High resolution structural and functional MRI of the hippocampus in young adults with Down syndrome

Katherine A Koenig; Se-Hong Oh; Melissa R Stasko; Elizabeth C Roth; H Gerry Taylor; Stephen Ruedrich; Z Irene Wang; James B Leverenz; Alberto C S Costa

doi:10.1093/braincomms/fcab088

High resolution structural and functional MRI of the hippocampus in young adults with Down syndrome

Brain Commun. 2021 Apr 19;3(2):fcab088. doi: 10.1093/braincomms/fcab088. eCollection 2021.

Authors

Katherine A Koenig¹, Se-Hong Oh^{1

2}, Melissa R Stasko³, Elizabeth C Roth³, H Gerry Taylor⁴, Stephen Ruedrich⁵, Z Irene Wang⁶, James B Leverenz⁷, Alberto C S Costa^{3

5}

Affiliations

¹ Imaging Sciences, Imaging Institute, Cleveland Clinic, Cleveland, OH 44195, USA.
² Department of Biomedical Engineering, Hankuk University of Foreign Studies, Yongin 449-791, Republic of Korea.
³ Department of Pediatrics, Case Western Reserve University, Cleveland, OH 44106, USA.
⁴ Abigail Wexner Research Institute at Nationwide Children's Hospital, and Department of Pediatrics, The Ohio State University, Columbus, OH 43215, USA.
⁵ Department of Psychiatry, University Hospitals, Cleveland, OH 44106, USA.
⁶ Epilepsy Center, Neurological Institute, Cleveland Clinic, Cleveland, OH 44195, USA.
⁷ Lou Ruvo Center for Brain Health, Neurological Institute, Cleveland Clinic, Cleveland, OH 44195, USA.

Abstract

Down syndrome is the phenotypic consequence of trisomy 21, with clinical presentation including both neurodevelopmental and neurodegenerative components. Although the intellectual disability typically displayed by individuals with Down syndrome is generally global, it also involves disproportionate deficits in hippocampally-mediated cognitive processes. Hippocampal dysfunction may also relate to Alzheimer's disease-type pathology, which can appear in as early as the first decade of life and becomes universal by age 40. Using 7-tesla MRI of the brain, we present an assessment of the structure and function of the hippocampus in 34 individuals with Down syndrome (mean age 24.5 years ± 6.5) and 27 age- and sex-matched typically developing healthy controls. In addition to increased whole-brain mean cortical thickness and lateral ventricle volumes (P < 1.0 × 10^-4), individuals with Down syndrome showed selective volume reductions in bilateral hippocampal subfields cornu Ammonis field 1, dentate gyrus, and tail (P < 0.005). In the group with Down syndrome, bilateral hippocampi showed widespread reductions in the strength of functional connectivity, predominately to frontal regions (P < 0.02). Age was not related to hippocampal volumes or functional connectivity measures in either group, but both groups showed similar relationships of age to whole-brain volume measures (P < 0.05). Finally, we performed an exploratory analysis of a subgroup of individuals with Down syndrome with both imaging and neuropsychological assessments. This analysis indicated that measures of spatial memory were related to mean cortical thickness, total grey matter volume and right hemisphere hippocampal subfield volumes (P < 0.02). This work provides a first demonstration of the usefulness of high-field MRI to detect subtle differences in structure and function of the hippocampus in individuals with Down syndrome, and suggests the potential for development of MRI-derived measures as surrogate markers of drug efficacy in pharmacological studies designed to investigate enhancement of cognitive function.

Keywords: Down syndrome; MRI; functional connectivity; hippocampus; spatial memory.

Grants and funding

P30 AG062428/AG/NIA NIH HHS/United States