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IC‐P‐067: THE BDNFVAL66MET SNP IS RELATED TO HIPPOCAMPAL CONNECTIVITY AND COGNITIVE DECLINE IN AUTOSOMAL DOMINANT ALZHEIMER'S DISEASE
Author(s) -
Franzmeier Nicolai,
Ren Jinyi,
Bateman Randall J.,
Morris John C.,
Levin Johannes,
Yakushev Igor,
Jucker Mathias,
Benzinger Tammie L.S.,
Ewers Michael
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.2018.06.2132
Subject(s) - hippocampus , hippocampal formation , neuroscience , episodic memory , alzheimer's disease , psychology , neurotrophic factors , cognitive decline , presenilin , resting state fmri , cognition , medicine , dementia , disease , receptor
amyloid b load. Here, in a genetically informative population of cognitively healthy, elderly identical twins, we compared this biomarker to a promising new candidate; white matter (WM) integrity measured by diffusion tensor imaging (DTI). Methods:Eightyeight genetically identical twin-pairs and 14 individual twins (n1⁄4190, mean age(SD)1⁄4 70 (7.5)) were selected from the EMIFAD PreclinAD study. Ab load, as a measure for amyloid aggregation, was quantified from [18F] Flutemetamol PET scans. Regional measurements of fractional anisotropy (FA) and mean diffusivity (MD), obtained with tract-based spatial statistics (TBSS) from FMRIB’s Software Library (FSL), were used as measures for WM integrity. Within-subject associations between amyloid aggregation and WM integrity were estimated using generalized estimating equations, correcting for twin dependency. A possible shared etiology between amyloid aggregation and WM integrity was further explored using a cross-twin cross-trait (CTCT) design, testing whether amyloid aggregation in a twin could predict WM integrity in the co-twin. Analyses were adjusted for age, sex and intracranial volume. Results:Amyloid aggregation predicted trends in increased FA and decreased MD. Regions of interest (ROIs) that met p 0.05 (uncorrected) are listed in table 1. After Bonferroni correction for multiple comparisons (0.05/23 tested ROIs1⁄40.002) our finding that amyloid aggregation was negatively associated with MD in the Corpus Callosum body remained significant (b1⁄40.188, p1⁄40.001). Results from CTCTanalysis were not significant. Conclusions:Our findings suggest that WM changes are potentially informative of pre-clinical AD stages. A longitudinal study is currently underway to confirm this. Interestingly, the present association with decreased MD suggests enhanced WM microstructure with amyloid aggregation in our unaffected population. This contradicts earlier studies in AD patients that reported increased MD with increased amyloid aggregation. A tentative explanation may be that there is a mechanism of WM compensation active during early amyloid pathology which breaks down at more advanced stages. Our data do not support a possible shared etiology between amyloid aggregation and WM integrity.