Motoric Cognitive Risk Syndrome : Predictor of Dementia and Age-Related Negative Outcomes

Cognitive disorders represent a leading cause of disability in the aging population, of which dementia has the highest global burden. Early signs of dementia such as slow gait and memory complaints are known to present well before the overt manifestation of the disease. Motoric cognitive risk (MCR) syndrome characterized by the simultaneous presence of gait disturbances and memory complaints in older subjects has been proposed to study the close interactions between the physical and cognitive domains as well as a possible approach to identify individuals at increased risk of dementia. In addition, studies have shown MCR as a predictor of other negative outcomes in older adults, including disability, falls and death. However, the concept of MCR is still in its early stage and approach to the syndrome is still not well established. This review aims to put together the various aspects of MCR syndrome including its pathophysiology, diagnosis, epidemiology, and relationship with other geriatric conditions

Insight, cognition and quality of life in Alzheimer's disease

Background: The detrimental impact of dementia upon patient health-related quality of life (HRQL) is well established, as is the importance of improving HRQL. However, relatively little is known about the natural history of HRQL in dementia and those factors influencing it. This limited knowledge potentially restricts the evaluation of the efficacy of interventions designed to improve HRQL. One such area concerns the relationship between HRQL and patient insight. It remains unclear what impact, if any, impaired insight has upon a patient's HRQL. The present study aimed to investigate the relationship between insight and HRQL in a sample of patients with Alzheimer's disease (AD) and their carers. Methods: 256 patients with AD were recruited as part of AddNeuroMed, a multicentre European AD biomarkers study. Of these, 174 completed a quality-of-life measure in addition to a comprehensive battery of clinical and neuropsychological assessments. Results: Insight was found to be differentially related to patient perceptions of HRQL in mild and moderate dementia. Within moderate dementia, impaired insight was associated with better perceived HRQL. Conversely, cognition, but not insight, was associated with impaired HRQL in mild dementia. Insight was not found to be associated with carer perceptions of patient HRQL. Conclusion: Impairment of insight is associated with better HRQL in moderate dementia. This finding has implications for interventions which focus on increasing patient awareness and orientation, as impairment of insight appears to have a positive impact upon HRQL

Inflammatory proteins in plasma are associated with severity of Alzheimer's disease.

Published onlineComparative StudyResearch Support, Non-U.S. Gov'tThis is a freely-available open access publication. Please cite the published version which is available via the DOI link in this record.Markers of Alzheimer's disease (AD) are being widely sought with a number of studies suggesting blood measures of inflammatory proteins as putative biomarkers. Here we report findings from a panel of 27 cytokines and related proteins in over 350 subjects with AD, subjects with Mild Cognitive Impairment (MCI) and elderly normal controls where we also have measures of longitudinal change in cognition and baseline neuroimaging measures of atrophy. In this study, we identify five inflammatory proteins associated with evidence of atrophy on MR imaging data particularly in whole brain, ventricular and entorhinal cortex measures. In addition, we observed six analytes that showed significant change (over a period of one year) in people with fast cognitive decline compared to those with intermediate and slow decline. One of these (IL-10) was also associated with brain atrophy in AD. In conclusion, IL-10 was associated with both clinical and imaging evidence of severity of disease and might therefore have potential to act as biomarker of disease progression.National Institute for Health Research (NIHR) Mental Health Biomedical Research Centre and Dementia Biomedical Research Unit at South London and Maudsley NHS Foundation Trust and King’s College LondonEuropean Union of the Sixth Framework progra

Education and older adults at the University of the Third Age

This article reports a critical analysis of older adult education in Malta. In educational gerontology, a critical perspective demands the exposure of how relations of power and inequality, in their myriad forms, combinations, and complexities, are manifest in late-life learning initiatives. Fieldwork conducted at the University of the Third Age (UTA) in Malta uncovered the political nature of elder-learning, especially with respect to three intersecting lines of inequality - namely, positive aging, elitism, and gender. A cautionary note is, therefore, warranted at the dominant positive interpretations of UTAs since late-life learning, as any other education activity, is not politically neutral.peer-reviewe

Effect of a 1-Year Nutritional Blend Supplementation on Plasma p-tau181 and GFAP Levels among Community-Dwelling Older Adults: A Secondary Analysis of the Nolan Trial

BACKGROUND: Observational studies and some randomized controlled trials have suggested that nutritional supplementation could be a possible intervention pathway to prevent cognitive decline and Alzheimer's disease (AD). As measuring amyloid-β and tau pathophysiology by positron emission tomography (PET) or cerebrospinal fluid (CSF) analyses may be perceived as complex, plasma versions of such biomarkers have emerged as more accessible alternatives with comparable capacity of predicting cognitive impairment. OBJECTIVES: This study aimed to evaluate the effect of a 1-year intervention with a nutritional blend on plasma p-tau181 and glial fibrillary acidic protein (GFAP) levels in community-dwelling older adults. Effects were further assessed in exploratory analyses within sub-cohorts stratified according to p-tau status (with the third tertile considered as high: ≥15.1 pg/ mL) and to apolipoprotein E (APOE) ε4 allele status. METHODS: A total of 289 participants ≥70 years (56.4% female, mean age 78.1 years, SD=4.7) of the randomized, double-blind, multicenter, placebo-controlled Nolan trial had their plasma p-tau181 assessed, and daily took either a nutritional blend (composed of thiamin, riboflavin, niacin, pantothenic acid, pyridoxine, biotin, folic acid, cobalamin, vitamin E, vitamin C, vitamin D, choline, selenium, citrulline, eicosapentaenoic acid - EPA, and docosahexaenoic acid - DHA) or placebo for 1 year. RESULTS: After 1-year, both groups presented a significant increase in plasma p-tau181 and GFAP values, with no effect of the intervention (p-tau181 between-group difference: 0.27pg/mL, 95%CI: -0.95, 1.48; p=0.665; GFAP between-group difference: -3.28 pg/mL, 95%CI: -17.25, 10.69; p=0.644). P-tau-and APOE ε4-stratified analyses provided similar findings. CONCLUSIONS: In community-dwelling older adults, we observed an increase in plasma p-tau181 and GFAP levels that was not different between the supplementation groups after one year

Health status of UK care home residents: a cohort study

Background: UK care home residents are often poorly served by existing healthcare arrangements. Published descriptions of residents’ health status have been limited by lack of detail and use of data derived from surveys drawn from social, rather than health, care records. Aim: to describe in detail the health status and healthcare resource use of UK care home residents Design and setting: a 180-day longitudinal cohort study of 227 residents across 11 UK care homes, 5 nursing and 6 residential, selected to be representative for nursing/residential status and dementia registration. Method: Barthel index (BI), Mini-mental state examination (MMSE), Neuropsychiatric index (NPI), Mini-nutritional index (MNA), EuroQoL-5D (EQ-5D), 12-item General Health Questionnaire (GHQ-12), diagnoses and medications were recorded at baseline and BI, NPI, GHQ-12 and EQ-5D at follow-up after 180 days. National Health Service (NHS) resource use data were collected from databases of local healthcare providers. Results: out of a total of 323, 227 residents were recruited. The median BI was 9 (IQR: 2.5–15.5), MMSE 13 (4–22) and number of medications 8 (5.5–10.5). The mean number of diagnoses per resident was 6.2 (SD: 4). Thirty per cent were malnourished, 66% had evidence of behavioural disturbance. Residents had contact with the NHS on average once per month. Conclusion: residents from both residential and nursing settings are dependent, cognitively impaired, have mild frequent behavioural symptoms, multimorbidity, polypharmacy and frequently use NHS resources. Effective care for such a cohort requires broad expertise from multiple disciplines delivered in a co-ordinated and managed way

Can We Distinguish Age-Related Frailty from Frailty Related to Diseases? Data from the MAPT Study

Abstract Background No study has tried to distinguish subjects that become frail due to diseases (frailty related to diseases) or in the absence of specific medical events; in this latter case, it is possible that aging process would act as the main frailty driver (age-related frailty). Objectives To classify subjects according to the origin of physical frailty: age-related frailty, frailty related to diseases, frailty of uncertain origin, and to compare their clinical characteristics. Materials and methods We performed a secondary analysis of the Multidomain Alzheimer Preventive Trial (MAPT), including 195 subjects ≥70 years non-frail at baseline who became frail during a 5-year follow-up (mean age 77.8 years ± 4.7; 70% female). Physical frailty was defined as presenting ≥3 of the 5 Fried criteria: weight loss, exhaustion, weakness, slowness, low physical activity. Clinical files were independently reviewed by two different clinicians using a standardized assessment method in order to classify subjects as: "age-related frailty", "frailty related to diseases" or "frailty of uncertain origin". Inconsistencies among the two raters and cases of uncertain frailty were further assessed by two other experienced clinicians. Results From the 195 included subjects, 82 (42%) were classified as age-related frailty, 53 (27%) as frailty related to diseases, and 60 (31%) as frailty of uncertain origin. Patients who became frail due to diseases did not differ from the others groups in terms of functional, cognitive, psychological status and age at baseline, however they presented a higher burden of comorbidity as measured by the Cumulative Illness Rating Scale (CIRS) (8.20 ± 2.69; vs 6.22 ± 2.02 frailty of uncertain origin; vs. 3.25 ± 1.65 age-related frailty). Time to incident frailty (23.4 months ± 12.1 vs. 39.2 ± 19.3 months) and time spent in a pre-frailty condition (17.1 ± 11.4 vs 26.6 ± 16.6 months) were shorter in the group of frailty related to diseases compared to age-related frailty. Orthopedic diseases (n=14, 26%) were the most common pathologies leading to frailty related to diseases, followed by cardiovascular diseases (n=9, 17%) and neurological diseases (n = 8, 15%). Conclusion People classified as age-related frailty and frailty related to diseases presented different frailty-associated indicators. Future research should target the underlying biological cascades leading to these two frailty classifications, since they could ask for distinct strategies of prevention and management

A blood gene expression marker of early Alzheimer's disease.

PublishedJournal ArticleResearch Support, N.I.H., ExtramuralResearch Support, Non-U.S. Gov'tA marker of Alzheimer's disease (AD) that can accurately diagnose disease at the earliest stage would significantly support efforts to develop treatments for early intervention. We have sought to determine the sensitivity and specificity of peripheral blood gene expression as a diagnostic marker of AD using data generated on HT-12v3 BeadChips. We first developed an AD diagnostic classifier in a training cohort of 78 AD and 78 control blood samples and then tested its performance in a validation group of 26 AD and 26 control and 118 mild cognitive impairment (MCI) subjects who were likely to have an AD-endpoint. A 48 gene classifier achieved an accuracy of 75% in the AD and control validation group. Comparisons were made with a classifier developed using structural MRI measures, where both measures were available in the same individuals. In AD and control subjects, the gene expression classifier achieved an accuracy of 70% compared to 85% using MRI. Bootstrapping validation produced expression and MRI classifiers with mean accuracies of 76% and 82%, respectively, demonstrating better concordance between these two classifiers than achieved in a single validation population. We conclude there is potential for blood expression to be a marker for AD. The classifier also predicts a large number of people with MCI, who are likely to develop AD, are more AD-like than normal with 76% of subjects classified as AD rather than control. Many of these people do not have overt brain atrophy, which is known to emerge around the time of AD diagnosis, suggesting the expression classifier may detect AD earlier in the prodromal phase. However, we accept these results could also represent a marker of diseases sharing common etiology.InnoMed, European Union of the Sixth Framework programAlzheimer’s Research UKJohn and Lucille van Geest FoundationNIHRBiomedical Research Centre for Mental Health, South London and Maudsley NHS Foundation TrustInstitute of Psychiatry Kings College LondonNIA/NIH RC

Recommendations for ICT use in Alzheimer's Disease assessment: Monaco CTAD expert meeting

International audienceAlzheimer disease (AD) and other related dementia represent a major challenge for health care systems within the aging population. It is therefore important to develop better instruments for assessing disease severity and disease progression to optimize patient's care and support to care provide rs, and also provide better tools for clinical research. In this area, Information and Communication Technologies (ICT) are of particular interest. Such techniques enable accurate and standardized assessments of patients' performance and actions in real time and real life situations. The aim of this article is to provide basic recommendation concerning the development and the use of ICT for Alzheimer's disease and related disorders. During he ICT and Mental Health workshop (CTAD meeting held in Monaco on the 30th October 2012) an expert panel was set up to prepare the first recommendations for the use of ICT in dementia research. The expert panel included geriatrician, epidemiologist, neurologist, psychiatrist, psychologist, ICT engineers, representatives from the industry and patient association. The recommendations are divided into three sections corresponding to 1/ the clinical targets of interest for the use of ICT, 2/ the cond itions, the type of sensors and the outputs (scores) that could be used and obtained, 3/ finally the last section concerns specifically the use of ICT within clinical trials

Mitochondrial dysfunction and immune activation are detectable in early Alzheimer's disease blood.

PublishedJournal ArticleResearch Support, Non-U.S. Gov'tAlzheimer's disease (AD), like other dementias, is characterized by progressive neuronal loss and neuroinflammation in the brain. The peripheral leukocyte response occurring alongside these brain changes has not been extensively studied, but might inform therapeutic approaches and provide relevant disease biomarkers. Using microarrays, we assessed blood gene expression alterations occurring in people with AD and those with mild cognitive changes at increased risk of developing AD. Of the 2,908 differentially expressed probes identified between the three groups (p < 0.01), a quarter were altered in blood from mild cognitive impairment (MCI) and AD subjects, relative to controls, suggesting a peripheral response to pathology may occur very early. There was strong evidence for mitochondrial dysfunction with decreased expression of many of the respiratory complex I-V genes and subunits of the core mitochondrial ribosome complex. This mirrors changes previously observed in AD brain. A number of genes encoding cell adhesion molecules were increased, along with other immune-related genes. These changes are consistent with leukocyte activation and their increased the transition from circulation into the brain. In addition to expression changes, we also found increased numbers of basophils in people with MCI and AD, and increased monocytes in people with an AD diagnosis. Taken together this study provides both an insight into the functional response of circulating leukocytes during neurodegeneration and also identifies potential targets such as the respiratory chain for designing and monitoring future therapeutic interventions using blood.InnoMed, European Union of the Sixth Framework programAlzheimer’s Research TrustJohn and Lucille van Geest FoundationNIHR Biomedical Research Centre for Mental Health at the South London and Maudsley NHS Foundation TrustInstitute of Psychiatry Kings College Londo