Imperial College London

DrRobertPerneczky

Faculty of MedicineSchool of Public Health

Visiting Professor
 
 
 
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Contact

 

+44 (0)20 3313 0611r.perneczky

 
 
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Location

 

10L05Lab BlockCharing Cross Campus

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Summary

 

Publications

Publication Type
Year
to

282 results found

Alexopoulos P, Roesler J, Werle L, Thierjung N, Lentzari I, Ortner M, Grimmer T, Laskaris N, Politis A, Gourzis P, Kurz A, Perneczky R, Alzheimers Disease Neuroimaging Initiativeet al., 2017, Fluid biomarker agreement and interrelation in dementia due to Alzheimer's disease., Journal of Neural Transmission, ISSN: 0300-9564

The cerebrospinal fluid (CSF) levels of β-amyloid 42, total tau, and phosphorylated tau 181 are supposed to be all continuously abnormal in dementia due to Alzheimer's disease (AD), being the most advanced disease stage. The aim of the present study, which included a monocentric and a multicentric sample (N = 119 and 178, respectively), was to investigate the degree of CSF biomarker agreement and interrelation in AD dementia. Based on previously published cut-off values, biomarker values were categorized as positive or negative for AD (dichotomization strategy) and as either positive, negative, or borderline (trichotomization strategy). The statistical analyses relied on distance correlation analysis and kappa (k) statistics. Poor agreement (k < 0.4) and low interrelations between the studied biomarkers were detected in all cases with the exception of the interrelation between the markers total tau and phosphorylated tau 181, especially in the monocentric sample. Interestingly, lower interrelation and agreement degrees were observed in carriers of the Apolipoprotein E ε4 allele compared to non-carriers. The clinical phenotype currently referred to as "AD dementia" is characterized by an inhomogeneous CSF biomarker profile, possibly mirroring the complex genesis of AD-typical dementia symptoms and pointing to the necessity of shedding more light on the hypothesis of biomarker stability over time in symptomatic AD.

Journal article

Webster L, Groskreutz D, Grinbergs-Saull A, Howard R, O'Brien JT, Mountain G, Banerjee S, Woods B, Perneczky R, Lafortune L, Roberts C, McCleery J, Pickett J, Bunn F, Challis D, Charlesworth G, Featherstone K, Fox C, Goodman C, Jones R, Lamb S, Moniz-Cook E, Schneider J, Shepperd S, Surr C, Thompson-Coon J, Ballard C, Brayne C, Burns A, Clare L, Garrard P, Kehoe P, Passmore P, Holmes C, Maidment I, Robinson L, Livingston Get al., 2017, Core outcome measures for interventions to prevent or slow the progress of dementia for people living with mild to moderate dementia: Systematic review and consensus recommendations, PLOS One, Vol: 12, ISSN: 1932-6203

BackgroundThere are no disease-modifying treatments for dementia. There is also no consensus on disease modifying outcomes. We aimed to produce the first evidence-based consensus on core outcome measures for trials of disease modification in mild-to-moderate dementia.Methods and findingsWe defined disease-modification interventions as those aiming to change the underlying pathology. We systematically searched electronic databases and previous systematic reviews for published and ongoing trials of disease-modifying treatments in mild-to-moderate dementia. We included 149/22,918 of the references found; with 81 outcome measures from 125 trials. Trials involved participants with Alzheimer’s disease (AD) alone (n = 111), or AD and mild cognitive impairment (n = 8) and three vascular dementia. We divided outcomes by the domain measured (cognition, activities of daily living, biological markers, neuropsychiatric symptoms, quality of life, global). We calculated the number of trials and of participants using each outcome. We detailed psychometric properties of each outcome. We sought the views of people living with dementia and family carers in three cities through Alzheimer’s society focus groups. Attendees at a consensus conference (experts in dementia research, disease-modification and harmonisation measures) decided on the core set of outcomes using these results. Recommended core outcomes were cognition as the fundamental deficit in dementia and to indicate disease modification, serial structural MRIs. Cognition should be measured by Mini Mental State Examination or Alzheimer's Disease Assessment Scale-Cognitive Subscale. MRIs would be optional for patients. We also made recommendations for measuring important, but non-core domains which may not change despite disease modification.LimitationsMost trials were about AD. Specific instruments may be superseded. We searched one database for psychometric properties.InterpretationThis is the first review to ident

Journal article

Skrobot OA, O'Brien J, Black S, Chen C, DeCarli C, Erkinjuntti T, Ford GA, Kalaria RN, Pantoni L, Pasquier F, Roman GC, Wallin A, Sachdev P, Skoog I, Ben-Shlomo Y, Passmore AP, Love S, Kehoe PG, Taragano FE, Kril J, Cavalieri M, Jellinger KA, Kovacs GG, Engelborghs S, Lafosse C, Bertolucci PH, Brucki S, Caramelli P, Alves TCDTF, Bocti C, Fulop T, Hogan DB, Hsiung GR, Kirk A, Leach L, Robillard A, Sahlas DJ, Guo Q, Tian J, Hokkanen L, Jokinen H, Benisty S, Deramecourt V, Hauw J, Lenoir H, Tsatali M, Tsolaki M, Sundar U, Coen RF, Korczyn AD, Altieri M, Baldereschi M, Caltagirone C, Caravaglios G, Di Carlo A, Di Piero V, Gainotti G, Galluzzi S, Logroscino G, Mecocci P, Moretti DV, Padovani A, Fukui T, Ihara M, Mizuno T, Kim SY, Akinyemi R, Baiyewu O, Ogunniyi A, Szczudlik A, Bastos-Leite AJ, Firmino H, Massano J, Verdelho A, Kruglov LS, Ikram MK, Kandiah N, Arana E, Barroso-Ribal J, Calatayud T, Cruz-Jentoft AJ, Lopez-Pousa S, Martinez-Lage P, Mataro M, Borjesson-Hanson A, Englund E, Laukka EJ, Qiu C, Viitanen M, Biessels GJ, de Leeuw F-E, den Heijer T, Exalto LG, Kappelle LJ, Prins ND, Richard E, Schmand B, van den Berg E, van der Flier WM, Bilgic B, Allan LM, Archer J, Attems J, Bayer A, Blackburn D, Brayne C, Bullock R, Connelly PJ, Farrant A, Fish M, Harkness K, Ince PG, Langhorne P, Mann J, Matthews FE, Mayer P, Pendlebury ST, Perneczky R, Peters R, Smithard D, Stephan BC, Swartz JE, Todd S, Werring DJ, Wijayasiri SN, Wilcock G, Zamboni G, Au R, Borson S, Bozoki A, Browndyke JN, Corrada MM, Crane PK, Diniz BS, Etcher L, Fillit H, Greenberg SM, Grinberg LT, Hurt SW, Lamar M, Mielke M, Ott BR, Perry G, Powers WJ, Ramos-Estebanez C, Reed B, Roberts RO, Romero JR, Saykin AJ, Seshadri S, Silbert L, Stern Y, Zarow Cet al., 2017, The Vascular Impairment of Cognition Classification Consensus Study, ALZHEIMERS & DEMENTIA, Vol: 13, Pages: 624-633, ISSN: 1552-5260

Journal article

Robb CE, Udeh-Momoh CUM, Wagenpfeil SW, Schope JS, Alexopoulos PA, Perneczky RPet al., 2017, Biomarkers and functional decline in prodromal Alzheimer’s disease, Journal of Alzheimers Disease, Vol: 58, Pages: 69-78, ISSN: 1875-8908

Background: Little is known of possible associations between Alzheimer’s disease (AD) biomarkers and instrumental activities of daily living (IADL) change over time.Objective: The present study seeks to identify relationships between baseline imaging and fluid biomarker profiles, and decline in IADL utilizing data collated from the Alzheimer’s Disease Neuroimaging Initiative (ADNI) cohort.Methods: Generalized estimating equations analysis, adjusted for cognitive deterioration, was applied to a cohort of 509 individuals from all stages of ADNI, including 156 healthy controls, 189 early mild cognitive impairment (MCI) patients and 164 MCI patients.Results: A significant correlation was found between baseline biomarkers, specifically CSF Aβ and FDG PET, and IADL change over a 3-year period in individuals with MCI. Importantly, comparable correlations between presence of pathological biomarker levels and temporal decline in both functional and cognitive performance were also noted.Discussion: We show that distinct baseline biomarkers may predict latent changes in IADL. Our results necessitate a revision of the commonly held view upholding cognitive changes as the predominant endpoint measure associated with presence of abnormal baseline biomarkers.

Journal article

Webster L, Groskreutz D, Grinbergs-Saull A, Howard R, O'Brien JT, Mountain G, Banerjee S, Woods B, Perneczky R, Lafortune L, Roberts C, McCleery J, Pickett J, Bunn F, Challis D, Charlesworth G, Featherstone K, Fox C, Goodman C, Jones R, Lamb S, Moniz-Cook E, Schneider J, Shepperd S, Surr C, Thompson-Coon J, Ballard C, Brayne C, Burke O, Burns A, Clare L, Garrard P, Kehoe P, Passmore P, Holmes C, Maidment I, Murtagh F, Robinson L, Livingston Get al., 2017, Development of a core outcome set for disease modification trials in mild to moderate dementia: a systematic review, patient and public consultation and consensus recommendations, HEALTH TECHNOLOGY ASSESSMENT, Vol: 21, Pages: 1-+, ISSN: 1366-5278

Background:There is currently no disease-modifying treatment available to halt or delay the progression of the disease pathology in dementia. An agreed core set of the best-available and most appropriate outcomes for disease modification would facilitate the design of trials and ensure consistency across disease modification trials, as well as making results comparable and meta-analysable in future trials.Objectives:To agree a set of core outcomes for disease modification trials for mild to moderate dementia with the UK dementia research community and patient and public involvement (PPI).Data sources:We included disease modification trials with quantitative outcomes of efficacy from (1) references from related systematic reviews in workstream 1; (2) searches of the Cochrane Dementia and Cognitive Improvement Group study register, Cochrane Central Register of Controlled Trials, Cumulative Index to Nursing and Allied Health Literature, EMBASE, Latin American and Caribbean Health Sciences Literature and PsycINFO on 11 December 2015, and clinical trial registries [International Standard Randomised Controlled Trial Number (ISRCTN) and clinicaltrials.gov] on 22 and 29 January 2016; and (3) hand-searches of reference lists of relevant systematic reviews from database searches.Review methods:The project consisted of four workstreams. (1) We obtained related core outcome sets and work from co-applicants. (2) We systematically reviewed published and ongoing disease modification trials to identify the outcomes used in different domains. We extracted outcomes used in each trial, recording how many used each outcome and with how many participants. We divided outcomes into the domains measured and searched for validation data. (3) We consulted with PPI participants about recommended outcomes. (4) We presented all the synthesised information at a conference attended by the wider body of National Institute for Health Research (NIHR) dementia researchers to reach consensus on a core

Journal article

Ferrari R, Wang Y, Vandrovcova J, Guelfi S, Witeolar A, Karch CM, Schork AJ, Fan CC, Brewer JB, Momeni P, Schellenberg GD, Dillon WP, Sugrue LP, Hess CP, Yokoyama JS, Bonham LW, Rabinovici GD, Miller BL, Andreassen OA, Dale AM, Hardy J, Desikan RSet al., 2017, Genetic architecture of sporadic frontotemporal dementia and overlap with Alzheimer's and Parkinson's diseases, JOURNAL OF NEUROLOGY NEUROSURGERY AND PSYCHIATRY, Vol: 88, Pages: 152-164, ISSN: 0022-3050

Journal article

Tudor Car L, El-Khatib M, Perneczky N, Papachristou N, Atun R, Rudan I, Car J, Vincent C, Majeed Aet al., 2017, Prioritizing problems in and solutions to homecare safety of people with dementia: supporting carers, streamlining care, BMC Geriatrics, Vol: 17, ISSN: 1471-2318

BackgroundDementia care is predominantly provided by carers in home settings. We aimed to identify the priorities for homecare safety of people with dementia according to dementia health and social care professionals using a novel priority-setting method.MethodsThe project steering group determined the scope, the context and the criteria for prioritization. We then invited 185 North-West London clinicians via an open-ended questionnaire to identify three main problems and solutions relating to homecare safety of people with dementia. 76 clinicians submitted their suggestions which were thematically synthesized into a composite list of 27 distinct problems and 30 solutions. A group of 49 clinicians arbitrarily selected from the initial cohort ranked the composite list of suggestions using predetermined criteria.ResultsInadequate education of carers of people with dementia (both family and professional) is seen as a key problem that needs addressing in addition to challenges of self-neglect, social isolation, medication nonadherence. Seven out of top 10 problems related to patients and/or carers signalling clearly where help and support are needed. The top ranked solutions focused on involvement and education of family carers, their supervision and continuing support. Several suggestions highlighted a need for improvement of recruitment, oversight and working conditions of professional carers and for different home safety-proofing strategies.ConclusionsClinicians identified a range of suggestions for improving homecare safety of people with dementia. Better equipping carers was seen as fundamental for ensuring homecare safety. Many of the identified suggestions are highly challenging and not easily changeable, yet there are also many that are feasible, affordable and could contribute to substantial improvements to dementia homecare safety.

Journal article

van der Zee J, Gijselinck I, Van Mossevelde S, Perrone F, Dillen L, Heeman B, Baumer V, Engelborghs S, De Bleecker J, Baets J, Gelpi E, Rojas-Garcia R, Clarimon J, Lleo A, Diehl-Schmid J, Alexopoulos P, Perneczky R, Synofzik M, Just J, Schoels L, Graff C, Thonberg H, Borroni B, Padovani A, Jordanova A, Sarafov S, Tournev I, de Mendonca A, Miltenberger-Miltenyi G, Simoes do Couto F, Ramirez A, Jessen F, Heneka MT, Gomez-Tortosa E, Danek A, Cras P, Vandenberghe R, De Jonghe P, De Deyn PP, Sleegers K, Cruts M, Van Broeckhoven C, Goeman J, Nuytten D, Smets K, Robberecht W, Van Damme P, De Bleecker J, Santens P, Dermaut B, Versijpt J, Michotte A, Ivanoiu A, Deryck O, Bergmans B, Delbeck B, Bruyland M, Willems C, Salmon E, Pastor P, Ortega-Cubero S, Benussi L, Ghidoni R, Binetti G, Hernandez I, Boada M, Ruiz A, Sorbi S, Nacmias B, Bagnoli S, Sanchez-Valle R, Llado A, Santana I, Almeida MR, Frisoni GB, Maetzler W, Matej R, Fraidakis MJ, Kovacs GG, Fabrizi GM, Testi Set al., 2017, TBK1 mutation spectrum in an extended European patient cohort with frontotemporal dementia and amyotrophic lateral sclerosis, Human Mutation, Vol: 38, Pages: 297-309, ISSN: 1098-1004

We investigated the mutation spectrum of the TANK-Binding Kinase 1 (TBK1) gene and its associated phenotypic spectrum by exonic resequencing of TBK1 in a cohort of 2,538 patients with frontotemporal dementia (FTD), amyotrophic lateral sclerosis (ALS), or FTD plus ALS, ascertained within the European Early-Onset Dementia Consortium. We assessed pathogenicity of predicted protein-truncating mutations by measuring loss of RNA expression. Functional effect of in-frame amino acid deletions and missense mutations was further explored in vivo on protein level and in vitro by an NFκB-induced luciferase reporter assay and measuring phosphorylated TBK1. The protein-truncating mutations led to the loss of transcript through nonsense-mediated mRNA decay. For the in-frame amino acid deletions, we demonstrated loss of TBK1 or phosphorylated TBK1 protein. An important fraction of the missense mutations compromised NFκB activation indicating that at least some functions of TBK1 are lost. Although missense mutations were also present in controls, over three times more mutations affecting TBK1 functioning were found in the mutation fraction observed in patients only, suggesting high-risk alleles (P = 0.03). Total mutation frequency for confirmed TBK1 LoF mutations in the European cohort was 0.7%, with frequencies in the clinical subgroups of 0.4% in FTD, 1.3% in ALS, and 3.6% in FTD-ALS.

Journal article

Alexopoulos P, Werle L, Roesler J, Thierjung N, Gleixner LS, Yakushev I, Laskaris N, Wagenpfeil S, Gourzis P, Kurz A, Perneczky Ret al., 2016, Conflicting cerebrospinal fluid biomarkers and progression to dementia due to Alzheimer's disease, Alzheimer's Research & Therapy, Vol: 8, ISSN: 1758-9193

Background:According to new diagnostic guidelines for Alzheimer’s disease (AD), biomarkers enable estimation ofthe individual likelihood of underlying AD pathophysiology and the associated risk of progression to AD dementiafor patients with mild cognitive impairment (MCI). Nonetheless, how conflicting biomarker constellations affectthe progression risk is still elusive. The present study explored the impact of different cerebrospinal fluid (CSF)biomarker constellations on the progression risk of MCI patients.Methods:A multicentre cohort of 469 patients with MCI and available CSF biomarker results and clinical follow-updata was considered. Biomarker values were categorized as positive for AD, negative or borderline. Progression riskdifferences between patients with different constellations of total Tau (t-Tau), phosphorylated Tau at threonine 181(p-Tau) and amyloid-beta 1–42 (Aβ42) were studied. Group comparison analyses and Cox regression modelswere employed.Results:Patients with all biomarkers positive for AD (N= 145) had the highest hazard for progression to dementiadue to AD, whilst patients with no positive biomarkers (N= 111) had the lowest. The risk of patients with onlyabnormal p-Tau and/or t-Tau (N= 49) or with positive Aβ42in combination with positive t-Tau or p-Tau (N= 119) issignificantly lower than that of patients with all biomarkers positive.Conclusions:The risk of progression to dementia due to AD differs between patients with different CSF biomarkerconstellations.

Journal article

Udeh-Momoh CT, Price G, Su B, Benjamin M, O'Driscoll C, Robb C, Bassil D, Ward H, Perneczky R, Middleton Let al., 2016, THE CHARIOT COGNITIVE RESERVE COMPOSITE: A CONSTRUCT AND PREDICTIVE VALIDITY STUDY, The 13th International Conference on Alxheimer's and Parkinson's Disease

Conference paper

Perneczky R, Tene O, Attems J, Giannakopoulos P, Ikram MA, Federico A, Sarazin M, Middleton LTet al., 2016, Is the time ripe for new diagnostic criteria of cognitive impairment due to cerebrovascular disease? Consensus report of the International Congress on Vascular Dementia working group, BMC Medicine, Vol: 14, ISSN: 1741-7015

BACKGROUND: Long before Alzheimer's disease was established as the leading cause of dementia in old age, cerebrovascular lesions were known to cause cognitive deterioration and associated disability. Since the middle of the last century, different diagnostic concepts for vascular dementia and related syndromes were put forward, yet no widely accepted diagnostic consensus exists to date. DISCUSSION: Several international efforts, reviewed herein, are ongoing to define cognitive impairment due to cerebrovascular disease in its different stages and subtypes. The role of biomarkers is also being discussed, including cerebrospinal fluid proteins, structural and functional brain imaging, and genetic markers. The influence of risk factors, such as diet, exercise and different comorbidities, is emphasised by population-based research, and lifestyle changes are considered for the treatment and prevention of dementia. CONCLUSION: To improve the diagnosis and management of vascular cognitive impairment, further progress has to be made in understanding the relevant pathomechanisms, including shared mechanisms with Alzheimer's disease; bringing together fragmented research initiatives in coordinated international programs; testing if known risk factors are modifiable in prospective interventional studies; and defining the pre-dementia and pre-clinical stages in line with the concept of mild cognitive impairment due to Alzheimer's disease.

Journal article

Hayhoe B, Majeed A, Perneczky R, 2016, General practitioner referrals to memory clinics: are referral criteria delaying the diagnosis of dementia?, Journal of the Royal Society of Medicine, Vol: 109, Pages: 410-415, ISSN: 1758-1095

Journal article

Vauzour D, Camprubi-Robles M, Miquel-Kergoat S, Andres-Lacueva C, Banati D, Barberger-Gateau P, Bowman GL, Caberlotto L, Clarke R, Hogervorst E, Kiliaan AJ, Lucca U, Manach C, Minihane A-M, Mitchell ES, Perneczky R, Perry H, Roussel A-M, Schuermans J, Sijben J, Spencer JPE, Thuret S, van de Rest O, Vandewoude M, Wesnes K, Williams RJ, Williams RSB, Ramirez Met al., 2016, Nutrition for the ageing brain: Towards evidence for an optimal diet, AGEING RESEARCH REVIEWS, Vol: 35, Pages: 222-240, ISSN: 1568-1637

As people age they become increasingly susceptible to chronic and extremely debilitating brain diseases. The precise cause of the neuronal degeneration underlying these disorders, and indeed normal brain ageing remains however elusive. Considering the limits of existing preventive methods, there is a desire to develop effective and safe strategies. Growing preclinical and clinical research in healthy individuals or at the early stage of cognitive decline has demonstrated the beneficial impact of nutrition on cognitive functions. The present review is the most recent in a series produced by the Nutrition and Mental Performance Task Force under the auspice of the International Life Sciences Institute Europe (ILSI Europe). The latest scientific advances specific to how dietary nutrients and non-nutrient may affect cognitive ageing are presented. Furthermore, several key points related to mechanisms contributing to brain ageing, pathological conditions affecting brain function, and brain biomarkers are also discussed. Overall, findings are inconsistent and fragmented and more research is warranted to determine the underlying mechanisms and to establish dose-response relationships for optimal brain maintenance in different population subgroups. Such approaches are likely to provide the necessary evidence to develop research portfolios that will inform about new dietary recommendations on how to prevent cognitive decline.

Journal article

Buschiazzo A, Frisoni G, Galluzzi S, Perneczky R, Drzezga A, van Berckel B, Ossenkoppele R, Guedj E, Didic M, Mecocci P, Dottorini M, Bauckneht M, Sambuceti G, Nobili F, Morbelli Set al., 2016, Interaction between education and clinical expression of Alzheimer's disease across European countries: an 18F-FDG PET study of the European Alzheimer's Disease Consortium (EADC), Annual Congress of the European-Association-of-Nuclear-Medicine (EANM), Publisher: SPRINGER, Pages: S116-S117, ISSN: 1619-7070

Conference paper

van der Zee J, Gijselinck I, Van Mossevelde S, Perrone F, Engelborghs S, De Bleecker J, Baets J, Gelpi E, Rojas-Garcia R, Clarimon J, Lleo A, Diehl-Schmid J, Alexopoulos P, Perneczky R, Synofzik M, Just J, Schoels L, Graff C, Thonberg H, Borroni B, Padovani A, Jordanova A, Sarafov S, Tournev I, de Mendonca A, Miltenberger-Miltenyi G, Simoes do Couto F, Ramirez A, Jessen F, Heneka MT, Gomez-Tortosa E, Danek A, Cras P, Vandenberghe R, De Jonghe P, De Deyn PP, Sleegers K, Cruts M, Van Broeckhoven Cet al., 2016, TBK1 loss-of function and dominant-negative mutations in an extended European cohort of FTD and ALS patients, 10th International Conference on Frontotemporal Dementias, Publisher: WILEY-BLACKWELL, Pages: 304-305, ISSN: 0022-3042

Conference paper

Majeed F, Hansell A, Saxena S, Millett C, Ward H, Harris M, Hayhoe B, Car J, Easton G, Donnelly CA, Perneczky R, Jarvelin MR, Ezzati M, Rawaf S, Vineis P, Ferguson N, Riboli Eet al., 2016, How would a decision to leave the European Union affect medical research and health in the United Kingdom?, Journal of the Royal Society of Medicine, Vol: 109, Pages: 216-218, ISSN: 1758-1095

Journal article

Bronner K, Perneczky R, McCabe R, Kurz A, Hamann Jet al., 2016, Which medical and social decision topics are important after early diagnosis of Alzheimer's Disease from the perspectives of people with Alzheimer's Disease, spouses and professionals?, BMC Research Notes, Vol: 9, ISSN: 1756-0500

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.

Journal article

Perneczky R, Guo LH, 2016, Plasma Proteomics Biomarkers in Alzheimer's Disease: Latest Advances and Challenges, Methods in Molecular Biology, Vol: 1303, Pages: 521-529, ISSN: 1940-6029

The recent paradigm shift towards a more biologically oriented definition of Alzheimer's disease (AD) in clinical settings increases the need for sensitive biomarkers that can be applied in population-based settings. Blood plasma is easily accessible and contains a large number of proteins related to cerebral processes. It is therefore an ideal candidate for AD biomarker discovery. The present chapter provides an overview of the current research landscape in relation to blood-based AD biomarkers. Both clinical and methodological issues are covered. A brief summary is given on two relevant laboratory techniques to ascertain blood biomarker changes due to AD; methodological and clinical challenges in the field are also discussed.

Journal article

Titov D, Diehl-Schmid J, Shi K, Perneczky R, Zou N, Grimmer T, Li J, Drzezga A, Yakushev Iet al., 2015, Metabolic connectivity for differential diagnosis of dementing disorders, Journal of Cerebral Blood Flow and Metabolism, Vol: 37, Pages: 252-262, ISSN: 0271-678X

Presently, visual and quantitative approaches for image-supported diagnosis of dementing disorders rely on regional intensity rather than on connectivity measurements. Here, we test metabolic connectivity for differentiation between Alzheimer’s disease and frontotemporal lobar degeneration. Positron emission tomography with 18F-fluorodeoxyglucose was conducted in 47 patients with mild Alzheimer’s disease, 52 patients with mild frontotemporal lobar degeneration, and 45 healthy elderly subjects. Sparse inverse covariance estimation and selection were used to identify patterns of metabolic, inter-subject covariance on the basis of 60 regional values. Relative to healthy subjects, significantly more pathological within-lobe connections were found in the parietal lobe of patients with Alzheimer’s disease, and in the frontal and temporal lobes of subjects with frontotemporal lobar degeneration. Relative to the frontotemporal lobar degeneration group, more pathological connections between the parietal and temporal lobe were found in the Alzheimer’s disease group. The obtained connectivity patterns differentiated between two patients groups with an overall accuracy of 83%. Linear discriminant analysis and univariate methods provided an accuracy of 74% and 69%, respectively. There are characteristic patterns of abnormal metabolic connectivity in mild Alzheimer’s disease and frontotemporal lobar degeneration. Such patterns can be utilized for single-subject analyses and might be more accurate in the differential diagnosis of dementing disorders than traditional intensity-based analyses.

Journal article

Lill CM, Rengmark A, Pihlstrom L, Fogh I, Shatunov A, Sleiman PM, Wang L-S, Liu T, Lassen CF, Meissner E, Alexopoulos P, Calvo A, Chio A, Dizdar N, Faltraco F, Forsgren L, Kirchheiner J, Kurz A, Larsen JP, Liebsch M, Linder J, Morrison KE, Nissbrandt H, Otto M, Pahnke J, Partch A, Restagno G, Rujescu D, Schnack C, Shaw CE, Shaw PJ, Tumani H, Tysnes O-B, Valladares O, Silani V, van den Berg LH, van Rheenen W, Veldink JH, Lindenberger U, Steinhagen-Thiessen E, Teipel S, Perneczky R, Hakonarson H, Hampel H, von Arnim CAF, Olsen JH, Van Deerlin VM, Al-Chalabi A, Toft M, Ritz B, Bertram Let al., 2015, The role of TREM2 R47H as a risk factor for Alzheimer's disease, frontotemporal lobar degeneration, amyotrophic lateral sclerosis, and Parkinson's disease, Alzheimers & Dementia, Vol: 11, Pages: 1407-1416, ISSN: 1552-5260

A rare variant in TREM2 (p.R47H, rs75932628) was recently reported to increase the risk of Alzheimer's disease (AD) and, subsequently, other neurodegenerative diseases, i.e. frontotemporal lobar degeneration (FTLD), amyotrophic lateral sclerosis (ALS), and Parkinson's disease (PD). Here we comprehensively assessed TREM2 rs75932628 for association with these diseases in a total of 19,940 previously untyped subjects of European descent. These data were combined with those from 28 published data sets by meta‐analysis. Furthermore, we tested whether rs75932628 shows association with amyloid beta (Aβ42) and total‐tau protein levels in the cerebrospinal fluid (CSF) of 828 individuals with AD or mild cognitive impairment. Our data show that rs75932628 is highly significantly associated with the risk of AD across 24,086 AD cases and 148,993 controls of European descent (odds ratio or OR = 2.71, P = 4.67 × 10−25). No consistent evidence for association was found between this marker and the risk of FTLD (OR = 2.24, P = .0113 across 2673 cases/9283 controls), PD (OR = 1.36, P = .0767 across 8311 cases/79,938 controls) and ALS (OR = 1.41, P = .198 across 5544 cases/7072 controls). Furthermore, carriers of the rs75932628 risk allele showed significantly increased levels of CSF‐total‐tau (P = .0110) but not Aβ42 suggesting that TREM2's role in AD may involve tau dysfunction.

Journal article

Granert O, Drzezga AE, Boecker H, Perneczky- R, Kurz A, Goetz J, van Eimeren T, Haeussermann Pet al., 2015, Metabolic Topology of Neurodegenerative Disorders: Influence of Cognitive and Motor Deficits, JOURNAL OF NUCLEAR MEDICINE, Vol: 56, Pages: 1916-1921, ISSN: 0161-5505

Journal article

Schulte EC, Fukumori A, Mollenhauer B, Hor H, Arzberger T, Perneczky R, Kurz A, Diehl-Schmid J, Huell M, Lichtner P, Eckstein G, Zimprich A, Haubenberger D, Pirker W, Bruecke T, Bereznai B, Molnar MJ, Lorenzo-Betancor O, Pastor P, Peters A, Gieger C, Estivill X, Meitinger T, Kretzschmar HA, Trenkwalder C, Haass C, Winkelmann Jet al., 2015, Rare variants in β-Amyloid precursor protein (APP) and Parkinson's disease, EUROPEAN JOURNAL OF HUMAN GENETICS, Vol: 23, Pages: 1328-1333, ISSN: 1018-4813

Journal article

Alexopoulos P, Roesler J, Thierjung N, Werle L, Buck D, Yakushev I, Gleixner L, Kagerbauer S, Ortner M, Grimmer T, Kübler H, Martin J, Laskaris N, Kurz A, Perneczky Ret al., 2015, Mapping CSF biomarker profiles onto NIA-AA guidelines for Alzheimer's disease., European Archives of Psychiatry and Clinical Neuroscience, Vol: 266, Pages: 587-597, ISSN: 1433-8491

The National Institute on Aging-Alzheimer's Association (NIA-AA) guidelines for Alzheimer's disease (AD) propose the categorization of individuals according to their biomarker constellation. Though the NIA-AA criteria for preclinical AD and AD dementia have already been applied in conjunction with imaging AD biomarkers, the application of the criteria using comprehensive cerebrospinal fluid (CSF) biomarker information has not been thoroughly studied yet. The study included a monocentric cohort with healthy (N = 41) and disease (N = 22) controls and patients with AD dementia (N = 119), and a multicentric sample with healthy controls (N = 116) and patients with AD dementia (N = 102). The CSF biomarkers β-amyloid 1-42, total tau, and phosphorylated tau at threonine 181 were measured with commercially available assays. Biomarker values were trichotomized into positive for AD, negative, or borderline. In controls the presence of normal CSF profiles varied between 13.6 and 25.4 % across the studied groups, while up to 8.6 % of them had abnormal CSF biomarkers. In 40.3-52.9 % of patients with AD dementia, a typical CSF profile for AD was detected. Approximately 40 % of the potential biomarker constellations are not considered in the NIA-AA guidelines, and more than 40 % of participants could not be classified into the NIA-AA categories with distinct biomarker constellations. Here, a refined scheme covering all potential biomarker constellations is proposed. These results enrich the discussion on the NIA-AA guidelines and point to a discordance between clinical symptomatology and CSF biomarkers even in patients with full-blown AD dementia, who are supposed to have a clearly positive for AD neurochemical profile.

Journal article

Li R, Perneczky R, Yakushev I, Foerster S, Kurz A, Drzezga A, Kramer Set al., 2015, Gaussian Mixture Models and Model Selection for [18F] Fluorodeoxyglucose Positron Emission Tomography Classification in Alzheimer’s Disease, PLOS One, Vol: 10, ISSN: 1932-6203

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.

Journal article

Ortner M, Kurz A, Alexopoulos P, Auer F, Diehl-Schmid J, Drzezga A, Foerster S, Foerstl H, Perneczky R, Sorg C, Yousefi BH, Grimmer Tet al., 2015, Small Vessel Disease, but Neither Amyloid Load nor Metabolic Deficit, Is Dependent on Age at Onset in Alzheimer's Disease, BIOLOGICAL PSYCHIATRY, Vol: 77, Pages: 704-710, ISSN: 0006-3223

Journal article

Li R, Perneczky R, Drzezga A, Kramer Set al., 2015, Efficient redundancy reduced subgroup discovery via quadratic programming, JOURNAL OF INTELLIGENT INFORMATION SYSTEMS, Vol: 44, Pages: 271-288, ISSN: 0925-9902

Journal article

Popp J, Wolfsgruber S, Heuser I, Peters O, Huell M, Schroeder J, Moeller H-J, Lewczuk P, Schneider A, Jahn H, Luckhaus C, Perneczky R, Froelich L, Wagner M, Maier W, Wiltfang J, Kornhuber J, Jessen Fet al., 2015, Cerebrospinal fluid cortisol and clinical disease progression in MCI and dementia of Alzheimer's type, NEUROBIOLOGY OF AGING, Vol: 36, Pages: 601-607, ISSN: 0197-4580

Journal article

Kloeppel S, Peter J, Ludl A, Pilatus A, Maier S, Mader I, Heimbach B, Frings L, Egger K, Dukart J, Schroeter ML, Perneczky R, Haeussermann P, Vach W, Urbach H, Teipel S, Huell M, Abdulkadir Aet al., 2015, Applying Automated MR-Based Diagnostic Methods to the Memory Clinic: A Prospective Study, JOURNAL OF ALZHEIMERS DISEASE, Vol: 47, Pages: 939-954, ISSN: 1387-2877

Journal article

Morbelli S, Brugnolo A, Bossert I, Buschiazzo A, Frisoni GB, Galluzzi S, van Berckel BNM, Ossenkoppele R, Perneczkyf R, Drzezga A, Didic M, Guedj E, Sambuceti G, Bottoni G, Arnaldi D, Picco A, De Carli F, Pagani M, Nobili Fet al., 2015, Visual Versus Semi-Quantitative Analysis of <SUP>18</SUP>F-FDG-PET in Amnestic MCI: An European Alzheimer's Disease Consortium (EADC) Project, JOURNAL OF ALZHEIMERS DISEASE, Vol: 44, Pages: 815-826, ISSN: 1387-2877

Journal article

Pagani M, De Carli F, Morbelli S, Oberg J, Chincarini A, Frisoni GB, Galluzzi S, Perneczky R, Drzezga A, van Berckel BNM, Ossenkoppele R, Didic M, Guedj E, Brugnolo A, Picco A, Arnaldi D, Ferrara M, Buschiazzo A, Sambuceti G, Nobili Fet al., 2015, Volume of interest-based [<SUP>18</SUP>F] fluorodeoxyglucose PET discriminates MCI converting to Alzheimer's disease from healthy controls. A European Alzheimer's Disease Consortium (EADC) study, NEUROIMAGE-CLINICAL, Vol: 7, Pages: 34-42, ISSN: 2213-1582

Journal article

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