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Perneczky R.,Imperial College London | Perneczky R.,West London Cognitive Disorders Treatment and Research Unit | Perneczky R.,TU Munich | Alexopoulos P.,TU Munich | Kurz A.,TU Munich
Trends in Molecular Medicine | Year: 2014

Recently revised diagnostic guidelines for Alzheimer's disease (AD) emphasise the use of biomarkers, heralding a paradigm shift towards a more biological definition of the disorder. Currently available biomarkers offer added diagnostic accuracy in certain situations, but their performance in terms of early diagnostic sensitivity and specificity does not fully live up to the desired standards. One feasible approach to improve the diagnostic and prognostic performance of AD biomarkers is to measure upstream events of amyloid precursor protein (APP) processing, which are at the core of the initial phase of AD pathogenesis. Here we review evidence on the APP processing enzymes and their cleavage products and discuss possible applications and limitations in their use as AD biomarkers. © 2013 Elsevier Ltd.

Bronner K.,TU Munich | Perneczky R.,TU Munich | Perneczky R.,Imperial College London | Perneczky R.,West London Cognitive Disorders Treatment and Research Unit | And 3 more authors.
BMC Research Notes | Year: 2016

Background: The relevance of early decision making will rise with increasing availability of early detection of Alzheimer's disease (AD) using brain imaging or biomarkers. Results: Five people with mild AD, six relatives and 13 healthcare professionals with experience in the management of AD were interviewed in a qualitative study regarding medical and social decision topics that emerge after early diagnosis of Alzheimer's disease. Medical treatment, assistance in everyday life and legal issues emerged as the main decision topics after an early diagnosis of AD. People with AD mostly got in contact with the health and social care system through the initiative of their spouses. They were usually aware of their illness and most received antidementia drugs and/or behavioural interventions. Following diagnosis people with AD received support by their spouses. Healthcare professionals were aware of the risk of excessive demand on relatives due to supporting their family member with AD. In the opinion of healthcare professionals legal issues should be arranged in time before patients lose their decisional capacity. In addition, people with AD and spouses reported various coping strategies, in particular "carry on as normal" after diagnosis but mostly are reluctant to actively plan for future stages of the disease. Conclusions: Due to the common desire to "carry on as usual" after a diagnosis of AD, many people with AD and spouses may miss the opportunity to discuss and decide on important medical and social topics. A structured approach e.g. a decision aid might support people with AD and spouses in their decision making process and thereby preserve persons' with AD autonomy before they lose the capacity in decision-making. © 2016 Bronner et al.

Li R.,TU Munich | Perneczky R.,TU Munich | Perneczky R.,Imperial College London | Perneczky R.,West London Cognitive Disorders Treatment and Research Unit | And 5 more authors.
PLoS ONE | Year: 2015

We present a method to discover discriminative brain metabolism patterns in [18F] fluorodeoxyglucose positron emission tomography (PET) scans, facilitating the clinical diagnosis of Alzheimer's disease. In the work, the term "pattern" stands for a certain brain region that characterizes a target group of patients and can be used for a classification as well as interpretation purposes. Thus, it can be understood as a so-called "region of interest (ROI)". In the literature, an ROI is often found by a given brain atlas that defines a number of brain regions, which corresponds to an anatomical approach. The present work introduces a semi-data-driven approach that is based on learning the characteristics of the given data, given some prior anatomical knowledge. A Gaussian Mixture Model (GMM) and model selection are combined to return a clustering of voxels that may serve for the definition of ROIs. Experiments on both an in-house dataset and data of the Alzheimer's Disease Neuroimaging Initiative (ADNI) suggest that the proposed approach arrives at a better diagnosis than a merely anatomical approach or conventional statistical hypothesis testing. © 2015 Li et al.

Ortner M.,TU Munich | Kurz A.,TU Munich | Alexopoulos P.,TU Munich | Auer F.,TU Munich | And 10 more authors.
Biological Psychiatry | Year: 2015

BACKGROUND: There is controversy concerning whether Alzheimer's disease (AD) with early onset is distinct from AD with late onset with regard to amyloid pathology and neuronal metabolic deficit. We hypothesized that compared with patients with early-onset AD, patients with late-onset AD have more comorbid small vessel disease (SVD) contributing to clinical severity, whereas there are no differences in amyloid pathology and neuronal metabolic deficit. METHODS: The study included two groups of patients with probable AD dementia with evidence of the AD pathophysiologic process: 24 patients with age at onset <60 years old and 36 patients with age at onset >70 years old. Amyloid deposition was assessed using carbon-11-labeled Pittsburgh compound B positron emission tomography, comorbid SVD was assessed using magnetic resonance imaging, and neuronal metabolic deficit was assessed using fluorodeoxyglucose positron emission tomography. Group differences of global and regional distribution of pathology were explored using region of interest and voxel-based analyses, respectively, carefully controlling for the influence of dementia severity, apolipoprotein E genotype, and in particular SVD. The pattern of cognitive impairment was determined using z scores of the subtests of the Consortium to Establish a Registry for Alzheimer's Disease Neuropsychological Assessment Battery. RESULTS: Patients with late-onset AD showed a significantly greater amount of SVD. No statistically significant differences in global or regional amyloid deposition or neuronal metabolic deficit between the two groups were revealed. However, when not controlling for SVD, subtle differences in fluorodeoxyglucose uptake between early-onset AD and late-onset AD groups were detectable. There were no significant differences regarding cognitive functioning. CONCLUSIONS: Age at onset does not influence amyloid deposition or neuronal metabolic deficit in AD. The greater extent of SVD in late-onset AD influences the association between neuronal metabolic deficit and clinical symptoms. © 2015 Society of Biological Psychiatry.

Li R.,TU Munich | Perneczky R.,Imperial College London | Perneczky R.,TU Munich | Perneczky R.,West London Cognitive Disorders Treatment and Research Unit | And 2 more authors.
Journal of Intelligent Information Systems | Year: 2015

Subgroup discovery is a task at the intersection of predictive and descriptive induction, aiming at identifying subgroups that have the most unusual statistical (distributional) characteristics with respect to a property of interest. Although a great deal of work has been devoted to the topic, one remaining problem concerns the redundancy of subgroup descriptions, which often effectively convey very similar information. In this paper, we propose a quadratic programming based approach to reduce the amount of redundancy in the subgroup rules. Experimental results on 12 datasets show that the resulting subgroups are in fact less redundant compared to standard methods. In addition, our experiments show that the computational costs are significantly lower than the costs of other methods compared in the paper. © 2013, Springer Science+Business Media New York.

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