Age and diagnostic performance of Alzheimer disease CSF biomarkers
2012 (English)In: Neurology, ISSN 0028-3878, E-ISSN 1526-632X, Vol. 78, no 7, 468-476 p.Article in journal (Refereed) Published
Objectives: Core CSF changes in Alzheimer disease (AD) are decreased amyloid beta(1-42), increased total tau, and increased phospho-tau, probably indicating amyloid plaque accumulation, axonal degeneration, and tangle pathology, respectively. These biomarkers identify AD already at the predementia stage, but their diagnostic performance might be affected by age-dependent increase of AD-type brain pathology in cognitively unaffected elderly. less thanbrgreater than less thanbrgreater thanMethods: We investigated effects of age on the diagnostic performance of CSF biomarkers in a uniquely large multicenter study population, including a cross-sectional cohort of 529 patients with AD dementia (median age 71, range 43-89 years) and 304 controls (67, 44-91 years), and a longitudinal cohort of 750 subjects without dementia with mild cognitive impairment (69, 43-89 years) followed for at least 2 years, or until dementia diagnosis. less thanbrgreater than less thanbrgreater thanResults: The specificities for subjects without AD and the areas under the receiver operating characteristics curves decreased with age. However, the positive predictive value for a combination of biomarkers remained stable, while the negative predictive value decreased only slightly in old subjects, as an effect of the high AD prevalence in older ages. less thanbrgreater than less thanbrgreater thanConclusion: Although the diagnostic accuracies for AD decreased with age, the predictive values for a combination of biomarkers remained essentially stable. The findings highlight biomarker variability across ages, but support the use of CSF biomarkers for AD even in older populations.
Place, publisher, year, edition, pages
American Academy of Neurology (AAN) , 2012. Vol. 78, no 7, 468-476 p.
National CategoryMedical and Health Sciences
IdentifiersURN: urn:nbn:se:liu:diva-75904DOI: 10.1212/WNL.0b013e3182477eedISI: 000300605100008OAI: oai:DiVA.org:liu-75904DiVA: diva2:510544
Funding Agencies|Swedish Brain Power||Swedish Research Council|140022006-6227KP2010-63P-21562-01-4K2011-61X-20401-05-6|Alzheimers Association|NIRG-08-90356|cNEUPRO||Lundbeck Foundation||Royal Swedish Academy of Sciences||Sahlgrenska University Hospital||Sahlgrenska Academy||Stiftelsen Psykiatriska Forskningsfonden||Stiftelsen Gamla Tjanarinnor||Uppsala Universitets Medicinska Fakultet stiftelse for psykiatrisk och neurologisk forskning||Swedish Brain Fund||Soderberg Foundation||Alzheimer Foundation, Sweden||Dementia Association, Sweden||Alzheimers Association||International College of Geriatric Psychoneuropharmacology||Schering-Plough Corp.||AADC Research Trust||Internationale Stichting Alzheimer Onderzoek||Center for Translational Molecular Medicine||American Alzheimer Association||Alzheimer Drug Discovery Foundation||Stichting Internationaal Parkinson Fonds||Hersenstichting Nederland||Lundbeck, Inc||Novartis||GE Healthcare||GlaxoSmithKline||DiaGenic ASA||Lundbeck, Inc.||Merck Serono||European Commission||B.R.A.H.M.S.||Biotech GmbH||Janssen||BMBF (German Ministry for Education and Research)||Trinity College Dublin, Ireland||State of Hess, Germany||Katharina-Hardt-Foundation||Thea-Goering-Foundation||Alzheimer Nederland||Stichting VUmc fonds||Innovation Fund||Swedish Research Council||Swedish municipalities (SKL)||Swedish Brain Power network||Gustav V and Queen Victorias Freemason Foundation||Pfizer Inc||Eisai Inc.||Knut & Alice Wallenberg Foundation||Bristol-Myers Squibb||Research Council, Sweden||Vastra Gotalandsregionen, Sweden||Swedish Brain Power Project||Swedish Council for Working Life and Social Research||Swedish Alzheimer Foundation||Stiftelsen for Gamla Tjanarinnor||King Gustaf V and Queen Victorias Foundation||Swedish State Support for Clinical Research||2012-03-162012-03-162012-03-16