Anatomy and physiology of the autonomic nervous system: Implication on the choice of diagnostic/monitoring tools in 2023.

The autonomic nervous system (ANS) harmoniously regulates all internal organic functions (heart rate, blood pressure, vasomotion, digestive tract motility, endocrinal secretions) and adapts them to the needs. It's the control of so-called vegetative functions, which allows homeostasis but also allostasis of our body. ANS is divided into two systems often understood as antagonistic and complementary: the sympathetic and the parasympathetic systems. However, we currently know of many situations of co-activation of the two systems. Long seen as acting through "reflex" control loops passing through the integration of peripheral information and the efferent response to the peripheral organ, more recent electrophysiological and brain functional imaging knowledge has been able to identify the essential role of the central autonomic network. This element complicates the understanding of the responses of the reflex loops classically used to identify and quantify dysautonomia. Finding the "ANS" tools best suited for the clinician in their daily practice is a challenge that we will attempt to address in this work.

Structural skin changes in elderly people investigated by reflectance confocal microscopy.

BACKGROUND: Reflectance confocal microscopy (RCM) is particularly suitable for the study of skin ageing because it provides nearly histological information in vivo and non-invasively. However, there are no studies that evaluated RCM skin features of a large population older than 70 years. OBJECTIVES: The aim of our investigation was to study age-related skin changes in an elderly population by RCM and to evaluate their topographical and gender differences. METHODS: We obtained RCM images of photoprotected (volar arm) and chronic (face) and intermittently photoexposed (dorsal forearm) body sites of 209 volunteers (105 women and 104 men, mean age: 77.5, range 74-81 years). 15 previously reported and new RCM parameters related to skin ageing were assessed. RESULTS: Photoexposed sites had thicker suprapapillary epidermis, more linear, distant and thin furrows, higher presence of mottled pigmentation, polycyclic papillae and coarse and huddled collagen and lower presence of dermal papillae than the photoprotected site. Irregular honeycomb pattern was not higher in photoexposed sites, indicating that it is probably more dependent on intrinsic ageing. Two ageing scores defined for facial skin ageing (epidermal disarray score and epidermal hyperplasia score) were found useful for the identification of photoageing. Gender differences only concerned some RCM parameters (i.e. thickness of different layers of the epidermis, furrows and collagen score) and some body sites, in line with the fact that women and men of our cohort had no major differences in clinically visible skin ageing. CONCLUSIONS: Our study confirmed that RCM is a powerful non-invasive technique to microscopically quantify ageing signs and our observations contribute to highlight the differences between intrinsic and extrinsic ageing.

Care through cohort studies: sociological survey of the PROOF cohort study on vascular and cognitive aging.

BACKGROUND: The success of health research depends on the involvement of participants. Few studies have examined the participation of subjects in cohorts. Drawing on a sociological survey on a French cohort around aging, this study proposes to question the nature of interactions between researchers and subjects that would help to understand the motivations of subjects to participate and remain in health research studies. METHODS: Qualitative study combining participant observation within the research laboratory that conducted the cohort and semi-structured interviews with subjects included in the cohort and with members of the research team. RESULTS: This study highlights the existence of two-way care: from the laboratory to the subjects and from the cohort to researchers. Health research seems to correspond to a complex association between subjects concerned with aging and the expected benefits of exceptional monitoring. Research is incorporated into subjects' daily lives, allowing a shift in the purpose of research from overmedicalization to medical safety that subjects experienced as a form of care. CONCLUSIONS: In cohort studies, care is understood as a form of attention to the person through high-quality medical follow-up. Aging is turned into a matter of concern that subjects, in collaboration with researchers, strive to control.

Long-lasting active lifestyle and successful cognitive aging in a healthy elderly population: The PROOF cohort.

OBJECTIVES: The aim of this study was to determine whether cognitive reserve in the elderly affects the evolution of cognitive performance and what its relationship is with active lifestyles in later life. METHODS: Cognitive performance was evaluated at baseline and 8 years later in 543 participants of the PROOF cohort, initially aged 67 years. Subjects were categorized as Cognitively Elite (CE), Cognitively Normal (CN) or Cognitively Impaired (CI) at each evaluation. At follow-up, demographic data and lifestyle, including social, intellectual and physical behaviors, were collected by questionnaires. RESULTS: As much as 69% (n=375) remained unchanged, while 25.5% (n=138) decreased and 5.5% (n=30) improved. When present, the reduction in cognitive status was most often limited to one level, but was dependent on the initial level, affecting up to 73% of the initially CN, but only 58% of the initially CE. Cognitive stability was significantly associated with the degree of social engagement at follow-up (CE: P=0.009; CN: P=0.025). CONCLUSION: In the healthy elderly, high cognitive ability predicts both cognitive ability and social involvement in later life. Cognitive decline by only one level may also extend the time to reach impairment, underlining the importance of the so-called cognitive reserve.

Subjective sleep and cognitive complaints in 65 year old subjects: a significant association. The PROOF cohort.

OBJECTIVE: The prevalence of subjective sleep and cognitive complaints increases with age. The purpose of this study was to investigate the link between subjective cognitive and sleep complaints in a population aged 65. DESIGN AND SETTING: analysis of a cohort of 1011 subjects aged 65 years old at time of inclusion. METHODS: Older people underwent a cognitive tests battery and a nocturnal polygraphy recording. Subjective cognitive difficulties were scored on the McNair and Kahn Scale. Subjective sleep complaints were evaluated according to the St. Mary's Hospital Sleep Questionnaire and the Epworth Sleepiness Scale score. RESULTS: In a 65 years old population, an association between subjective cognitive difficulties and poor sleep quality was observed. This remained significant after adjustment on gender, depression score, anxiety, educational level, medication intake, Apnea/Hypopnea index, Body Mass Index and Mini-Mental State Examination (OR = 2.1; p = 0.0002). Similar significant association was demonstrated between subjective cognitive difficulties and daytime sleepiness (OR = 2.6; p = 0.0007). CONCLUSION: There was a significant association between subjective cognitive and sleep complaints, and daytime sleepiness in our population of older people.

Seven-year predictors of self-rated health and life satisfaction in the elderly: the PROOF study.

OBJECTIVES: To investigate the relationship between cognitive performance, affective state, metabolic syndrome and 7-year follow-up self-rated health (SRH) and perceived life satisfaction (PLS). DESIGN: Analysis of a prospective cohort study. SETTING: The PROOF study, including 1011 elderly community residents. PARTICIPANTS: Six hundred and fifty seven subjects completed metabolic syndrome (Met S) variables, neuropsychological and affective measurements at baseline, and then returned a 7-year follow-up questionnaire which included SRH and PLS. MEASUREMENTS: The prospective association between cognitive function, Met S and each of its components, and affective disorders and subsequent subjective health and quality of life was examined. Covariates included educational level and use of tobacco. The analyses were made in men and women separately. RESULTS: In multivariate models, the presence of Met S was significantly associated to weaker SRH (OR = 2.78, p = 0.009 in men and OR = 2.0, p = 0.02 in women). Higher triglycerides rate were associated with weaker SRH in men (OR = 2.23, p = 0.002) and higher fasting glucose in women (OR = 2.54, p = 0.006). Global Met S and abdominal obesity was significantly associated to weaker PLS in women only (respectively OR = 2.70, p = 0.0002 and OR = 1.9, p = 0.02). Depressive symptoms were significantly associated to both weaker SRH and PLS in men (OR = 1.30, p = 0.002; OR = 1.44, p < 0.0001 for SRH and PLS respectively) and in woman (OR = 1.09, p = 0.04; OR = 1.26, p < 0.0001 for SRH and PLS respectively). Anxiety was linked to both weaker SRH and PLS in women (OR = 1.17, p = 0.002 and 0R = 1.11, p = 0.03 for SRH and PLS respectively). Finally, lower executive function was associated with weaker PLS in men (OR = 0.43, p = 0.0005). CONCLUSION: metabolic syndrome and certain of its components, anxiety and depressive symptoms, are independent predictors of poorer subjective health and quality of life as assessed over a period of 7 years in a population of a non-demented aging community. Moreover, executive performance was linked to subsequent quality of life in men. Many of these factors being treatable, our findings point to the necessity of providing preventive care strategies by the management of cardiovascular risk factors and anxio-depressive symptoms.

[Autonomic regulation and bradycardia during the neonatal period]. / Régulation autonomique et bradycardies néonatales.

The high frequency of bradycardia observed during the neonatal period requires cardiac monitoring but also understanding its intrinsic mechanisms, including responsiveness of the autonomic nervous system (ANS). Heart rate variability and spontaneous baroreflex analysis can help understand the autonomic dysregulation of cardiorespiratory control, possibly responsible for sudden infant death. In clinical neonatology practice, neonatal bradycardia does not warrant continuation of monitoring if it remains isolated, asymptomatic, and short (<10 s), followed by a rapid cardiac acceleration indicating an adapted sympathetic response. Further evaluation of ANS responsiveness is possible for newborns including analyzing the complexity of the heart rate and respiratory variability. This allows better targeting children with high risk after discharge. The real-time evaluation of autonomic regulation could become a valuable tool in clinical practice.

Sympathetic overactivity due to sleep fragmentation is associated with elevated diurnal systolic blood pressure in healthy elderly subjects: the PROOF-SYNAPSE study.

AIMS: Sleep fragmentation is a landmark of sleep disorders, because microarousals are systematically associated with sympathetic surges (i.e., sympathetic arousals). However, the impact of sympathetic sleep fragmentation on blood pressure (BP) remains understudied. We assessed the relationships between 24 h ambulatory BP monitoring, the autonomic arousal index (AAI) derived from pulse transit time, and heart rate variability indices. We hypothesized that repeated sympathetic arousals during sleep are associated with elevated BP in a large population of elderly volunteers. METHODS AND RESULTS: Volunteer subjects (n = 780, 57.4% women) with a mean age of 68.7 years and free of known sleep-disordered breathing, coronary heart diseases, and neurological disorders underwent polygraphy, 24 h ECG Holter monitoring, and 24 h ambulatory BP monitoring. Multivariate regressions showed that sleep fragmentation, expressed by AAI, was associated with elevated diurnal (P = 0.008) and 24 h (P = 0.005) systolic BP and higher risk for 24 h [odds ratio (OR): 1.70 (1.04-2.80), P = 0.036] systolic hypertension, independently of confounders such as sleep-disordered breathing, body mass index, sex, diabetes, hypercholesterolaemia, and self-reported sleep duration and quality. Increased AAI was associated with higher nocturnal and diurnal low-frequency power (P < 0.001) and low-to-high-frequency ratio (P < 0.001), suggesting nocturnal and diurnal sympathetic overactivity. CONCLUSION: In healthy elderly subjects, repetitive sympathetic arousals during sleep are associated with elevated systolic BP and higher risk of hypertension, after controlling for confounders. Sympathetic overactivity is the proposed underlying mechanism. CLINICAL TRIAL REGISTRATION: NCT00766584 and NCT00759304.

[Chronic cough in the elderly is associated with expiratory flow limitation]. / La toux chronique du sujet âgé est associée à une limitation expiratoire des débits.

As chronic respiratory symptoms and the presence of expiratory flow limitation (EFL) are commonly reported in the elderly, we investigated whether they were associated in a population of 75 years old volunteers. We analyzed the results of a prevalence survey of chronic respiratory symptoms and respiratory infections, and performed spirometry and measured EFL after application of a negative expiratory pressure at the mouth (NEP). EFL was present in 170 (46%) subjects, a chronic cough in 49 (13%), chronic sputum in 58 (29%) and a history of respiratory infection in 62 (17%). Chronic cough and the composite outcome "chronic cough or sputum" were significantly associated with the presence of EFL (respectively 60% vs. 43%, OR=2.04 [1.09 to 3.78], P=0.023, and 56% vs. 43%, OR=1.74 [1.05 to 2.87], P=0.04), after controlling for smoking or airway obstruction. History of respiratory infections were not associated with an increased prevalence of EFL. We concluded that the presence of a LED could be an interesting indicator of respiratory aging. Its detection could be advocated in elderly subjects presenting with respiratory symptoms.

Sex differences in obstructive sleep apnoea in an elderly French population.

Obstructive sleep apnoea (OSA) affects females and males differently, and increases in prevalence with age. The aim of the present study was to characterise clinical, anthropometric and polygraphic sex differences in a large elderly OSA population. A total of 641 subjects aged 68 yrs were examined. Measurements of fat mass, using dual-energy X-ray absorptiometry (DEXA) and polygraphy, were obtained in all subjects. An apnoea/hypopnoea index (AHI) of >15 events·h⁻¹ identified the presence of OSA. OSA was diagnosed in 57% of the sample, 34% having a mild form and 23% having an AHI of >30 events·h⁻¹. Females with OSA exhibited a lower AHI, less severe hypoxaemia and greater peripheral fat mass, and frequently reported anxiety and depression. Comparison of females with and without OSA did not reveal significant differences in clinical, anthropometric and DEXA data. After adjustment for body mass index, hypertension, diabetes, smoking, anxiety and depression, logistic regression analysis revealed that the presence of hypertension was significantly associated with OSA risk in females (OR 1.52, p = 0.04). In a general community healthy population, the prevalence of undiagnosed OSA in females increases with age, with a risk similar to that in males. In females, the clinical spectrum, anthropometric data and fat distribution appear to be more sex-related than OSA-dependent. The occurrence of OSA contributes to hypertensive risk in elderly females.

Decrease in gait variability while counting backward: a marker of "magnet effect"?

Counting backward (CB) and walking are both rhythmic tasks. An improvement of CB performance has been reported while walking, and has been interpreted as a "magnet effect" which is the tendency of biological oscillators to attract each other. The objective of this study was to compare the coefficient of variation (CoV) of stride time (ST) and the number of enumerated figures while single- and dual-tasking between older adults who increased and decreased their CoV of ST while CB. The number of enumerated figures and the CoV of ST under single-task (i.e., CB while sitting or walking alone) and dual-task (i.e., CB while walking) were measured among 100 community-dwelling older subjects (mean, 69.8 ± 0.07 years). Subjects were separated into two groups according to the dual-task-related changes in CoV of ST (i.e., either above or below the mean value of CoV of ST under single-task). Seventeen participants decreased their CoV of ST while CB compared to usual walking (2.6 ± 1.6% vs. 2.0 ± 1.3%, P < 0.001), while 83 increased their CoV of ST (1.7 ± 0.6% vs 3.4 ± 2.3%, P < 0.001). The subjects who decreased their CoV of ST had a tendency to enumerate more figures while walking compared to sitting (20.9 ± 6.3 vs 19.4 ± 4.7, P = 0.046) unlike those who increased their CoV of ST (20.3 ± 5.0 vs 21.8 ± 6.0 while sitting, P = 0.001). We found that most of subjects had worse gait and CB performance while dual-tasking. Conversely, a limited number of subjects improved significantly their gait performance and simultaneously had a tendency to improve their CB performance while walking compared to sitting. This behavior was observed only among subjects with the highest gait variability and could be interpreted as an implicit strategy based on the "magnet effect".

Metabolic syndrome and short-term and long-term heart rate variability in elderly free of clinical cardiovascular disease: the PROOF study.

OBJECTIVE: Autonomic nervous system (ANS) activity decrease has been associated with a higher risk of sudden cardiovascular and cerebrovascular disease. Thus, we explored the relationship between ANS control of the cardiovascular system and metabolic syndrome. METHODS: We analyzed the relationship with both short-term and long-term heart rate variability (HRV) and metabolic syndrome in the cross-sectional PROgnostic indicator OF cardiovascular and cerebrovascular events (PROOF) cohort study of 1,011 elderly subjects recruited amongst the inhabitants of the city of Saint Etienne, France, aged 65.6 ± 0.8 years at the inclusion date. Physical examination included measurements of height, weight, systolic and diastolic blood pressure, waist circumference, and biological parameters. HRV variables were measured over 5-min, nighttime, and 24-h periods using Holter monitoring. RESULTS: After adjustment for current type 2 diabetes, depression, and smoking, we found that metabolic syndrome status, high-density lipoprotein cholesterol (HDL-C), and waist circumference were significantly (p < 0.05) associated with total power, very-low frequency, low-frequency/high-frequency (LF/HF) ratio, and normalized LF. HDL-C and metabolic syndrome status were significantly associated with decreased long-term HRV variables. Both nighttime and 24-h HRV showed closer associations with metabolic syndrome than did short-term HRV (5-min). Metabolic syndrome severity was associated with a decrease in both the long-term and short-term HRV variables. CONCLUSIONS: ANS control alteration of the cardiovascular system was more pronounced when evaluated by long-term than short-term HRV recordings, particularly in women.

Is tidal expiratory flow limitation predictive of sleep-related disorders in the elderly?

Sleep-related disorders represent an important health burden and their prevalence increases with age. In patients with snoring or sleepiness, the presence of expiratory flow limitation (EFL), determined via the negative expiratory pressure (NEP) method, is related to the apnoea/hypopnoea index (AHI). In this study, we examined whether EFL can be used to predict obstructive sleep apnoea syndrome (OSAS) in healthy asymptomatic older subjects. A group of 72-yr-old subjects (n = 448, 44% males) with a mean body mass index of 25.5±3.8 kg·m(-2) were examined. All subjects underwent spirometry, NEP (-5 cmH(2)O, sitting position) and ventilatory polygraphy (VP). Spirometry was within normal values in 88% of the group and EFL was present in 143 (32%) subjects with a higher prevalence in females (89 out of 249 versus 54 out of 199 in females and males, respectively). VP showed an AHI<15 h(-1) in 238 subjects (53%) and OSAS with an AHI ≥15 h(-1) in 47%. EFL was found in 15% of subjects with OSAS. Consequently, EFL had low sensitivity and specificity in the prediction of OSAS (31.4% and 67.7%, respectively). We conclude that the prevalence of EFL is elevated in healthy older subjects and cannot be used to predict the presence of sleep-related disorders in an older population.

Sickle cell disease: selected aspects of pathophysiology.

Sickle cell disease (SCD), a genetically-determined pathology due to an amino acid substitution (i.e., valine for glutamic acid) on the beta-chain of hemoglobin, is characterized by abnormal blood rheology and periods of painful vascular occlusive crises. Sickle cell trait (SCT) is a typically benign variant in which only one beta chain is affected by the mutation. Although both SCD and SCT have been the subject of numerous studies, information related to neurological function and transfusion therapy is still incomplete: an overview of these areas is presented. An initial section provides pertinent background information on the pathology and clinical significance of these diseases. The roles of three factors in the clinical manifestations of the diseases are then discussed: hypoxia, autonomic nervous system regulation and blood rheology. The possibility of a causal relationship between these three factors and sudden death is also examined. It is concluded that further studies in these specific areas are warranted. It is anticipated that the outcome of such research is likely to provide valuable insights into the pathophysiology of SCD and SCT and will lead to improved clinical management and enhanced quality of life.

Association between ambulatory 24-hour blood pressure levels and cognitive performance: a cross-sectional elderly population-based study.

OBJECTIVE: The aim of this study was to examine the cross-sectional association between ambulatory 24-h blood pressure levels and cognitive performance while considering the effects of potential confounders among community-dwelling adults aged 65 years and older. METHODS: Based on a cross-sectional design, 1011 subjects (mean age 66.2 +/- 0.8 years; 60.2% women) were recruited prospectively. Average levels of systolic blood pressure (SBP) and diastolic blood pressure (DBP) were computed for a 24-h period. Cognitive performance was assessed by Folstein's Mini-Mental State Examination, immediate and delay recall subtests of the French version of the Free and Cued Selective Reminding Test, and Trail Making Test A and B. Age at baseline evaluation, gender, education level, anxiety, depression, cardiovascular risk factors, antihypertensive drugs use, and body mass index were used as confounders in data analysis. RESULTS: Multivariate logistic regression showed that, compared with low DBP level (i.e., <80 mmHg) used as reference value, only a high DBP level (i.e., >or=90 mmHg) was significantly associated with lower performance in immediate recall (adjusted odds ratio [OR] = 2.7 [1.3;5.9] for full model, and adjusted OR = 2.6 [1.2;5.4] for the stepwise backward model). Furthermore, the stepwise backward selection showed that male gender (adjusted OR = 2.2 [1.4;3.3]) and depression (adjusted OR = 2.4 [1.3;4.6]) were also significantly associated with low performance in immediate recall, whereas a high education level was associated with high performance (adjusted OR = 0.9 [0.8;0.9]). CONCLUSIONS: The findings show that only high DBP was associated with lower episodic memory performance compared with low DBP level in the studied sample. Further research is needed to corroborate and explain this finding.

Association between C-reactive protein and unrecognised sleep-disordered breathing in the elderly.

Elevated levels of C-reactive protein (CRP) have been reported in patients with sleep-disordered breathing (SDB) and may represent an inflammatory marker of cardiovascular risk. However, the association of CRP with SBD in presumed healthy elderly subjects is unknown. In total, 851 (58.5% females) 68-yr-old subjects, who were free of any known cardiac or sleep disorders, were prospectively examined. Subjects underwent unattended polygraphy, and the apnoea/hypopnoea index (AHI) and oxyhaemoglobin desaturation index (ODI) were assessed. Elevated levels of CRP were found on the morning after the sleep study in patients with more severe SDB. A significant correlation was found between CRP levels, time spent at night with arterial oxygen saturation <90% and ODI. No association was found between CRP levels and AHI. After adjustments for body mass index, smoking status, hypertension, diabetes and dyslipidaemia, a significant association remained between CRP levels and ODI >10 events.h(-1). CRP levels were frequently increased in a large sample of elderly subjects free of major cardiovascular disease. CRP levels were not correlated with the AHI and the indices of sleep fragmentation; the ODI >10 events.h(-1) was the strongest predictor of raised CRP level. The present results suggest that, in the elderly, intermittent hypoxaemia may underlie inflammatory processes leading to cardiovascular morbidity.

Cognitive complaints, neuropsychological performance and affective disorders in elderly community residents.

BACKGROUND: Previous studies have assessed the relationship between subjective cognitive complaints and objective impairment. While some of them found that cognitive complaints were explained by affective disorders, other researches found a relationship between cognitive complaints and neuropsychological performance. Most of them focused on memory functioning. However, elderly normal adults also display a decline in executive functions. This study aimed to assess the relationship between cognitive complaints, objective memory and executive performance and affective disorders. METHODS: This study was carried out with 937 community-dwelling elderly individuals recruited from the electoral list of the city of Saint-Etienne, France. Cognitive complaints were assessed using the MacNair scale. Cognitive performances were measured via a large battery of memory and executive-performance tests chosen for their capacity to detect subtle cognitive impairment. Anxiety and depressive symptoms were assessed using scales devised by Pichot and Goldberg. RESULTS: Cognitive complaints were associated with lower scores on verbal-memory tests and several executive-performance tests. Moreover, affective disorders were related to some of the executive-performance test scores, but they were not related to scores on the Free and Cued Selective Reminding Test, Digit Symbol Substitution Test and Trail Making B scores. CONCLUSIONS: Cognitive complaints of the elderly can reflect objective memory and executive-performance impairments, independent of affective disorders. Cognitive complaints should be assessed using both memory and executive-performance tests.