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Common variants in Alzheimer's disease and risk stratification by polygenic ris...

de Rojas, Itziar; Moreno-Grau, Sonia; Tesi, Niccolo; Grenier-Boley, Benjamin; Andrade, Victor; Jansen, Iris E.; Pedersen, Nancy L.; Stringa, Najada

Genetic discoveries of Alzheimer's disease are the drivers of our understanding, and together with polygenetic risk stratification can contribute towards planning of feasible and efficient preventive and curative clinical trials. We first perform a large genetic association study by merging all available case-control datasets and by-proxy study results (discovery n = 409,435 and validation size n = 58,190). Her...


Biomarker-based prognosis for people with mild cognitive impairment (ABIDE) : a...

van Maurik, Ingrid S; Vos, Stephanie J.; Bos, Isabelle; Bouwman, Femke H; Teunissen, Charlotte E.; Scheltens, Philip; Barkhof, Frederik; Frolich, Lutz

Background: Biomarker-based risk predictions of dementia in people with mild cognitive impairment are highly relevant for care planning and to select patients for treatment when disease-modifying drugs become available. We aimed to establish robust prediction models of disease progression in people at risk of dementia. Methods: In this modelling study, we included people with mild cognitive impairment (MCI) fro...


Biomarker-based prognosis for people with mild cognitive impairment (ABIDE): a ...

van Maurik, Ingrid S.; Vos, Stephanie J.; Bos, Isabelle; Bouwman, Femke H.; Teunissen, Charlotte E.; Scheitens, Philip; Barkhof, Frederik; Frolich, Lutz

Background Biomarker-based risk predictions of dementia in people with mild cognitive impairment are highly relevant for care planning and to select patients for treatment when disease-modifying drugs become available. We aimed to establish robust prediction models of disease progression in people at risk of dementia. Methods In this modelling study, we included people with mild cognitive impairment (MCI) from ...


Analysis of shared heritability in common disorders of the brain

Anttila, Verneri; Bulik-Sullivan, Brendan; Finucane, Hilary K.; Walters, Raymond K.; Bras, Jose; Duncan, Laramie; Escott-Price, Valentina

Disorders of the brain can exhibit considerable epidemiological comorbidity and often share symptoms, provoking debate about their etiologic overlap. We quantified the genetic sharing of 25 brain disorders from genome-wide association studies of 265,218 patients and 784,643 control participants and assessed their relationship to 17 phenotypes from 1,191,588 individuals. Psychiatric disorders share common varian...


The frequency and influence of dementia risk factors in prodromal Alzheimer's d...

Bos, Isabelle; Vos, Stephanie J.; Frölich, Lutz; Kornhuber, Johannes; Wiltfang, Jens; Maier, Wolfgang; Peters, Oliver; Rüther, Eckhart

We investigated whether dementia risk factors were associated with prodromal Alzheimer's disease (AD) according to the International Working Group-2 and National Institute of Aging-Alzheimer's Association criteria, and with cognitive decline. A total of 1394 subjects with mild cognitive impairment from 14 different studies were classified according to these research criteria, based on cognitive performance and ...


Prevalence of cerebral amyloid pathology in persons without dementia

Jansen, Willemijn J.; Ossenkoppele, Rik; Knol, Dirk L.; Tijms, Betty M.; Scheltens, Philip; Verhey, Frans R. J.; Visser, Pieter Jelle; Aalten, Pauline

Importance: Cerebral amyloid-β aggregation is an early pathological event in Alzheimer disease (AD), starting decades before dementia onset. Estimates of the prevalence of amyloid pathology in persons without dementia are needed to understand the development of AD and to design prevention studies. Objective: To use individual participant data meta-analysis to estimate the prevalence of amyloid pathology as meas...


Prevalence and prognosis of Alzheimer’s disease at the mild cognitive impairmen...

Vos, Stephanie J. B.; Verhey, Frans; Frölich, Lutz; Kornhuber, Johannes; Wiltfang, Jens; Maier, Wolfgang; Peters, Oliver; Rüther, Eckart; Nobili, Flavio

Three sets of research criteria are available for diagnosis of Alzheimer's disease in subjects with mild cognitive impairment: the International Working Group-1, International Working Group-2, and National Institute of Aging-Alzheimer Association criteria. We compared the prevalence and prognosis of Alzheimer's disease at the mild cognitive impairment stage according to these criteria. Subjects with mild cognit...


Biomarkers for Alzheimer's disease therapeutic trials

Hampel, Harald; Wilcock, Gordon; Andrieu, Sandrine; Aisen, Paul; Blennow, Kaj; Broich, K.; Carrillo, Maria; Nick, C. Fox; Frisoni, Giovanni B.

The development of disease-modifying treatments for Alzheimer's disease requires innovative trials with large numbers of subjects and long observation periods. The use of blood, cerebrospinal fluid or neuroimaging biomarkers is critical for the demonstration of disease-modifying therapy effects on the brain. Suitable biomarkers are those which reflect the progression of AD related molecular mechanisms and neuro...


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