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O1‐01‐02: The cognitive and brain volumetric trajectories of healthy elderly controls with either Alzheimer's pathology, neurodegeneration (SNAP), or both
Author(s) -
Burnham Samantha,
Bourgeat Pierrick,
Doré Vincent,
Brown Belinda M.,
Salvado Olivier,
Martins Ralph N.,
Macaulay Lance,
Ames David,
Masters Colin L.,
Rowe Christopher C.,
Villemagne Victor L.
Publication year - 2015
Publication title -
alzheimer's and dementia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 6.713
H-Index - 118
eISSN - 1552-5279
pISSN - 1552-5260
DOI - 10.1016/j.jalz.2015.07.028
Subject(s) - neurodegeneration , cognition , medicine , cognitive decline , alzheimer's disease , disease , brain aging , dementia , psychology , neuroscience , pathology
preclinical stages, and examine the longitudinal cognitive outcomes of individuals in each stage. Methods: We included 212 cognitively normal individuals (mean age 66. 8, females1⁄4132), with a clinical dementia rating (CDR) of 0. All participants had clinical data and ameasurement of hippocampal volume on MRI, abeta1-42 and tau in CSF and amyloid binding on [C]Pittsburgh Compound B (PiB) PET, all within one year. Cutoffs to denote abnormality were determined using ROC analysis comparing cognitively normal individuals to those with very mild dementia (CDR1⁄40.5) and a clinical AD diagnosis. Subtle cognitive impairmentwasdefinedusingacompositeof threeneuropsychological tests. Using CSF biomarkers alone, neuroimaging markers alone, and using an integrated approach the cohort was classified into Stages 1-3, Suspected Non-Alzheimer Pathophysiology (SNAP), a normal or an unclassified group (Table 1). Longitudinal progression to CDR>0 was modeled using survival analyses.Results: Controlling for appropriate covariates, correlations between CSF Ab 42 and the mean cortical PIB binding potential (MCBP) were significant (r1⁄4.39, p<.0001), while the relationships between adjusted hippocampal volume and CSF (r1⁄4.04, p1⁄4.52) and ptau (r1⁄4.03, p1⁄4.62) were not (Figures 1 & 2). Individuals classified as Stage 2 and 3 were at an elevated risk of later dementia relative to those in Stage 0. (Figures 3-5) Conclusions:The NIA-AA preclinical stages successfully stratify dementia risk using both CSF and neuroimaging biomarkers. Measures of amyloid were highly congruent, while measures of neurodegeneration were often incongruent. This suggests that such markers cannot be used interchangeably to represent the same pathology.