Dopamine is a key neurotransmitter involved in physiological processes such as motor control, motivation, reward, cognitive function, and maternal and reproductive behaviors. Therefore, dysfunctions of the dopaminergic system are related to a plethora of human diseases. Dopamine, via different circuitries implicated in compulsive behavior, reward, and habit formation, also represents a key player in substance use disorder and the formation and perpetuation of mechanisms leading to addiction. Here, we propose dopamine as a model not only of neurotransmission but also of neuromodulation capable of modifying neuronal architecture. Abuse of substances like methamphetamine, cocaine, and alcohol and their consumption over time can induce changes in neuronal activities. These modifications lead to synaptic plasticity and finally to morphological and functional changes, starting from maladaptive neuro-modulation and ending in neurodegeneration.

Background: Age-related loss of skeletal muscle strength and mass is linked to adverse postoperative outcomes in older individuals with sarcopenia. Half of patients suffer from severe associated osteoarthritis requiring orthopedic interventions. Mitigating the onset and progression of sarcopenia before surgery is essential to improve the prognosis and reduce surgical complications. The aim of this research was to innovatively explore whether the preoperative period could be the appropriate timeframe to empower surgical resilience, through prehabilitation and dietary supplementation, in older sarcopenic patients undergoing knee arthroplasty. Methods: The current literature concerning the effectiveness of prehabilitation and dietary supplementation before knee arthroplasty in sarcopenic older individuals was reviewed, following the SANRA criteria, between December 2023 and February 2024. The study inclusion criteria were as follows: (1) prehabilitation and/or dietary supplementation interventions; (2) human participants aged 65 years and older; (3) relevant outcome reporting (functional status, postoperative complications, and patient-reported outcomes); and (4) articles written in English The extracted information included study characteristics, demographics, intervention details, outcomes, and the main findings. Results: Merged prehabilitation and dietary supplementation strategies extrapolated from the current literature and involving strength, resistance, balance, and flexibility training, as well as essential amino acids, iron, vitamin D, adenosine triphosphate, and glucosamine sulphate supplementation, could improve the functional capacity, ability to withstand the upcoming surgical stressors, and postoperative outcomes in older people undergoing knee arthroplasty. Conclusions: Addressing complex links between knee osteoarthritis and sarcopenia in older individuals undergoing knee arthroplasty requires a multidimensional approach. Prehabilitation emerges as a crucial preliminary step, allowing the optimization of surgical outcomes. Nutraceutical integration, included in a comprehensive care plan, could have a synergic effect in achieving prehabilitation goals. Those interventions are essential for surgical resilience, in terms of muscle function preservation, recovery acceleration, and overall quality of life enhancement. Intensive collaboration among specialists could advance knowledge and the sharable consensus concerning the critical and evolutive field of perioperative care.

During aging, many physiological systems spontaneously change independent of the presence of chronic diseases. The reward system is not an exception and its dysfunction generally includes a reduction in dopamine and glutamate activities and the loss of neurons of the ventral tegmental area (VTA). These impairments are even more pronounced in older persons who have neurodegenerative diseases and/or are affected by cognitive and motoric frailty. All these changes may result in the occurrence of cognitive and motoric frailty and accelerated progression of neurodegenerative diseases, such as Alzheimer’s and Parkinson’s diseases. In particular, the loss of neurons in VTA may determine an acceleration of depressive symptoms and cognitive and motor frailty trajectory, producing an increased risk of disability and mortality. Thus, we hypothesize the existence of a loop between reward system dysfunction, depression, and neurodegenerative diseases in older persons. Longitudinal studies are needed to evaluate the determinant role of the reward system in the onset of motoric-cognitive risk syndrome.

Vitamin D is a group of lipophilic hormones with pleiotropic actions. It has been traditionally related to bone metabolism, although several studies in the last decade have suggested its role in sarcopenia, cardiovascular and neurological diseases, insulin-resistance and diabetes, malignancies, and autoimmune diseases and infections. In the pandemic era, by considering the response of the different branches of the immune system to SARS-CoV-2 infection, our aims are both to analyse, among the pleiotropic effects of vitamin D, how its strong multimodal modulatory effect on the immune system is able to affect the pathophysiology of COVID-19 disease and to emphasise a possible relationship between the well-known circannual fluctuations in blood levels of this hormone and the epidemiological trend of this infection, particularly in the elderly population. The biologically active form of vitamin D, or calcitriol, can influence both the innate and the adaptive arm of the immune response. Calcifediol levels have been found to be inversely correlated with upper respiratory tract infections in several studies, and this activity seems to be related to its role in the innate immunity. Cathelicidin is one of the main underlying mechanisms since this peptide increases the phagocytic and germicidal activity acting as chemoattractant for neutrophils and monocytes, and representing the first barrier in the respiratory epithelium to pathogenic invasion. Furthermore, vitamin D exerts a predominantly inhibitory action on the adaptive immune response, and it influences either cell-mediated or humoral immunity through suppression of B cells proliferation, immunoglobulins production or plasma cells differentiation. This role is played by promoting the shift from a type 1 to a type 2 immune response. In particular, the suppression of Th1 response is due to the inhibition of T cells proliferation, pro-inflammatory cytokines production (e.g., INF-γ, TNF-α, IL-2, IL-17) and macrophage activation. Finally, T cells also play a fundamental role in viral infectious diseases. CD4 T cells provide support to B cells antibodies production and coordinate the activity of the other immunological cells; moreover, CD8 T lymphocytes remove infected cells and reduce viral load. For all these reasons, calcifediol could have a protective role in the lung damage produced by COVID-19 by both modulating the sensitivity of tissue to angiotensin II and promoting overexpression of ACE-2. Promising results for the potential effectiveness of vitamin D supplementation in reducing the severity of COVID-19 disease was demonstrated in a pilot clinical trial of 76 hospitalised patients with SARS-CoV-2 infection where oral calcifediol administration reduced the need for ICU treatment. These interesting results need to be confirmed in larger studies with available information on vitamin D serum levels.

Atrial Fibrillation can be considered a geriatric syndrome for its prevalence and incidence, its impact on patients’ quality of life, and Health Systems’ economy. The European Society of Cardiology 2024 guidelines introduce a recommendation for maintaining vitamin K antagonist therapy over switching to direct oral anticoagulants in clinically stable elderly patients with atrial fibrillation. This article explores the implications of this indication for the geriatric clinical context. The focus will also be devoted to the need for the stratification of older patients with atrial fibrillation, making an appropriate distinction between frailty and disability.

The paradigm of the framing of Parkinson’s disease (PD) has undergone significant revision in recent years, making this neurodegenerative disease a multi-behavioral disorder rather than a purely motor disease. PD affects not only the “classic” substantia nigra at the subthalamic nuclei level but also the nerve nuclei, which are responsible for sleep regulation. Sleep disturbances are the clinical manifestations of Parkinson’s disease that most negatively affect the quality of life of patients and their caregivers. First-choice treatments for Parkinson’s disease determine amazing effects on improving motor functions. However, it is still little known whether they can affect the quantity and quality of sleep in these patients. In this perspective article, we will analyze the treatments available for this specific clinical setting, hypothesizing a therapeutic approach in relation to neurodegenerative disease state.