Subtle hippocampal deformities in breast cancer survivors with reduced episodic memory and self-reported cognitive concerns

Alexandra C Apple, Anthony J Ryals, Kathryn I Alpert, Lynne I Wagner, Pei-An Shih, Mehmet Dokucu, David Cella, Frank J Penedo, Joel L Voss, Lei Wang, Alexandra C Apple, Anthony J Ryals, Kathryn I Alpert, Lynne I Wagner, Pei-An Shih, Mehmet Dokucu, David Cella, Frank J Penedo, Joel L Voss, Lei Wang

Abstract

Cancer survivors have lingering cognitive problems, however the anatomical basis for these problems has yet to be fully elucidated. Clinical studies as well as animal models of chemotherapy have pinpointed cell and volume loss to the hippocampus, however, few studies have performed shape analysis of the hippocampus on cancer survivors. This study used high-dimensional deformation mapping analysis to test whether localized hippocampal deformation differs in breast cancer survivors who received adjuvant chemotherapy coupled with hormone blockade therapy, and if deformation was related to subjective self-reported concerns and cognitive performance. 3 T MRI images were acquired from 16 pre-menopausal breast cancer survivors and 18 healthy controls without a history of cancer. Breast cancer survivors had undergone chemotherapy within the eighteen months prior to the study, and were receiving estrogen-blockade therapy at the time of the study. Automated high-dimensional deformation mapping was used to compare localized hippocampal deformation differences between groups. Self-reported subjective concerns were assessed using Neuro-QOL Cognitive Function assessment, whereas cognitive performance was evaluated using the NIH Toolbox Cognition Battery. Relative to healthy controls, cancer survivors showed significantly more inward hippocampal deformation, worse self-reported cognitive functioning, and inferior episodic memory test score. This study is the first of its kind to examine the relationship between hippocampal deformity and cognitive impairment in cancer survivors.

Keywords: Cancer-related cognitive impairment (CRCI); Hippocampus; NIH toolbox; Neurocognitive.

Figures

Fig. 1
Fig. 1
Hippocampal deformity clusters after controlling for age. Inward deformation (blue and purple) as calculated from parameter estimates (t-values) of a vertex-wise difference in the deformation amplitude between controls and survivors (multiple comparison correction by Random Field Theory, FWER p < 0.05). Surface analysis yielded three significant clusters. The first cluster had 1651 vertices (out of 13,322), the second 576, and the third 714, with cluster-level p values of 5.503e-06, 0.000606, and 0.00385, respectively (SurfStat results data).

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