Choice of reference area in studies of Alzheimer's disease using positron emission tomography with fluorodeoxyglucose-F18

At present, there is still no consensus on the choice of the reference area in positron emission tomography (PET) studies of Alzheimer's disease (AD). In this study, PET scans with fluorodeoxyglucose-F18 were carried out in the following groups of subjects: 47 patients with probable AD, 8 patients with mild cognitive impairment, and 15 age-similar healthy subjects. Scans normalized to the cerebral global mean (CGM), cerebellum (CBL), and the primary sensorimotor cortex (SMC). We evaluated the effect of the different count normalization procedures on the accuracy of (18)F-FDG PET to detect AD-specific metabolic abnormalities (voxel-based group comparison) and to differentiate between patient…

Harmonized benchmark labels of the hippocampus on magnetic resonance: The EADC-ADNI project

Abstract Background A globally harmonized protocol (HarP) for manual hippocampal segmentation based on magnetic resonance has been recently developed by a task force from European Alzheimer's Disease Consortium (EADC) and Alzheimer's Disease Neuroimaging Initiative (ADNI). Our aim was to produce benchmark labels based on the HarP for manual segmentation. Methods Five experts of manual hippocampal segmentation underwent specific training on the HarP and segmented 40 right and left hippocampi from 10 ADNI subjects on both 1.5 T and 3 T scans. An independent expert visually checked segmentations for compliance with the HarP. Descriptive measures of agreement between tracers were intraclass cor…

Metabolic and structural connectivity within the default mode network relates to working memory performance in young healthy adults.

Abstract Studies of functional connectivity suggest that the default mode network (DMN) might be relevant for cognitive functions. Here, we examined metabolic and structural connectivity between major DMN nodes, the posterior cingulate (PCC) and medial prefrontal cortex (MPFC), in relation to normal working memory (WM). DMN was captured using independent component analysis of [18F]fluorodeoxyglucose positron emission tomography (FDG-PET) data from 35 young healthy adults (27.1 ± 5.1 years). Metabolic connectivity, a correlation between FDG uptake in PCC and MPFC, was examined in groups of subjects with (relative to median) low (n = 18) and high (n = 17) performance on digit span backward te…

Impact of Resilience on the Association Between Amyloid-β and Longitudinal Cognitive Decline in Cognitively Healthy Older Adults

The present study aims at investigating if the association between amyloid-β and longitudinal cognitive decline in cognitively healthy elderly is modulated by resilience capacity. Resilience capacity was quantified by education, which is a common proxy of resilience and has been shown to be related to a wide range of behaviors promoting resilience. Analyses were conducted with longitudinal cognitive data from the Alzheimer's Disease Neuroimaging Initiative (ADNI). 276 cognitively healthy older individuals (≥56 years) were included in the study. Baseline amyloid pathology was quantified using CSF amyloid-β 1-42 measurements. Longitudinal cognitive decline was assessed using ADAS13, Clinical …

Increased CSF APPs-  levels in patients with Alzheimer disease treated with acitretin

Objective: We investigated induction of α-secretase A disintegrin and metalloprotease 10 (ADAM10) by the synthetic retinoid acitretin (Neotigason; Actavis, Munchen-Riem, Germany) in patients with mild to moderate Alzheimer disease (AD) via measurement of CSF content of α-secretase–derived amyloid precursor protein (APPs-α). Methods: Twenty-one patients clinically diagnosed with mild to moderate AD received acitretin (30 mg per day) or placebo in a 4-week double-blind study. Primary endpoint was the difference of CSF APPs-α ratios calculated from the APPs-α levels after treatment and at baseline. We monitored safety and tolerability of the treatment. In addition, we assessed biomarkers such …

The Impact of Age on the Association Between Physical Activity and White Matter Integrity in Cognitively Healthy Older Adults

Cognition emerges from coordinated processing among distributed cortical brain regions, enabled through interconnected white matter networks. Cortical disconnection caused by age-related decline in white matter integrity (WMI) is likely to contribute to age-related cognitive decline. Physical activity (PA) has been suggested to have beneficial effects on white matter structure. However, its potential to counteract age-related decline in WMI is not yet well established. The present explorative study analyzed if PA was associated with WMI in cognitively healthy older adults and if this association was modulated by age. Forty-four cognitively healthy older individuals (aged 60–88 years) with d…

CNS manifestations of Fabry's disease

Summary Background Fabry's disease is a rare hereditary lysosomal storage disease with multiorgan involvement. Deficiency of α-galactosidase A activity leads to accumulation of neutral glycosphingolipids, especially in vascular endothelial and smooth-muscle cells. Along with progressive renal and cardiac dysfunction, stroke is a major and often life-threatening burden of the disease. Cerebral vasculopathy, confirmed by neuropathological, neuroradiological, and functional studies, occurs commonly and leads to ischaemic cerebrovascular events at an early age. Recent developments Fabry's disease is an X-linked disease and women have been regarded as only mildly affected carriers. However, rese…

Training labels for hippocampal segmentation based on the EADC-ADNI harmonized hippocampal protocol

Abstract Background The European Alzheimer's Disease Consortium and Alzheimer's Disease Neuroimaging Initiative (ADNI) Harmonized Protocol (HarP) is a Delphi definition of manual hippocampal segmentation from magnetic resonance imaging (MRI) that can be used as the standard of truth to train new tracers, and to validate automated segmentation algorithms. Training requires large and representative data sets of segmented hippocampi. This work aims to produce a set of HarP labels for the proper training and certification of tracers and algorithms. Methods Sixty-eight 1.5 T and 67 3 T volumetric structural ADNI scans from different subjects, balanced by age, medial temporal atrophy, and scanner…

Corrigendum to ‘State dependent posterior hippocampal volume increases in patients with major depressive disorder’ [J. Affect. Disord. 135 (1–3) (2011) 405–409]

Structural integrity of the corpus callosum predicts long-term transfer of fluid intelligence-related training gains in normal aging

Although cognitive training usually improves cognitive test performance, the capability to transfer these training gains into respective or functionally related cognitive domains varies significantly. Since most studies demonstrate rather limited transfer effects in older adults, aging might be an important factor in transfer capability differences. This study investigated the transfer capability of logical reasoning training gains to a measure of Fluid Intelligence (Gf) in relation to age, general intelligence, and brain structural integrity as measured by diffusion tensor imaging. In a group of 41 highly educated healthy elderly, 71% demonstrated successful transfer immediately after a 4-…

Fatigue in SLE: diagnostic and pathogenic impact of anti-N-methyl-D-aspartate receptor (NMDAR) autoantibodies.

ObjectivesWe explored the impact of circulating anti-N-methyl-D-aspartate receptor (NMDAR) antibodies on the severity of fatigue in patients with systemic lupus erythematosus (SLE).MethodsSerum samples of 426 patients with SLE were analysed for the presence of antibodies to the NR2 subunit of the NMDAR. In parallel, the severity of fatigue was determined according to the Fatigue Scale for Motor and Cognitive functions questionnaire. In a subgroup of patients with SLE, the hippocampal volume was correlated with the levels of anti-NR2 antibodies. Isolated immunoglobulin G from patients with anti-NR2 antibodies were used for murine immunohistochemical experiments and functional assays on neuro…

Quality of Life in Dementia: Impact of Cognition and Insight on Applicability of the SF-36

Comparability of measures of quality of life in dementia and in other diagnostic groups, such as mild cognitive impairment, normal aging, or other diseases, is highly desirable. However, the impact of cognitive deficits and impaired insight on applicability and validity of generic instruments is sparsely studied.Sixty patients with dementia [38 women; age: mean (SD) = 78.7 (6.4) years; Mini-Mental State Examination (MMSE): mean (SD) = 20.2 (6.0)] recruited as part of the start-modem study, a multicenter care research study in Germany, completed the generic instrument SF-36 and the specific instrument Quality of Life-Alzheimer's Disease (QOL-AD).QOL-AD self-rating scores [mean (SD) = 32.8 (5…

Metabolic connectivity as index of verbal working memory

Positron emission tomography (PET) data are commonly analyzed in terms of regional intensity, while covariant information is not taken into account. Here, we searched for network correlates of healthy cognitive function in resting state PET data. PET with [18F]-fluorodeoxyglucose and a test of verbal working memory (WM) were administered to 35 young healthy adults. Metabolic connectivity was modeled at a group level using sparse inverse covariance estimation. Among 13 WM-relevant Brodmann areas (BAs), 6 appeared to be robustly connected. Connectivity within this network was significantly stronger in subjects with above-median WM performance. In respect to regional intensity, i.e., metaboli…

Gruppentherapeutische Frühintervention für Patienten im Frühstadium der Alzheimererkrankung und deren Angehörige - Eine Pilotstudie

Subject Pilot study on an early-interventional group therapy for patients with incipient Alzheimer disease and their relatives. The present study investigates whether scientific progress in terms of earlier time of diagnostic certainty can be used for psychoeducation, maintenance of positive activities and prevention of comorbid depressive episodes. Methods 12 patients (66.8 +/- 5.8 years, MMSE 24.0 +/- 4.0) together with 12 relatives have been treated with a bi-weekly group therapy program. Results For the patients treatment resulted in reduced anxiety, anergia and withdrawal, for their relatives reduced sleep disturbances, irascibility, and aggressiveness have been found. Only one of the …

Functional relevance and diagnostic utility of ROI-based and voxel-based diffusion-tensor imaging analyses in mild cognitive impairment

Association of Structural Global Brain Network Properties with Intelligence in Normal Aging

Higher general intelligence attenuates age-associated cognitive decline and the risk of dementia. Thus, intelligence has been associated with cognitive reserve or resilience in normal aging. Neurophysiologically, intelligence is considered as a complex capacity that is dependent on a global cognitive network rather than isolated brain areas. An association of structural as well as functional brain network characteristics with intelligence has already been reported in young adults. We investigated the relationship between global structural brain network properties, general intelligence and age in a group of 43 cognitively healthy elderly, age 60–85 years. Individuals were assessed cross-sect…

In vivo imaging of dopamine receptors in a model of temporal lobe epilepsy

Alterations in dopamine neurotransmission in animal models of epilepsies have been frequently demonstrated using invasive neuroscience or ex vivo techniques. We aimed to test whether corresponding alterations could be detected by noninvasive in vivo brain imaging with positron emission tomography (PET) in the chronic phase of the rat pilocarpine model of temporal lobe epilepsy.Six pilocarpine-treated Wistar rats exhibiting spontaneous recurrent seizures and nine control rats were studied with PET using [(18)F]-fallypride, a high-affinity dopamine D(2/3) receptor ligand. Parametric images of [(18)F]-fallypride specific binding were calculated using a reference tissue method, and the two grou…

Differential associations of age with volume and microstructure of hippocampal subfields in healthy older adults

Hippocampal atrophy in advanced healthy aging has frequently been reported. However, the vulnerability of different hippocampal subfields to age-related atrophy is still a source of debate. Moreover, the association of age with the microstructural integrity of subfields is largely unknown. In this study, we investigated the associations between age and volume as well as microstructural integrity of hippocampal subfields using a three-dimensional (3D) surface mapping approach. Forty-three healthy older adults spanning the age range from 60 to 85 years underwent T1-weighted and diffusion-tensor imaging. Analyses demonstrated an association of age with hippocampal volume predominantly in the m…

Prävention im Alter – Was ist gesichert?

Herz- und Kreislauferkrankungen sind die haufigsten Todesursachen in Deutschland. Da das Alter fur die meisten Herz- und Kreislauferkrankungen ein eigenstandiger und unabhangiger Risikofaktor ist, sind alte Menschen hiervon besonders betroffen, wobei das Risiko mit steigendem Lebensalter sogar exponentiell ansteigt. Dies gilt v. a. fur den Bluthochdruck, der wiederum der wichtigste Risikofaktor fur die koronare Herzkrankheit (KHK; Herzkranzgefaserkrankung), die Herzinsuffizienz (Herzschwache) sowie den Schlaganfall ist. Ein weiterer Risikofaktor ist der Diabetes mellitus, der insbesondere das Risiko fur die Entwicklung einer Herzinsuffizienz erhoht, aber auch fur die anderen genannten Krank…

Von der symptomatischen zur kausalen Therapie?

Until today the pharmacological therapy of Alzheimer’s disease (AD) is still limited to symptomatic temporary improvement or stabilization of cognitive performance and activities of daily living, and the reduction of neuropsychiatric symptoms of the disease. Available symptomatic treatment options are the acetylcholinesterase inhibitors (ACh-I) donepezil, galantamine, rivastigmine, and the partial N-Methyl-D-Aspartat-(NMDA)-antagonist memantine. Further substances with symptomatic targets, especially selective acetylcholine and histamine receptors, are currently under development. Numerous of disease-modifying substances mainly targeting components of the amyloidogenic pathway of AD are pre…

Functional implications of hippocampal volume and diffusivity in mild cognitive impairment.

Abstract Hippocampal atrophy has been related to mild cognitive impairment (MCI) and early Alzheimer disease (AD), but the diagnostic significance of cross-sectionally determined hippocampal volumes is still ambiguous. Diffusion-Tensor-Imaging (DTI) in MCI patients revealed an association of microstructural changes in hippocampal areas with verbal memory decline. MRI volumetry and DTI were combined to investigate 18 MCI patients attending a memory clinic, and 18 carefully age- and gender-matched healthy controls. Neuropsychological testing, high resolution T1-weighted volume MRI scans, and DTI scans with regions-of-interest in hippocampal areas were applied. Left hippocampal volume was sign…

Validating the DemTect with 18-Fluoro-2-Deoxy-Glucose Positron Emission Tomography as a Sensitive Neuropsychological Screening Test for Early Alzheimer Disease in Patients of a Memory Clinic

<i>Objectives:</i> The first study to validate the diagnostic value of the DemTect, a short neuropsychological screening test for dementia (8–10 min), using 18-fluoro-2-deoxy-glucose positron emission tomography (FDG-PET) in patients of a memory clinic. <i>Methods:</i> DemTect results were compared to the clinical diagnosis and to FDG-PET as a reference method for the early in vivo detection of Alzheimer’s disease (AD). <i>Results:</i> 38 patients (age 65.2 ± 9.8 years, 16 men, 22 women) were investigated using clinical standard examination, FDG-PET, and cranial magnetic resonance imaging. According to NINCDS-ADRDA and Petersen’s criteria, 18 patients had…

Stage-dependent agreement between cerebrospinal fluid proteins and FDG-PET findings in Alzheimer's disease.

Cerebral hypometabolism and abnormal levels of amyloid beta (Aβ), total (t-tau) and phosphorylated tau (ptau) proteins in cerebrospinal fluid (CSF) are established biomarkers of Alzheimer's disease (AD). We examined the agreement between these biomarkers in a single center study of patients with AD of severity extending over a wide range. Forty seven patients (MMSE 21.4 ± 3.6, range 13-28 points) with incipient and probable AD underwent positron emission tomography with [18F]-fluorodeoxyglucose (FDG-PET) and lumbar puncture for CSF assays of Aβ1-42, p-tau181, and t-tau. All findings were classified as either positive or negative for AD. Statistical analyses were performed for the whole samp…

MRI- and PET-Based Imaging Markers for the Diagnosis of Alzheimer’s Disease

Imaging markers of early neurodegeneration play an important role for the definition of predementia and preclinical stages of Alzheimer’s disease according to the newly proposed diagnostic consensus c

1012 – Evaluation of a risk-scale for anticholinergic side-effects in elderly psychiatric inpatients

Introduction Many commonly prescribed drugs have anticholinergic properties which can induce side-effects e.g. delirium, especially in an ageing brain with increased sensitivity. Risk-assessment before starting therapy may prevent such sideeffects. Objectives We rated anticholinergic pharmacological properties of prescribed medication and compared the theoretical risk with side-effects in clinical practice. Aims The scale should improve the safety of pharmacotherapy in gerontopsychiatry. Methods Based on five publications that considered anticholinergic properties of drugs, a risk-scale was established. Riskpoints for all drugs were summarized to a total score. Patients were selected from T…

Basilar Artery Diameter Is a Potential Screening Tool for Fabry Disease in Young Stroke Patients

<i>Background:</i> Fabry disease (FD) is a rare hereditary lysosomal storage disease that has been highlighted as a possible etiology of stroke at a young age. Enlarged basilar artery diameters (BADs) have been demonstrated in FD, and we hypothesize that they might be useful for the screening of FD in young stroke patients. The aim of this study was to compare BADs of young stroke patients without FD to those of FD patients and of healthy age-matched controls. <i>Methods:</i> BADs were measured using MR angiography in 3 age- and gender-matched groups: 25 FD patients (aged 36.5 ± 11.0 years), 26 non-FD stroke patients and 20 healthy controls. <i>Results:</i&g…

Ultrastructural Hippocampal and White Matter Alterations in Mild Cognitive Impairment: A Diffusion Tensor Imaging Study

Mild cognitive impairment (MCI) is considered to be a transitional stage between normal aging and dementia. In Alzheimer’s disease (AD), white matter structural pathology is due to Wallerian degeneration and central angiopathy. However, in MCI patients, the presence and extent of white matter alterations as a possible correlate of impaired memory function and as predictor of subsequent progression to AD is not clarified yet. Diffusion tensor imaging (DTI) reveals the ultrastructural integrity of cerebral white matter tracts. Therefore, it could detect pathological processes that modify tissue integrity in patients with MCI. In our prospective study, conventional and diffusion tensor MR scan…

Predicting conversion to dementia in mild cognitive impairment by volumetric and diffusivity measurements of the hippocampus.

In our prospective study of diffusion tensor imaging (DTI), we measured hippocampal mean diffusivity (MD) and volumes in amnestic mild cognitive impairment (MCI). Thirteen MCI patients were followed-up by clinical assessment over a mean 112-year period. MCI patients who converted to dementia (6 of 13) during the observation period had slightly elevated left hippocampal mean diffusivity at baseline compared with MCI patients who remained clinically stable. Hippocampal volumes as well as baseline verbal memory and MMSE did not differ significantly between stable MCI patients and converters. Hippocampal diffusivity was superior to hippocampal volumes for prediction of conversion to dementia in…

Color-coded diffusion-tensor-imaging of posterior cingulate fiber tracts in mild cognitive impairment.

Abstract Different processes like microvascular dysfunction, free radical toxicity, β-amyloid deposits, and Wallerian degeneration can cause functionally relevant disturbances of cerebral neuronal networks by myelin degeneration. Color-coded diffusion-tensor-imaging (ccDTI) allows the structural identification and quantification of myelinated fiber tracts. Particularly, posterior cingulate fiber tracts, which are regarded as important neuronal substrates of the network representing memory processing can be localized only imprecisely by conventional magnetic resonance imaging techniques. The posterior cingulate bundles were assessed by ccDTI in 17 patients with amnestic mild cognitive impair…

Experimental evidence for a motivational origin of cognitive impairment in major depression.

BackgroundDiagnostic criteria and empirical evidence support the existence of cognitive deficits in depression. However, depressed mood, loss of interest and low self-efficacy might influence cognitive performance.MethodGoal-setting instructions were used to promote motivation in depressed patients and control subjects during neuropsychological assessment. The resulting performance was compared with performance using standard instructions. Sixty in-patients with non-psychotic unipolar depression and 60 age- and education-matched healthy control subjects were assessed with standard neuropsychological tests [the Auditory Verbal Learning Test (AVLT), the Digit Symbol Test (DST), the Regensburg…

Therapeutic Drug Monitoring for Patients With Alzheimer Dementia to Improve Treatment With Donepezil

BACKGROUND Aiming to verify that therapeutic drug monitoring has the potential to optimize treatment with acetylcholine esterase inhibitors of patients with Alzheimer dementia, this study investigated whether serum concentrations of donepezil are associated with clinical improvement. METHODS Clinical improvement was measured using the clinical global impression (CGI) scale, and donepezil concentrations were measured in serum by a high-performance liquid chromatographic method with spectrophotometric detection. RESULTS In total, 206 serum samples from 106 patients (49.5% female) were retrospectively available for analysis. Patients included were treated under everyday conditions. Their mean …

Erfasst der FBT lokale visuelle Informationsverarbeitung bei Autismus-Spektrum-Störungen?

Fragestellung: Der kognitive Phänotyp von Autismus-Spektrum-Störungen (ASS) ist unter anderem durch eine Neigung zu lokaler Informationsverarbeitung (schwacher zentraler Kohärenz) gekennzeichnet. Es wurde untersucht, ob der Fragmentierte Bilder Test (FBT) diese Präferenz zu erfassen vermag. Methodik: Die FBT-Leistungen 15 autistischer, 16 depressiver und 16 schizophrener Patienten sowie von 16 typisch entwickelten Kontrollpersonen wurden verglichen. Mit dem Embedded Figures Test (EFT) und dem Mosaiktest (MT) wurden ebenfalls validierte Tests lokaler Informationsverarbeitung erhoben. Ergebnisse: Patienten mit ASS zeigten eine Präferenz für lokale Informationsverarbeitung, d. h. Beeinträchti…

Association between cingulum bundle structure and cognitive performance: an observational study in major depression.

AbstractBackgroundMajor depression can be regarded as a systemic neurobehavioral disorder resulting from dysfunction of the limbic-cortical networks. The cingulum bundle represents a major association fiber tract of those networks. The aim of our study was to determine the association of brain structural tissue markers of the cingulum bundle and cognitive function in patients with major depression.MethodsRegion-of-interest-based analyses of the middle-anterior and middle-posterior cingulum bundle fractional anisotropy (FA) and mean diffusivity (MD) using color-coded diffusion-tensor imaging and neuropsychological assessment in 14 patients with major depression.ResultsFA of the middle-anteri…

IC‐P‐050: The European diffusion tensor imaging study in dementia (EDSD): Physical phantom study and multimodal clinical study on the diagnosis of Alzheimer's disease

State dependent posterior hippocampal volume increases in patients with major depressive disorder.

Abstract Background The hippocampal formation has been implicated in etiology and therapy response in major depressive disorder (MDD). However, prospective longitudinal studies investigating volumes in hippocampal subregions and their association with clinical findings are still lacking. Methods Global and regional hippocampal volumes and neuropsychological performance were assessed longitudinally in 15 young patients with unipolar early onset MDD who responded to therapy and 13 matched healthy control subjects. Results Although volumes at baseline did not differ between groups, patients with MDD showed significant posterior hippocampal volume increases during the treatment course (mean obs…

Enzyme Replacement Therapy Stabilized White Matter Lesion Progression in Fabry Disease

<b><i>Background:</i></b> The central nervous system manifestations in Fabry disease (FD) include progressive white matter lesions (WMLs) and stroke. Due to progressive microvascular involvement, men and women with FD over 35 years of age develop WMLs. Moreover, the prevalence of stroke has been estimated to be 12 times higher in FD compared with the general population. Enzyme replacement therapy (ERT) is available and has shown beneficial effects on renal, cardiac, and peripheral nerve function in FD, but the ERT effect on the progression of WMLs, or the reduction in cerebrovascular events, remains unknown. <b><i>Methods:</i></b> The WML burd…

P2‐401: Reliability of DTI: A european multicenter study

Feasibility and utility of a cognitive screening for risk stratification in hospitalized older patients

OBJECTIVES To determine whether the Mini-Cog can be applied by nursing staff to hospitalized elderly patients for cognitive impairment associated risk stratification. METHODS This explorative prospective multicenter cohort study was carried out among 2522 patients aged 70 and older, hospitalized due to physical illness in eight hospitals in Rhineland-Palatinate, Germany. All patients were asked to conduct the Mini-Cog at the day of admission and were clustered into low-performance, intermediate-performance, and good-performance categories by trained nursing staff and two experienced geronto-psychiatrists as gold standard. Complications in the course of the treatment were monitored. RESULTS …

Association of elevated phospho-tau levels with alzheimer-typical 18F-Fluoro-2-Deoxy-D-Glucose positron emission tomography findings in patients with mild cognitive impairment

Abstract Background Mild cognitive impairment is considered to be a transitional stage between normal aging and dementia. Phosphorylated tau protein in cerebrospinal fluid and even more decrements of cerebral glucose metabolism in parietal, temporal, or cingulate regions have shown favorable specificity for the diagnosis of Alzheimer dementia and could be useful supplementary tools to determine Alzheimer pathology in early stages. Methods We measured cerebrospinal fluid tau phosphorylated at threonine 181 protein, cerebrospinal fluid total tau, and cerebral glucose metabolism using 18F-fluoro-2-deoxy-D-glucose positron emission tomography in 16 patients with mild cognitive impairment and ag…

Einführung – Charakteristik des Alters und Demografie

Alter ist zunachst einmal ganz wertfrei eine chronologische Angabe. Nicht selten werden Personen oder Gegenstande bereits bei ihrer Nennung, z. B. durch Angabe ihres Entstehungsjahrgangs mit einer Altersangabe konnotiert. Auch dies mag zunachst neutral erscheinen, erhalt jedoch relativ rasch durch begleitende Attribute einen wertenden Charakter. Dies kann sowohl eine negative Charakterisierung, z. B. veraltet bedeuten, aber auch durchaus positive Konnotationen durch Begriffe wie gereift oder klassisch enthalten.

Cerebrospinal Fluid Tau Protein Levels and <sup>18</sup>F-Fluorodeoxyglucose Positron Emission Tomography in the Differential Diagnosis of Alzheimer’s Disease

<i>Aims:</i> In this study, we aimed to compare cerebrospinal fluid (CSF) levels of total tau (t-tau), phosphorylated tau (p-tau<sub>181</sub>) and positron emission tomography with <sup>18</sup>F-fluorodeoxyglucose (FDG-PET) in the differential diagnosis of Alzheimer’s disease (AD) under clinical conditions. <i>Method:</i> 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, sensitiv…

Psychiatrische und neuropsychologische Auffälligkeiten bei Patienten mit Morbus Fabry: Literaturübersicht

Fabry Disease (FD) is an X-linked lysosomal storage disorder (prevalence about 1 : 100 000) caused by a genetic defect associated with a lack of alpha-galactosidase A (alpha-GAL) enzyme activity. As a consequence, neutral glycosphingolipides can not be cleaved and metabolized, and accumulate in lysosomes of several tissues, particularly in vascular endothelium and smooth muscle cells. The most prominent symptoms comprise pain attacks and acroparesthesia, angiokeratoma, corneal opacity, renal and cardiac dysfunction, hypo- and anhidrosis, gastrointestinal symptoms, and cerebrovascular dysfunction with vertigo, headache, and cerebral ischemia. Characteristic symptoms of FD can occur in male a…

Diagnostic utility of hippocampal size and mean diffusivity in amnestic MCI

Hippocampus atrophy is a frequent finding in mild cognitive impairment (MCI), whereas diffusion-tensor-imaging (DTI) has demonstrated its value to detect subtle brain tissue changes in several neuropsychiatric diseases including MCI. To compare the diagnostic accuracy of both methods, high resolution MRI scans for hippocampus volumetry, and co-registered DTI-scans for ROI-based mean diffusivity (MD) and fractional anisotropy (FA) were carried out in 18 patients with amnestic MCI (7 females, age 67.3+/-8.7 years, MMSE 25.2+/-2.2) and 18 controls (age 66.9+/-9.0 years, MMSE 28.7+/-1.0). Diagnostic properties of normalized hippocampus volume (HV) and DTI measures with regard to MCI status were…

CSF APPsα and Phosphorylated Tau Protein Levels in Mild Cognitive Impairment and Dementia of Alzheimer's Type

We exploratively measured APPs alpha, a secreted fragment of the non-amyloidogenic cleavage of amyloid precursor protein via a-secretase, and tau protein phosphorylated at threonine 181 (p tau) in the cerebrospinal fluid of 10 patients with mild cognitive impairment, 20 patients with dementia of Alzheimer's type, and 10 controls. Cerebrospinal fluid APPs alpha and p tau levels were correlated with cognitive performance. P tau levels were significantly elevated in mild cognitive impairment and in patients with dementia of Alzheimer's type, APPs alpha levels were significantly reduced in patients with dementia of Alzheimer's type compared to the controls. APPs alpha levels were associated wit…

Neuropsychiatric symptoms and brain structural alterations in Fabry disease

Background:  Neuropsychiatric symptoms (NPS), mainly cognitive deficits up to dementia and depressive syndromes have been described repeatedly in Fabry disease (FD). However, examinations regarding the pattern, extent, and frequency of the NPS in FD are still lacking. Moreover, the relationship between NPS and brain structural alterations in FD is unknown. The aim of this study was 1) to characterize NPS in a relatively large cohort of adult subjects with FD, and 2) to explore the association of cognitive performance and depressive syndromes with the FD-typical brain structural findings. Methods:  Twenty-five Fabry patients (age 36.5 ± 11.0) with mild to moderate disease involvement and 20 …

Association of basal forebrain volumes and cognition in normal aging.

The basal forebrain cholinergic system (BFCS) is known to undergo moderate neurodegenerative alterations during normal aging and severe atrophy in Alzheimer's disease (AD). It has been suggested that functional and structural alterations of the BFCS mediate cognitive performance in normal aging and AD. But, it is still unclear to what extend age-associated cognitive decline can be related to BFCS in normal aging. We analyzed the relationship between BFCS volume and cognition using MRI and a comprehensive neuropsychological test battery in a cohort of 43 healthy elderly subjects spanning the age range from 60 to 85 years. Most notably, we found significant associations between general intell…

Therapie des Apathie-Syndroms bei Alzheimer-Demenz

Zusammenfassung: Das Apathie-Syndrom lässt sich auffassen als ein Mangel an selbst-initiiertem Verhalten (motorisch, sprachlich, kognitiv, affektiv). Apathie stellt das häufigste neuropsychiatrische Symptom der Alzheimer-Demenz dar und kann in Verbindung gebracht werden mit stärker beeinträchtigter Alltagsfunktion, rascherer Progredienz des kognitiven Abbaus und deutlicher reduzierter Lebensqualität der betreuenden Angehörigen. Trotz weitestgehend fehlender Evidenzbasierung gibt es ein Reihe therapeutischer Optionen, die in der vorliegenden Übersichtsarbeit zusammengefasst und bewertet werden. Nach Ausschluss eines depressiven Syndroms stehen hierbei die Unterstützung der Betreuenden durch…

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

There 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 elderly 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 exploratory multi-center study, we examined the relationships between cognitive reserve, as measured by educa…

Cerebrovascular involvement in fabry disease: current status of knowledge.

Fabry disease (FD) is a rare and highly debilitating lysosomal storage disorder that results from a total lack of, or deficiency in, the enzyme α-galactosidase A (α-Gal A) because of mutations in the GLA gene.1 FD is inherited as an X-linked trait; many of the male patients develop a classic severe phenotype with early onset of symptoms, whereas heterozygous females exhibit phenotypes ranging from asymptomatic to major involvement of vital organs.2 Most families inherit private mutations; to date, >600 mutations have been identified and are listed in the online FD database (Fabry-database.org).3 The deficiency in α-Gal A causes the accumulation of globotriaosylceramide (GL-3; also abbreviat…

SPM-based count normalization provides excellent discrimination of mild Alzheimer's disease and amnestic mild cognitive impairment from healthy aging☆

Statistical comparisons of [(18)F]FDG PET scans between healthy subjects and patients with Alzheimer's disease (AD) or amnestic mild cognitive impairment (aMCI) using Statistical Parametric Mapping (SPM) usually require normalization of regional tracer uptake via ROIs defined using additional software. Here, we validate a simple SPM-based method for count normalization. FDG PET scans of 21 mild, 15 very mild AD, 11 aMCI patients and 15 age-matched controls were analyzed. First, we obtained relative increases in the whole patient sample compared to controls (i.e. areas relatively preserved in patients) with proportional scaling to the cerebral global mean (CGM). Next, average absolute counts…

Hausarztbasierte Demenzversorgung: Effektivität früher psychosozialer Beratung der Angehörigen

Hintergrund und Fragestellung: Bei der Versorgung von Patienten mit Demenzerkrankungen besitzen Psychoedukation und professionelle Unterstutzung betreuender Angehoriger unstrittig einen hohen Stellenwert. Im Rahmen eines hausarztbasierten Versorgungsansatzes ging vorliegende Untersuchung der Frage nach, ob eine professionelle psychosoziale Beratung der betroffenen Familien – zeitnah zur Demenzdiagnose – das Risiko fur Depressionen der betreuenden Angehorigen reduziert. Patienten und Methodik: 42 Patienten mit diagnostizierter Demenz und ihre betreuenden Angehorigen nahmen an der prospektiven, randomisierten Studie und der Nachuntersuchung nach 18 Monaten teil. 29 Patienten erhielten zeitnah…

Apolipoprotein A1 in Cerebrospinal Fluid Is Insufficient to Distinguish Alzheimer's Disease from Other Dementias in a Naturalistic, Clinical Setting.

Apolipoprotein A1 (ApoA1) is the major protein component of the high-density lipoprotein and involved in cholesterol transport. Disruption of cholesterol homeostasis has been identified as a contributing factor for Alzheimer's disease (AD). Moreover, polymorphisms of ApoA1 have been associated with higher risk of disease onset and cognitive decline. Therefore, ApoA1 has been suggested as a biomarker in AD. Here, we tested a small cohort of AD and non-AD dementia patients and measured levels of ApoA1 in cerebrospinal fluid. Our results indicate that ApoA1 might not be applicable to distinguish AD from other forms of dementia.

Increased hippocampal head diffusivity predicts impaired episodic memory performance in early Alzheimer's disease

Recent neuroanatomical and functional neuroimaging studies indicate that the anterior part of the hippocampus, rather than the whole structure, may be specifically involved in episodic memory. In the present work, we examined whether anterior structural measurements are superior to other regional or global measurements in mapping functionally relevant degenerative alterations of the hippocampus in Alzheimer's disease (AD). Twenty patients with early AD (MMSE 25.7+/-1.7) and 18 healthy controls were studied using magnetic resonance and diffusion-tensor imaging. Using a regions-of-interest analysis, we obtained volumetric and diffusivity measures of the hippocampal head and body-tail-section …

Detection of Depression in Acute Schizophrenia: Sensitivity and Specificity of 2 Standard Observer Rating Scales

Objective: To compare the psychometric properties of the Calgary Depression Rating Scale (CDRS) and the Hamilton Depression Rating Scale (HDRS) for severity assessment of depression in acute schizophrenia. Method: During clinical routine treatment, we investigated 119 inpatients with acute schizophrenia, using the CDRS, the HDRS, and a global 4-point Depression Severity Scale (DEP-SEV). We compared CDRS and HDRS sum scores regarding their diagnostic accuracy, with global severity of depression as the criterion. We estimated sensitivity and specificity on the basis of receiver operating characteristic curves. Results: According to global clinical ratings (DEP-SEV), 31% of patients had no dep…

Dyadic Wind of Change: New Approaches to Improve Biopsychological Stress Regulation in Patients with Dementia and Their Spousal Caregivers

Patients with dementia (PWD) and their caregivers experience long-term stress, leading to accelerated disease progression and to stress-related morbidity. Previous research focused on intrapersonal biopsychological stress responses. Quite recently, dyadic interrelations between caregivers and PWD and their effects on stress and caregiver burden have received more attention, giving rise to dyadic intervention studies. However, while it is of importance to consider both the patient and the caregiver from a dyadic point of view, evaluation of these dyadic interventions considering underlying mechanisms is still lacking. We therefore extend the current literature on dyadic processes between PWD…

Resilience in Informal Caregivers of People Living with Dementia in the Face of COVID-19 Pandemic-Related Changes to Daily Life

Abstract. Informal caregivers of people living with dementia (PwD) are at increased risk for the development of stress-related physical and mental illness. Nevertheless, because of differing resilience, they show interindividual differences in their ability to cope. Particularly during the COVID-19 pandemic, with the associated pandemic control measures and pandemic-related changes to daily life, resilience might be further challenged, and stress might consequently increase. Therefore, we review the evidence on informal caregivers’ experience during the COVID-19 pandemic regarding effects of the pandemic control measures on (a) the caregiver’s health, (b) the care recipient’s health, (c) th…

The EADC-ADNI Harmonized Protocol for manual hippocampal segmentation on magnetic resonance : Evidence of validity

BackgroundAn international Delphi panel has defined a harmonized protocol (HarP) for the manual segmentation of the hippocampus on MR. The aim of this study is to study the concurrent validity of the HarP toward local protocols, and its major sources of variance.MethodsFourteen tracers segmented 10 Alzheimer's Disease Neuroimaging Initiative (ADNI) cases scanned at 1.5 T and 3T following local protocols, qualified for segmentation based on the HarP through a standard web-platform and resegmented following the HarP. The five most accurate tracers followed the HarP to segment 15 ADNI cases acquired at three time points on both 1.5 T and 3T.ResultsThe agreement among tracers was relatively low…

Functional relevant loss of long association fibre tracts integrity in early Alzheimer's disease.

Abstract The aim of our study was to quantify the structural integrity of the long association fibre tracts in early Alzheimer's disease (AD) and to correlate the findings with the cognitive performance of the patients. We conducted region-of-interest-based analyses of color-coded diffusion-tensor imaging in 12 patients with early AD (age 69.8 ± 8.0 years; MMSE 25.3 ± 1.8) and 16 age- and education-matched healthy controls. Early AD patients showed significantly decreased fractional anisotropy (FA) of the cingulate bundles and the inferior fronto-occipital fascicles bilaterally, whereas FA values of the superior longitudinal fascicles (second division) did not differ significantly between p…

FDG-PET and CSF phospho-tau for prediction of cognitive decline in mild cognitive impairment

Specific patterns of cortical glucose metabolism disturbances and increased CSF phospho-tau (p-tau(181)) concentrations could be demonstrated to predict cognitive decline and shift to dementia in amnestic mild cognitive impairment (MCI). But comparisons of both diagnostic tools have not been undertaken so far. The aim of the study was to compare (18)F-fluoro-2-deoxy-d-glucose positron emission tomography (FDG-PET) findings and CSF phospho-tau (p-tau(181)) measurements in the prediction of cognitive deterioration and conversion to dementia in MCI. During follow-up (mean 19 months) eight of 16 patients (50%) showed progressive cognitive decline, and four patients shifted to dementia. Patholog…

Gruppentherapeutische Behandlung bei beginnender dementieller Erkrankung

Es liegen nur wenige Studien zur Wirksamkeit von Gruppenpsychotherapie bei beginnenden dementiellen Erkrankungen vor. Deshalb wurde die Arbeit in den größeren Rahmen der empirischen Evidenz von Psychotherapie bei Demenz gestellt. Zusätzlich wurden die Wirkfaktoren der Gruppentherapie (Yalom, 2007) theoretisch auf die Symptome und Probleme der Patienten mit beginnender Demenz bezogen und die therapeutischen Ansatzpunkte wurden abgeleitet. Dieses theoretische Potential der Gruppentherapie wurde mit den Ergebnissen der vorliegenden Studien zu Gruppentherapie bei Demenz und beginnender dementieller Erkrankung abgeglichen. Aus den Gemeinsamkeiten und Unterschieden wurden erste Hinweise auf die …

Introduction and Psychometric Validation of the Resilience and Strain Questionnaire (ResQ-Care)— A Scale on the Ratio of Informal Caregivers' Resilience and Stress Factors

Background: Informal caregivers are a particularly vulnerable population at risk for adverse health outcomes. Likewise, there are many scales available assessing individual caregiver burden and stress. Recently, resilience in caregivers gained increasing interest and scales started to assess resilience factors as well. Drawing on a homeostatic model, we developed a scale assessing both caregivers' stress and resilience factors. We propose four scales, two covering stress and two covering resilience factors, in addition to a sociodemographic basic scale. Based on the stress:resilience ratio, the individual risk of adverse health outcomes and suggestions for interventions can be derived.Metho…

“Abnormal Response to Negative Feedback”

Zusammenfassung: Es wurden alkoholabhängige Patienten unter Stressbedingungen neuropsychologisch untersucht. Fragestellung: Zeigt sich wie bei depressiven Patienten eine abnorme Reaktion auf negative Rückmeldung oder gar eine generelle Stressanfälligkeit? Die alkoholabhängigen Patienten wurden in der Testbatterie zur Aufmerksamkeitsprüfung (TAP) nach negativer Rückmeldung tendenziell langsamer und die Kontrollpersonen tendenziell schneller. Insgesamt ergab sich ein signifikanter Unterschied in Visuellem Scanning und Reaktionswechsel. Damit ist die “abnormal response to negative feedback” nicht spezifisch für depressive Patienten. Unter 90 dBA Lärm als Stressor zeigten sich dagegen keine Ef…

Brain structural alterations in Fabry disease: ROI-based and voxel-based analyses of diffusion tensor imaging parameters

Pathophysiologische Aspekte hirnstruktureller Veränderungen bei Morbus Fabry: Literaturübersicht

Fabry Disease (FD) is a rare X-linked lysosomal storage disorder caused by deficiency of alpha-galactosidase A (alpha-GAL) enzyme activity. Neutral glycosphingolipides (esp. Gb3) accumulate in lysosomes of several tissues, particularly in vascular endothelium and smooth muscle cells. Cerebral manifestations that might be mainly due to progressive cerebrovascular dysfunction, are one major and often life-threatening burden of the disease. We reviewed the present literature concerning brain structural alterations in FD and discuss the possibly relevant underlying pathophysiological aspects of these disturbances. Cerebrovascular events (TIA, stroke) occur in FD at a rather early age. In female…

Multicenter stability of diffusion tensor imaging measures: a European clinical and physical phantom study.

Diffusion tensor imaging (DTI) detects white matter damage in neuro-psychiatric disorders, but data on reliability of DTI measures across more than two scanners are still missing. In this study we assessed multicenter reproducibility of DTI acquisitions based on a physical phantom as well as brain scans across 16 scanners. In addition, we performed DTI scans in a group of 26 patients with clinically probable Alzheimer's disease (AD) and 12 healthy elderly controls at one single center. We determined the variability of fractional anisotropy (FA) measures using manually placed regions of interest as well as automated tract based spatial statistics and deformation based analysis. The coefficie…

Low-dose agalsidase beta treatment in male pediatric patients with Fabry disease: A 5-year randomized controlled trial.

Abstract Background Fabry disease is a rare, X-linked, lifelong progressive lysosomal storage disorder. Severely deficient α-galactosidase A activity in males is associated with the classic phenotype with early-onset, multisystem manifestations evolving to vital organ complications during adulthood. We assessed the ability of 2 low-dose agalsidase beta regimens to lower skin, plasma, and urine globotriaosylceramide (GL-3) levels, and influence clinical manifestations in male pediatric Fabry patients. Methods In this multicenter, open-label, parallel-group, phase 3b study, male patients aged 5–18 years were randomized to receive agalsidase beta at 0.5 mg/kg 2-weekly (n = 16) or 1.0 mg/kg 4-w…

Voxel based analyses of diffusion tensor imaging in Fabry disease

Background: Fabry disease (FD) is a lysosomal storage disorder that is associated with marked cerebrovascular disease. Conventional MRI shows an extensive load of white matter lesions (WMLs) already at an early stage in FD. Objective: Investigator independent and sensitive quantification of brain structural changes in clinically affected men and women with FD. Methods: The authors performed a voxel-based analysis of diffusion tensor images (DTI) in 25 FD patients and 20 age-matched normal controls. Results: DTI revealed significant increases of cerebral white matter diffusivity (MD) in FD patients that were pronounced in the periventricular white matter. Even the subgroup of patients withou…

Limited agreement between biomarkers of neuronal injury at different stages of Alzheimer's disease

Abstract New diagnostic criteria for Alzheimer's disease (AD) treat different biomarkers of neuronal injury as equivalent. Here, we quantified the degree of agreement between hippocampal volume on structural magnetic resonance imaging, regional glucose metabolism on positron emission tomography, and levels of phosphorylated tau in cerebrospinal fluid (CSF) in 585 subjects from all phases of the AD Neuroimaging Initiative. The overall chance-corrected agreement was poor (Cohen κ, 0.24–0.34), in accord with a high rate of conflicting findings (26%–41%). Neither diagnosis nor APOE e4 status significantly influenced the distribution of agreement between the biomarkers. The degree of agreement t…

Diffusion Tensor Imaging of the Hippocampus in MCI and Early Alzheimer's Disease

The hippocampus is among the first brain structures to be affected by Alzheimer's disease (AD) pathology. Microstructural alterations within this region have been quantified in vivo using diffusion tensor imaging (DTI), a relatively novel MRI-based technique for mapping diffusion properties of water. Existing evidence indicates that DTI-derived mean diffusivity (MD) of the anterior hippocampus is more predictive than ordinary volumetric indices of the degree of episodic memory impairment in patients with early AD. Thus, altered MD of the (anterior) hippocampus might be highly indicative of hippocampal dysfunction, thereby potentially qualifying this measure as a candidate marker for monitor…

Demenzleitlinien: was in der Praxis ankommen sollte

Hintergrund und Fragestellung: Leitlinien wissenschaftlicher Fachgesellschaften verstehen sich als Orientierungshilfe fur die arztliche Tatigkeit, besonders auch fur die tagliche Arbeit niedergelassener Arzte. An der Erstellung von Leitlinien sind Praktiker in der Regel nicht direkt beteiligt, sondern nur mittelbar uber Standesvertreter. Leitlinien werden in einem Konsensprozess als eine Zusammenschau von 1. aus klinischen Studien beobachteter wissenschaftlicher Evidenz zur Wirksamkeit und Nebenwirkungen und 2. der Berucksichtigung von gesundheitssystemrelevanten Aspekten von gesundheitlichem Nutzen und Kostenaspekten erstellt, ohne die in der Flache vorliegenden Voraussetzungen berucksicht…

Screening for Cognitive Impairment in Hospitalized Older Patients

Abstract. This study develops a screening method for older patients based on nursing procedure to predict complications associated with cognitive impairment during a hospital stay. This multicenter diagnostic cohort study among older hospitalized patients was carried out in eight primary-care hospitals. Following admission of the patients, trained nurses conducted a structured interview and the Mini-Cog as gold standard for cognitive status; complications during the hospital stay were also monitored. In a second step, the structured interview combined with the Mini-Cog revealed whether there was any abnormality in the interview, making it possible to validly and reliably as well as sensiti…

IC‐P‐122: Association of hippocampus head diffusivity and episodic memory performance in early Alzheimer's disease

Diaschisis-Like Association of Hippocampal Atrophy and Posterior Cingulate Cortex Hypometabolism in Cognitively Normal Elderly Depends on Impaired Integrity of Parahippocampal Cingulum Fibers.

Hippocampal atrophy and hypometabolism of the posterior cingulate cortex (PCC), early markers of Alzheimer's disease (AD), have been shown to be associated in late mild cognitive impairment and early AD via atrophy of connecting cingulum fibers. Recently, a direct association of hippocampal atrophy and PCC hypometabolism has been shown in cognitively normal elderly. We aimed to investigate if this association might be modulated by partly non-hippocampogenic alterations of parahippocampal cingulum (PHC) integrity. 45 cognitively healthy elderly aged 59 to 89 years were included from the Alzheimer's Disease Neuroimaging Initiative. Hippocampal volumes and PCC glucose metabolism were measured …