Testing Van Gool’s Hypothesis: A Method to Predict Side Effects of Cholinesterase Inhibitors in Patients with Cellular Degenerative and Vascular Dementia

This study investigates a method to predict medical outcome of cholinesterase inhibitors in patients with Alzheimer’s disease (AD) and vascular dementia (VaD). Van Gool predicts that patients with cholinergic deficit symptoms will benefit from treatment whereas patients without will experience side effects because of overstimulation of the cholinergic system. We predicted that AD and VaD patients with a longer RT experience fewer side effects than patients with a faster response and that VaD patients have a longer RT than AD patients. A number of 71 patients with AD or VaD diagnosis were included. A sustained attention task was administered, as well as the MMSE and a questionnaire about side effects. Results indicated that VaD patients with a longer RT reported fewer side effects. Furthermore, patients with VaD had a longer RT than patients with AD. MMSE was negatively correlated with RT in the VaD group. Thus, the performance on the attention task seems associated with suffering from side effects and thus tends to predict medical outcome in VaD, but not in AD. Perhaps this attention task was not sensitive enough to measure cholinergic deficit symptoms in AD patients. Furthermore, different doses of medication might confound the effect for the AD group.

Developing Interventions for Frailty

Frailty is a well-recognised, complex syndrome, predominantly affecting older people. Currently, there are two main conceptualizations of frailty: the phenotypic and the accumulated deficit models, with the phenotypic model being more widely applied in clinical research. Based on these models, we contend that a number of the phenotypic frailty components (weakness, slowness, and low energy expenditure) are potentially reversible. This paper outlines the results of a frailty research program. It summarizes the initial frailty treatment model and reports its effectiveness. Briefly, the effect of a twelve-month individually tailored multifactorial, interdisciplinary intervention targeting frailty was compared with usual care. The intervention reduced phenotypically defined frailty and improved mobility. Further, it is contended that there is evidence of substantial unmet need due to treatment fragmentation and the absence of a comprehensive approach for this population. Our paper then outlines the current stage of our research in which the model is now being extended to prefrailty. Interventions aimed at reversing the frailty syndrome or its consequences are only in their early stages. There is significant scope for future research to identify optimal management programs for frail older people.

Outcome Measures for Dementia in the Advanced Stage and at the End of Life

Increasing life span and lack of medication for prevention or treatment of progressive dementias will significantly increase the number of individuals with advanced dementia worldwide. Providing optimal care for them will stretch health care resources and will require evaluation of different treatment strategies. This paper is presenting measures that may be used in this patient population. Evaluation of global goals of palliative care may include measuring quality of life by QUALID scale, comfort by DS-DAT scale, and engagement by MPES scale. Symptom control may be achieved by measuring pain by PAINAD or PACSLAC scales, by evaluating behavioral symptoms and their management (agitation by SOAPD scale, apathy by AES scale and rejection of care by RTC-DAT scale), and by monitoring patients for dyspnea using RDOS scale. Outcomes of palliative care at the end of life may be evaluated by EOLD-CAD scale and by determining family satisfaction with care (EOLD-SWC). Items included in these scales, psychometric properties, and research use of these scales are described. It is hoped that information in this paper will stimulate research interest in this important area.

CSF Biomarkers of Alzheimer’s Disease: Impact on Disease Concept, Diagnosis, and Clinical Trial Design

Data from clinicopathologic and biomarker studies have converged to support the view of Alzheimer’s disease (AD) as a continuum, with pathology developing decades prior to the onset of cognitive symptoms which culminate as dementia at the end stage of the disease. This concept is impacting disease nomenclature, diagnostic criteria, prognostic potential, and clinical trial design. Revisions to diagnostic criteria to incorporate biomarker results have recently been proposed in order to increase the confidence of AD as the underlying etiology of a clinical impairment and to permit a diagnosis of AD across the disease continuum, eventually perhaps in the asymptomatic period. Individuals in this preclinical stage are receiving intense focus as a targeted population for secondary prevention trials aimed at identifying disease-modifying therapies that have the best chance of preserving normal cognitive function. The goal is to bring validated biomarkers to clinical practice for the purpose of disease diagnosis, prognosis, and evaluation of therapeutic efficacy once disease-modifying treatments become available. Realization of this goal requires worldwide biomarker standardization efforts, consensus among researchers and clinicians regarding the clinical utility of assessing biomarkers in patient care settings, and eventually the endorsement and adoption of such procedures and practices into global health care systems.

Biodemographic Analyses of Longitudinal Data on Aging, Health, and Longevity: Recent Advances and Future Perspectives

Biodemography became one of the most innovative and fastest growing areas in demography. This progress is fueled by the growing variability and amount of relevant data available for analyses as well as by methodological developments allowing for addressing new research questions using new approaches that can better utilize the potential of these data. In this review paper, we summarize recent methodological advances in biodemography and their diverse practical applications. Three major topics are covered: (1) computational approaches to reconstruction of age patterns of incidence of geriatric diseases and other characteristics such as recovery rates at the population level using Medicare claims data; (2) methodological advances in genetic and genomic biodemography and applications to research on genetic determinants of longevity and health; and (3) biodemographic models for joint analyses of time-to-event data and longitudinal measurements of biomarkers collected in longitudinal studies on aging. We discuss how such data and methodology can be used in a comprehensive prediction model for joint analyses of incomplete datasets that take into account the wide spectrum of factors affecting health and mortality transitions including genetic factors and hidden mechanisms of aging-related changes in physiological variables in their dynamic connection with health and survival.

Application of Traditional Medical Ideas to Geriatric Syndrome

Background. Japan is a superaging society, with the percentage of persons aged >65 years increasing year after year. Traditional medicine (TM) for elderly has been practiced worldwide for thousands of years. Treatment methods for aspiration pneumonia, gait disorder, glaucoma, and bowel symptoms have been developed. The ideas of acupuncture, moxibustion, and herbal medicine have been implemented in modern medical settings, and medical devices using heat transfer engineering and nanotechnology have been developed. An ultrasound scanner can be used for the evaluation of effects and indications for these therapeutic measures. Objectives. To review published literature and our studies that evaluated medical treatments for the elderly on the basis of ideas of TM. Search Methods. We searched Pubmed, Scopus, and reference lists of relevant clinical trials. Authors’ Conclusions. Many studies were found. But there are insufficient data on the effects of traditional medical therapies and further research is needed. TM therapies vary widely and studies of these therapies that ascertain practical application are essential for the utilization of ideas of TM in modern medicine. Moreover, to verify practical application, a quantitative evaluation index is necessary. Nonetheless, modalities using ideas of TM may be promising treatments for some diseases in the elderly.

Oxidative Stress and Proteostasis Network: Culprit and Casualty of Alzheimer’s-Like Neurodegeneration

Free radical-mediated damage to proteins is particularly important in aging and age-related neurodegenerative diseases, because in the majority of cases it is a non-reversible phenomenon that requires clearance systems for removal. Major consequences of protein oxidation are loss of protein function and the formation of large protein aggregates, which are often toxic to cells if allowed to accumulate. Deposition of aggregated, misfolded, and oxidized proteins may also result from the impairment of protein quality control (PQC) system, including protein unfolded response, proteasome, and autophagy. Perturbations of such components of the proteostasis network that provides a critical protective role against stress conditions are emerging as relevant factor in triggering neuronal death. In this outlook paper, we discuss the role of protein oxidation as a major contributing factor for the impairment of the PQC regulating protein folding, surveillance, and degradation. Recent studies from our group and from others aim to better understand the link between Down syndrome and Alzheimer’s disease neuropathology. We propose oxidative stress and alteration of proteostasis network as a possible unifying mechanism triggering neurodegeneration.

Psychoeducational Interventions for Family Caregivers of Seniors across Their Life Trajectory: An Evidence-Based Research Program to Inform Clinical Practice

Family caregivers of the elderly are growing in number and the care they are called upon to deliver in industrialized countries is becoming increasingly demanding and complex. Empirical research shows that the caregiving situation can have a significant impact on the health of these caregivers often on account of stress, physical and psychological exhaustion, and a sense of being overwhelmed. In this context, the quality of life of these caregivers depends in large part on professional educational and support interventions. The purpose of this paper is to present three innovative psychoeducational intervention programs developed and empirically tested by the research team of the Université de Montréal’s (Québec, Canada) Chair in Nursing Care for Seniors and Their Families over the past fifteen years. These interventions have been developed together with family caregivers experiencing different stressful situations across their care trajectory. The results of evaluative studies of these programs provide evidence to inform professional clinical practice. Future directions for caregiving research are discussed.

Currently Available Biomarkers and Strategies for the Validation of Novel Candidates for Neurochemical Dementia Diagnostics in Alzheimer’s Disease and Mild Cognitive Impairment

The number of people afflicted with Alzheimer’s disease (AD) and other types of dementing conditions has grown exponentially in the last decades. This review focuses on the diagnostic role of the classic cerebrospinal fluid (CSF) biomarkers of neurochemical dementia diagnostics (NDD) and critically discusses potential strategies for the development and validation of novel potential candidates. In some countries, NDD is already established as a routine diagnostic tool, used for the evaluation of patients with cognitive impairments. On the other hand, preanalytical and technical issues, partly discussed in this paper, prevent NDD from the general acceptance worldwide. Currently, two groups of biomarkers in the CSF are considered in NDD: amyloid β (Aβ) peptides and Tau proteins, including the hyperphosphorylated forms of the latter (pTau). The analyses of these two groups of biomarkers can reveal pathologic alterations as early as twenty years before the onset of clinical symptoms. In mild cognitive impairment (MCI), NDD can reliably predict which individuals are at risk of converting to AD. The roles of biomarkers of amyloid β deposition in the brain tissue (including the CSF concentration of Aβ42) and biomarkers of neurodegeneration (including the CSF concentrations of Tau/pTau proteins) are reflected in the currently proposed diagnostic criteria for AD and MCI.