Reconceptualization of the Erlangen Score for the Assessment of Dementia Risk: The ERlangen Score.

BACKGROUND: The established Erlangen Score (ES) for the interpretation of cerebrospinal fluid (CSF) biomarkers in the diagnostics of Alzheimer's disease (AD) uses markers of amyloidopathy and tauopathy, equally weighted to form an easy-interpretable ordinal scale. However, these biomarkers are not equally predictive for AD. OBJECTIVE: The higher weighting of the Aß42/Aß40 ratio, as a reconceptualized ERlangen Score (ERS), was tested for advantages in diagnostic performance. METHODS: Non-demented subjects (N = 154) with a mean follow up of 5 years were assigned to a group ranging from 0 to 4 in ES or ERS. Psychometric trajectories and dementia risk were assessed. RESULTS: The distribution of subjects between ES and ERS among the groups differed considerably, as grouping allocated 32 subjects to ES group 2, but only 2 to ERS group 2. The discriminative accuracy between the ES (AUC 73.2%, 95% CI [64.2, 82.2]) and ERS (AUC 72.0%, 95% CI [63.1, 81.0]) for dementia risk showed no significant difference. Without consideration of the Aß42/Aß40 ratio in ES grouping, the optimal cut-off of the ES shifted to ≥2. CONCLUSIONS: The ERS showed advantages over the ES in test interpretation with comparable overall test performance, as fewer cases were allocated to the intermediate risk group. The established cut-off of ≥2 can be maintained for the ERS, whereas it must be adjusted for the ES when determining the Aß42/Aß40 ratio.

Self-management with alcohol over lifespan: psychological mechanisms, neurobiological underpinnings, and risk assessment.

Self-management includes all behavioural measures and cognitive activities aimed at coping with challenges arising throughout the lifespan. While virtually all of these challenges can be met without pharmacological means, alcohol consumption has long been instrumentalized as a supporting tool to help coping with problems arising selectively at adolescence, adulthood, and ageing. Here, we present, to our knowledge, the first systematic review of alcohol instrumentalization throughout lifespan. We searched MEDLINE, Google Scholar, PsycINFO and CINAHL (from Jan, 1990, to Dec, 2022) and analysed consumption patterns, goals and potential neurobiological mechanisms. Evidence shows a regular non-addictive use of alcohol to self-manage developmental issues during adolescence, adulthood, and ageing. Alcohol is selectively used to overcome problems arising from dysfunctional personality traits, which manifest in adolescence. A large range of psychiatric disorders gives rise to alcohol use for the self-management of distinct symptoms starting mainly in adulthood. We identify those neuropharmacological effects of alcohol that selectively serve self-management under specific conditions. Finally, we discuss the adverse effects and associated risks that arise from the use of alcohol for self-management. Even well-controlled alcohol use adversely impacts health. Based on these findings, we suggest the implementation of an entirely new view. Health policy action may actively embrace both sides of the phenomenon through a personalized informed use that allows for harm-controlled self-management with alcohol.

Apathy in patients with Alzheimer's disease is a cost-driving factor.

BACKGROUND: Apathy is the most frequent neuropsychiatric symptom in patients with dementia of the Alzheimer's type (DAT). We analyzed the influence of apathy on the resource use of DAT patients and their caregivers. METHODS: Included were baseline data of 107 DAT patients from a randomized clinical trial on apathy treatment. The Resource Utilization in Dementia (RUD) instrument assessed costs over a 1-month period prior to baseline. Cost predictors were determined via a least absolute shrinkage and selection operator (LASSO). RESULTS: On average, total monthly costs were €3070, of which €2711 accounted for caregivers' and €359 for patients' costs. An increase of one point in the Apathy Evaluation Scale resulted in a 4.1% increase in total costs. DISCUSSION: Apathy is a significant cost driving factor for total costs in mild to moderate DAT. Effective treatment of apathy might be associated with reduced overall costs in DAT.

[The Cost of Early Diagnosis of Cognitive Decline in German Memory Clinics]. / Kosten der Diagnostik kognitiver Störungen in deutschen Gedächtnisambulanzen.

Dementias are expensive diseases: the net annual cost in European healthcare is about € 28.000 per case with a strong stage dependency, of which medical care accounts for about 19%. Diagnostic costs, on the other hand, account for only a small proportion of the total costs. With changes in the guidelines, biomarker tests are becoming increasingly important. At present, the concrete economic impact of biomarker-based diagnosis is largely unknown. To determine the actual costs of diagnostic procedures based on guidelines, we conducted a survey among the members of the German Memory Clinic Network (DNG). From 15 expert centres, the staff engagement time for all procedures was collected. Based on the individual engagement times of the different professions, the total of personnel costs for diagnostics was calculated using current gross personnel costs. The total sum of diagnostic costs (personnel plus procedures) was calculated for three different scenarios e. g. € 633,97 for diagnostics without biomarkers, € 1.214,90 for diagnostics with CSF biomarkers and € 4.740,58 € for diagnostics with FDG- plus Amyloid-PET. In addition, the actual diagnostic costs of the current practice in expert memory clinics were estimated, taking into account personnel costs, costs for the different procedures and the frequency of their use across all patients. This results in total average costs of € 1.394,43 per case as the mean across all centres (personnel costs € 351,72, costs for diagnostic procedures € 1.042,71). The results show that state-of-the-art diagnosis of dementia and pre-dementia states, such as mild cognitive impairment (MCI) requires financial resources, which are currently not fully reimbursed in Germany. The need for a biomarker-based etiological diagnosis of dementia and pre-dementia states will increase, due to availability of disease-modifying treatments. Therefore, the current gap of reimbursement must be filled by new models of compensation.

Update on structured pain assessment for the documentation of diagnosis-independent symptoms and signs associated with pain.

Concerning the diagnosis and therapy of pain syndromes, standardized descriptions similar to those used in the examination of psychopathological findings via the system produced by the AMDP ("Arbeitsgemeinschaft für Methodik und Dokumentation in der Psychiatrie", i. e., the working group establishing standardized methodology and documentation within psychiatry) are still lacking. Therefore, the authors of this article have founded a working group to establish standardized methodology and documentation for symptoms and signs associated with pain, although not at a diagnosis-specific level, in order to promote standardization in the documentation of pain and rating of the symptoms associated with a given set of medical results. This article presents a system for documenting the symptoms and signs associated with pain globally and independently of the diagnosis (Structured Pain Assessment System) with nomenclature that is inspired by the AMDP system. The objective of this working group is to develop documentation for a uniform multidimensional pain assessment (with defined terminology) that serves as a comparable and unified standard in the field.

Lower digit ratio (2D:4D) in alcohol dependence: Confirmation and exploratory analysis in a population-based study of young men.

Moderately sized, case-control studies have related alcohol dependence in middle-aged in-patients to lower second-to-fourth finger length ratio (2D:4D), a proxy for prenatal hyperandrogenization. As primary aim, we here intended to confirm that lower 2D:4D is also associated with Diagnostic and Statistical Manual of Mental Disorders (DSM)-IV/-5 alcohol dependence and alcohol use disorder in a large population-based cohort of young males. Exploratory aims included underlying mechanisms. We analyzed self-reported data on 2D:4D, DSM-IV/-5 criteria, anticipated subjective responses to alcohol, and willingness to purchase alcoholic drinks from 4989 Swiss men of the Cohort Study on Substance Use Risk Factors (C-SURF). The mean of right-hand 2D:4D and left-hand 2D:4D was lower in men with DSM-IV alcohol dependence than in those without (0.975 vs 0.981, P = .035) and lower in men with moderate to severe (0.974) than in those with mild (0.982, P = .001) or no (0.981, P = .003) DSM-5 alcohol use disorder. Moreover, mean 2D:4D was lower in those reporting recent use of health services due to substance use problems (0.968 vs 0.981, P = .046). Lower mean 2D:4D correlated with a stronger anticipation to feel high following alcohol consumption (total cohort: ρ = -0.033, P = .026) and with a willingness to purchase more higher-priced alcoholic drinks (DSM-IV alcohol dependence subgroup: ρmin = -0.162, P = .002). This is the first population-based study on young males to demonstrate lower 2D:4D in DSM-IV alcohol dependence, DSM-5 alcohol use disorder, and the related use of health care services. We also provide novel insight into cognitive-behavioral mechanisms. These results should help to establish more effective preventive and therapeutic strategies targeting 2D:4D and prenatal androgen exposure.

Interlaboratory proficiency processing scheme in CSF aliquoting: implementation and assessment based on biomarkers of Alzheimer's disease.

BACKGROUND: In this study, we tested to which extent possible between-center differences in standardized operating procedures (SOPs) for biobanking of cerebrospinal fluid (CSF) samples influence the homogeneity of the resulting aliquots and, consequently, the concentrations of the centrally analyzed selected Alzheimer's disease biomarkers. METHODS: Proficiency processing samples (PPSs), prepared by pooling of four individual CSF samples, were sent to 10 participating centers, which were asked to perform aliquoting of the PPSs into two secondary aliquots (SAs) under their local SOPs. The resulting SAs were shipped to the central laboratory, where the concentrations of amyloid beta (Aß) 1-42, pTau181, and albumin were measured in one run with validated routine analytical methods. Total variability of the concentrations, and its within-center and between-center components, were analyzed with hierarchical regression models. RESULTS: We observed neglectable variability in the concentrations of pTau181 and albumin across the centers and the aliquots. In contrast, the variability of the Aß1-42 concentrations was much larger (overall coefficient of variation 31%), with 28% of the between-laboratory component and 10% of the within-laboratory (i.e., between-aliquot) component. We identified duration of the preparation of the aliquots and the centrifugation force as two potential confounders influencing within-center variability and biomarker concentrations, respectively. CONCLUSIONS: Proficiency processing schemes provide objective evidence for the most critical preanalytical variables. Standardization of these variables may significantly enhance the quality of the collected biospecimens. Studies utilizing retrospective samples collected under different local SOPs need to consider such differences in the statistical evaluations of the data.

Physical activity and energy expenditure during depressive episodes of major depression.

BACKGROUND: Recent data suggest a substantial association between physical activity and depressive symptoms, but there is a lack of research evaluating the physical activity levels in patients suffering from unipolar depression across different stages of disease in an objective way. The aim of the present pilot study was to objectively examine physical activity levels of this patient group compared to healthy controls. METHODS: Physical activity performance of 19 patients with major depressive episode and 19 healthy controls was assessed at three different time points using a multisensory armband device (SenseWear® Pro3 Armband) and was reported as total energy expenditure (TEE), active energy expenditure (EE), metabolic equivalents (METs), physical activity (PA) and time of lying down (LD), in each case over 24h. RESULTS: Over all measurements, depressive patients presented a significantly lower mean TEE and EE over 24h. Moreover, the patient group showed significantly shorter duration of PA and lower average MET over 24h. When depressive symptoms abated, physical activity parameters significantly increased in the patient group. Correlation analyses demonstrated a significant relation between depressive status/anhedonia and parameters of physical activity, especially in healthy subjects. LIMITATIONS: Results represented valid data for inpatients only. CONCLUSION: Acute unipolar depression was associated with a significantly lower level of physical activity and showed a significant increase in parallel to clinical improvement. Electronic monitoring of physical activity may be an additional tool for evaluating and controlling therapeutic effects.

The psychophysical assessment of odor valence: does an anchor stimulus influence the hedonic evaluation of odors?

Olfactory stimuli are experienced primarily in terms of their hedonic tone and the assessment of olfactory hedonic estimates is a prevalent task in scientific and industrial contexts. However, measuring conditions are poorly standardized. Our study aims to fill this gap, focusing on the influence of anchor stimuli on olfactory hedonic evaluations, frequency of anchor presentation, and temporal stability of results. In n = 31 subjects, hedonic estimates for the 16 odors of the Sniffin' Sticks identification task were assessed on a visual analog rating scale under 4 measuring conditions (nonanchor, pleasant anchor, neutral anchor, unpleasant anchor). To test for stability over time, n = 10 subjects were reassessed 2, 4, and 6 months after original testing. To analyze for possible effects of single versus repeated anchor presentation, n = 15 subjects were retested 2 months after the original session in a multiple anchor presentation format. Statistical analysis revealed significant differences between the 4 anchor conditions, thus highlighting the necessity of specifying assessment methods in scientific research. No significant differences between timepoints were observed, indicating a high temporal stability of olfactory hedonic evaluations, especially from timepoint T2 onward. No overall significant effects of single versus multiple anchor presentation were detected. Findings might help to further standardize testing procedures.

[Liaison psychiatry. An analytic view using the example of a German university hospital]. / Psychiatrischer Liaisondienst. Eine analytische Betrachtung am Beispiel einer deutschen Universitätsklinik.

OBJECTIVE: Analysis of liaison psychiatry cases of a university hospital. METHODS: Descriptive analysis on the basis of all psychiatric consultations realized in the year 2008 at the university hospital of Erlangen. RESULTS: About 1% of all patients with somatic diseases receive a psychiatric treatment by the liaison psychiatry at the same time. Suspected and final diagnosis of correspond in only one third of cases. The diagnoses are focused on only a few diseases. Suicidality is confirmed in a small number of cases. Most commonly a medicamentous treatment is recommended, above all antidepressant and typical neuroleptics. CONCLUSIONS: The interdisciplinary treatment of patients with somatic diseases by the liaison psychiatry is an increasingly used instrument of other disciplines and serves to optimize the diagnostic and therapeutic efficiency of public health.

Unsuitable readability levels of patient information pertaining to dementia and related diseases: a comparative analysis.

BACKGROUND: Our study investigated the readability of printed material about dementia that is offered to patients and caregivers. METHODS: Comparisons of various brochures (at least three standard pages in length) on dementia and related disorders were made using automated measuring by the SMOG readability index grade. RESULTS: 118 brochures were assessed (25 in English, 93 in German), for which the mean readability was found to be high school/college level as measured by the SMOG readability index (grade 13.6 +/- 1.8). No differences in readability were observed between materials produced by pharmaceutical companies and other sources. Furthermore, recently published brochures were not more readable than older ones. Shorter brochures, English brochures and those containing medical facts were easier to read than longer ones, those written in German or brochures primarily addressing psychosocial care/social issues. The sentence length was above the 20 word recommendation in 25% of the brochures. The average font size of the brochure texts was small (mean font size 11.1 +/- 1.6 point) with only 25% of brochures having a font size of 12 or more, as recommended. CONCLUSIONS: Written patient information and educational material of more than three standard pages is often published at unsuitably high readability levels using small fonts. Information material about dementia should be designed and tested prior to distribution among patients and caregivers. Future studies should address material shorter than three pages and material for younger caregivers.

An assessment of the potential value of elevated homocysteine in predicting alcohol-withdrawal seizures.

PURPOSE: Higher homocysteine levels were found in actively drinking patients with alcohol dependence. Recent studies have shown that high homocysteine levels are associated with alcohol-withdrawal seizures. The aim of the present study was to calculate the best predictive cutoff value of plasma homocysteine levels in actively drinking alcoholics (n = 88) with first-onset alcohol-withdrawal seizures. METHODS: The present study included 88 alcohol-dependent patients of whom 18 patients had a first-onset withdrawal seizure. All patients were active drinkers and had an established diagnosis of alcohol dependence, according to the Diagnostic and Statistical Manual of Mental Disorders (DSM-IV). Sensitivity and specificity were calculated by using every homocysteine plasma level found in the study population as cut-off value. A Bayes theorem was used to calculate positive (PPV) and negative (NPV) predictive values for all cutoff values used. RESULTS: The highest combined sensitivity and specificity was reached at a homocysteine plasma cutoff value of 23.9 microM. Positive predictive values ranged from 0.23 to 0.745; the maximum was reached at a homocysteine plasma level of 41.7 microM. Negative predictive values ranged from 0.50 to 0.935, with a maximum at a homocysteine plasma level of 15.8 microM. CONCLUSIONS: Homocysteine levels above this cutoff value on admission are a useful screening tool to identify actively drinking patients at higher risk of alcohol-withdrawal seizures. This pilot study gives further hints that biologic markers may be helpful to predict patients at risk for first-onset alcohol-withdrawal seizures.