Neuroimaging of individuals with Down's syndrome at-risk for dementia: evidence for possible compensatory events

Abstract

Background: We report functional and structural brain indicators that may precede the onset of dementia in individuals with Down's syndrome (DS).

Methods: Middle-aged adults with DS (n=19), a group known to be at high risk for dementia, were studied with (1) positron emission tomography (PET) to determine cerebral glucose metabolic rate (GMR), (2) structural magnetic resonance imaging (MRI) to determine gray matter volume (GM), and (3) ratings of potential dementia indicators based on a structured interview of caregiver observations designed to evaluate individuals with low intelligence.

Results: Although none of the participants showed clinical signs of dementia, ratings of dementia indicators were correlated to both functional and structural imaging. The strongest correlations (p<.05, corrected for multiple comparisons) included the combination of higher GMR and decreased GM volume in parts of the temporal cortex, including the parahippocampus/hippocampus, in the thalamus, caudate, and frontal lobe (BA 47).

Interpretation: The combination of increased GMR overlapping with less gray matter in these areas may be consistent with a compensatory brain response to an early stage of the disease process.

Figure 1

Correlations between increased glucose metabolic rate (GMR) assessed with PET and higher dementia ratings (left panels) and, correlations between decreased gray matter (GM) assessed with VBM and higher dementia ratings (right panels); all correlations (p<.001). Names and anatomical locations for these areas are shown in table 1.

Figure 2

LEFT: Areas where both increased PET glucose metabolic rate and decreased VBM gray matter correlate to higher dementia ratings (p<.05, corrected). Row A shows the parahippocampus/hippocampus, row B shows the caudate, row C shows middle temporal gyrus. RIGHT: Areas where both increased PET glucose metabolic rate and increased VBM gray matter correlate to higher dementia ratings‥ Row A shows BA 47 (p<.001); row B shows the pons and row C shows the inferior temporal gyrus, BA 20 (p<.05, corrected). Names and anatomical locations for all overlapping areas are shown in tables 2 and 3.

Figure 3

Scatterplots show the correlations between of DMR total score (rank) with GMR (left) and GM (right). GMR and GM normalized values are taken from the maximum voxel within the parahippocampal cluster shown in table 2 (co-ordinates −34, −50, 1) representing the area with the strongest overlap of GMR (positive) and GM (negative) correlations with DMR ratings.