René J. F. Melis

Aging with multimorbidity: A systematic review of the literature

A literature search was carried out to summarize the existing scientific evidence concerning occurrence, causes, and consequences of multimorbidity (the coexistence of multiple chronic diseases) in the elderly as well as models and quality of care of persons with multimorbidity. According to pre-established inclusion criteria, and using different search strategies, 41 articles were included (four of these were methodological papers only). Prevalence of multimorbidity in older persons ranges from 55 to 98%. In cross-sectional studies, older age, female gender, and low socioeconomic status are factors associated with multimorbidity, confirmed by longitudinal studies as well. Major consequences of multimorbidity are disability and functional decline, poor quality of life, and high health care costs. Controversial results were found on multimorbidity and mortality risk. Methodological issues in evaluating multimorbidity are discussed as well as future research needs, especially concerning etiological factors, combinations and clustering of chronic diseases, and care models for persons affected by multiple disorders. New insights in this field can lead to the identification of preventive strategies and better treatment of multimorbid patients.

Defeating Alzheimer's disease and other dementias: a priority for European science and society

Defeating Alzheimers disease and other dementias : a priority for European science and society

The development of the Older Persons and Informal Caregivers Survey Minimum DataSet (TOPICS-MDS): A large-scale data sharing initiative

Introduction In 2008, the Ministry of Health, Welfare and Sport commissioned the National Care for the Elderly Programme. While numerous research projects in older persons’ health care were to be conducted under this national agenda, the Programme further advocated the development of The Older Persons and Informal Caregivers Survey Minimum DataSet (TOPICS-MDS) which would be integrated into all funded research protocols. In this context, we describe TOPICS data sharing initiative (www.topics-mds.eu). Materials and Methods A working group drafted TOPICS-MDS prototype, which was subsequently approved by a multidisciplinary panel. Using instruments validated for older populations, information was collected on demographics, morbidity, quality of life, functional limitations, mental health, social functioning and health service utilisation. For informal caregivers, information was collected on demographics, hours of informal care and quality of life (including subjective care-related burden). Results Between 2010 and 2013, a total of 41 research projects contributed data to TOPICS-MDS, resulting in preliminary data available for 32,310 older persons and 3,940 informal caregivers. The majority of studies sampled were from primary care settings and inclusion criteria differed across studies. Discussion TOPICS-MDS is a public data repository which contains essential data to better understand health challenges experienced by older persons and informal caregivers. Such findings are relevant for countries where increasing health-related expenditure has necessitated the evaluation of contemporary health care delivery. Although open sharing of data can be difficult to achieve in practice, proactively addressing issues of data protection, conflicting data analysis requests and funding limitations during TOPICS-MDS developmental phase has fostered a data sharing culture. To date, TOPICS-MDS has been successfully incorporated into 41 research projects, thus supporting the feasibility of constructing a large (>30,000 observations), standardised dataset pooled from various study protocols with different sampling frameworks. This unique implementation strategy improves efficiency and facilitates individual-level data meta-analysis.

Cerebrospinal fluid alpha-synuclein does not discriminate between dementia disorders.

Alpha-synuclein is the major constituent of Lewy bodies found in neurons in dementia with Lewy bodies (DLB) and might be of diagnostic value as a biomarker for DLB. We hypothesized that, as a consequence of increased accumulation of alpha-synuclein intraneuronally in DLB, the levels of alpha-synuclein in cerebrospinal fluid (CSF) of DLB patients would be lower than in other dementias. Our objective was to investigate the CSF levels of alpha-synuclein in several dementia disorders compared to control levels and to investigate the diagnostic value of CSF alpha-synuclein as a marker to discriminate between DLB and other types of dementia. We analyzed the levels of alpha-synuclein in CSF of 40 DLB patients, 131 patients with Alzheimers disease, 28 patients with vascular dementia, and 39 patients with frontotemporal dementia. We did not find any significant differences in CSF alpha-synuclein levels between DLB patients and patients with Alzheimers disease, vascular dementia or frontotemporal dementia. We conclude that in clinically diagnosed patients, alpha-synuclein does not appear to be a useful biomarker for the differentiation between DLB and other types of dementia.

Effectiveness of dementia follow-up care by memory clinics or general practitioners: randomised controlled trial.

Objective To examine the effectiveness of post-diagnosis dementia treatment and coordination of care by memory clinics compared with general practitioners. Design Multicentre randomised controlled trial. Setting Nine memory clinics and 159 general practitioners in the Netherlands. Participants 175 patients with a new diagnosis of mild to moderate dementia living in the community and their informal caregivers. Interventions Usual care provided by memory clinic or general practitioner. Main outcome measures Caregiver rated quality of life of the patient measured with the quality of life in Alzheimer’s disease instrument and self perceived burden of the informal caregiver measured with the sense of competence questionnaire (intention to treat analysis). Results The quality of life of the patients in the memory clinic group was 0.5 (95% confidence interval −0.7 to 1.6) points higher than in the general practitioner group. Caregivers’ burden was 2.4 (−5.8 to 1.0) points lower in the memory clinic group than in the general practitioner group. Conclusion No evidence was found that memory clinics were more effective than general practitioners with regard to post-diagnosis treatment and coordination care for patients with dementia. Without further evidence on the effectiveness of these modalities, other arguments, such as cost minimisation, patients’ preferences, or regional health service planning, can determine which type of dementia care is offered. Trial registration Clinical trials NCT00554047.

The ICTUS Study: A Prospective longitudinal observational study of 1,380 AD patients in Europe. Study design and baseline characteristics of the cohort.

The long-term objective of the ICTUS study is to identify milestones in Alzheimer’s disease (AD) progression and to develop a model to predict disease course in individual AD patients in Europe. The secondary objectives are to describe the patterns of prescribing, and the socioeconomic impact of AD in Europe. Between 2003 and 2005 1,380 patients with probable AD were recruited in specialised (secondary care) clinics in 12 European countries. Their mean age was 76 years and they had a mean of 8.0 ± (SD) 4.6 years of education. Thirty-five percent were male. The mean MMSE score was 20.4 ± (SD) 4.0. Forty-three percent had very mild dementia (CDR 0.5) and 44% had mild dementia (CDR 1). All patients completed baseline evaluation and biannual follow-up is ongoing. The goals of the current study are to describe the specific methods for recruitment in this crosscultural setting and the characteristics of the inception ICTUS cohort, including clinical features, co-morbidity, neuropsychological performance, neuropsychiatric symptoms, functional impairment and social burden.

Heat waves and dehydration in the elderly

Recognising the early warning signs can save lives

A more efficient enzyme-linked immunosorbent assay for measurement of α-synuclein in cerebrospinal fluid

We describe a modification of a previously described assay for the quantification of alpha-synuclein in naive cerebrospinal fluid, which allows for a more efficient quantification of alpha-synuclein. Detection limit of the assay is 3.8 ng/ml and the assay is linear until 300 ng/ml. Inter-assay and intra-assay coefficients of variation are below 15% in a wide range of concentrations. Mean recovery of the assay is 94%. The 95% upper limit of the reference range (p95) in a group of neurological controls above the age of 45 years is 62 ng/ml. This assay can be routinely applied for quantification of alpha-synuclein in cerebrospinal fluid, but not in serum, and this may serve as a possible biomarker for alpha-synucleinopathies such as Parkinsons disease and multiple system atrophy.

The influence of multimorbidity on clinical progression of dementia in a population-based cohort

Introduction Co-occurrence with other chronic diseases may influence the progression of dementia, especially in case of multiple chronic diseases. We aimed to verify whether multimorbidity influenced cognitive and daily functioning during nine years after dementia diagnosis compared with the influence in persons without dementia. Methods In the Kungsholmen Project, a population-based cohort study, we followed 310 persons with incident dementia longitudinally. We compared their trajectories with those of 679 persons without dementia. Progression was studied for cognition and activities of daily life (ADLs), measured by MMSE and Katz Index respectively. The effect of multimorbidity and its interaction with dementia status was studied using individual growth models. Results The mean (SD) follow-up time was 4.7 (2.3) years. As expected, dementia related to both the decline in cognitive and daily functioning. Irrespective of dementia status, persons with more diseases had significantly worse baseline daily functioning. In dementia patients having more diseases also related to a significantly faster decline in daily functioning. Due to the combination of lower functioning in ADLs at baseline and faster decline, dementia patients with multimorbidity were about one to two years ahead of the decline of dementia patients without any co-morbidity. In persons without dementia, no significant decline in ADLs over time was present, nor was multimorbidity related to the decline rate. Cognitive decline measured with MMSE remained unrelated to the number of diseases present at baseline. Conclusion Multimorbidity was related to baseline daily function in both persons with and without dementia, and with accelerated decline in people with dementia but not in non-demented individuals. No relationship of multimorbidity with cognitive functioning was established. These findings imply a strong interconnection between physical and mental health, where the greatest disablement occurs when both somatic and mental disorders are present.

Association between Hypocretin-1 and Amyloid-β42 Cerebrospinal Fluid Levels in Alzheimer’s Disease and Healthy Controls

Alzheimers disease is associated with sleep disorders. Recently, animal studies demonstrated a link between hypocretin, a sleep-regulation neurotransmitter, and AD pathology. In this study, we investigated the circadian rhythm of hypocretin-1 in Alzheimers Disease (AD) patients and controls. Moreover, we assessed the relation between CSF hypocretin-1 and amyloid-β. A continuous CSF sampling study via indwelling intrathecal catheter was performed to collect hourly CSF samples of six patients with AD (59-85 yrs, MMSE 16-26) and six healthy volunteers (64-77 yrs). CSF hypocretin-1 and Aβ42 concentrations were determined at 8 individual time points over 24 hours. A circadian pattern was assessed by fitting a 24 hour sine curve to the hypocretin-1 data using mixed model analysis. Clinical diagnosis and Aβ42 were entered into the model as time invariant covariates to determine differences between AD and controls, and correlate Aβ42 to hypocretin-1 levels. A hypocretin-1 circadian rhythm with an amplitude of 11.5 pg/ml was found in clinical AD patients, which did not differ from the control group (7.15 pg/ml). Lower mean CSF Aβ42 levels were related to lower hypocretin-1 levels; 1.6 pg/ml hypocretin-1 per 10 pg/ml Aβ42 (p=0.03), and a higher amplitude of the hypocretin-1 circadian rhythm (0.4 pg/ml, p=0.03). CSF hypocretin-1 has a circadian rhythm for which we could show no difference between AD and controls. However, the association between mean Aβ42 levels and mean hypocretin-1 levels and amplitude may suggest a relationship between AD pathology and hypocretin disturbance, which could hold possibilities for treatment of AD related sleep disorders.