Birgitt Wiese

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.

Age- and gender-specific prevalence of depression in latest-life – Systematic review and meta-analysis

OBJECTIVE The objective of the study is to systematically analyze the prevalence of depression in latest life (75+), particularly focusing on age- and gender-specific rates across the latest-life age groups. DESIGN Relevant articles were identified by systematically searching the databases MEDLINE, Web of Science, Cochrane Library and Psycinfo and relevant literature from 1999 onwards was reviewed. Studies based on the community-based elderly population aged 75 years and older were included. Quality of studies was assessed. Meta-analysis was performed using random effects model. RESULTS 24 studies reporting age- and gender-specific prevalence of depression were found. 13 studies had a high to moderate methodical quality. The prevalence of major depression ranged from 4.6% to 9.3%, and that of depressive disorders from 4.5% to 37.4%. Pooled prevalence was 7.2% (95% CI 4.4-10.6%) for major depression and 17.1% (95% CI 9.7-26.1%) for depressive disorders. Potential sources of high heterogeneity of prevalence were study design, sampling strategy, study quality and applied diagnostics of latest life depression. CONCLUSIONS Despite the wide variation in estimates, it is evident that latest life depression is common. To reduce variability of study results, particularly sampling strategies (inclusion of nursing home residents and severe cognitively impaired individuals) for the old age study populations should be addressed more thoroughly in future research.

Inter-laboratory and inter-observer reproducibility of immunohistochemical assessment of the Ki-67 labelling index in a large multi-centre trial.

Proliferative activity of tumour cells, as assessed by the Ki‐67 labelling index, has been suggested as a potential prognostic indicator in many neoplastic diseases. Meaningful application of the immunohistochemically determined tumour cell growth fraction in clinical decision‐making requires information about its inter‐laboratory reproducibility. To assess the reproducibility of Ki‐67 determined growth fraction, a multi‐centre immunohistochemical trial was performed with 172 participating laboratories, each testing 30 different tissue samples. Evaluating 5160 Ki‐67 labelling indices with a newly developed tissue microarray, good inter‐observer reproducibility but high inter‐laboratory variability was found. Reassessment of all stainings revealed considerable inter‐laboratory differences in the intensity and frequency of labelled nuclei, suggesting that antigen retrieval or staining techniques are predominantly responsible for the inter‐laboratory variability found in this trial. Consequently, cut‐off levels for Ki‐67, suggested to distinguish prognostic subgroups in tumours, appear to have limited reproducibility in a multi‐centre approach. It is concluded that there is a need to standardize the immunohistochemical determination of the Ki‐67 labelling index when it is used as a prognostic indicator in surgical pathology. Copyright

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.

The influence of age, gender and socio-economic status on multimorbidity patterns in primary care. first results from the multicare cohort study

BackgroundMultimorbidity is a phenomenon with high burden and high prevalence in the elderly. Our previous research has shown that multimorbidity can be divided into the multimorbidity patterns of 1) anxiety, depression, somatoform disorders (ADS) and pain, and 2) cardiovascular and metabolic disorders. However, it is not yet known, how these patterns are influenced by patient characteristics. The objective of this paper is to analyze the association of socio-demographic variables, and especially socio-economic status with multimorbidity in general and with each multimorbidity pattern.MethodsThe MultiCare Cohort Study is a multicentre, prospective, observational cohort study of 3.189 multimorbid patients aged 65+ randomly selected from 158 GP practices. Data were collected in GP interviews and comprehensive patient interviews. Missing values have been imputed by hot deck imputation based on Gower distance in morbidity and other variables. The association of patient characteristics with the number of chronic conditions is analysed by multilevel mixed-effects linear regression analyses.ResultsMultimorbidity in general is associated with age (+0.07 chronic conditions per year), gender (-0.27 conditions for female), education (-0.26 conditions for medium and -0.29 conditions for high level vs. low level) and income (-0.27 conditions per logarithmic unit). The pattern of cardiovascular and metabolic disorders shows comparable associations with a higher coefficient for gender (-1.29 conditions for female), while multimorbidity within the pattern of ADS and pain correlates with gender (+0.79 conditions for female), but not with age or socioeconomic status.ConclusionsOur study confirms that the morbidity load of multimorbid patients is associated with age, gender and the socioeconomic status of the patients, but there were no effects of living arrangements and marital status. We could also show that the influence of patient characteristics is dependent on the multimorbidity pattern concerned, i.e. there seem to be at least two types of elderly multimorbid patients. First, there are patients with mainly cardiovascular and metabolic disorders, who are more often male, have an older age and a lower socio-economic status. Second, there are patients mainly with ADS and pain-related morbidity, who are more often female and equally distributed across age and socio-economic groups.Trial registrationISRCTN89818205

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.

Comorbidity of alcohol and substance dependence with attention-deficit/hyperactivity disorder (ADHD).

AIMS Attention-deficit/hyperactivity disorder (ADHD) is of great clinical importance not only because of its high prevalence but also due to the frequent comorbid illnesses that are connected with this disorder. Several studies were able to demonstrate that ADHD constitutes a significant risk factor for the exacerbation of habit-forming illnesses, i.e. addictions. METHODS We conducted a study on 152 adult patients with alcohol dependence (n = 91) or multiple substance addiction (n = 61) to determine whether or not these patients were affected by ADHD. For retrospective assessment of childhood ADHD, the WURS-k was used as well as the DSM-IV symptom checklist for ADHD. The CAARS was used to assess the persisting symptoms of ADHD in adults. RESULTS 20.9% (WURS-k) or 23.1% (DSM-IV diagnostic criteria) of the alcohol-dependent patients showed evidence of retrospective ADHD affliction in childhood. With the help of CAARS, ADHD was proved to be persistent in 33.3% of the adult patients. In the group of substance-addicted patients 50.8% (WURS-k) and 54.1% (DSM-IV) presented with diagnostic criteria for ADHD in childhood and 65.5% (CAARS) showed evidence of ADHD persisting in adulthood. CONCLUSIONS These results reveal that habit-forming illnesses can be associated with a high comorbidity with ADHD, expressed in the form of alcohol abuse and also in consumption of illegal drugs. The results underline the great importance of early and adequate diagnostics and therapy of ADHD for the prevention of habit-forming illnesses.

Tissue Array Technology for Testing Interlaboratory and Interobserver Reproducibility of Immunohistochemical Estrogen Receptor Analysis in a Large Multicenter Trial

Semiquantitative immunohistochemical assessment of estrogen receptor (ER) is used to predict the likelihood of response to antiestrogen therapy in breast carcinoma. If semiquantitative immunohistochemical analysis leads to therapeutic decisions, the importance of standardization and quality control increases. ER assessment reproducibility was studied among 172 laboratories using tissue microarray slides with 20 tissue spots negative and 10 tissue spots expressing ER at low, medium, or high levels. More than 80% of the laboratories demonstrated ER positivity in the medium- and high-expressing tissue spots, but only about 43% succeeded with tissue spots with low expression. Poor interlaboratory agreement was based on insufficient retrieval efficacy as shown by additional tests using autoclave pretreatment. The immunohistochemical scores used to quantify therapeutic target molecules remain inconclusive as long as progress toward standardized immunohistochemical procedures and evaluation is not achieved. Tissue microarray technology has proved its suitability for large-scale immunohistochemical trials, giving rise to new dimensions in control assessment.

Anatomical progression of coronary artery disease in humans as seen by prospective, repeated, quantitated coronary angiography. Relation to clinical events and risk factors. The INTACT Study Group.

BackgroundAt present, there is extensive knowledge on the clinical course of coronary artery disease (CAD), whereas data on the underlying anatomical changes and their relation to clinical events are still limited. Methods and ResultsWe investigated progression and regression of CAD prospectively over 3 years in 230 patients (average age, 53.2 years) with mild to moderate disease by applying quantitated, repeated coronary angiography. Minimal stenotic diameters, segment diameters, and percent stenosis were analyzed by the computer-assisted Coronary Angiography Analysis System (CAAS). Progression was defined either as an increase in percent stenosis of preexisting stenoses by ≥20% including occlusions or as formation of new stenoses ≥20% and new occlusions in previously angiographically “normal” segments. At first angiography, we found 838 stenoses ≥20% (average degree, 39.3%) and 135 occlusions in the four major coronary branches (4.23 lesions per patient). At second angiography, 82 (9.8%) of the preexisting stenoses had progressed, 15 of them up to occlusion (1.8% preocclusion degree averaging 46.6%; 29.7–65.6%). In addition, there were 144 newly formed stenoses (average degree, 39.2%) and 10 new occlusions. Hence, 25 (2.6%) of all stenoses had become occluded. Altogether, 129 patients (56.1%) showed progression: 68 (29.6%) with new lesions only, 27 (11.7%) with preexisting lesions, and 34 (14.8%) with both types. Regression (decrease in degree of stenoses ≥20%) was present in 29 stenoses (3.6%) and 28 patients (12%). The incidence of new myocardial infarctions was low, with three originating from occluding preexisting stenoses and one from new stenoses; hence, only four (16%) of the 25 new occlusions led to myocardial infarctions. Risk factor analysis showed that cigarette smoking correlated significantly with the formation of new lesions (p=0.001), whereas total cholesterol correlated with the further progression of preexisting stenoses (p=0.017) but not with the incidence of new lesions. ConclusionsIn patients with mild to moderate CAD, the angiographic progression is slow (in this study 18.7% of patients and 7% of stenoses per year) but exceeds regression (4.1% of patients and 1.2% of stenoses per year). Progression is predominantly seen in the formation of new coronary stenoses and less in growth of preexisting ones. Most of the stenoses were of a low degree (<50%), clinically not manifest including those going into occlusion and leading to myocardial infarction. Progression was influenced by risk factors, especially cigarette smoking (formation of new lesions) and high cholesterol levels (progression of preexisting stenoses).