Jana Prokein

Prediction of survival after liver transplantation by pre-transplant parameters

Objective. Score-based medical urgency criteria are used for necessity-oriented liver transplantation (OLT) but lead to an increasing number of complications in patients with reduced post-OLT survival. A prediction of outcome would improve preoperative patient selection and management. Material and methods. One-hundred-and-thirty-three consecutive adult patients (63.9% men, mean age 47.4±11.2 years) given transplants between May 2004 and November 2005 at the Hannover Medical School were analysed retrospectively using univariate and multivariate methods. Results. Indications were: 27.1% viral hepatitis, 19.6% primary sclerosing cholangitis, 15.0% alcoholic liver disease, 7.5% metabolic liver disease, 6.8% primary biliary cirrhosis. Overall, 12-month patient survival was 81.2%. The mean MELD score at OLT was 14.5±5.3 and 12-month survival with MELD >16 (71.7%) and <16 (86.2%) differed significantly (p=0.041). Predictors of 12-month mortality included age (53.2±9.4 versus 46.1±11.2 years; p=0.004), lower cholinesterase (2.9±1.88 versus 3.7±2.02 kU/l; p=0.026) and serum creatinine (160.4±186.8 versus 77.7±31.6 µmol/l; p=0.007), with creatinine and cholinesterase as independent parameters. Based on these parameters, a model for predicting patient survival after liver transplantation was calculated and validated in a second independent cohort of 87 OLT patients. This score identified a high-risk group and a low-risk group (overall survival 47.4 versus 91.2%; p<0.001) with a specificity of 87.3% and a sensitivity of 68.75%. Conclusion. Age, pre-OLT creatinine and cholinesterase are predictors of short-term post-OLT survival and may be helpful as a bedside score in pre-OLT clinical management, outcome prediction and decision-making.

Relative Impact of Multimorbid Chronic Conditions on Health-Related Quality of Life – Results from the MultiCare Cohort Study

Background Multimorbidity has a negative impact on health-related quality of life (HRQL). Previous studies included only a limited number of conditions. In this study, we analyse the impact of a large number of conditions on HRQL in multimorbid patients without preselecting particular diseases. We also explore the effects of these conditions on the specific dimensions of HRQL. Materials and Methods This analysis is based on a multicenter, prospective cohort study of 3189 multimorbid primary care patients aged 65 to 85. The impact of 45 conditions on HRQL was analysed. The severity of the conditions was rated. The EQ-5D, consisting of 5 dimensions and a visual-analogue-scale (EQ VAS), was employed. Data were analysed using multiple ordinary least squares and multiple logistic regressions. Multimorbidity measured by a weighted count score was significantly associated with lower overall HRQL (EQ VAS), b = −1.02 (SE: 0.06). Parkinson’s disease had the most pronounced negative effect on overall HRQL (EQ VAS), b = −12.29 (SE: 2.18), followed by rheumatism, depression, and obesity. With regard to the individual EQ-5D dimensions, depression (OR = 1.39 to 3.3) and obesity (OR = 1.44 to 1.95) affected all five dimensions of the EQ-5D negatively except for the dimension anxiety/depression. Obesity had a positive effect on this dimension, OR = 0.78 (SE: 0.07). The dimensions “self-care”, OR = 4.52 (SE: 1.37) and “usual activities”, OR = 3.59 (SE: 1.0), were most strongly affected by Parkinson’s disease. As a limitation our sample may only represent patients with at most moderate disease severity. Conclusions The overall HRQL of multimorbid patients decreases with an increasing count and severity of conditions. Parkinson’s disease, depression and obesity have the strongest impact on HRQL. Further studies should address the impact of disease combinations which require very large sample sizes as well as advanced statistical methods.

Age of major depression onset, depressive symptoms, and risk for subsequent dementia: results of the German study on Ageing, Cognition, and Dementia in Primary Care Patients (AgeCoDe).

BACKGROUND Whether late-onset depression is a risk factor for or a prodrome of dementia remains unclear. We investigated the impact of depressive symptoms and early- v. late-onset depression on subsequent dementia in a cohort of elderly general-practitioner patients (n = 2663, mean age = 81.2 years). METHOD Risk for subsequent dementia was estimated over three follow-ups (each 18 months apart) depending on history of depression, particularly age of depression onset, and current depressive symptoms using proportional hazard models. We also examined the additive prediction of incident dementia by depression beyond cognitive impairment. RESULTS An increase of dementia risk for higher age cut-offs of late-onset depression was found. In analyses controlling for age, sex, education, and apolipoprotein E4 genotype, we found that very late-onset depression (aged ≥ 70 years) and current depressive symptoms separately predicted all-cause dementia. Combined very late-onset depression with current depressive symptoms was specifically predictive for later Alzheimers disease (AD; adjusted hazard ratio 5.48, 95% confidence interval 2.41-12.46, p < 0.001). This association was still significant after controlling for cognitive measures, but further analyses suggested that it was mediated by subjective memory impairment with worries. CONCLUSIONS Depression might be a prodrome of AD but not of dementia of other aetiology as very late-onset depression in combination with current depressive symptoms, possibly emerging as a consequence of subjectively perceived worrisome cognitive deterioration, was most predictive. As depression parameters and subjective memory impairment predicted AD independently of objective cognition, clinicians should take this into account.

Prognosis of Mild Cognitive Impairment in General Practice: Results of the German AgeCoDe Study

PURPOSE The concept of mild cognitive impairment (MCI) has recently been introduced into the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) as mild neurocognitive disorder, making it a formal diagnosis. We investigated the prognostic value of such a diagnosis and analyzed the determinants of the future course of MCI in the AgeCoDe study (German Study on Ageing, Cognition, and Dementia in Primary Care Patients). METHODS We recruited 357 patients with MCI aged 75 years or older from primary care practices and conducted follow-up with interviews for 3 years. Depending on the course of impairment over time, the patients were retrospectively split into 4 groups representing remittent, fluctuating, stable, and progressive courses of MCI. We performed ordinal logistic regression analysis and classification and regression tree (CART) analysis. RESULTS Overall, 41.5% of the patients had remission of symptoms with normal cognitive function 1.5 and 3 years later, 21.3% showed a fluctuating course, 14.8% had stable symptoms, and 22.4% had progression to dementia. Patients were at higher risk for advancing from one course to the next along this spectrum if they had symptoms of depression, impairment in more than 1 cognitive domain, or more severe cognitive impairment, or were older. The result on a test of the ability to learn and reproduce new material 10 minutes later was the best indicator at baseline for differentiating between remittent and progressive MCI. Symptoms of depression modified the prognosis. CONCLUSIONS In primary care, about one-quarter of patients with MCI have progression to dementia within the next 3 years. Assessments of memory function and depressive symptoms are helpful in predicting a progressive vs a remittent course. When transferring the concept of MCI into clinical diagnostic algorithms (eg, DSM-5), however, we should not forget that three-quarters of patients with MCI stayed cognitively stable or even improved within 3 years. They should not be alarmed unnecessarily by receiving such a diagnosis.

Assessing cognitive changes in the elderly: Reliable Change Indices for the Mini‐Mental State Examination

Stein J, Luppa M, Maier W, Wagner M, Wolfsgruber S, Scherer M, Köhler M, Eisele M, Weyerer S, Werle J, Bickel H, Mösch E, Wiese B, Prokein J, Pentzek M, Fuchs A, Leicht H, König H‐H, Riedel‐Heller SG for the AgeCoDe Study Group. Assessing cognitive changes in the elderly: Reliable Change Indices for the Mini‐Mental State Examination.

Apolipoprotein E epsilon 4 genotype and a physically active lifestyle in late life: analysis of gene–environment interaction for the risk of dementia and Alzheimer's disease dementia

BACKGROUND As physical activity may modify the effect of the apolipoprotein E (APOE) ε4 allele on the risk of dementia and Alzheimers disease (AD) dementia, we tested for such a gene-environment interaction in a sample of general practice patients aged ⩾75 years. METHOD Data were derived from follow-up waves I-IV of the longitudinal German study on Ageing, Cognition and Dementia in Primary Care Patients (AgeCoDe). The Kaplan-Meier survival method was used to estimate dementia- and AD-free survival times. Multivariable Cox regression was used to assess individual associations of APOE ε4 and physical activity with risk for dementia and AD, controlling for covariates. We tested for gene-environment interaction by calculating three indices of additive interaction. RESULTS Among the randomly selected sample of 6619 patients, 3327 (50.3%) individuals participated in the study at baseline and 2810 (42.5%) at follow-up I. Of the 2492 patients without dementia included at follow-up I, 278 developed dementia (184 AD) over the subsequent follow-up interval of 4.5 years. The presence of the APOE ε4 allele significantly increased and higher physical activity significantly decreased risk for dementia and AD. The co-presence of APOE ε4 with low physical activity was associated with higher risk for dementia and AD and shorter dementia- and AD-free survival time than the presence of APOE ε4 or low physical activity alone. Indices of interaction indicated no significant interaction between low physical activity and the APOE ε4 allele for general dementia risk, but a possible additive interaction for AD risk. CONCLUSIONS Physical activity even in late life may be effective in reducing conversion to dementia and AD or in delaying the onset of clinical manifestations. APOE ε4 carriers may particularly benefit from increasing physical activity with regard to their risk for AD.

A hierarchy of predictors for dementia-free survival in old-age: results of the AgeCoDe study

Progression from cognitive impairment (CI) to dementia is predicted by several factors, but their relative importance and interaction are unclear.

Elevated HbA1c is associated with increased risk of incident dementia in primary care patients.

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 Alzheimers 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%.

The role of spousal loss in the development of depressive symptoms in the elderly — Implications for diagnostic systems

BACKGROUND In the revised version of the Diagnostic and Statistical Manual of Mental Disorders (DSM) the Mood Disorder Workgroup for DSM-V the bereavement exclusion criterion for the diagnosis of major depression has been eliminated. AIM To investigate the impact of bereavement on the incidence of depression and depressive symptoms in the elderly. METHOD Participants over 75 years from the longitudinal German Study on Ageing, Cognition, and Dementia in Primary Care Patients (AgeCoDe) that were still married at baseline were investigated (n=1,193). Data from four follow-ups (time frame: 6 years) were investigated. The response rate at baseline was 50.3%. Three clinical endpoints were analyzed: depressive symptoms according to Geriatric Depression Scale (1) GDS≥6, (2) GDS≥10, and (3) Major Depression (MD). The effect of loss was investigated using random-effects regression models. RESULTS Experiencing a loss of spouse was predictive of a higher incidence in GDS≥6 (OR 4.52, 95% CI 2.6-7.9) and 10 (OR 5.59, 95% CI 1.8-17.0) even after adjusting for age, gender, impairment at baseline, and GDS score at baseline. Associations with MD were not significant (OR 1.77, 96% CI 0.9-3.5). CONCLUSIONS Older adults experiencing the loss of their spouse are more likely to display elevated levels of depressive symptoms, that may reach a concerning level of severity.

Incident Subjective Cognitive Decline Does Not Predict Mortality in the Elderly – Results from the Longitudinal German Study on Ageing, Cognition, and Dementia (AgeCoDe)

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. Methods 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. Results 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. Conclusion 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.