Frailty, Disability and Physical Exercise in the Aging Process and in Chronic Kidney Disease

Frailty in the elderly is a state of vulnerability to poor resolution of homoeostasis after a stressor event and is a consequence of cumulative decline in many physiological systems during a lifetime. This cumulative decline depletes homoeostatic reserves until minor stressor events trigger disproportionate changes in health status. It is usually associated to adverse health outcomes and to one-year mortality risk. Physical exercise has found to be effective in preventing frailty and disability in this population. Chronic kidney disease (CKD) is also a clinical condition where protein energy-wasting, sarcopenia and dynapenia ,very common symptoms in the frail elderly, may occur. Moreover elderly and CKD patients are both affected by an impaired physical performance that may be reversed by physical exercise with an improvement of the survival rate. These similarities suggest that frailty may be a common pathway of aging and CKD that may induce disability and that can be prevented by a multidimensional approach in which physical exercise plays an important role

Information and Communication Technologies for the Activities of Daily Living in Older Patients with Dementia: A Systematic Review

Background: Significant innovations have been introduced in recent years in the application of information and communication technologies (ICTs) to support healthcare for patients with dementia. Objective: In the present systematic review, our goal is to keep track of ICT concepts and approaches to support the range of activities of daily living for people with dementia and to provide a snapshot of the effect that technology is having on patients' self-reliance. Methods: We reviewed the literature and identified systematic reviews of cohort studies and other authoritative reports. Our selection criteria included: (1) activities of daily living, (2) ICT, and (3) dementia. Results: We identified 56 studies published between 2000 and 2015, of which 26 met inclusion criteria. The present systematic review revealed many ICT systems that could purportedly support the range of activities of daily living for patients with dementia. The results showed five research bodies: 1) technologies used by patients with dementia, 2) technologies used by caregivers, 3) monitoring systems, 4) ambient assistive living with ICTs, and 5) tracking and wayfinding. Conclusions: There is a potential for ICTs to support dementia care at home and to improve quality of life for caregivers, reducing healthcare costs and premature institutional care for these patients

Non-Pharmacological Approaches in the Treatment of Dementia

Currently, a pharmacological disease-modifying treatment for dementia is not available, but different non-pharmacological approaches appear to be useful. In this chapter, we describe traditional treatments such as cognitive and emotion-oriented interventions, sensory and multi-sensory stimulation interventions and also potentially alternative interesting options such as behavioural therapy, animal-assisted therapy, home-adaptation therapy and assistive technologies to support patient with dementia. Many non-pharmacological treatments have reported benefits in multiple research studies, but there is a need for further Randomized controlled trials (RCTs) with an adequate sample size to improve the strength of evidence in order to apply these approaches

Old Age and Women’s Identity

Female identity is a dynamic concept, and it has been a very discussed issue by contemporary cultural critic. How does old age affect identity construction and perception in elderly woman? Has feminine gender an impact in subjective well-being? Psychological changes of midlife women have been as conflicting as the idea that society has about them. Personality changes after young adulthood in women is a controversial matter. Erikson proposed that women might not develop identities in early adulthood as men do. In fact, he argued that women develop them later, in the context of an intimate relationship. Moreover, identity development appears to have important consequences for midlife well-being. For example, Vandewater et al. found that women’s midlife well-being was facilitated by earlier attainment of a well-articulated identity. In these situations accomplishment of developmentally earlier tasks (identity formation) sets the stage for later psychological health. Our work sheds additional light on how women live this period of life in terms of happiness and purpose of life

Neuropsychiatric Symptoms, Endophenotypes, and Syndromes in Late-Onset Alzheimer's Disease: Focus on APOE Gene

Neuropsychiatric symptoms, previously denominated as behavioural and psychological symptoms of dementia, are common features of Alzheimer's disease (AD) and are one of the major risk factors for institutionalization. At present, the role of the apolipoprotein E (APOE) gene in the development of neuropsychiatric symptoms in AD patients is unclear. In this paper, we summarized the findings of the studies of neuropsychiatric symptoms and neuropsychiatric syndromes/endophenotypes in AD in relation to APOE genotypes, with special attention to the possible underlying mechanisms. While some studies failed to find a significant association between APOE and neuropsychiatric symptoms in late-onset AD, other studies reported a significant association between the APOE ε4 allele and an increase in agitation/aggression, hallucinations, delusions, and late-life depression or anxiety. Furthermore, some negative studies that focused on the distribution of APOE genotypes between AD patients with or without neuropsychiatric symptoms further emphasized the importance of subgrouping neuropsychiatric symptoms in distinct neuropsychiatric syndromes. Explanations for the variable findings in the existing studies included differences in patient populations, differences in the assessment of neuropsychiatric symptomatology, and possible lack of statistical power to detect associations in the negative studies

Can a Positive Allosteric Modulation of GABAergic Receptors Improve Motor Symptoms in Patients with Parkinson's Disease? The Potential Role of Zolpidem in the Treatment of Parkinson's Disease

At present, patients with advanced Parkinson's disease (PD) are unsatisfactorily controlled by currently used anti-Parkinsonian dopaminergic drugs. Various studies suggest that therapeutic strategies based on nondopaminergic drugs might be helpful in PD. Zolpidem, an imidazopyridine widely used as sleep inducer, shows high affinity only for G A B A A receptors containing the \u3b1-1 subunit and facilitates GABAergic neurotransmission through a positive allosteric modulation of G A B A A receptors. Various observations, although preliminary, consistently suggest that in PD patients zolpidem may induce beneficial (and sometimes remarkable) effects on motor symptoms even after single doses and may also improve dyskinesias. Since a high density of zolpidem binding sites is in the two main output structures of the basal ganglia which are abnormally overactive in PD (internal globus pallidus, GPi, and substantia nigra pars reticulata, SNr), it was hypothesized that in PD patients zolpidem may induce through G A B A A receptors an inhibition of GPi and SNr (and, possibly, of the subthalamic nucleus also), resulting in an increased activity of motor cortical areas (such as supplementary motor area), which may give rise to improvement of motor symptoms of PD. Randomized clinical trials are needed in order to assess the efficacy, safety, and tolerability of zolpidem in treating motor symptoms of PD

Age-related hearingimpairment and frailty in Alzheimer’s disease: interconnected associations and mechanisms

Among potentially modifiable age-related conditions linked to dementia, Alzheimer’s disease (AD),and late-life cognitive disorders, age-related hearing impairment (ARHI) or resbycusis is themost widely diffused sensory disorder and one of the principal causes of chronic disability inolder adults (Gates and Mills, 2005). The impairments of peripheral (sensory or strial) and central(predominantly neural) auditory pathways, diagnosed with different procedures, are often variouslyimbricated in determining ARHI, with mixed clinical findings (Gates and Mills, 2005). A growingbody of epidemiological evidence linking ARHI with late-life cognitive disorders (Panza et al.,2015a) suggested the potential for correcting hearing loss so that elders can function better alsofrom a cognitive point of view with appropriate treatment.ARHI is also a substantial marker for frailty in older age, another age-related clinical conditionfor identifying older persons at elevated risk for numerous adverse health outcomes such asfalls, institutionalization, hospitalization, disability, and death (Rodríguez-Mañas, 2013). Frailtyis as a multidimensional syndrome characterized by a nonspecific state of vulnerability, reducedmultisystem physiological reserve, and decreased resistance to stressors (Rodríguez-Mañas, 2013).Although there is no consensus regarding the operational definition of frailty, in general, twoare the most frequently used approaches: the first is the physical or “phenotypic” model offrailty, while the second is based on deficit accumulation, measured with the so called frailtyindexes, and defined as an accumulation of health-related deficits and disorders (Rodríguez-Mañas,2013). However, also psychological, cognitive and social factors are part of this multidimensionalsyndrome, with great influence on its definition and treatment. Cognition has already beensuggested as a possible component of frailty with increased risk of adverse outcomes. Therefore, theprevention of cognitive-related adverse outcomes including delirium (Eeles et al., 2012) and late-life cognitive disorders (Robertson et al., 2013; Panza et al., 2015b) may be possible also throughfrailty prevention

To translate pharmacogenetics in geriatrics: towards a personalized medicine

Geriatric wards represented a very interesting clinical setting in which an increased drugs use rise the prevalence of adverse drug reactions (ADRs) and therapeutic failures (TFs). These are not independent phenomena, but the severe counterposed manifestations of a continuum of phenotypes in which the better drug response is the midpoint. Age-related changes in the regulation of cytochrome P450 (CYP) genes, encoding the most common drugmetabolizing enzymes, might be responsible of the observed age-associated drift towards ADRs and TFs. In this review article, a complete impression of the CYP pharmacogenetics and epigenetics is reported in the context of increasing age, in which epigenetic CYP-gene regulation might change. Physiological age-related changes in DNA-methylation, the main epigenetic mechanisms regulating gene expression in humans, results in a physiological decrease in CYP gene expression with advancing age. This may be one of the physiological changes that, together with an increased drug use, contributed to raise the prevalence of severe responder phenotypes in older age

Coffee, tea, and caffeine consumption and prevention of late-life cognitive decline and dementia: A systematic review

A prolonged preclinical phase of more than two decades before the onset of dementia suggested that initial brain changes of Alzheimer’s disease (AD) and the symptoms of advanced AD may represent a unique continuum. Given the very limited therapeutic value of drugs currently used in the treatment of AD and dementia, preventing or postponing the onset of AD and delaying or slowing its progression are becoming mandatory. Among possible reversible risk factors of dementia and AD, vascular, metabolic, and lifestyle-related factors were associated with the development of dementia and late-life cognitive disorders, opening new avenues for the prevention of these diseases. Among diet-associated factors, coffee is regularly consumed by millions of people around the world and owing to its caffeine content, it is the best known psychoactive stimulant resulting in heightened alertness and arousal and improvement of cognitive performance. Besides its short-term effect, some case-control and cross-sectional and longitudinal population-based studies evaluated the long-term effects on brain function and provided some evidence that coffee, tea, and caffeine consumption or higher plasma caffeine levels may be protective against cognitive impairment/decline and dementia. In particular, several cross-sectional and longitudinal population-based studies suggested a protective effect of coffee, tea, and caffeine use against late-life cognitive impairment/decline, although the association was not found in all cognitive domains investigated and there was a lack of a distinct dose-response association, with a stronger effect among women than men. The findings on the association of coffee, tea, and caffeine consumption or plasma caffeine levels with incident mild cognitive impairment and its progression to dementia were too limited to draw any conclusion. Furthermore, for dementia and AD prevention, some studies with baseline examination in midlife pointed to a lack of association, although other case-control and longitudinal population-based studies with briefer follow-up periods supported favourable effects of coffee, tea, and caffeine consumption against AD. Larger studies with longer follow-up periods should be encouraged, addressing other potential bias and confounding sources, so hopefully opening new ways for diet-related prevention of dementia and AD

Autophagy and mitophagy biomarkers are reduced in sera of patients with Alzheimer's disease and mild cognitive impairment

Dementia is a neurocognitive disorder characterized by a progressive memory loss and impairment in cognitive and functional abilities. Autophagy and mitophagy are two important cellular processes by which the damaged intracellular components are degraded by lysosomes. To investigate the contribution of autophagy and mitophagy in degenerative diseases, we investigated the serum levels of specific autophagic markers (ATG5 protein) and mitophagic markers (Parkin protein) in a population of older patients by enzyme-linked immunosorbent assay. Two hundred elderly (≥65 years) outpatients were included in the study: 40 (20 F and 20 M) with mild-moderate late onset Alzheimer's disease (AD); 40 (20 F and 20 M) affected by vascular dementia (VAD); 40 with mild cognitive impairment (MCI); 40 (20 F and 20 M) with "mixed" dementia (MD); 40 subjects without signs of cognitive impairment were included as sex-matched controls. Our data indicated that, in serum samples, ATG5 and Parkin were both elevated in controls, and that VAD compared with AD, MCI and MD (all p < 0.01). Patients affected by AD, MD, and MCI showed significantly reduced circulating levels of both ATG5 and Parkin compared to healthy controls and VAD individuals, reflecting a significant down-regulation of autophagy and mitophagy pathways in these groups of patients. The measurement of serum levels of ATG5 and Parkin may represent an easily accessible diagnostic tool for the early monitoring of patients with cognitive decline