Although mortality in old age has significantly decreased over the last fifty years in the developed world, there still remains a large inter-individual variability in ageing trajectories,... Show more Although mortality in old age has significantly decreased over the last fifty years in the developed world, there still remains a large inter-individual variability in ageing trajectories, morbidity and mortality. In the three parts of this thesis, we examined three interacting systems that have been identified as contributing to a slower pace of ageing, namely glucose/insulin metabolism (part I), the thyroid axis (part II), and the autonomic nervous system (part III). We found that familial longevity is associated with a stronger association of insulin parameters with microstructural brain parameters, and by higher TSH secretion, in the absence of differences in basal energy metabolism or differences in heart rate and its variability. Using specialized MRI techniques, we showed that subtle changes in microstructural brain parenchymal homogeneity in relation to insulin can be detected, even in brain tissue that appears normal on conventional MR imaging sequences. Insulin (rather than glucose), seemed to be a stronger indicator of micro- structural brain integrity in normo-glycemic older adults. Furthermore, intranasal application of insulin improved brain perfusion in parietal and occipital gray matter and in the thalamus of older adults. These results deepen our understanding of the physiological mechanisms and processes that underlie the ageing process. Show less
Current evidence on older adults is derived from population-based cohort studies and randomized controlled trials, which may not include frail individuals. Data are lacking on older outpatients, a... Show moreCurrent evidence on older adults is derived from population-based cohort studies and randomized controlled trials, which may not include frail individuals. Data are lacking on older outpatients, a potentially diverse population. Therefore, we initiated the Milan Geriatrics 75+ Cohort Study, a prospective hospital-based outpatient cohort study. Chapter 1 of this thesis provides a background on the controversies regarding the homeostasis of older adults. Chapter 2, 3 and 4 report findings from the Milan Geriatrics 75+ Cohort Study. Chapter 2 explores the association between blood pressure and cognition, and whether it varies according to age and functional status. Chapter 3 examines the relationship between blood pressure and mortality risk, and whether it varies according to functional and cognitive status. Chapter 4 investigates the association between thyroid status and mortality risk in euthyroid older adults, and whether it differs by sex and age. Chapter 5 and 6 report findings from the PROSPER cohort, which includes older adults at high cardiovascular risk. Chapter 5 presents new evidence on the association of heart rate and heart rate variability with functional decline. Chapter 6 analyses the relationship between blood pressure variability and functional decline. Chapter 7 summarises and discusses the main findings of this thesis. Show less
A high heart rate and a low heart rate variability at rest are established predictors of various forms of functional impairment, morbidity, and mortality [1–6]. Two explanations can be given for... Show moreA high heart rate and a low heart rate variability at rest are established predictors of various forms of functional impairment, morbidity, and mortality [1–6]. Two explanations can be given for these associations. On one hand, a high heart rate and a low heart rate variability are thought to reflect dysfunction of the flexible autonomic regulation of the heart rate in particular and of the body's functioning in general that arises during ageing [3–5]. On the other hand, a high heart rate and a low heart rate variability are brought about by cardiovascular risk factors, such as obesity, hyperlipidaemia, diabetes, hypertension, and physical inactivity [2,3,7–9]. Since research on heart rate and heart rate variability has almost exclusively been conducted in western populations with an affluent sedentary lifestyle and high prevalences of these risk factors, it has been difficult to determine whether or not heart rate and heart rate variability are associated with functional impairment, morbidity, and mortality independently of cardiovascular risk factors. Show less
