Phenoconversion from probable rapid eye movement sleep behavior disorder to mild cognitive impairment to dementia in a population-based sample

© 2017 The Authors Introduction Rapid eye movement sleep behavior disorder (RBD) is strongly associated with synucleinopathies. In 2012, we reported an increased risk of mild cognitive impairment (MCI) and Parkinson disease (PD) in cognitively normal Olmsted County, Minnesota, residents, aged 70 to 89 years with probable RBD. Here, we examine their progression to dementia and other neurodegenerative phenotypes. Methods Fifteen participants with RBD who were diagnosed with either MCI or PD were longitudinally followed, and their subsequent clinical courses were reviewed. Results Over 6.4 ± 2.9 years, six of the 14 participants with MCI developed additional neurodegenerative signs, five of whom had Lewy body disease features. Four of them progressed to dementia at a mean age 84.8 ± 4.9 years, three of whom met the criteria for probable dementia with Lewy bodies. One subject with PD developed MCI, but not dementia. Discussion Our findings from the population-based sample of Olmsted County, Minnesota, residents suggest that a substantial number of RBD patients tend to develop overt synucleinopathy features over time, and RBD patients who develop MCI and subsequent dementia have clinical features most consistent with dementia with Lewy bodies

An intelligent multi-agent memory assistant

World population is ageing and increasingly scarce resources are required to cover the needs of everyone adequately. Medical conditions, especially memory problems, restrict the daily life of a broad slice of the elderly population, affect their independence. To prevent this, providing the right care and assistance while having in mind the costs implicated is essential. One possible path is to work with resources that we already have today and create innovative solutions to achieve the required level of support. There are not many solution either technological or not to prevent memory loss. In this work we present a possible solution aimed at restoring or maintaining the independence of elderly people, through the use of so-called Memory Assistants. We thus present an Intelligent Multi-Agent Memory Assistant designed to help people with memory problems remember their events and activities. The implementation of an event manager, free time manger, medication remainder and a sensory system, to manage and monitor the user, we aim to improve their quality of life and increase their independence

Does the diurnal cycle of cortisol explain the relationship between physical performance and cognitive function in older adults?

Background Regular physical activity is a promising strategy to treat and prevent cognitive decline. The mechanisms that mediate these benefits are not fully clear but physical activity is thought to attenuate the harmful effects of chronic psychological stress and hypercortisolism on cognition. However, the circadian pattern of cortisol secretion is complex and it is not known which aspects are most closely associated with increased cognitive function and better physical performance. This is the first study to simultaneously measure cognitive function, the diurnal cycle of salivary cortisol and physical performance in older adults, without cognitive impairment (n = 30) and with amnestic Mild Cognitive Impairment (aMCI) (n = 30). Results Regression analysis showed that better cognitive function was associated with better physical performance. A greater variance in cortisol levels across the day from morning to evening was associated with better cognitive function and physical performance. Conclusions The results support the idea that a more dynamic cortisol secretion pattern is associated with better cognitive function and physical performance even in the presence of cognitive impairment, but our results could not confirm a mediating role in this relationship

The effects of an extensive exercise programme on the progression of Mild Cognitive Impairment (MCI): study protocol for a randomised controlled trial

Background Exercise interventions to prevent dementia and delay cognitive decline have gained considerable attention in recent years. Human and animal studies have demonstrated that regular physical activity targets brain function by increasing cognitive reserve. There is also evidence of structural changes caused by exercise in preventing or delaying the genesis of neurodegeneration. Although initial studies indicate enhanced cognitive performance in patients with mild cognitive impairment (MCI) following an exercise intervention, little is known about the effect of an extensive, controlled and regular exercise regimen on the neuropathology of patients with MCI. This study aims to determine the effects of an extensive exercise programme on the progression of MCI. Methods/design This randomised controlled clinical intervention study will take place across three European sites. Seventy-five previously sedentary patients with a clinical diagnosis of MCI will be recruited at each site. Participants will be randomised to one of three groups. One group will receive a standardised 1-year extensive aerobic exercise intervention (3 units of 45 min/week). The second group will complete stretching and toning (non-aerobic) exercise (3 units of 45 min/week) and the third group will act as the control group. Change in all outcomes will be measured at baseline (T0), after six months (T1) and after 12 months (T2). The primary outcome, cognitive performance, will be determined by a neuropsychological test battery (CogState battery, Trail Making Test and Verbal fluency). Secondary outcomes include Montreal Cognitive Assessment (MoCA), cardiovascular fitness, physical activity, structural changes of the brain, quality of life measures and measures of frailty. Furthermore, outcome variables will be related to genetic variations on genes related to neurogenesis and epigenetic changes in these genes caused by the exercise intervention programme. Discussion The results will add new insights into the prevailing notion that exercise may slow the rate of cognitive decline in MCI

Assessing the presence of shared genetic architecture between Alzheimer's disease and major depressive disorder using genome-wide association data

We are grateful to the families and individuals who took part in the GS:SFHS and UKB studies, and to all those involved in participant recruitment, data collection, sample processing and QC, including academic researchers, clinical staff, laboratory technicians, clerical workers, IT staff, statisticians and research managers. This work is supported by the Wellcome Trust through a Strategic Award, reference 104036/Z/ 14/Z. We acknowledge with gratitude the financial support received from the Dr Mortimer and Theresa Sackler Foundation. This research has been conducted using the GS:SFHS and UK Biobank (project #4844) resources. GS:SFHS received core funding from the Chief Scientist Office of the Scottish Government Health Directorates [CZD/16/6] and the Scottish Funding Council [HR03006]. UKB was established using funding from the Wellcome Trust, Medical Research Council, the Scottish Government Department of Health, and the Northwest Regional Development Agency. DJP, IJD, TCR and AMM are members of the University of Edinburgh Centre for Cognitive Ageing and Cognitive Epidemiology, part of the cross council Lifelong Health and Wellbeing Initiative (MR/K026992/1). TCR is supported by Alzheimer's Scotland, through the Marjorie MacBeath bequest. Funding from the Biotechnology and Biological Sciences Research Council and Medical Research Council is gratefully acknowledged. We are grateful for the use of summary data from the International Genomics of Alzheimer's Project and the Major Depressive Disorder working group of the Psychiatric Genomics Consortium.Peer reviewedPublisher PD

Depressive symptoms in younger women and men with acute myocardial infarction:Insights from the VIRGO Study

BACKGROUND: Depression was recently recognized as a risk factor for adverse medical outcomes in patients with acute myocardial infarction (AMI). The degree to which depression is present among younger patients with an AMI, the patient profile associated with being a young AMI patient with depressive symptoms, and whether relevant sex differences exist are currently unknown. METHODS AND RESULTS: The Variation in Recovery: Role of Gender on Outcomes of Young AMI Patients (VIRGO) study enrolled 3572 patients with AMI (67.1% women; 2:1 ratio for women to men) between 2008 and 2012 (at 103 hospitals in the United States, 24 in Spain, and 3 in Australia). Information about lifetime history of depression and depressive symptoms experienced over the past 2 weeks (Patient Health Questionnaire; a cutoff score ≥10 was used for depression screening) was collected during index AMI admission. Information on demographics, socioeconomic status, cardiovascular risk, AMI severity, perceived stress (14‐item Perceived Stress Scale), and health status (Seattle Angina Questionnaire, EuroQoL 5D) was obtained through interviews and chart abstraction. Nearly half (48%) of the women reported a lifetime history of depression versus 1 in 4 in men (24%; P<0.0001). At the time of admission for AMI, more women than men experienced depressive symptoms (39% versus 22%, P<0.0001; adjusted odds ratio 1.64; 95% CI 1.36 to 1.98). Patients with more depressive symptoms had higher levels of stress and worse quality of life (P<0.001). Depressive symptoms were more prevalent among patients with lower socioeconomic profiles (eg, lower education, uninsured) and with more cardiovascular risk factors (eg, diabetes, smoking). CONCLUSIONS: A high rate of lifetime history of depression and depressive symptoms at the time of an AMI was observed among younger women compared with men. Depressive symptoms affected those with more vulnerable socioeconomic and clinical profiles

Developmental deletion of amyloid precursor protein precludes transcriptional and proteomic responses to brain injury

INTRODUCTION: Amyloid precursor protein (APP) undergoes striking changes following traumatic brain injury (TBI). Considering its role in the control of gene expression, we investigated whether APP regulates transcription and translation following TBI. METHODS: We assessed brain morphology (n = 4–9 mice/group), transcriptome (n = 3 mice/group), proteome (n = 3 mice/group), and behavior (n = 17–27 mice/group) of wild‐type (WT) and APP knock‐out (KO) mice either untreated or 10‐weeks following TBI. RESULTS: After TBI, WT mice displayed transcriptional programs consistent with late stages of brain repair, hub genes were predicted to impact translation and brain proteome showed subtle changes. APP KO mice largely replicated this transcriptional repertoire, but showed no transcriptional nor translational response to TBI. DISCUSSION: The similarities between WT mice following TBI and APP KO mice suggest that developmental APP deficiency induces a condition reminiscent of late stages of brain repair, hampering the control of gene expression in response to injury. Highlights: 10‐weeks after TBI, brains exhibit transcriptional profiles consistent with late stage of brain repair. Developmental APP deficiency maintains brains perpetually in an immature state akin to late stages of brain repair. APP responds to TBI by changes in gene expression at a transcriptional and translational level. APP deficiency precludes molecular brain changes in response to TBI

The Italian multiple sclerosis register

The past decade has seen extraordinary increase in worldwide availability of and access to several large multiple sclerosis (MS) databases and registries. MS registries represent powerful tools to provide meaningful information on the burden, natural history, and long-term safety and effectiveness of treatments. Moreover, patients, physicians, industry, and policy makers have an active interest in real-world observational studies based on register data, as they have the potential to answer the questions that are most relevant to daily treatment decision-making. In 2014, the Italian MS Foundation, in collaboration with the Italian MS clinical centers, promoted and funded the creation of the Italian MS Register, a project in continuity with the existing Italian MS Database Network set up from 2001. Main objective of the Italian MS Register is to create an organized multicenter structure to collect data of all MS patients for better defining the disease epidemiology, improving quality of care, and promoting research projects in high-priority areas. The aim of this article is to present the current framework and network of the Italian MS register, including the methodology used to improve the quality of data collection and to facilitate the exchange of data and the collaboration among national and international groups

Discomfort and agitation in older adults with dementia

<p>Abstract</p> <p>Background</p> <p>A majority of patients with dementia present behavioral and psychological symptoms, such as agitation, which may increase their suffering, be difficult to manage by caregivers, and precipitate institutionalization. Although internal factors, such as discomfort, may be associated with agitation in patients with dementia, little research has examined this question. The goal of this study is to document the relationship between discomfort and agitation (including agitation subtypes) in older adults suffering from dementia.</p> <p>Methods</p> <p>This correlational study used a cross-sectional design. Registered nurses (RNs) provided data on forty-nine residents from three long-term facilities. Discomfort, agitation, level of disability in performing activities of daily living (ADL), and severity of dementia were measured by RNs who were well acquainted with the residents, using the Discomfort Scale for patients with Dementia of the Alzheimer Type, the Cohen-Mansfield Agitation Inventory, the ADL subscale of the Functional Autonomy Measurement System, and the Functional Assessment Staging, respectively. RNs were given two weeks to complete and return all scales (i.e., the Cohen-Mansfield Agitation Inventory was completed at the end of the two weeks and all other scales were answered during this period). Other descriptive variables were obtained from the residents' medical file or care plan.</p> <p>Results</p> <p>Hierarchical multiple regression analyses controlling for residents' characteristics (sex, severity of dementia, and disability) show that discomfort explains a significant share of the variance in overall agitation (28%, <it>p </it>< 0.001), non aggressive physical behavior (18%, <it>p </it>< 0.01) and verbally agitated behavior (30%, <it>p </it>< 0.001). No significant relationship is observed between discomfort and aggressive behavior but the power to detect this specific relationship was low.</p> <p>Conclusion</p> <p>Our findings provide further evidence of the association between discomfort and agitation in persons with dementia and reveal that this association is particularly strong for verbally agitated behavior and non aggressive physical behavior.</p

The implementation of the serial trial intervention for pain and challenging behaviour in advanced dementia patients (STA OP!): a clustered randomized controlled trial

<p>Abstract</p> <p>Background</p> <p>Pain (physical discomfort) and challenging behaviour are highly prevalent in nursing home residents with dementia: at any given time 45-80% of nursing home residents are in pain and up to 80% have challenging behaviour. In the USA Christine Kovach developed the serial trial intervention (STI) and established that this protocol leads to less discomfort and fewer behavioural symptoms in moderate to severe dementia patients. The present study will provide insight into the effects of implementation of the Dutch version of the STI-protocol (STA OP!) in comparison with a control intervention, not only on behavioural symptoms, but also on pain, depression, and quality of life. This article outlines the study protocol.</p> <p>Methods/Design</p> <p>The study is a cluster randomized controlled trial in 168 older people (aged >65 years) with mild or moderate dementia living in nursing homes. The clusters, Dutch nursing homes, are randomly assigned to either the intervention condition (training and implementation of the STA OP!-protocol) or the control condition (general training focusing on challenging behaviour and pain, but without the step-wise approach). Measurements take place at baseline, after 3 months (end of the STA OP! training period) and after 6 months.</p> <p>Primary outcome measures are symptoms of challenging behaviour (measured with the Cohen-Mansfield Agitation Inventory (CMAI) and the Neuropsychiatric Inventory-Nursing Home version (NPI-NH)), and pain (measure with the Dutch version of the Pain Assessment Checklist for Seniors (PACSLAC-D) and the Minimum Data Set of the Resident Assessment Instrument (MDS-RAI) pain scale). Secondary outcome measures include symptoms of depression (Cornell and MDS-RAI depression scale), Quality of Live (Qualidem), changes in prescriptions of analgesics and psychotropic drugs, and the use of non-pharmacological comfort interventions (e.g. snoezelen, reminiscence therapy).</p> <p>Discussion</p> <p>The transfer from the American design to the Dutch design involved several changes due to the different organisation of healthcare systems. Specific strengths and limitations of the study are discussed.</p> <p>Trial registration</p> <p>Netherlands Trial Register (NTR): <a href="http://www.trialregister.nl/trialreg/admin/rctview.asp?TC=1967">NTR1967</a></p