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P1‐431: APOE‐DEPENDENT LONGITUDINAL CHANGES IN DEFAULT MODE NETWORK FUNCTIONAL CONNECTIVITY IN SUBJECTIVE MEMORY COMPLAINERS
Author(s) -
Chiesa Patrizia A.,
Cavedo Enrica,
Potier Marie-Claude,
Lista Simone,
Dubois Bruno,
Thiebaut de Schotten Michel,
Hampel Harald
Publication year - 2018
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.2018.06.440
Subject(s) - default mode network , apolipoprotein e , precuneus , posterior cingulate , longitudinal study , psychology , neuroscience , hippocampus , anterior cingulate cortex , cognition , disease , medicine , pathology
Background:Effects of the risk allele APOE ε4 were tested on PET and CSF biomarkers of tau and amyloid pathology, atrophy and cognitive impairment in Alzheimer’s disease (AD) patients. Methods: Patients at the prodromal or dementia stages of AD were included (n1⁄446 APOE ε4-positive and n1⁄419 APOE ε4-negative). Tau PET imaging was done using the F-AV-1451 tracer. Amyloid PET imaging was done using the F-Flutemetamol. CSF amyloid b-42 (Ab42), total-tau and phosphorylated-tau were quantified. All patients had Ab-pathology, determined by low CSF Ab42 concentrations. Results: Tau biomarkers, cortical thickness, and cognitive profiles differed by APOE ε4 status. APOE ε4negative patients had significantly greater tau load, measured both by F-AV-1451 and CSF tau biomarkers. Correlations between FAV-1451 and CSF tau biomarkers were strongest in APOE ε4-negative patients. APOE ε4-positive patients had a higher ratio of FAV-1451 in the entorhinal cortex versus in the overall cortex, compared to APOE ε4-negative patients. APOE ε4-negative patients had reduced cortical thickness, especially in the parietal cortex. APOE ε4 and F-AV-1451 interacted to predict cortical thickness, with greater effects of F-AV-1451 on atrophy in APOE ε4-negative patients. APOE ε4 and F-AV-1451 were independent predictors of cognition, but showed distinct effects on different cognitive tests. APOE ε4-positive patients had slightly greater cortical b-amyloid load thanAPOE ε4-negative patients, measured by F-Flutemetamol. Conclusions:Our findings suggest that APOE genotype influences differences in disease pathways, both through differential development and spread of tau pathology, and through effects on cognitive outcomes that may involve non-tau-related mechanisms.