Synergism between fornix microstructure and beta amyloid accelerates memory decline in clinically normal older adults

The fornix is the primary efferent white matter tract of the hippocampus and is implicated in episodic memory. In this study, we investigated whether baseline measures of altered fornix microstructure and elevated beta amyloid (A beta) burden influence prospective cognitive decline. A secondary goal examined whether A beta burden is negatively associated with fornix microstructure. 253 clinically normal older adults underwent diffusion-weighted imaging and Pittsburgh Compound B positron emission tomography at baseline. We applied a novel streamline tractography protocol to reconstruct a fornix bundle in native space. Cognition was measured annually in domains of episodic memory, executive function, and processing speed (median follow-up = 4.0 +/- 1.4 years). After controlling for covariates, linear mixe-deffects models demonstrated an interaction of fornix microstructure with A beta burden on episodic memory, such that combined lower fornix microstructure and higher A beta burden was associated with accelerated decline. By contrast, associations with executive function and processing speed were not significant. There was no cross-sectional association between A beta burden and fornix microstructure. In conclusion, altered fornix microstructure may accelerate memory decline in preclinical Alzheimer's disease. (C) 2019 Elsevier Inc. All rights reserved.