Certified normal: Alzheimer's disease biomarkers and normative estimates of cognitive functioning

NEUROBIOLOGY OF AGING

卷:43

Article

Hassenstab, Jason^1,2,3  Chasse, Rachel^1,2  Grabow, Perri^1,4  Benzinger, Tammie L. S.^1,5,6  Fagan, Anne M.^1,2,7  Xiong, Chengjie^1,8  Jasielec, Mateusz⁸  Grant, Elizabeth^1,8  Morris, John C.^1,2,9,10,11 

[1] Washington Univ, Sch Med, Charles F & Joanne Knight Alzheimers Dis Res Ctr, St Louis, MO USA

[2] Washington Univ, Sch Med, Dept Neurol, St Louis, MO 63110 USA

[3] Washington Univ, Dept Psychol & Brian Sci, St Louis, MO USA

[4] Univ Missouri, Dept Psychol, 8001 Nat Bridge Rd, St Louis, MO 63121 USA

[5] Washington Univ, Sch Med, Dept Radiol, St Louis, MO 63110 USA

[6] Univ Missouri, Dept Neurol Surg, St Louis, MO 63121 USA

[7] Washington Univ, Sch Med, Hope Ctr Neurol Disorders, St Louis, MO USA

[8] Washington Univ, Sch Med, Dept Biostat, St Louis, MO USA

[9] Washington Univ, Sch Med, Dept Pathol & Immunol, St Louis, MO USA

[10] Washington Univ, Sch Med, Dept Phys Therapy, St Louis, MO USA

[11] Washington Univ, Sch Med, Dept Occupat Therapy, St Louis, MO USA

关键词: Alzheimer's disease;    Biomarkers;    Cognition;    Normative data;    Memory;    Preclinical disease;   

DOI  :  10.1016/j.neurobiolaging.2016.03.014

来源: Elsevier

【 摘 要 】

Normative samples drawn from older populations may unintentionally include individuals with preclinical Alzheimer's disease (AD) pathology, resulting in reduced means, increased variability, and overestimation of age effects on cognitive performance. A total of 264 cognitively normal (Clinical Dementia Rating = 0) older adults were classified as biomarker negative (Robust Normal, n = 177) or biomarker positive (Preclinical Alzheimer's Disease [PCAD], n = 87) based on amyloid imaging, cerebrospinal fluid biomarkers, and hippocampal volumes. PCAD participants performed worse than robust normals on nearly all cognitive measures. Removing PCAD participants from the normative sample yielded higher means and less variability on episodic memory, visuospatial ability, and executive functioning measures. These results were more pronounced in participants aged 75 years and older. Notably, removing PCAD participants from the sample significantly reduced age effects across all cognitive domains. Applying norms from the robust normal sample to a separate cohort did not improve Clinical Dementia Rating classification when using standard deviation cutoff scores. Overall, removing individuals with biomarker evidence of preclinical AD improves normative sample quality and substantially reduces age effects on cognitive performance but provides no substantive benefit for diagnostic classifications. (C) 2016 Elsevier Inc. All rights reserved.

【 授权许可】

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