Key result
Young adults with Down syndrome show reduced hippocampal volume and functional connectivity vs healthy controls.
Why the study?
Individuals with Down syndrome exhibit disproportionate deficits in hippocampally-mediated cognitive processes and early Alzheimer’s-type pathology, but detailed hippocampal structure and function assessments are lacking.
Observational (n=61)
p-value: p=<0.005
High-field 7-tesla MRI can detect subtle differences in hippocampal structure and function in young adults with Down syndrome, suggesting its potential as a surrogate marker for pharmacological studies.
7T MRI may detect hippocampal changes in Down syndrome; leaves open validation as surrogate marker for trials.
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.
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Koenig et al. (2021) conducted an observational in Down syndrome (n=61). Down syndrome vs. Typically developing healthy controls was evaluated on Volume of bilateral hippocampal subfields cornu Ammonis field 1, dentate gyrus, and tail (p=<0.005). Young adults with Down syndrome showed selective volume reductions in bilateral hippocampal subfields (P<0.005) and reduced functional connectivity (P<0.02) compared to healthy controls.
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