Cerebrospinal Fluid Tau Protein Levels and F-18-Fluorodeoxyglucose Positron Emission Tomography in the Differential Diagnosis of Alzheimer's Disease

Aims: In this study, we aimed to compare cerebrospinal fluid (CSF) levels of total tau (t-tau), phosphorylated tau (p-tau(181)) and positron emission tomography with F-18-fluorodeoxyglucose (FDG-PET) in the differential diagnosis of Alzheimer's disease (AD) under clinical conditions. Method: In a cross-sectional, blinded, single-center study, we examined a sample of 75 unselected memory clinic patients with clinical diagnoses of dementia of Alzheimer type (DAT; n = 24), amnestic mild cognitive impairment (MCI; n = 16), other dementias (n = 13) and nondemented controls (n = 22). Discriminative accuracy, sensitivity and specificity were calculated and compared using ROC analyses. Results: p-tau(181) and FDG-PET were comparable in separating DAT from controls (sensitivity: 67 vs. 79%; specificity: 91% for both) and patients with other dementias (sensitivity: 71 vs. 79%; specificity: 100% for both). The sensitivity of p-tau 181 in differentiating MCI patients from controls was significantly (p < 0.05) superior to that of FDG-PET (75 vs. 44%) at a comparably high specificity (82 vs. 91%); t-tau measures were less accurate in all analyses. Conclusions: FDG-PET and CSF p-tau(181) levels are able to discriminate DAT in heterogeneous and unselected samples with a high accuracy. CSF p-tau(181) might be somewhat superior for a sensitive detection of patients with MCI. Copyright (C) 2010 S. Karger AG, Base

Cognitive reserve impacts on inter-individual variability in resting-state cerebral metabolism in normal aging

peer reviewedThere is a great deal of heterogeneity in the impact of aging on cognition and cerebral functioning. One potential factor contributing to individual differences among the elders is the cognitive reserve, which designates the partial protection from the deleterious effects of aging that lifetime experience provides. Neuroimaging studies examining task-related activation in elderly people suggested that cognitive reserve takes the form of more efficient use of brain networks and/or greater ability to recruit alternative networks to compensate for age-related cerebral changes. In this multi-centre study, we examined the relationships between cognitive reserve, as measured by education and verbal intelligence, and cerebral metabolism at rest (FDG-PET) in a sample of 74 healthy older participants. Higher degree of education and verbal intelligence was associated with less metabolic activity in the right posterior temporoparietal cortex and the left anterior intraparietal sulcus. Functional connectivity analyses of resting-state fMRI images in a subset of 41 participants indicated that these regions belong to the default mode network and the dorsal attention network respectively. Lower metabolism in the temporoparietal cortex was also associated with better memory abilities. The findings provide evidence for an inverse relationship between cognitive reserve and resting-state activity in key regions of two functional networks respectively involved in internal mentation and goal-directed attention

Characterization of early disease status in treatment-naive male paediatric patients with Fabry disease enrolled in a randomized clinical trial.

Trial designThis analysis characterizes the degree of early organ involvement in a cohort of oligo-symptomatic untreated young patients with Fabry disease enrolled in an ongoing randomized, open-label, parallel-group, phase 3B clinical trial.MethodsMales aged 5-18 years with complete α-galactosidase A deficiency, without symptoms of major organ damage, were enrolled in a phase 3B trial evaluating two doses of agalsidase beta. Baseline disease characteristics of 31 eligible patients (median age 12 years) were studied, including cellular globotriaosylceramide (GL-3) accumulation in skin (n = 31) and kidney biopsy (n = 6; median age 15 years; range 13-17 years), renal function, and glycolipid levels (plasma, urine).ResultsPlasma and urinary GL-3 levels were abnormal in 25 of 30 and 31 of 31 patients, respectively. Plasma lyso-GL-3 was elevated in all patients. GL-3 accumulation was documented in superficial skin capillary endothelial cells (23/31 patients) and deep vessel endothelial cells (23/29 patients). The mean glomerular filtration rate (GFR), measured by plasma disappearance of iohexol, was 118.1 mL/min/1.73 m(2) (range 90.4-161.0 mL/min/1.73 m(2)) and the median urinary albumin/creatinine ratio was 10 mg/g (range 4.0-27.0 mg/g). On electron microscopy, renal biopsy revealed GL-3 accumulation in all glomerular cell types (podocytes and parietal, endothelial, and mesangial cells), as well as in peritubular capillary and non-capillary endothelial, interstitial, vascular smooth muscle, and distal tubules/collecting duct cells. Lesions indicative of early Fabry arteriopathy and segmental effacement of podocyte foot processes were found in all 6 patients.ConclusionsThese data reveal that in this small cohort of children with Fabry disease, histological evidence of GL-3 accumulation, and cellular and vascular injury are present in renal tissues at very early stages of the disease, and are noted before onset of microalbuminuria and development of clinically significant renal events (e.g. reduced GFR). These data give additional support to the consideration of early initiation of enzyme replacement therapy, potentially improving long-term outcome.Trial registrationClinicalTrials.gov NCT00701415

Robust automated detection of microstructural white matter degeneration in Alzheimer’s disease using machine learning classification of multicenter DTI data

Diffusion tensor imaging (DTI) based assessment of white matter fiber tract integrity can support the diagnosis of Alzheimer’s disease (AD). The use of DTI as a biomarker, however, depends on its applicability in a multicenter setting accounting for effects of different MRI scanners. We applied multivariate machine learning (ML) to a large multicenter sample from the recently created framework of the European DTI study on Dementia (EDSD). We hypothesized that ML approaches may amend effects of multicenter acquisition. We included a sample of 137 patients with clinically probable AD (MMSE 20.6±5.3) and 143 healthy elderly controls, scanned in nine different scanners. For diagnostic classification we used the DTI indices fractional anisotropy (FA) and mean diffusivity (MD) and, for comparison, gray matter and white matter density maps from anatomical MRI. Data were classified using a Support Vector Machine (SVM) and a Naïve Bayes (NB) classifier. We used two cross-validation approaches, (i) test and training samples randomly drawn from the entire data set (pooled cross-validation) and (ii) data from each scanner as test set, and the data from the remaining scanners as training set (scanner-specific cross-validation). In the pooled cross-validation, SVM achieved an accuracy of 80% for FA and 83% for MD. Accuracies for NB were significantly lower, ranging between 68% and 75%. Removing variance components arising from scanners using principal component analysis did not significantly change the classification results for both classifiers. For the scanner-specific cross-validation, the classification accuracy was reduced for both SVM and NB. After mean correction, classification accuracy reached a level comparable to the results obtained from the pooled cross-validation. Our findings support the notion that machine learning classification allows robust classification of DTI data sets arising from multiple scanners, even if a new data set comes from a scanner that was not part of the training sample

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

Depression bei Demenz

Werheid K. Depression bei Demenz. In: Fellgiebel A, Hautzinger M, eds. Altersdepression. Ein interdisziplinäres Handbuch. Berlin ; Heidelberg: Springer ; 2017: 237-243

Public knowledge and attitudes about mental health in older age in Germany – Focus on dementia and late-life depression

Older people with mental disorders represent a particularly vulnerable group in the health care system. Despite this, mental disorders in this group often remain undiagnosed or are not treated in accordance with guidelines, potentially due to a lack of knowledge or unfavorable attitudes regarding mental disorders in older individuals. Therefore, in an anonymous online survey of 1,284 participants (71.8% female, mean age 52.3 ± 18.0 years), we assessed knowledge and attitudes regarding mental health in old age in general and regarding dementia and late-life depression in particular. Regression analyses were conducted to determine predictors of higher knowledge and more favorable attitudes based on sociodemographic data. On average, participants answered 11 ± 2 out of 15 of the knowledge questions correctly. Items on the prevention of dementia, late-life depression symptoms, and associated suicide risk were most likely to be answered incorrectly. Participants showed less favorable attitudes towards people living with dementia than towards people with late-life depression, and higher knowledge scores were associated with more favorable attitudes. Our findings highlight a clear need for psychoeducation in the field of dementia and late-life depression, with a special emphasis on prevention-related knowledge. Fostering knowledge in this area is highly relevant, as it might positively influence attitudes towards older people with mental disorders, in turn facilitating health care and health-promoting behavior among older people

Connectivity within the default mode network is related to working memory performance in young but not elderly healthy adults

peer reviewe

Eight-Year Follow-Up of Neuropsychiatric Symptoms and Brain Structural Changes in Fabry Disease.

Brain structural alterations and neuropsychiatric symptoms have been described repeatedly in Fabry disease, yet cognitive deficits have been shown to be only mild. Here, we aimed to investigate neuropsychiatric symptoms and brain structure longitudinally. We expected no clinically relevant increase of neuropsychiatric symptoms in parallel to increased brain structural alterations. We assessed 14 Fabry patients (46.1 ± 10.8 years) who had participated in our investigation eight years ago. Patients engaged in neuropsychiatric testing, as well as structural magnetic resonance imaging and angiography to determine white matter lesions, hippocampal volume, and the diameter of the larger intracranial arteries. While Fabry patients did not differ on cognitive performance, they showed progressive and significant hippocampal volume loss over the 8-year observation period. White matter lesions were associated with older age and higher white matter lesion load at baseline, but did not reach statistical significance when comparing baseline to follow-up. Likewise, intracranial artery diameters did not increase significantly. None of the imaging parameters were associated with the neuropsychiatric parameters. Depression frequency reduced from 50% at baseline to 21% at follow-up, but it did not reach significance. This investigation demonstrates clinical stability in cognitive function, while pronounced hippocampal atrophy is apparent throughout the 8 years. Our middle-aged Fabry patients appeared to compensate successfully for progressive hippocampal volume loss. The hippocampal volume decline indicates brain regional neuronal involvement in Fabry disease