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Front Aging Neurosci. 2018 Jun 25;10:193. doi: 10.3389/fnagi.2018.00193. eCollection 2018.

Amyloid-β, Tau, and Cognition in Cognitively Normal Older Individuals: Examining the Necessity to Adjust for Biomarker Status in Normative Data.

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Department of Psychiatry and Neuropsychology, Alzheimer Center Limburg, School for Mental Health and Neuroscience Maastricht University, Maastricht, Netherlands.
University Hospital Leuven, Belgium.
Laboratory for Cognitive Neurology, Department of Neurosciences KU Leuven, Leuven, Belgium.
Alzheimer Research Centre KU Leuven, Leuven, Belgium.
Center for Research and Advanced Therapies CITA-Alzheimer Foundation, San Sebastián, Spain.
Alzheimer Center and Department of Neurology, Neuroscience Campus Amsterdam, VU University Medical Center VU University Amsterdam, Amsterdam, Netherlands.
Department of Biological Psychology VU University Amsterdam, Amsterdam, Netherlands.
Department of Neurology Hospital de la Santa Creu i Sant Pau, Barcelona, Spain.
Section for Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, University of Gothenburg Sahlgrenska Academy, Gothenburg, Sweden.
Nuffield Department of Clinical Neurosciences University of Oxford, Oxford, United Kingdom.
Alzheimer's Disease & Other Cognitive Disorders Unit, Hopsital Clínic Consorci Institut D'Investigacions Biomediques August Pi I Sunyer (IDIBAPS), Barcelona, Spain.
Barcelona Beta Brain Research Center Unversitat Pompeu Fabra, Barcelona, Spain.
Institut National de la Santé et de la Recherche Médicale UMR-S U1237, Université de Caen-Normandie GIP Cyceron, Caen, France.
Institut National de la Santé et de la Recherche Médicale U1077, Université de Caen Normandie Ecole Pratique des Hautes Etudes, Caen, France.
CHU de Caen Service de Neurologie, Caen, France.
1st Department of Neurology University General Hospital of Thessaloniki AHEPA, Thessaloniki, Greece.
Division of Clinical Geriatrics, Department of Neurobiology, Caring Sciences and Society (NVS) Karolinska Institutet, Stockholm, Sweden.
Department of Geriatric Medicine, Karolinska University Hospital Huddinge Karolinska Institutet, Stockholm, Sweden.
Department of Psychiatry Norrtälje Hospital Tiohundra, Norrtälje, Sweden.
Danish Dementia Research Centre, Rigshospitalet, Copenhagen University Hospital University of Copenhagen, Copenhagen, Denmark.
Janssen Pharmaceutical Research and Development Titusville, NJ, United States.


We investigated whether amyloid-β (Aβ) and tau affected cognition in cognitively normal (CN) individuals, and whether norms for neuropsychological tests based on biomarker-negative individuals would improve early detection of dementia. We included 907 CN individuals from 8 European cohorts and from the Alzheimer's disease Neuroimaging Initiative. All individuals were aged above 40, had Aβ status and neuropsychological data available. Linear mixed models were used to assess the associations of Aβ and tau with five neuropsychological tests assessing memory (immediate and delayed recall of Auditory Verbal Learning Test, AVLT), verbal fluency (Verbal Fluency Test, VFT), attention and executive functioning (Trail Making Test, TMT, part A and B). All test except the VFT were associated with Aβ status and this influence was augmented by age. We found no influence of tau on any of the cognitive tests. For the AVLT Immediate and Delayed recall and the TMT part A and B, we calculated norms in individuals without Aβ pathology (Aβ- norms), which we validated in an independent memory-clinic cohort by comparing their predictive accuracy to published norms. For memory tests, the Aβ- norms rightfully identified an additional group of individuals at risk of dementia. For non-memory test we found no difference. We confirmed the relationship between Aβ and cognition in cognitively normal individuals. The Aβ- norms for memory tests in combination with published norms improve prognostic accuracy of dementia.


Alzheimer's disease; amyloid-beta; cognition; neuropsychological examination; normative data; tau

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