Michael Pentzek

Prediction of Dementia by Subjective Memory Impairment Effects of Severity and Temporal Association With Cognitive Impairment

CONTEXT Subjective memory impairment (SMI) is receiving increasing attention as a pre-mild cognitive impairment (MCI) condition in the course of the clinical manifestation of Alzheimer disease (AD). OBJECTIVES To determine the risk for conversion to any dementia, dementia in AD, or vascular dementia by SMI, graded by the level of SMI-related worry and by the temporal association of SMI and subsequent MCI. DESIGN Longitudinal cohort study with follow-up examinations at 1(1/2) and 3 years after baseline. SETTING Primary care medical record registry sample. PARTICIPANTS A total of 2415 subjects without cognitive impairment 75 years or older in the German Study on Aging, Cognition and Dementia in Primary Care Patients. MAIN OUTCOME MEASURES Conversion to any dementia, dementia in AD, or vascular dementia at follow-up 1 or follow-up 2 predicted by SMI with or without worry at baseline and at follow-up 2 predicted by different courses of SMI at baseline and MCI at follow-up 1. RESULTS In the first analysis, SMI with worry at baseline was associated with greatest risk for conversion to any dementia (hazard ratio [HR], 3.53; 95% confidence interval [CI], 2.07-6.03) or dementia in AD (6.54; 2.82-15.20) at follow-up 1 or follow-up 2. The sensitivity was 69.0% and the specificity was 74.3% conversion to dementia in AD. In the second analysis, SMI at baseline and MCI at follow-up 1 were associated with greatest risk for conversion to any dementia (odds ratio [OR], 8.92; 95% CI, 3.69-21.60) or dementia in AD (19.33; 5.29-70.81) at follow-up 2. Furthermore, SMI at baseline and amnestic MCI at follow-up 1 increased the risk for conversion to any dementia (OR, 29.24; 95% CI, 8.75-97.78) or dementia in AD (60.28; 12.23-297.10), with a sensitivity of 66.7% and a specificity of 98.3% for conversion to dementia in AD. CONCLUSION The prediction of dementia in AD by SMI with subsequent amnestic MCI supports the model of a consecutive 3-stage clinical manifestation of AD from SMI via MCI to dementia.

AD dementia risk in late MCI, in early MCI, and in subjective memory impairment

To compare the risk of developing Alzheimers disease (AD) dementia in late mild cognitive impairment (LMCI), early MCI (EMCI), and subjective memory impairment (SMI) with normal test performance.

Mild Cognitive Impairment in General Practice: Age-Specific Prevalence and Correlate Results from the German Study on Ageing, Cognition and Dementia in Primary Care Patients (AgeCoDe)

Background: Although mild cognitive impairment (MCI) represents a high-risk factor for developing dementia, little is known about the prevalence of MCI among patients of general practitioners (GPs). Aims: Estimation of age-specific prevalence for original and modified concepts of MCI and their association with sociodemographic, medical and genetic (apoE Ε4 genotype) factors among patients of GPs. Methods: A GP practice sample of 3,327 individuals aged 75+ was assessed by structured clinical interviews. Results: Prevalence was 15.4% (95% CI = 14.1–16.6) for original and 25.2% (95% CI = 23.7–26.7) for modified MCI. Rates increased significantly with older age. Positive associations were found for apoE Ε4 allele, vascular diseases and depressive symptoms. Conclusion: MCI is frequent in elderly patients of GPs. GPs have a key position in secondary prevention and care of incipient cognitive deterioration up to the diagnosis of dementia.

Prevalence and risk factors for depression in non-demented primary care attenders aged 75 years and older

BACKGROUND Depression among the elderly is an important public health issue. The aims of this study were to report the prevalence of depression and to determine the impact of socio-demographic variables, functional impairment and medical diagnoses, lifestyle factors, and mild cognitive impairment on depression as part of the German Study on Ageing, Cognition and Dementia in Primary Care Patients (AgeCoDe Study). METHODS Included in the cross-sectional survey were 3327 non-demented subjects aged 75 and over attending general practitioners (GPs) (n=138) in an urban area of Germany. The GDS-15 Geriatric Depression Scale was used to measure depression with a threshold of <6/6+. Associations with social and clinical risk factors were assessed by means of multiple logistic regression models. RESULTS The prevalence of depression was 9.7% (95% confidence interval 8.7-10.7). In a univariate analysis, the following variables were significantly associated with depression: female gender, increasing age, living alone, divorce, lower educational status, functional impairment, comorbid somatic disorder, mild cognitive impairment, smoking, and abstinence from alcohol. After full adjustment for confounding variables, odds ratios for depression were significantly higher only for functional impairment, smoking, and multi-domain mild cognitive impairment. LIMITATIONS Recruitment procedures might have led to an underestimation of current prevalence. The cross-sectional data did not allow us to analyze the temporal relationship between risk factors and depression. CONCLUSIONS The prevalence of depression in the elderly is high and remains high into old age. In designing prevention programs, it is important to call more attention to the impact of functional and cognitive impairment on depression.

Prediction of dementia in primary care patients.

Background Current approaches for AD prediction are based on biomarkers, which are however of restricted availability in primary care. AD prediction tools for primary care are therefore needed. We present a prediction score based on information that can be obtained in the primary care setting. Methodology/Principal Findings We performed a longitudinal cohort study in 3.055 non-demented individuals above 75 years recruited via primary care chart registries (Study on Aging, Cognition and Dementia, AgeCoDe). After the baseline investigation we performed three follow-up investigations at 18 months intervals with incident dementia as the primary outcome. The best set of predictors was extracted from the baseline variables in one randomly selected half of the sample. This set included age, subjective memory impairment, performance on delayed verbal recall and verbal fluency, on the Mini-Mental-State-Examination, and on an instrumental activities of daily living scale. These variables were aggregated to a prediction score, which achieved a prediction accuracy of 0.84 for AD. The score was applied to the second half of the sample (test cohort). Here, the prediction accuracy was 0.79. With a cut-off of at least 80% sensitivity in the first cohort, 79.6% sensitivity, 66.4% specificity, 14.7% positive predictive value (PPV) and 97.8% negative predictive value of (NPV) for AD were achieved in the test cohort. At a cut-off for a high risk population (5% of individuals with the highest risk score in the first cohort) the PPV for AD was 39.1% (52% for any dementia) in the test cohort. Conclusions The prediction score has useful prediction accuracy. It can define individuals (1) sensitively for low cost-low risk interventions, or (2) more specific and with increased PPV for measures of prevention with greater costs or risks. As it is independent of technical aids, it may be used within large scale prevention programs.

Clinical recognition of dementia and cognitive impairment in primary care: a meta-analysis of physician accuracy.

Mitchell AJ, Meader N, Pentzek M. Clinical recognition of dementia and cognitive impairment in primary care: a meta‐analysis of physician accuracy.

Net costs of dementia by disease stage.

Leicht H, Heinrich S, Heider D, Bachmann C, Bickel H, van den Bussche H, Fuchs A, Luppa M, Maier W, Mösch E, Pentzek M, Rieder‐Heller SG, Tebarth F, Werle J, Weyerer S, Wiese B, Zimmermann T, König H‐H, for the AgeCoDe study group. Net costs of dementia by disease stage.

Risk factors for incident mild cognitive impairment – results from the German Study on Ageing, Cognition and Dementia in Primary Care Patients (AgeCoDe)

Luck T, Riedel‐Heller SG, Luppa M, Wiese B, Wollny A, Wagner M, Bickel H, Weyerer S, Pentzek M, Haller F, Moesch E, Werle J, Eisele M, Maier W, van den Bussche H, Kaduszkiewicz H for the AgeCoDe Study Group. Risk factors for incident mild cognitive impairment – results from the German Study on Ageing, Cognition and Dementia in Primary Care Patients (AgeCoDe).

Current alcohol consumption and its relationship to incident dementia: results from a 3-year follow-up study among primary care attenders aged 75 years and older

OBJECTIVE to investigate prospectively the relationship between current alcohol consumption (quantity and type of alcohol) and incident overall dementia and Alzheimer dementia. METHOD the study is based on individuals (75+) attending general practitioners in Germany: 3,202 subjects free of dementia were studied at baseline, 1.5 years and 3 years later by means of structured clinical interviews including detailed assessment of current alcohol consumption and DSM-IV dementia diagnoses. Associations between alcohol consumption (in grams of ethanol), type of alcohol (wine, beer, mixed alcohol beverages) and incident dementia were examined using Cox proportional hazard models, controlling for several confounders. RESULTS incident overall dementia occurred in 217 of 3,202 participants over a mean follow-up period of 3 years. Significant relationships were found between alcohol consumption (prevalence at baseline: 50.0%) and incident overall dementia (adjusted hazard ratio (HR) 0.71, 95% CI 0.53-0.96), respectively, incident Alzheimer dementia (adjusted HR 0.58, 95% CI 0.38-0.89). With regard to quantity of alcohol and type of alcohol, all hazard ratios were found to be lower than 1. CONCLUSION in agreement with meta-analyses that include younger age groups, our study suggests that light-to-moderate alcohol consumption is inversely related to incident dementia, also among individuals aged 75 years and older.

Longitudinal Predictors of Institutionalization in Old Age.

Objective To investigate time-dependent predictors of institutionalization in old age using a longitudinal approach. Methods 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. Results 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. Conclusion 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.