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Neurobiol Aging. 2019 Sep;81:38-46. doi: 10.1016/j.neurobiolaging.2019.05.005. Epub 2019 May 16.

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

Author information

1
Department of Psychiatry, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA; Hurvitz Brain Sciences Research Program, Sunnybrook Research Institute, Toronto, Ontario, Canada.
2
Department of Radiology, Athinoula A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
3
Department of Neurology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA; Florey Institutes of Neuroscience and Mental Health, Melbourne and Melbourne School of Psychological Science, University of Melbourne, Melbourne, Australia; Department of Neurology, Center for Alzheimer Research and Treatment, Brigham and Women's Hospital, Boston, MA, USA.
4
Department of Neurology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA; Department of Neurology, Center for Alzheimer Research and Treatment, Brigham and Women's Hospital, Boston, MA, USA; Division of Nuclear Medicine and Molecular Imaging, Massachusetts General Hospital, Boston, MA, USA.
5
Department of Radiology, Athinoula A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA; Department of Neurology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA; Department of Neurology, Center for Alzheimer Research and Treatment, Brigham and Women's Hospital, Boston, MA, USA.
6
Department of Radiology, Athinoula A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA; Department of Neurology, Icahn School of Medicine at Mount Sinai, New York, NY, USA. Electronic address: trey.hedden@mssm.edu.

Abstract

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 (Aβ) burden influence prospective cognitive decline. A secondary goal examined whether Aβ 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 mixed-effects models demonstrated an interaction of fornix microstructure with Aβ burden on episodic memory, such that combined lower fornix microstructure and higher Aβ 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 Aβ burden and fornix microstructure. In conclusion, altered fornix microstructure may accelerate memory decline in preclinical Alzheimer's disease.

KEYWORDS:

Beta amyloid; Episodic memory; Fornix; Preclinical Alzheimer's disease; White matter diffusion

PMID:
31207468
PMCID:
PMC6732225
[Available on 2020-09-01]
DOI:
10.1016/j.neurobiolaging.2019.05.005

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