subjects suffering from moderate (AHI 15-30) or severe OSAH. After adjustment, the independent association between severe OSAH and 24-h systolic hypertension remained significant (OR 2.42, 95% CI 1.1-5.4). The relationship was further reinforced when SRBD severity was expressed using ODI >10 · h(-1). The impact of unrecognised SRBD on BP levels also exists at the age of 68 yrs. The hypoxaemic load appears to be the pathophysiological cornerstone for such a relationship.

Obstructive sleep apnea and the metabolic syndrome in an elderly healthy population: the SYNAPSE cohort.

BACKGROUND: Obstructive sleep apnea syndrome (OSA) has been recently considered as a cause and a component of the metabolic syndrome (MetS), previous studies showing the presence of OSA in about half of middle-aged patients having MetS. To date, no study has considered the association of OSA and MetS in the elderly. In this study we examine the prevalence of MetS and its strength association among healthy elderly OSA subjects. METHODS: A cohort of 806 subjects aged 68.5 years, participants of a 7-year follow-up study, was examined. All subjects underwent clinical evaluation, blood sample measurements, and an at-home polygraphy. OSA was assessed as an apnea/hypopnea index (AHI) >15, and MetS was diagnosed according to the Adult Treatment Panel III. RESULTS: In the total group, 9.8% of cases met criteria for MetS with a prevalence similar in men and women. Of the entire group with Mets, 51.3% were women and 48.7% men. OSA was diagnosed in 55.9% of the sample, and among the OSA group, 12.5% had MetS. Oxyhemoglobin desaturation index (ODI, p < 0.0001) and AHI (p = 0.003) were found significantly higher in subjects with MetS than in those without it. Most of MetS components were significantly associated with AHI and ODI, the relationship stronger with ODI. After adjustment for covariables such as obesity, gender, and presence of diabetes, ODI was independently associated with three MetS components, glycemia (p < 0.0001), hypertension (p = 0.002), and triglyceride levels (p = 0.02). Sleepiness, autonomic arousal index, and sleep duration had no effect on the metabolic parameters. CONCLUSIONS: In elderly subjects, the association between OSA and MetS was stronger for hyperglycemia and hypertension. Among factors explaining this association, hypoxemia appears to be the most important factor without any effect of indices of sleep fragmentation, sleep duration, and sleepiness.

Diabetes, impaired fasting glucose, and cognitive decline in a population of elderly community residents.

BACKGROUND AND AIMS: Diabetes and impaired fasting glucose, as well as cognitive impairment, are common in the elderly. Although several cross-sectional studies have demonstrated the influence of diabetes on cognitive impairment, only a few longitudinal studies have assessed the relationship between diabetes, impaired fasting glucose and cognitive decline in non-demented elderly community dwellers, by means of extensive neuropsychological batteries. The present study assesses the relationship between baseline diabetes, impaired fasting glucose (IFG) and 2- year evolution of memory, attention and executive performance in a sample of non-demented elderly subjects. DESIGN: Population-based cohort study [(PROgnostic indicator OF cardiovascular and cerebrovascular events (PROOF)]. PARTICIPANTS: One hundred and sixty-three community dwellers aged 65 years without dementia at recruitment. MAIN OUTCOME MEASURES: Memory, attention and executive performance. RESULTS: A significant association was observed between baseline diabetes mellitus and a higher 2-year decline in the Trial Making Test B and Stroop test exploring attention and executive function. This effect remained significant after adjusting for age, gender, education, anxiety and depressive symptoms, as well as other cardiovascular risk factors (F=2.41; p=0.007). Instead, no relationship was observed between IFG and cognitive decline. CONCLUSIONS: Our study showed that, in a sample of elderly non-demented community dwellers, diabetes mellitus (but not IFG) is associated with a higher decline in selective attention and executive functioning. These results emphasize the importance of detecting and man- aging diabetes and impaired fasting glucose, in order to prevent cognitive impairment and dementia.

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.

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.

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.

Cognitive function and sleep related breathing disorders in a healthy elderly population: the SYNAPSE study.

STUDY OBJECTIVES: Sleep related breathing disorders (SRBD) are risk factors for cognitive dysfunction in middle-aged subjects, but this association has not been observed in the elderly. We assess the impact of SRBD on cognitive performance in a large cohort of healthy elderly subjects. DESIGN: Cross-sectional study examining the association between subjective memory test, neuropsychological battery testing and SRBD in the elderly. SETTING: Community-based sample in home and research clinical settings. PARTICIPANTS: 827 subjects, 58.5% women, aged 68 y at study entry, participated in the study. All were free of previously diagnosed SRBD, coronary heart disease, and neurological disorders, including stroke and dementia. Clinical interview, neurological assessment, polygraphy, and extensive cognitive testing were conducted for all participants. INTERVENTION: N/A. MEASUREMENT AND RESULTS: SRBD (apnea-hypopnea index [AHI] > 15 events/h) was diagnosed in 445 (53%) subjects, 167 (37%) of them with AHI > 30. Minimal daytime sleepiness was found in the group; 9.2% of the population had an Epworth Sleepiness Scale score > 10. No significant association was found between AHI, nocturnal hypoxemia, and cognitive scores. Comparison of mild vs severe cases showed a trend toward lower cognitive scores with AHI > 30, affecting delayed recall and Stroop test. CONCLUSIONS: The impact of undiagnosed SRBD on cognitive function appeared quite limited in a generally older healthy population, and only slightly affected severe cases. The implication of undiagnosed SRBD on the cognitive impairment in elderly subjects remains hypothetical and needs to be prospectively studied.