[Politicians' Personal Physicians: careers and complications from King David until today]. / Leib- und Seelenärzte Karrieren und Komplikationen von König David bis heute.

Court physicians need to deal with a clientele posing particular personality problems (e. g. rex inutilis) in a difficult environment characterized by specific health issues (morbi aulici) and they may have to avoid serious risks or want to seek great opportunities (medicus politicus). Very few have been successful as King David, a former music therapist without a medical degree, or the dentist and president Gurbanguly Berdimuhamedow. Several became victims of fatal circumstances. Not all could resist temptation of questionable literary fame at the expense of confidentiality. All told, a career close to high profile leaders needs to be considered carefully as risks may outweigh benefits.

FDG-PET underscores the key role of the thalamus in frontotemporal lobar degeneration caused by C9ORF72 mutations.

C9ORF72 mutations are the most common cause of familial frontotemporal lobar degeneration (FTLD) and amyotrophic lateral sclerosis (ALS). MRI studies have investigated structural changes in C9ORF72-associated FTLD (C9FTLD) and provided first insights about a prominent involvement of the thalamus and the cerebellum. Our multicenter, 18F-fluorodeoxyglucose positron-emission tomography study of 22 mutation carriers with FTLD, 22 matched non-carriers with FTLD, and 23 cognitively healthy controls provided valuable insights into functional changes in C9FTLD: compared to non-carriers, mutation carriers showed a significant reduction of glucose metabolism in both thalami, underscoring the key role of the thalamus in C9FTLD. Thalamic metabolism did not correlate with disease severity, duration of disease, or the presence of psychotic symptoms. Against our expectations we could not demonstrate a cerebellar hypometabolism in carriers or non-carriers. Future imaging and neuropathological studies in large patient cohorts are required to further elucidate the central role of the thalamus in C9FTLD.

Rescue of long-range circuit dysfunction in Alzheimer's disease models.

Alzheimer's disease (AD) is associated with defects of synaptic connectivity. Such defects may not be restricted to local neuronal interactions but may extend to long-range brain activities, such as slow-wave oscillations that are particularly prominent during non-rapid eye movement (non-REM) sleep and are important for integration of information across distant brain regions involved in memory consolidation. There is increasing evidence that sleep is often impaired in AD, but it is unclear whether this impairment is directly related to amyloid-ß (Aß) pathology. Here we demonstrate that slow-wave activity is severely altered in the neocortex, thalamus and hippocampus in mouse models of AD amyloidosis. Most notably, our results reveal an Aß-dependent impairment of slow-wave propagation, which causes a breakdown of the characteristic long-range coherence of slow-wave activity. The finding that the impairment can be rescued by enhancing GABAAergic inhibition identifies a synaptic mechanism underlying Aß-dependent large-scale circuit dysfunction.

Vitamin D deficiency, cognitive impairment and dementia: a systematic review and meta-analysis.

BACKGROUND: Recent preventive strategies for patients with cognitive impairment include the identification of modifiable somatic risk factors like vitamin D deficiency. METHODS: A systematic literature research and meta-analysis were conducted to assess the association of cognitive impairment and vitamin D deficiency. RESULTS: Data from cross-sectional and longitudinal studies suggest an association between cognitive impairment and vitamin D deficiency. Meta-analysis of 5 cross-sectional and 2 longitudinal studies comprising 7,688 participants showed an increased risk of cognitive impairment in those with low vitamin D compared with normal vitamin D (OR 2.39, 95% CI 1.91-3.00; p < 0.0001). CONCLUSIONS: Methodological limitations of these studies comprise heterogeneity of study populations, different forms of cognitive assessment, the problem of reverse causality, different definitions of vitamin D deficiency and inconsistent control for confounders. As the value of vitamin D substitution in cognitive impairment remains doubtful, a long-time major placebo-controlled randomized trial of vitamin D supplementation in participants with mild cognitive impairment (MCI) should be started.

Cerebrospinal fluid BACE1 activity and brain amyloid load in Alzheimer's disease.

The secretase BACE1 is fundamentally involved in the development of cerebral amyloid pathology in Alzheimer's disease (AD). It has not been studied so far to what extent BACE1 activity in cerebrospinal fluid (CSF) mirrors in vivo amyloid load in AD. We explored associations between CSF BACE1 activity and fibrillar amyloid pathology as measured by carbon-11-labelled Pittsburgh Compound B positron emission tomography ([¹¹C]PIB PET). [¹¹C]PIB and CSF studies were performed in 31 patients with AD. Voxel-based linear regression analysis revealed significant associations between CSF BACE1 activity and [¹¹C]PIB tracer uptake in the bilateral parahippocampal region, the thalamus, and the pons. Our study provides evidence for a brain region-specific correlation between CSF BACE1 activity and in-vivo fibrillar amyloid pathology in AD. Associations were found in areas close to the brain ventricles, which may have important implications for the use of BACE1 in CSF as a marker for AD pathology and for antiamyloid treatment monitoring.

The clock drawing test and questionable dementia: reliability and validity.

OBJECTIVES: In order to evaluate the suitability of the clock drawing test (CDT) for the detection of questionable dementia (QD), we assessed the inter-rater reliabilities and intercorrelations of four common scoring methods of the CDT in a sample of non-demented subjects and determined the concurrent validity. METHODS: The study sample consisted of 253 discharged general hospital patients, aged between 65 and 85 years. Subjects were screened for cognitive impairment during their hospital stay. Four to six weeks after discharge each non-demented patient was visited at home and interviewed by a trained psychologist. The interview procedure included a cognitive test battery incorporating the CDT, the Mini-Mental State Examination (MMSE), the Syndrome Short Test (SKT), and a verbal fluency test (VF). The criteria of the Clinical Dementia Rating (CDR) were used to differentiate between cognitively normal subjects and those with QD. Clock drawings were scored independently and blindly by two raters according to four different methods. The agreement between raters was assessed, as well as the agreement between the different scoring methods. The association of gender, education, age, test performance and CDR-rating with CDT scores was examined. Accuracy of the CDT for the detection of QD was calculated. RESULTS: Inter-rater reliabilities were high for all four scoring methods. However, substantial differences among the scoring methods were observed, the proportion of abnormal test results varying between 9% and 50%. The CDT correlated significantly with MMSE, SKT and VF, but correlation coefficients were low (r = 0.13 to r = 0.32). Furthermore, CDT scores were influenced by age, gender, and education. Sensitivity of the CDT for QD was 66%, specificity was 65%; the negative predictive value was 73%, the positive predictive value 58%. CONCLUSION: In a sample of non-demented elderly, the reliability of the CDT was sufficiently high, but the different scoring methods were not equivalent. When established cut-off scores were used, the proportion of abnormal CDTs were significantly different. Concurrent validity with other common cognitive tests was unsatisfactory. The CDT lacks sufficient sensitivity and specificity for the identification of QD and should not be used alone to screen for possible prodromal stages of dementing illnesses. The association of age, gender and level of education with CDT scores should be taken into account by clinicians using the CDT.