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[P1–253]: LONGITUDINAL DIFFERENCES IN THE PROGRESSION FROM MCI TO AD BETWEEN HISPANIC AND NON‐HISPANIC SUBJECTS
Author(s) -
MartinezTorteya Antonio,
MoralesHenríquez Daniela S.,
TamezPeña Jose
Publication year - 2017
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.2017.06.269
Subject(s) - neuropsychology , autoregressive model , longitudinal study , longitudinal data , audiology , psychology , medicine , cognition , demography , statistics , mathematics , psychiatry , sociology
Background:Biomarkers offer the potential for an unbiased, objective picture of underlying disease pathology. Classical AD biomarkers such as cerebrospinal fluid (CSF) beta-amyloid (Ab1-42) and total-tau (t-tau) are considered suitable endpoints in clinical trials of preventative treatments, providing a clear picture of the development of AD pathology in the clinically silent stage (preclinical) of the disease. Methods:We performed a correlation analysis on a selection of biochemical (CSF Ab1-42, and CSF t-tau), neurophysiological (FDG-PET), volumetric (hippocampal volume), and cognitive markers, using the Alzheimer’s Disease Neuroimaging Initiative (ADNI) dataset, at baseline and longitudinally. We describe 4 biological (biochemical) phenotypes (CSF Ab1-42 >1⁄4 192 pg/mL and CSF t-tau<1⁄4 93 pg/mL as normal) at baseline, and compare thesewith clinically derived diagnostic groupings. Per capita rate of changes in CSFAb and t-tau are quantified, and population estimates, in addition to individual trajectories, are assessed in relation to their biological phenotype and change in cognitive diagnosis. Results:A strong, inverse correlation was found between CSF Ab1-42 and CSF t-tau (r 1⁄4 -0.43), as well as CSF Ab1-42 and ADAScog-11 (r 1⁄4 -0.38). A ‘phase’ plot of the concentrations of Ab1-42 and t-tau, show a highly non-linear “right angle” relationship. We observe strong but imperfect concordance between biological phenotypes and cognitive diagnosis, 63% of ADdiagnoses individuals present with an ‘AD typical’ biological phenotype while 49.8% of cognitively normal (CN) individuals present with a ‘CN typical’ phenotype at baseline. A small per capita annual rate of change is observed in CSF Ab1-42 and CSF t-tau concentrations relative to variance. The greatest per capita rate of change in Ab occurs in CN individuals who do not progress to MCI/AD across follow-up (CN-NP), mean rate of -2.4 pg/mL/ year, and those with progressive MCI (MCI-P) accumulate the largest amount of t-tau, mean rate of 2.2 pg/mL/year. Conclusions: Our findings support the ordering of biomarker changes suggested by the amyloid cascade hypothesis. The high variance in CSF Ab and t-tau concentrations, within subjects longitudinally, impairs quantification and visualisation of individual biomarker trajectories. The phase plots of Ab1-42 versus t-tau suggest a highly non-linear dynamic between the two variables.