[Show abstract][Hide abstract] ABSTRACT: Objective:
Subjective cognitive decline (SCD) might represent the first symptomatic representation of Alzheimer's disease (AD), which is associated with increased mortality. Only few studies, however, have analyzed the association of SCD and mortality, and if so, based on prevalent cases. Thus, we investigated incident SCD in memory and mortality.
Data were derived from the German AgeCoDe study, a prospective longitudinal study on the epidemiology of mild cognitive impairment (MCI) and dementia in primary care patients over 75 years covering an observation period of 7.5 years. We used univariate and multivariate Cox regression analyses to examine the relationship of SCD and mortality. Further, we estimated survival times by the Kaplan Meier method and case-fatality rates with regard to SCD.
Among 971 individuals without objective cognitive impairment, 233 (24.0%) incidentally expressed SCD at follow-up I. Incident SCD was not significantly associated with increased mortality in the univariate (HR = 1.0, 95% confidence interval = 0.8-1.3, p = .90) as well as in the multivariate analysis (HR = 0.9, 95% confidence interval = 0.7-1.2, p = .40). The same applied for SCD in relation to concerns. Mean survival time with SCD was 8.0 years (SD = 0.1) after onset.
Incident SCD in memory in individuals with unimpaired cognitive performance does not predict mortality. The main reason might be that SCD does not ultimately lead into future cognitive decline in any case. However, as prevalence studies suggest, subjectively perceived decline in non-memory cognitive domains might be associated with increased mortality. Future studies may address mortality in such other cognitive domains of SCD in incident cases.
[Show abstract][Hide abstract] ABSTRACT: Background:
The clinical use of carotid intima media thickness (cIMT) requires normal values, which may be subject to variation of geographical factors, ethnicity or measurement details. The influence of these factors has rarely been studied. The aim of this study was to determine whether normative cIMT values and their association with event risk are generalizable across populations.
Meta-analysis of individual participant data.
From 22 general population cohorts from Europe, North America and Asia we selected subjects free of cardiovascular disease. Percentiles of cIMT and cIMT progression were assessed separately for every cohort. Cox proportional hazards models for vascular events were used to estimate hazard ratios for cIMT in each cohort. The estimates were pooled across Europe, North America and Asia, with random effects meta-analysis. The influence of geography, ethnicity and ultrasound protocols on cIMT values and on the hazard ratios was examined by meta-regression.
Geographical factors, ethnicity and the ultrasound protocol had influence neither on the percentiles of cIMT and its progression, nor on the hazard ratios of cIMT for vascular events. Heterogeneity for percentiles of cIMT and cIMT progression was too large to create meaningful normative values.
The distribution of cIMT values is too heterogeneous to define universal or regional population reference values. CIMT values vary widely between different studies regardless of ethnicity, geographic location and ultrasound protocol. Prediction of vascular events with cIMT values was more consistent across all cohorts, ethnicities and regions.
Full-text · Article · Jan 2016 · European Journal of Preventive Cardiology
[Show abstract][Hide abstract] ABSTRACT: Introduction:
Cerebrospinal fluid (CSF) biomarkers improve the diagnostic accuracy for Alzheimer's disease (AD), even at the predementia stage of the disease. The ε4-allele of apolipoprotein E (ApoE ε4), female sex, and older age are well-known risk factors for AD. It is unclear how these risk factors affect the CSF biomarkers in patients with AD.
The objective of this study was to investigate the associations of ApoE ε4, sex, and age with CSF biomarker levels in a unicenter sample of patients with AD that includes a high proportion of patients with early-onset AD (EOAD).
The CSF levels of amyloid-β 1-42 (Aβ1-42) and total-tau of 117 subjects with mild to moderate AD (55 late-onset AD and 62 EOAD) were assessed. All subjects underwent ApoE genotyping, clinical evaluation, comprehensive neuropsychological assessments, and neuroimaging. Associations between CSF biomarker levels, ApoE ε4 allele frequency, age, and sex were evaluated.
In the whole patient sample and in the late-onset AD subgroup ε4 homozygous subjects had significantly lower CSF Aβ1-42 levels compared with ε4 heterozygous subjects and ε4 noncarriers. This association was not detected in the EOAD group. Age group, sex, and severity of cognitive decline did not have a significant impact on CSF Aβ1-42 levels. No significant associations were found between ApoE ε4 allele frequency and CSF total-tau levels.
ApoE ε4 allele is associated with a reduction of CSF Aβ1-42 levels. This result is consistent with the findings of several previous studies. In the subgroup of patients with EOAD this association was not replicated. Larger studies are necessary to further investigate associations between ApoE ε4 allele frequency and CSF biomarker levels in patients with EOAD.
Full-text · Article · Dec 2015 · Neuropsychiatric Disease and Treatment
[Show abstract][Hide abstract] ABSTRACT: Objective:
To investigate time-dependent predictors of institutionalization in old age using a longitudinal approach.
In a representative survey of the German general population aged 75 years and older predictors of institutionalization were observed every 1.5 years over six waves. Conditional fixed-effects logistic regressions (with 201 individuals and 960 observations) were performed to estimate the effects of marital status, depression, dementia, and physical impairments (mobility, hearing and visual impairments) on the risk of admission to old-age home or nursing home. By exploiting the longitudinal data structure using panel econometric models, we were able to control for unobserved heterogeneity such as genetic predisposition and personality traits.
The probability of institutionalization increased significantly with occurrence of widowhood, depression, dementia, as well as walking and hearing impairments. In particular, the occurrence of widowhood (OR = 78.3), dementia (OR = 154.1) and substantial mobility impairment (OR = 36.7) were strongly associated with institutionalization.
Findings underline the strong influence of loss of spouse as well as dementia on institutionalization. This is relevant as the number of old people (a) living alone and (b) suffering from dementia is expected to increase rapidly in the next decades. Consequently, it is supposed that the demand for institutionalization among the elderly will increase considerably. Practitioners as well as policy makers should be aware of these upcoming challenges.
[Show abstract][Hide abstract] ABSTRACT: Objectives: To investigate time-dependent predictors of frailty in old age longitudinally.
Setting: Elderly individuals were recruited via GP offices at six study centers in Germany. The course of frailty was observed over 1.5 years (follow up wave 4 and follow up wave 5).
Participants: 1,602 individuals aged 80 years and older (mean age 85.4 years SD 3.2, with mean CSHA CFS 3.5 SD 1.6) at follow up wave 4.
Measurements: Frailty was assessed by using the Canadian Study of Health and Aging Clinical Frailty Scale (CSHA CFS), ranging from 1 (very fit) to 7 (severely frail).
Results: Fixed effects regressions revealed that frailty increased significantly with increasing age (β=.2) as well as the occurrence of depression (β=.5) and dementia (β=.8) in the total sample. Changes in marital status and comorbidity did not affect frailty. While the effects of depression and dementia were significant in women, these effects did not achieve statistical significance in men.
Conclusion: Our findings highlight the role of aging as well as the occurrence of dementia and depression for frailty. Specifically, in order to delay frailty in old age, developing interventional strategies to prevent depression might be a fruitful approach.
Full-text · Article · Dec 2015 · The Journal of Nutrition Health and Aging
[Show abstract][Hide abstract] ABSTRACT: In this article three research questions are addressed: (1) Is there an association between socioeconomic status (SES) and patient-reported outcomes in a cohort of multimorbid patients? (2) Does the association vary according to SES indicator used (income, education, occupational position)? (3) Can the association between SES and patient-reported outcomes (self-rated health, health-related quality of life and functional status) be (partly) explained by burden of disease?
Analyses are based on the MultiCare Cohort Study, a German multicentre, prospective, observational cohort study of multimorbid patients from general practice. We analysed baseline data and data from the first follow-up after 15 months (N = 2,729). To assess burden of disease we used the patients’ morbidity data from standardized general practitioner (GP) interviews based on a list of 46 groups of chronic conditions including the GP’s severity rating of each chronic condition ranging from marginal to very severe.
In the cross-sectional analyses SES was significantly associated with the patient-reported outcomes at baseline. Associations with income were more consistent and stronger than with education and occupational position. Associations were partly explained (17% to 44%) by burden of disease. In the longitudinal analyses only income (but not education and occupational position) was significantly related to the patient-reported outcomes at follow-up. Associations between income and the outcomes were reduced by 18% to 27% after adjustment for burden of disease.
Results indicate social inequalities in self-rated health, functional status and health related quality of life among older multimorbid patients. As associations with education and occupational position were inconsistent, these inequalities were mainly due to income. Inequalities were partly explained by burden of disease. However, even among patients with a similar disease burden, those with a low income were worse off in terms of the three patient-reported outcomes under study.
Full-text · Article · Dec 2015 · International Journal for Equity in Health
[Show abstract][Hide abstract] ABSTRACT: Hintergrund: Behaviorale und psychiatrische Symptome der Demenz (BPSD) treten häufig komorbid neben den kognitiven Kernsymptomen auf. Das Zusammenspiel von BPSD, kognitiven Störungen und körperlicher Erkrankung kann die akute Patientenversorgung im Allgemeinkrankenhaus erheblich erschweren und zu Belastungen bei Patienten und Pflege führen. Mit der General Hospital Study (GHoSt) wurde zum ersten Mal eine repräsentative Schätzung der Prävalenz von BPSD in deutschen Allgemeinkrankenhäusern vorgenommen.
Methode: In GHoSt wurden Patienten (≥65 Jahre) von 33 zufällig ausgewählten Allgemeinkrankenhäusern in Bayern und Baden-Württemberg während ihres Aufenthalts untersucht. Demenz gemäß DSM-IV wurde auf der Basis von neuropsychologischen Tests und Auskünften von Pflegekräften und Angehörigen diagnostiziert. BPSD wurden mit einer modifizierten Version des Neuropsychiatric Inventory Questionnaire (NPI-Q) in Interviews mit Pflegekräften ermittelt. Der NPI-Q erfragt das Auftreten von elf BPSD (ja/nein) und die jeweilige Belastung für den Pflegenden (0-5). Die hier aufgeführten Ergebnisse beziehen sich ausschließlich auf die Daten aus Bayern, da die baden-württembergischen bis Anmeldeschluss noch nicht vorlagen. Die auf dem Kongress präsentierten Ergebnisse werden sich auf den vollständigen Datensatz beziehen.
Ergebnisse: Von 686 untersuchten Patienten wurde bei 129 (18,8%) eine Demenz diagnostiziert. Achtundneunzig (76,0%) dieser Patienten mit Demenz zeigten mindestens ein BPSD während ihres Aufenthalts (Spannweite 1-7). In 81 Fällen wurden die Symptome als belastend empfunden. Schlafstörungen (37,2%), Angst (30,2%) und depressive Symptome (27,9%), motorische Unruhe (26,4%) und Aggression (23,3%) waren die häufigsten BPSD. Aggression, motorische Unruhe und Schlafstörungen verursachten die größte Belastung. Im Vergleich zu Patienten ohne Demenz zeigten Patienten mit Demenz mehr BPSD (p<0,001) und verursachten höhere Belastungen (p<0,001).
Diskussion: BPSD treten bei der Mehrheit von Krankenhauspatienten mit Demenz auf. Vom Pflegepersonal werden insbesondere die expansiven Symptome als starke Belastung empfunden.
[Show abstract][Hide abstract] ABSTRACT: Purpose:
The causality between social predictors and HRQoL in old age remains almost unclear as only a few studies have examined the influence of social support on HRQoL in a longitudinal setting. Moreover, available studies investigating gender differences in the effect of social support on HRQoL in old age have been solely cross-sectional. Consequently, the aim of this study was to examine whether social support affects health-related quality of life (HRQoL) in old age and whether this effect is moderated by gender.
In a population-based cohort (N = 2443) of people aged 75 years and older in Germany, the development of HRQoL was prospectively observed over a 3-year period. Quality of life was quantified by using the visual analogue scale of the EQ-5D instrument. Social support was assessed by using the 14-item form of the questionnaire for social support (F-SozU K-14). In order to control for unobserved heterogeneity, fixed-effects regression analysis was used.
In the total sample (β = 0.55, p < 0.05) and in men (β = 1.39, p < 0.001), a strong positive impact of social support on HRQoL was found. There was no significant effect of social support on HRQoL in women. The effect of social support on HRQoL was significantly moderated by gender (p < 0.05).
Findings accentuate the fundamental role of social support in HRQoL in old age. Particularly in men, it is therefore crucial to strengthen the social ties in old age.
No preview · Article · Oct 2015 · Quality of Life Research
[Show abstract][Hide abstract] ABSTRACT: Purpose:
Care provided in the community for dementia patients on an individual basis may be very time consuming. Yet, little is known about the factors affecting caregiving time for community-dwelling dementia patients. Thus, we aimed to investigate the predictors of informal and formal caregiving time for these patients in a longitudinal approach.
Caregiving time for n = 126 community-dwelling dementia patients was assessed by proxy interviews in four assessments at 6-month intervals (1.5 years of longitudinal follow-up; AgeCoDe study). Measurement of informal caregiving time was based on a German adaptation of the Resource Utilization in Dementia questionnaire. Dementia severity was measured by the Clinical Dementia Rating (CDR). We used random effects models to estimate the effects of sociodemographic variables (age, gender, marital status and education), comorbidity and dementia severity on informal and formal caregiving time.
At the first assessment, mean age was 85.0 years (±3.2 years). The majority of patients was female (65.9 %), not married (divorced, single, widowed: 55.6 %) and had primary education (63.5 %). Furthermore, mean GDS was 4.4 (±0.8) and mean MMSE was 20.1 (±5.1). According to CDR, 43 individuals had very mild dementia, 55 individuals had mild dementia and 28 individuals had moderate/severe dementia. Moreover, mean total caregiving time was 3.4 h per day (±4.0). Thereof the main part represents informal caregiving time (2.3 h ± 3.4), whereas formal caregiving time was 1.2 h (±2.4). Dementia severity was associated with total caregiving time, mainly influenced by informal caregiving time. Age was positively associated with total caregiving time, driven by formal caregiving time, while being married was positively associated with total caregiving time, mainly affected by informal caregiving time. All need categories of informal caregiving time were strongly related to dementia severity, whereas none of the categories of formal caregiving time were related to dementia severity.
Our findings extend previous studies that found an association between informal caregiving time and dementia severity. Moreover, our findings highlight the role of informal care for community-dwelling dementia patients in Germany. Informal caregiving time strongly increases with dementia severity. Consequently, as the number of patients suffering from dementia is expected to increase considerably in the next decades, there is a paramount need to strengthen the informal care system to meet patients' needs.
No preview · Article · Oct 2015 · Social Psychiatry and Psychiatric Epidemiology
[Show abstract][Hide abstract] ABSTRACT: Human episodic memory performance is linked to the function of specific brain regions, including the hippocampus; declines as a result of increasing age; and is markedly disturbed in Alzheimer disease (AD), an age-associated neurodegenerative disorder that primarily affects the hippocampus. Exploring the molecular underpinnings of human episodic memory is key to the understanding of hippocampus-dependent cognitive physiology and pathophysiology.
To determine whether biologically defined groups of genes are enriched in episodic memory performance across age, memory encoding-related brain activity, and AD.
In this multicenter collaborative study, which began in August 2008 and is ongoing, gene set enrichment analysis was done by using primary and meta-analysis data from 57 968 participants. The Swiss cohorts consisted of 3043 healthy young adults assessed for episodic memory performance. In a subgroup (n = 1119) of one of these cohorts, functional magnetic resonance imaging was used to identify gene set-dependent differences in brain activity related to episodic memory. The German Study on Aging, Cognition, and Dementia in Primary Care Patients cohort consisted of 763 elderly participants without dementia who were assessed for episodic memory performance. The International Genomics of Alzheimer's Project case-control sample consisted of 54 162 participants (17 008 patients with sporadic AD and 37 154 control participants). Analyses were conducted between January 2014 and June 2015. Gene set enrichment analysis in all samples was done using genome-wide single-nucleotide polymorphism data.
Episodic memory performance in the Swiss cohort and German Study on Aging, Cognition, and Dementia in Primary Care Patients cohort was quantified by picture and verbal delayed free recall tasks. In the functional magnetic resonance imaging experiment, activation of the hippocampus during encoding of pictures served as the phenotype of interest. In the International Genomics of Alzheimer's Project sample, diagnosis of sporadic AD served as the phenotype of interest.
In the discovery sample, we detected significant enrichment for genes constituting the calcium signaling pathway, especially those related to the elevation of cytosolic calcium (P = 2 × 10-4). This enrichment was replicated in 2 additional samples of healthy young individuals (P = .02 and .04, respectively) and a sample of healthy elderly participants (P = .004). Hippocampal activation (P = 4 × 10-4) and the risk for sporadic AD (P = .01) were also significantly enriched for genes related to the elevation of cytosolic calcium.
By detecting consistent significant enrichment in independent cohorts of young and elderly participants, this study identified that calcium signaling plays a central role in hippocampus-dependent human memory processes in cognitive health and disease, contributing to the understanding and potential treatment of hippocampus-dependent cognitive pathology.
[Show abstract][Hide abstract] ABSTRACT: Mean body weight gradually increases with age. Yet, little data exists on the prevalence of excess weight in populations aged 80 years or older. Moreover, little is known about predictors of overweight and obesity in old age. Thus, the purpose of this study was: To present data on the prevalence of excess weight in old age in Germany, to investigate predictors of excess weight in a cross-sectional approach and to examine factors affecting excess weight in a longitudinal approach.
Subjects consisted of 1,882 individuals aged 79 years or older. The course of excess weight was observed over 3 years. Excess weight was defined as follows: Overweight (25 kg/m(2) ≤ BMI < 30 kg/m(2)) and obesity (BMI ≥ 30 kg/m(2)). We used fixed effects regressions to estimate effects of time dependent variables on BMI, and overweight or obesity, respectively.
The majority was overweight (40.0 %) or obese (13.7 %). Cross-sectional regressions revealed that BMI was positively associated with younger age, severe walking impairments and negatively associated with cognitive impairments. Excess weight was positively associated with younger age, elementary education, walking impairments and physical inactivity, while excess weight was negatively associated with cognitive impairment. Longitudinal regressions showed that age and severely impaired walking disabilities reduced BMI. The probability of transitions to excess weight decreased considerably with older age and occurrence of severe walking impairments (overweight).
Marked differences between predictors in cross- and longitudinal setting exist, underlining the complex nature of excess weight in old age.
[Show abstract][Hide abstract] ABSTRACT: Objective
Dementia is known to increase mortality, but the relative loss of life years and contributing factors are not well established. Thus, we aimed to investigate mortality in incident dementia from disease onset.Method
Data were derived from the prospective longitudinal German AgeCoDe study. We used proportional hazards models to assess the impact of sociodemographic and health characteristics on mortality after dementia onset, Kaplan–Meier method for median survival times.ResultsOf 3214 subjects at risk, 523 (16.3%) developed incident dementia during a 9-year follow-up period. Median survival time after onset was 3.2 years (95% CI = 2.8–3.7) at a mean age of 85.0 (SD = 4.0) years (≥2.6 life years lost compared with the general German population). Survival was shorter in older age, males other dementias than Alzheimer's, and in the absence of subjective memory complaints (SMC).Conclusion
Our findings emphasize that dementia substantially shortens life expectancy. Future studies should further investigate the potential impact of SMC on mortality in dementia.
Full-text · Article · Jun 2015 · Acta Psychiatrica Scandinavica
[Show abstract][Hide abstract] ABSTRACT: To investigate the coevolution of depression and health-related quality of life (HRQoL) in old age.
In a representative survey of the German general population aged 75 years and older, the course of HRQoL and depression was observed over 4.5 years (3 waves). HRQoL was assessed by the Visual Analogue Scale (EQ VAS) of the EQ-5D instrument, while the Geriatric Depression Scale was used to measure depression. A panel vector autoregressive model was used to account for the complex coevolution of depression and HRQoL. Unobserved heterogeneity was taken into account by taking the first differences.
We revealed a robust negative association between an initial change in HRQoL and a subsequent change in depression score, with substantial sex differences: In women there was a robust association, while in men the significance of this association depended on the model specification. Surprisingly, in the total sample and in both sexes, no robust association between an initial increase in depression and a subsequent change in HRQoL was found.
Findings indicate that the direction of evolution from HRQoL to depression deserves more attention. Furthermore, treatment of depression in late life should aim at improving HRQoL in which remission of depressive symptoms is necessary but not sufficient.
Full-text · Article · May 2015 · Quality of Life Research
[Show abstract][Hide abstract] ABSTRACT: Background: Our objectives were (1) to test the association between the report of subjective cognitive decline (SCD) and prospective objective cognitive performance in high age individuals and (2) to study the course of longitudinal cognitive performance before and after the first report of SCD. Methods: Cognitively normal elderly participants of the German Study on Ageing, Cognition, and Dementia study (N=2330) with SCD (subjective decline in memory with and without associated concerns) and without SCD at baseline were assessed over 8 years with regard to immediate and delayed verbal recall, verbal fluency, working memory, and global cognition. Baseline performance and cognitive trajectories were compared between groups. In addition, cognitive trajectories before and after the initial report of SCD (incident SCD) were modelled in those without SCD at baseline. Results: Baseline performance in the SCD group was lower and declined more steeply in immediate and delayed verbal recall than in the control group (no SCD at baseline). This effect was more pronounced in the SCD group with concerns. Incident SCD was preceded by decline in immediate and delayed memory and word fluency. Conclusions: SCD predicts future memory decline. Incident SCD is related to previous cognitive decline. The latter finding supports the concept of SCD indicating first subtle decline in cognitive performance that characterizes preclinical Alzheimer's disease.
[Show abstract][Hide abstract] ABSTRACT: The aim of the study was to investigate the psychometric properties of a Short Form of the Mini-Mental State Examination (SMMSE) for the screening of dementia in older primary care patients. Data were obtained from a large longitudinal cohort study of initially nondemented individuals recruited via primary care chart registries and followed at 18-month intervals. Item and scale parameters for MMSE and SMMSE scores were analyzed and cross-validated for 2 follow-up assessments (n1 = 2,657 and n2 = 2,274). Binary logistic regression and receiver-operating-characteristic (ROC) curve analyses were conducted in order to assess diagnostic accuracy parameters for MMSE and SMMSE scores. Cross-sectional differentiation between dementia-free and dementia patients yielded moderate to good results for MMSE and SMMSE scores. With regard to most diagnostic accuracy parameters, SMMSE scores did not outperform the MMSE scores. The current study provides first evidence regarding the psychometric properties of the SMMSE score in a sample of older primary care patients. However, our findings do not confirm previous findings that the SMMSE is a more accurate screening instrument for dementia than the original MMSE. Further studies are needed in order to assess and to develop short, reliable and valid instruments for routine cognitive screening in clinical practice and primary care settings. (PsycINFO Database Record
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No preview · Article · Mar 2015 · Psychological Assessment
[Show abstract][Hide abstract] ABSTRACT: Type 2 diabetes mellitus (T2DM) is a risk factor of dementia. The effect of T2DM treatment quality on dementia risk, however, is unclear. 1,342 elderly individuals recruited via general practitioner registries (AgeCoDe cohort) were analyzed. This study analyzed the association between HbA1c level and the incidence of all-cause dementia (ACD) and of Alzheimer's disease dementia (referred to here as AD). HbA1c levels ≥6.5% were associated with 2.8-fold increased risk of incident ACD (p = 0.027) and for AD (p = 0.047). HbA1c levels ≥7% were associated with a five-fold increased risk of incident ACD (p = 0.001) and 4.7-fold increased risk of incident AD (p = 0.004). The T2DM diagnosis per se did not increase the risk of either ACD or AD. Higher levels of HbA1c are associated with increased risk of ACD and AD in an elderly population. T2DM diagnosis was not associated with increased risk if HbA1c levels were below 7%.
No preview · Article · Dec 2014 · Journal of Alzheimer's disease: JAD