How does allostatic load relate to cognitive ability, depressive symptoms and other measures of physiological weathering in older age?

Allostasis is the process through which the human body aims to achieve homeostasis - long-term physiological stability in each of its systems - through short-term changes. If someone experiences chronic stress or repeated bouts of stress, their allostatic systems can experience wear and tear and enter a state of allostatic load. The thesis first considered how allostatic load is operationalised. It outlined problems with modelling allostatic load as a latent factor, including concerns based on psychometric and substantive studies. This chapter also posited desirable qualities of allostatic load operationalisations. The subsequent substantive chapters were empirical studies that explored the role of allostatic load in successful ageing. In the first three of four studies, we fitted latent growth curve models to data from Waves 1-4 of the Lothian Birth Cohort 1936 (n [M age] at Waves 1-4 = 1,091 [69.5 years], 866 [72.5 years], 697 [76.3 years], 550 [79.3 years]). Additional models tested the role of non-random dropout. The first of these studies investigated how allostatic load relates to four other measures of physiological weathering: [Klemera-Doubal] biological age; extrinsic epigenetic age; intrinsic epigenetic age; and telomere length. Allostatic load was most strongly related to biological age, which is an age-linked measure calculated using some of the same biomarkers as allostatic load. At Wave 1, higher allostatic load was related to older biological age, with a moderate effect size (r [SE] = .28 [.05], p < .001). Greater increase over time in allostatic load was strongly related to accelerated biological ageing (r [SE] = .53 [.15], p < .001). However, most correlations between physiological weathering measures were small, which suggested that they index different aspects of physiological weathering. The next study found that at Wave 1, higher allostatic load was related to lower general cognitive ability, with a small effect size (r [SE] = -.13 [.04], p = .004). However, after controlling for the variance related to participant dropout, the relationship was attenuated by around a third (r [SE] = -.08 [.04], p = .08). The third Lothian Birth Cohort 1936 study found that at Wave 1, higher allostatic load was related to having more depressive symptoms, with a small-to-moderate effect size (r [SE] = .19 [.05], p < .001). These studies also went beyond previous research by testing relationships of associated changes over time. These tests suggested changes in allostatic load are not strongly related to changes in cognitive ability and depressive symptoms. The last empirical study in this thesis used data from the Scotland-based 36-Day-Sample (n range for models = 280-332; M age at cognitive testing = 78.2 years). In this study, producing more cortisol during the first 45 minutes after waking was related to higher general cognitive ability (β [SE] = 0.14 [0.07], Bayes factor10 [BF10] = 5.23), but the total cortisol produced during the waking day was not related to general cognitive ability (BF10 < 1/3). We also found that in carriers of the e4 allele of the apolipoprotein E gene, some measures of cortisol dynamics were more negatively associated with residualised immediate recall scores and some measures of total cortisol production were more negatively associated with residualised Raven’s matrices scores. Additionally, this study found that depressive symptoms were related to lower general cognitive ability (β [SE] = -0.15 [0.08], BF10 = 3.47), but the relationship was not more negative in e4 allele carriers (β [SE] = 0.08 [0.07], BF10 = 0.21). The final chapter considered the results in a wider context, as well as possible future directions. We discussed the limitations of our allostatic load measure, which did not include any hypothalamic–pituitary–adrenal axis biomarkers. We also considered the constraints on generalisability of all allostatic load findings given the heterogeneity of the operationalisations used. We questioned the clinical utility of allostatic load measurement for cognitive decline and depressive illness, given the small effect sizes we obtained for the relevant relationships. Finally, we concluded that future research will benefit from using larger samples and teasing apart how these relationships vary based on the allostatic load biomarkers and operationalisations used

Induction of Hebbian associative plasticity through paired non-invasive brain stimulation of premotor-motor areas to elucidate the network's functional role

The ventral premotor cortex (PMv) is believed to play a pivotal role in a multitude of visuomotor behaviors, such as sensory-guided goal-directed visuomotor transformations, arbitrary visuomotor mapping, and hyper-learnt visuomotor associations underlying automatic imitative tendencies. All these functions are likely carried out through the copious projections connecting PMv to the primary motor cortex (M1). Yet, causal evidence investigating the functional relevance of the PMv-M1 network remains elusive and scarce. In the studies reported in this thesis we addressed this issue using a transcranial magnetic stimulation (TMS) protocol called cortico-cortical paired associative stimulation (ccPAS), which relies on multisite stimulation to induce Hebbian spike-timing dependent plasticity (STDP) by repeatedly stimulating the pathway connecting two target areas to manipulate their connectivity. Firstly, we show that ccPAS protocols informed by both short- and long-latency PMv-M1 interactions effectively modulate connectivity between the two nodes. Then, by pre-activating the network to apply ccPAS in a state-dependent manner, we were able to selectively target specific functional visuo-motor pathways, demonstrating the relevance of PMv-M1 connectivity to arbitrary visuomotor mapping. Subsequently, we addressed the PMv-to-M1 role in automatic imitation, and demonstrated that its connectivity manipulation has a corresponding impact on automatic imitative tendencies. Finally, by combining dual-coil TMS connectivity assessments and ccPAS in young and elderly individuals, we traced effective connectivity of premotor-motor networks and tested their plasticity and relevance to manual dexterity and force in healthy ageing. Our findings provide unprecedent causal evidence of the functional role of the PMv-to-M1 network in young and elderly individuals. The studies presented in this thesis suggest that ccPAS can effectively modulate the strength of connectivity between targeted areas, and coherently manipulate a networks’ behavioral output. Results open new research prospects into the causal role of cortico-cortical connectivity, and provide necessary information to the development of clinical interventions based on connectivity manipulation

New Trends in Sport and Exercise Medicine

The practice of regular physical activity has been proposed as a determinant in many disciplines, from wellness to physiotherapy; in fact, it reduces the risks of cardiovascular diseases and diabetes. Moreover, physical exercise decreases the incidence of some types of cancer, such as breast and colon cancer. Finally, rehabilitation protocols need correct exercise training to reach the complete “return to play” of patients. Unfortunately, the mechanisms associated with the beneficial effects of physical activity are still under study. Therefore, advances in all aspects of sport and exercise medicine will be relevant for physicians, recreational sport practitioners and elite athletes. This was the aim of this Special Issue, “New trends in sport and exercise medicine”, which achieved great success. Sixteen papers have been published, which are briefly described below. They range from mobile applications in physiotherapy to changes in bioactive lipids in half-marathoners. However, sport and exercise medicine are broad subjects and require more papers to clarify their different aspects. Therefore, we proposed a new Special Issue to continue on this path and gain new insights into sport and exercise medicine

Analytical validation of innovative magneto-inertial outcomes: a controlled environment study.

peer reviewe

The Impact of the COVID-19 Emergency on the Quality of Life of the General Population

COVID-19 is a pandemic that has forced many states to declare restrictive measures in order to prevent its wider spread. These measures are necessary to protect the health of adults, children, and people with disabilities. Long quarantine periods could cause an increase in anxiety crises, fear of contagion, and post-traumatic stress disorder (frustration, boredom, isolation, fear, insomnia, difficulty concentrating). Post-traumatic stress disorder (PTSD) is a condition that can develop in subjects who have been or have witnessed a traumatic, catastrophic, or violent event, or who have become aware of a traumatic experience that happened to a loved one. In fact, from current cases, it emerges that the prevalence of PTSD varies from 1% to 9% in the general population and can reach 50%–60% in subgroups of subjects exposed to traumas considered particularly serious. PTSD develops as a consequence of one or more physical or psychological traumatic events, such as exposure to natural disasters such as earthquakes, fires, floods, hurricanes, tsunamis; wars, torture, death threats; road accidents, robbery, air accidents; diseases with unfavorable prognoses; complicated or traumatic mourning; physical and sexual abuse and abuse during childhood; victimization and discrimination based on gender, sexual orientation, gender identity. It can also develop following changes in lifestyle habits caused by the COVID-19 epidemic

The Impact of the COVID-19 Emergency on the Quality of Life of the General Population

COVID-19 is a pandemic that has forced many states to declare restrictive measures in order to prevent its wider spread. These measures are necessary to protect the health of adults, children, and people with disabilities.Long quarantine periods could cause an increase in anxiety crises, fear of contagion, and post-traumatic stress disorder (frustration, boredom, isolation, fear, insomnia, and difficulty concentrating).Post-traumatic stress disorder (PTSD) is a condition that can develop in subjects who have witnessed a traumatic, catastrophic, or violent event, or who have become aware of a traumatic experience that happened to a loved one.In fact, from current cases, it emerges that the prevalence of PTSD varies from 1% to 9% in the general population and can reach 50%–60% in subgroups of subjects exposed to traumas considered particularly serious. PTSD develops as a consequence of one or more physical or psychological traumatic events, such as exposure to natural disasters such as earthquakes, fires, floods, hurricanes, tsunamis; wars, torture, death threats; road accidents, robbery, air accidents; diseases with unfavorable prognoses; complicated or traumatic mourning; physical and sexual abuse and abuse during childhood; or victimization and discrimination based on gender, sexual orientation, or gender identity. It can also develop following changes in lifestyle habits caused by the COVID-19 epidemic.Thank you for reading the manuscripts in this Special Issue, "The Impact of the COVID-19 Emergency on the Quality of Life of the General Population"