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Copyright of Prävention und Gesundheitsförderung is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

The physiological basis of resilience to age-associated and AD-typical neurodegenerative pathology is still not well understood. So far, the established resilience factor intelligence has been shown to be associated with white matter network global efficiency, a key constituent of which are highly connected hubs. However, hub properties have also been shown to be impaired in AD. Individual predisposition or vulnerability of hub properties may thus modulate the impact of pathology on cognitive outcome and form part of the physiological basis of resilience. 85 cognitively normal elderly subjects and patients with MCI with DWI, MRI and AV45-PET scans were included from ADNI. We reconstructed the global WM networks in each subject and characterized hub-properties of GM regions using graph theory by calculating regional betweenness centrality. Subsequently, we investigated whether regional GM volume (GMV) and structural WM connectivity (WMC) of more hub-like regions was more associated with resilience, quantified as cognitive performance independent of amyloid burden, tau and WM lesions. Subjects with higher resilience showed higher increased regional GMV and WMC in more hub-like compared to less hub-like GM-regions. Additionally, this association was in some instances further increased at elevated amounts of brain pathology. Higher GMV and WMC of more hub-like regions may contribute more to resilience compared to less hub-like regions, reflecting their increased importance to brain network efficiency, and may thus form part of the neurophysiological basis of resilience. Future studies should investigate the factors leading to higher GMV and WMC of hubs in non-demented elderly with higher resilience. [ABSTRACT FROM AUTHOR]

Copyright of Zeitschrift für Gerontologie und Geriatrie is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

The present work aims at providing a methodological approach for the investigation of resilience factors and mechanisms in normal aging, Alzheimer's disease (AD) and other neurodegenerative disorders. By expanding and re-conceptualizing traditional regression approaches, we propose an approach that not only aims at identifying potential resilience factors but also allows for a differentiation between general and dynamic resilience factors in terms of their association with pathology. Dynamic resilience factors are characterized by an increasing relevance with increasing levels of pathology, while the relevance of general resilience factors is independent of the amount of pathology. Utility of the approach is demonstrated in age and AD-related brain pathology by investigating widely accepted resilience factors, including education and brain volume. Moreover, the approach is used to test hippocampal volume as potential resilience factor. Education and brain volume could be identified as general resilience factors against age and AD-related pathology. Beyond that, analyses highlighted that hippocampal volume may not only be disease target but also serve as a potential resilience factor in age and AD-related pathology, particularly at higher levels of tau-pathology (i.e. dynamic resilience factor). Given its unspecific and superordinate nature the approach is suitable for the investigation of a wide range of potential resilience factors in normal aging, AD and other neurodegenerative disorders. Consequently, it may find a wide application and thereby promote the comparability between studies. [ABSTRACT FROM AUTHOR]

To promote health-conscious behavior in the aging society and gain insight into the sources of knowledge on which preventive strategies are based, analyzing the behavior of elderly people who are recognized as highly health conscious may be useful. We focused on the use of Ginkgo biloba, which is commonly considered to be effective in preventing cognitive decline and dementia, among elderly adults. A total of 1,672 questionnaires were distributed among geriatric participants (60-94 years) who attended university lectures at 22 universities throughout Germany. Response rate was 36.1 %. We collected data on demographic characteristics, preventive strategies (use of Ginkgo and other supplements), health-conscious behavior, sources of knowledge concerning health behavior, and factors associated with the participants' concept of aging. The prevalence of Ginkgo use was 15.3 %. Ginkgo was assumed to be effective for cognitive enhancement and the treatment of cognitive decline by two thirds of the surveyed participants and one third believed Ginkgo to be effective for preventing dementia. Ginkgo use was significantly higher among participants using natural remedies and herbal and food supplements. The use of Ginkgo was recommended by physicians (57.3 %), chemists (16 %), and healthcare magazines (10.7 %). Food supplements were taken by 65.8 % of the sample: this percentage was significantly higher among subjects who exhibited health-conscious behavior. 'Knowledge' about strategies to enhance cognition or prevent cognitive decline among the elderly do not appear to be evidence based. Thus, there is a need to establish reliable and independent sources of scientific information for healthcare professionals and the general public. [ABSTRACT FROM AUTHOR]

Purpose: Hypometabolism of the posterior cingulate cortex (PCC) in early Alzheimer's disease (AD) is thought to arise in part due to AD-specific neuronal damage to the hippocampal formation. Here, we explored the association between microstructural alterations within the hippocampus and whole-brain glucose metabolism in subjects with AD, also in relation to episodic memory impairment. Methods: Twenty patients with early AD (Mini-Mental State Examination 25.7 ± 1.7) were studied with [F]fluorodeoxyglucose (FDG) positron emission tomography and diffusion tensor imaging. Episodic memory performance was assessed using the free delayed verbal recall task (DVR). Voxel-wise relative FDG uptake was correlated to diffusivity indices of the hippocampus, followed by extraction of FDG uptake values from significant clusters. Linear regression analysis was performed to test for unique contributions of diffusivity and metabolic indices in the prediction of memory function. Results: Diffusivity in the left anterior hippocampus negatively correlated with FDG uptake primarily in the left anterior hippocampus, parahippocampal gyrus and the PCC ( p < 0.005). The same correlation pattern was found for right hippocampal diffusivity ( p < 0.05). In linear regression analysis, left anterior hippocampal diffusivity and FDG uptake from the PCC cluster were the only significant predictors for performance on DVR, together explaining 60.6% of the variance. We found an inverse association between anterior hippocampal diffusivity and PCC glucose metabolism, which was in turn strongly related to episodic memory performance in subjects with early AD. Conclusion: These findings support the diaschisis hypothesis of AD and implicate a dysfunction of structures along the hippocampal output pathways as a significant contributor to the genesis of episodic memory impairment. [ABSTRACT FROM AUTHOR]

Abnormal microstructural integrity and glucose metabolism of the hippocampus are common in subjects with Alzheimer's disease (AD) that typically manifest as episodic memory impairment. The above-tissue alterations can be captured in vivo using diffusion tensor imaging (DTI) and positron emission tomography with [18F]fluorodeoxyglucose (FDG-PET). Here, we explored relationships between the above neuroimaging and cognitive markers of early AD-specific hippocampal damage. Twenty patients with early AD (MMSE 25.7 ± 1.7) were studied using DTI and FDG-PET. Episodic memory performance was assessed using the free delayed verbal recall task (DVR). In the between-modality correlation analysis, FDG uptake was strongly associated with diffusivity in the left anterior hippocampus only ( r = −0.81, p < 0.05 Bonferroni's corrected for multiple tests). Performance on DVR significantly correlated with left anterior ( r = −0.80, p < 0.05) and left mean ( r = −0.72, p < 0.05) hippocampal diffusivity, while the correlation with left anterior FDG uptake did not reach statistical significance ( r = 0.52, n.s.). DTI-derived diffusivity of the anterior hippocampus might be a sensitive early marker of hippocampal dysfunction as reflected at the synaptic and cognitive levels. This neurobiological distinction of the anterior hippocampus might be related to the disruption of the perforant pathway that is known to occur early in the course of AD. [ABSTRACT FROM AUTHOR]

CSF phospho-tau (p-tau181) levels have shown good diagnostic utility in differential diagnosis of Alzheimer disease (AD). Unlike total-tau (t-tau), age related changes of this promising biomarker are sparsely studied. The aim of the study was to determine whether p-tau181 is dependent on age, cognitive status or gender in patients with different neurological diseases who underwent diagnostic lumbar puncture and who had no clinical evidence of neurodegenerative diseases. CSF levels of p-tau181 and total-tau (t-tau) of 46 neurologic patients (age range 22–89 years; 22 male, 24 female) were analyzed. Clinical diagnoses were cerebral ischaemia ( n = 6), multiple sclerosis ( n = 13), epileptic seizures ( n = 3), polyneuropathy ( n = 9) and other neurological diagnoses ( n = 15). Cognitive performance was assessed by the German version of the CERAD battery. The mean level of p-tau181 was in accordance with previous findings in neurological patients (42.8 ± 15.3 pg/ml) and did not differ between neurological diseases. In contrast to t-tau ( r = 0.38; P = 0.009), p-tau181 did not correlate significantly to age ( r = 0.15; P = 0.308). No influence of cognitive status or gender on p-tau181 levels could be detected. The study corroborates the independence of p-tau181 from age, cognitive status, gender and a wide spectrum of neurological diseases. The findings suggest that neither age related neurodegenerative processes nor ischaemic or inflammatory processes are accompanied by tau protein phosphorylation. In contrast, the data support the view that p-tau181 seems to be a sign of the highly AD-specific pattern of tau phosphorylation during formation of neurofibrillary tangles. [ABSTRACT FROM AUTHOR]

Fabry disease (FD) is a lysosomal storage disorder that is associated with marked cerebrovascular disease. Conventional MRI shows a progressive load of white matter lesions (WMLs) due to cerebral vasculopathy in the course of FD. To quantify brain structural changes in clinically affected male and female patients with FD we performed a prospective Diffusion–Tensor Imaging (DTI) study in 27 adult Fabry patients (13m, 14f) and 21 age–matched controls (12 m, 9f). Global Mean Diffusivity (MD) was increased in FD (P = 0.003) whereas global Fractional Anisotropy (FA) did not differ significantly between FD and controls. Even FD patients without significant WMLs (9m, 9f) showed increased global MD (P = 0.004). Regions of interest with significant MD elevations were located in the frontal, parietal and temporal white matter. No differences of thalamic and hippocampal DTI measurements could be detected between FD and controls. DTI parameters did not differ between male and female patients. The data provide the first evidence of a pattern of marked structural brain tissue alterations in adult FD male and female patients even without WMLs. DTI seems to be an appropriate diagnostic tool to quantify brain tissue integrity in FD. Moreover, this method could be favorable for longitudinal assessment of brain structure alterations in FD, and for monitoring the cerebral effects of enzyme replacement therapy. [ABSTRACT FROM AUTHOR]

Background and Purpose The use of early prognostic data provided by various scores in critically ill stroke patients remains unclear. We tested the performance of the Simplified Acute Physiology Score (SAPS) II in prediction of mortality of acute stroke patients in the NeuroCriticalCareUnit (NCCU). Methods During one year every patient admitted to the NCCUs at 2 University hospitals for cerebral ischemia (CI) or intracerebral hemorrhage (ICH) and intubated was included in this study. Data for SAPS (I)/II and the Glasgow Coma Scale (GCS) were collected, and mortality at 10 days, 90 days and 1 year was determined. Prognostic performance of all scores was tested by calculation of receiver operating curve (ROC) and by Cox regression analysis. Results 90 patients were included in the study, 49 with ICH and 41 with CI. Mortality after 10 days was 32.2%, after 3 months 58.9% and after 1 year 67.8%. Compared by their area under curve the predictive values were overall quite good for both SAPS (I) (0.77) and SAPS II (0.77) as well as GCS. Motor subscore was equal to total GCS (0.75 vs. 0.73). In Cox regression models all three scores were independent predictors of fatal outcome. Conclusion SAPS II and SAPS (I) but also the GCS are valuable tools for prediction of short and long-term mortality in acute stroke patients treated in NCCU. The GCS as a predictor for mortality in stroke patients could be further simplified by using its subscore ‘best motor response’ alone. [ABSTRACT FROM AUTHOR]

Copyright of Klinische Neuroradiologie is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

The metalloprotease ADAM10 is a drug target in Alzheimer's disease, where it cleaves the amyloid precursor protein (APP) and lowers amyloid‐beta. Yet, ADAM10 has additional substrates, which may cause mechanism‐based side effects upon therapeutic ADAM10 activation. However, they may also serve—in addition to APP—as biomarkers to monitor ADAM10 activity in patients and to develop APP‐selective ADAM10 activators. Our study demonstrates that one such substrate is the neuronal cell adhesion protein NrCAM. ADAM10 controlled NrCAM surface levels and regulated neurite outgrowth in vitro in an NrCAM‐dependent manner. However, ADAM10 cleavage of NrCAM, in contrast to APP, was not stimulated by the ADAM10 activator acitretin, suggesting that substrate‐selective ADAM10 activation may be feasible. Indeed, a whole proteome analysis of human CSF from a phase II clinical trial showed that acitretin, which enhanced APP cleavage by ADAM10, spared most other ADAM10 substrates in brain, including NrCAM. Taken together, this study demonstrates an NrCAM‐dependent function for ADAM10 in neurite outgrowth and reveals that a substrate‐selective, therapeutic ADAM10 activation is possible and may be monitored with NrCAM. Synopsis: The authors provide new insights into the neurobiology of the α‐secretase ADAM10 and show that its therapeutic activation in Alzheimer's disease may be feasible without causing mechanism‐based side effects. Importantly, in human CSF ADAM10 activation may be monitored with its substrate NrCAM as a new biomarker. NrCAM is sequentially cleaved by furin, ADAM10 and γ‐secretase.ADAM10 regulates neurite outgrowth by controlling NrCAM's cell surface expression.Substrate selective ADAM10 activation is feasible and may be monitored by using NrCAM as a companion diagnostic. The authors provide new insights into the neurobiology of the α‐secretase ADAM10 and show that its therapeutic activation in Alzheimer's disease may be feasible without causing mechanism‐based side effects. Importantly, in human CSF ADAM10 activation may be monitored with its substrate NrCAM as a new biomarker. [ABSTRACT FROM AUTHOR]