Dentate Gyrus Volume Mediates the Effect of Fornix Microstructure on Memory Formation in Older Adults

TY - JOUR

T1 - Dentate Gyrus Volume Mediates the Effect of Fornix Microstructure on Memory Formation in Older Adults

AU - Hayek, Dayana

AU - Thams, Friederike

AU - Flöel, Agnes

AU - Antonenko, Daria

N1 - Copyright © 2020 Hayek, Thams, Flöel and Antonenko.

PY - 2020

Y1 - 2020

N2 - Age-related deterioration in white and gray matter is linked to cognitive deficits. Reduced microstructure of the fornix, the major efferent pathway of the hippocampus, and volume of the dentate gyrus (DG), may cause age-associated memory decline. However, the linkage between these anatomical determinants and memory retrieval in healthy aging are poorly understood. In 30 older adults, we acquired diffusion tensor and T1-weighted images for individual deterministic tractography and volume estimation. A memory task, administered outside of the scanner to assess retrieval of learned associations, required discrimination of previously acquired picture-word pairs. The results showed that fornix fractional anisotropy (FA) and left DG volumes were related to successful retrieval. These brain-behavior associations were observed for correct rejections, but not hits, indicating specificity of memory network functioning for detecting false associations. Mediation analyses showed that left DG volume mediated the effect of fornix FA on memory (48%), but not vice versa. These findings suggest that reduced microstructure induces volume loss and thus negatively affects retrieval of learned associations, complementing evidence of a pivotal role of the fornix in healthy aging. Our study offers a neurobehavioral model to explain variability in memory retrieval in older adults, an important prerequisite for the development of interventions to counteract cognitive decline.

AB - Age-related deterioration in white and gray matter is linked to cognitive deficits. Reduced microstructure of the fornix, the major efferent pathway of the hippocampus, and volume of the dentate gyrus (DG), may cause age-associated memory decline. However, the linkage between these anatomical determinants and memory retrieval in healthy aging are poorly understood. In 30 older adults, we acquired diffusion tensor and T1-weighted images for individual deterministic tractography and volume estimation. A memory task, administered outside of the scanner to assess retrieval of learned associations, required discrimination of previously acquired picture-word pairs. The results showed that fornix fractional anisotropy (FA) and left DG volumes were related to successful retrieval. These brain-behavior associations were observed for correct rejections, but not hits, indicating specificity of memory network functioning for detecting false associations. Mediation analyses showed that left DG volume mediated the effect of fornix FA on memory (48%), but not vice versa. These findings suggest that reduced microstructure induces volume loss and thus negatively affects retrieval of learned associations, complementing evidence of a pivotal role of the fornix in healthy aging. Our study offers a neurobehavioral model to explain variability in memory retrieval in older adults, an important prerequisite for the development of interventions to counteract cognitive decline.

U2 - 10.3389/fnagi.2020.00079

DO - 10.3389/fnagi.2020.00079

M3 - SCORING: Journal article

C2 - 32265687

VL - 12

JO - FRONT AGING NEUROSCI

JF - FRONT AGING NEUROSCI

SN - 1663-4365

M1 - 79

ER -