Semi-quantification and grading of amyloid PET: A project of the European Alzheimer's Disease Consortium (EADC).

BACKGROUND: amyloid-PET reading has been classically implemented as a binary assessment, although the clinical experience has shown that the number of borderline cases is non negligible not only in epidemiological studies of asymptomatic subjects but also in naturalistic groups of symptomatic patients attending memory clinics. In this work we develop a model to compare and integrate visual reading with two independent semi-quantification methods in order to obtain a tracer-independent multi-parametric evaluation. METHODS: We retrospectively enrolled three cohorts of cognitively impaired patients submitted to 18F-florbetaben (53 subjects), 18F-flutemetamol (62 subjects), 18F-florbetapir (60 subjects) PET/CT respectively, in 6 European centres belonging to the EADC. The 175 scans were visually classified as positive/negative following approved criteria and further classified with a 5-step grading as negative, mild negative, borderline, mild positive, positive by 5 independent readers, blind to clinical data. Scan quality was also visually assessed and recorded. Semi-quantification was based on two quantifiers: the standardized uptake value (SUVr) and the ELBA method. We used a sigmoid model to relate the grading with the quantifiers. We measured the readers accord and inconsistencies in the visual assessment as well as the relationship between discrepancies on the grading and semi-quantifications. CONCLUSION: It is possible to construct a map between different tracers and different quantification methods without resorting to ad-hoc acquired cases. We used a 5-level visual scale which, together with a mathematical model, delivered cut-offs and transition regions on tracers that are (largely) independent from the population. All fluorinated tracers appeared to have the same contrast and discrimination ability with respect to the negative-to-positive grading. We validated the integration of both visual reading and different quantifiers in a more robust framework thus bridging the gap between a binary and a user-independent continuous scale.

[Therapy of dementia with antipsychotics and antidepressives]. / Therapie mit Antipsychotika und Antidepressiva bei Demenzen.

In dementia depressive symptoms, anxiety, hallucinations and delusions often occur and are accompanied by unspecific behavioral changes. A targeted pharmacotherapy is complicated by the underlying cognitive impairment and physical comorbidities. The current review focusses on recent evidence on the use of antidepressives and antipsychotics for psychotic disturbances, agitation and depression in dementia and analyzes currently published randomized controlled clinical trials and meta-analyses. The evidence on the use of antipsychotics for different indications favors risperidone, with lower evidence levels for quetiapine and aripiprazole, whereas haloperidol should be avoided. Increased mortality and the risk of cerebrovascular events due to antipsychotics are of major concern. With respect to antidepressives, the benefit of antidepressive pharmacotherapy in dementia is critically discussed because of limited efficacy and increased side effects; however, selective serotonin reuptake inhibitors (SSRI), such as citalopram and sertraline have demonstrated efficacy on neuropsychiatric behavioral symptoms in general. These conclusions on the risk-benefit ratio of antidepressives and antipsychotics in dementia are in accordance with the recommendations of the German Society of Neurology and German Association for Psychiatry, Psychotherapy and Psychosomatics (DGN/DGPPN) S3 guidelines on the treatment of dementia.

Progression of Alzheimer disease in Europe: data from the European ICTUS study.

The clinical progression of Alzheimer disease (AD) was studied in European subjects under treatment with AChE inhibitors (AChE-I) in relation to geographical location over a 2-years period. One thousand three hundred and six subjects from 11 European countries were clustered into 3 regions (North, South, West) and investigated with biannual follow-up over 2 years. Primary outcomes were cognitive, functional and behavioral measures. Caregiver burden, hospital admission and admission to nursing home were also recorded. Participant cognitive function declined non-linearly over time (MMSE: -1.5 pts/first year, -2.5 pts/second year; ADAScog: + 3.5 pts/first year, + 4.8 pts/second year), while the progression of behavioral disturbances (NPI scale) was linear. Neither scale showed regional differences, and progression of the disease was similar across Europe despite different health care systems. Functional decline (ADL, IADL) tended to progress more rapidly in Southern Europe (p=0.09), while progression of caregiver burden (Zarit Burden Interview) was most rapid in Northern Europe (5.6 pts/y, p=0.04). Incidences of hospital admission (10.44, 95%CI: 8.13-12.75, p < 0.001) and admission to nursing home (2.97, 95%CI: 1.83-4.11, p < 0.001) were lowest in Southern Europe. In general cognitive and functional decline was slower than in former cohorts. European geographical location reflecting differences in culture and in health care system does not impact on the progression of AD but does influence the management of AD subjects and caregiver burden.

[Attitudes toward dementia management in Germany - Data from the IMPACT survey (Important Perspectives on Alzheimer's Care and Treatment)]. / Einstellungen und Wahrnehmungen zur Demenz-Versorgung in Deutschland. Daten aus der IMPACT-Umfrage.

AIM: To assess attitudes and opinions of primary care physicians, neuropsychiatrists, care givers, and community members regarding the management of dementia in Germany. METHODS: The IMPACT survey, a 30-minute web-based questionnaire conducted between April and May 2009, queried 350 subjects in Germany (200 community members, 100 physicians, 50 caregivers of patients with dementia) as a subpopulation of 1800 subjects involved in the management of dementia subjects across Europe. RESULTS: Community members favored dementia-screening (p < 0.001) in healthy elderly and wanted to know a diagnosis of dementia as early as possible (p = 0.092). German physicians regarded dementia as underdiagnosed and undertreated, they acknowledged the effectiveness of available antidementia drugs and saw the major reason for not-prescribing in the costs of drugs. CONCLUSION: Professional knowledge about dementia has to be enhanced and financial restrictions have to be reduced to improve dementia management on all levels of medical care.

Venlafaxin-associated post-ictal asystole during electroconvulsive therapy.

While post-stimulus asystoles occur quite often during electroconvulsive therapy (ECT) post-ictal or post-seizure sinus bradycardias or even asystoles are rare events. We report the case of an 82-year-old female patient with a current major depressive episode, who developed the rare event of a post-ictal asystole of 6 s and 4 ventricular escape beats during ECT. In the past this patient with a bipolar disorder and mild Alzheimer's disease had already been frequently treated with ECT with good success and no adverse events. Relevant comedication was venlafaxin, quetiapine, donepezil and clonidine, anesthesia was performed with ketamine and succinylcholine. Concurrent medication was completely unchanged compared to previous ECT sessions with the exception of venlafaxine, presumably at high serum levels. In summary, in line with some already existing reports, we expect the noradrenergic action of venlafaxin to have contributed substantially to the post-ictal asystole and want to indicate that the combination of ECT and venlafaxin might be harmful--especially in the elderly population.

[Epidemiology of cholelithiasis among professionally active persons in the Katowice province]. / Epidemiologia kamicy pecherzyka zólciowego u ludzi zawodowo czynnych w województwie katowickim.

In the workplaces of the City of Katowice 2867 subjects in 5 age groups were studied by inquiry, physical examination and gallbladder ultrasonography. Calculi in the gallbladder were found in 344 subjects that is 11.99%. The prevalence of calculi was much higher in females, and in both sexes it increased with age. The study confirms the value of USG in the diagnosis of gallbladder calculi and the possibility of its use for screening of the general population.

[Peripheral blood neutrophils in automobile tire factory workers in the light of cytochemical studies]. / Granulocyty obojetnochlonne krwi obwodowej u pracowników zakladów opon samochodowych w swietle badan cytochemicznych.

In 73 workers producing rubber mixtures and tubes the number and percentage composition of white peripheral blood cells as well as the NBT reduction test and cytochemical reactions to lactic (LDH) and succinic (SDH) dehydrogenases in neutrophils were estimated. The amount and percentage composition only slightly differed from controls. The NBT reduction index and the reactivity of LDH and SDH tests in neutrophils were elevated.