TY - JOUR
T1 - Certified normal
T2 - Alzheimer's disease biomarkers and normative estimates of cognitive functioning
AU - Hassenstab, Jason
AU - Chasse, Rachel
AU - Grabow, Perri
AU - Benzinger, Tammie L.S.
AU - Fagan, Anne M.
AU - Xiong, Chengjie
AU - Jasielec, Mateusz
AU - Grant, Elizabeth
AU - Morris, John C.
N1 - Publisher Copyright:
© 2016 Elsevier Inc.
PY - 2016/7/1
Y1 - 2016/7/1
N2 - 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.
AB - 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.
KW - Alzheimer's disease
KW - Biomarkers
KW - Cognition
KW - Memory
KW - Normative data
KW - Preclinical disease
UR - http://www.scopus.com/inward/record.url?scp=84963964149&partnerID=8YFLogxK
U2 - 10.1016/j.neurobiolaging.2016.03.014
DO - 10.1016/j.neurobiolaging.2016.03.014
M3 - Article
C2 - 27255812
AN - SCOPUS:84963964149
SN - 0197-4580
VL - 43
SP - 23
EP - 33
JO - Neurobiology of Aging
JF - Neurobiology of Aging
ER -