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Predicting Cognitive Decline across Four Decades in Mutation Carriers and Non-carriers in Autosomal-Dominant Alzheimer’s Disease

Published online by Cambridge University Press:  12 January 2017

Ove Almkvist ,
Elena Rodriguez-Vieitez ,
Steinunn Thordardottir ,
Kaarina Amberla ,
Karin Axelman ,
Hans Basun ,
Anne Kinhult-Ståhlbom ,
Lena Lilius ,
Anne Remes  and
Lars-Olof Wahlund
...Show all authors
Ove Almkvist*
Affiliation:
Karolinska Institutet, Center for Alzheimer Research, Department of Neurobiology Care Sciences and Society, Division of Translational Alzheimer Neurobiology, Stockholm, Sweden Department of Geriatric Medicine, Karolinska University Hospital at Huddinge, Stockholm, Sweden Department of Psychology, Stockholm University, Stockholm, Sweden
Elena Rodriguez-Vieitez
Affiliation:
Karolinska Institutet, Center for Alzheimer Research, Department of Neurobiology Care Sciences and Society, Division of Translational Alzheimer Neurobiology, Stockholm, Sweden
Steinunn Thordardottir
Affiliation:
Department of Geriatric Medicine, Karolinska University Hospital at Huddinge, Stockholm, Sweden Karolinska Institutet, Center for Alzheimer Research, Department of Neurobiology Care Sciences and Society, Division of Neurogeriatrics, Stockholm, Sweden
Kaarina Amberla
Affiliation:
Department of Geriatric Medicine, Karolinska University Hospital at Huddinge, Stockholm, Sweden
Karin Axelman
Affiliation:
Department of Geriatric Medicine, Karolinska University Hospital at Huddinge, Stockholm, Sweden
Hans Basun
Affiliation:
Department of Public Health and Caring Sciences/Geriatrics, Uppsala University, Uppsala, Sweden
Anne Kinhult-Ståhlbom
Affiliation:
Department of Geriatric Medicine, Karolinska University Hospital at Huddinge, Stockholm, Sweden Karolinska Institutet, Center for Alzheimer Research, Department of Neurobiology Care Sciences and Society, Division of Neurogeriatrics, Stockholm, Sweden
Lena Lilius
Affiliation:
Department of Geriatric Medicine, Karolinska University Hospital at Huddinge, Stockholm, Sweden
Anne Remes
Affiliation:
Department of Neurology, Institute of Clinical Medicine Neurology, University of Eastern Finland, Kuopio, Finland
Lars-Olof Wahlund
Affiliation:
Department of Geriatric Medicine, Karolinska University Hospital at Huddinge, Stockholm, Sweden Karolinska Institutet, Center for Alzheimer Research, Department of Neurobiology Care Sciences and Society, Division of Clinical Geriatrics, Stockholm, Sweden
Matti Viitanen
Affiliation:
Department of Geriatric Medicine, Karolinska University Hospital at Huddinge, Stockholm, Sweden Karolinska Institutet, Center for Alzheimer Research, Department of Neurobiology Care Sciences and Society, Division of Clinical Geriatrics, Stockholm, Sweden Department of Geriatrics, Turku City Hospital, Turku, Finland University of Turku, Turku, Finland
Lars Lannfelt
Affiliation:
Department of Public Health and Caring Sciences/Geriatrics, Uppsala University, Uppsala, Sweden
Caroline Graff
Affiliation:
Department of Geriatric Medicine, Karolinska University Hospital at Huddinge, Stockholm, Sweden Karolinska Institutet, Center for Alzheimer Research, Department of Neurobiology Care Sciences and Society, Division of Neurogeriatrics, Stockholm, Sweden
*
Correspondence and reprint requests to: Ove Almkvist, Karolinska Institutet, Center for Alzheimer Research; Department of Neurobiology Care Sciences and Society, Division of Translational Alzheimer Neurobiology, SE-14157 Huddinge, Sweden. E-mail: ove.almkvist@ki.se
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Abstract

Objectives: The aim of this study was to investigate cognitive performance including preclinical and clinical disease course in carriers and non-carriers of autosomal-dominant Alzheimer’s disease (adAD) in relation to multiple predictors, that is, linear and non-linear estimates of years to expected clinical onset of disease, years of education and age. Methods: Participants from five families with early-onset autosomal-dominant mutations (Swedish and Arctic APP, PSEN1 M146V, H163Y, and I143T) included 35 carriers (28 without dementia and 7 with) and 44 non-carriers. All participants underwent a comprehensive clinical evaluation, including neuropsychological assessment at the Memory Clinic, Karolinska University Hospital at Huddinge, Stockholm, Sweden. The time span of disease course covered four decades of the preclinical and clinical stages of dementia. Neuropsychological tests were used to assess premorbid and current global cognition, verbal and visuospatial functions, short-term and episodic memory, attention, and executive function. Results: In carriers, the time-related curvilinear trajectory of cognitive function across disease stages was best fitted to a formulae with three predictors: years to expected clinical onset (linear and curvilinear components), and years of education. In non-carriers, the change was minimal and best predicted by two predictors: education and age. The trajectories for carriers and non-carriers began to diverge approximately 10 years before the expected clinical onset in episodic memory, executive function, and visuospatial function. Conclusions: The curvilinear trajectory of cognitive functions across disease stages was mimicked by three predictors in carriers. In episodic memory, executive and visuospatial functions, the point of diverging trajectories occurred approximately 10 years ahead of the clinical onset compared to non-carriers. (JINS, 2017, 23, 195–203)

Keywords

Autosomal-dominantAlzheimer’s diseaseMutation carrierCognitionPredictorsAge of onset
Type
Research Articles
Information
Journal of the International Neuropsychological Society , Volume 23 , Issue 3 , March 2017 , pp. 195 - 203
Copyright
Copyright © The International Neuropsychological Society 2017 

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