Hippocampal hyperactivation associated with cortical thinning in Alzheimer's disease signature regions in non-demented elderly adults - PubMed (original) (raw)

Hippocampal hyperactivation associated with cortical thinning in Alzheimer's disease signature regions in non-demented elderly adults

Deepti Putcha et al. J Neurosci. 2011.

Abstract

Alzheimer's disease (AD) is associated with functional and structural alterations in a distributed network of brain regions supporting memory and other cognitive domains. Functional abnormalities are present in mild cognitive impairment (MCI) with evidence of early hyperactivity in medial temporal lobe regions, followed by failure of hippocampal activation as dementia develops. Atrophy in a consistent set of cortical regions, the "cortical signature of AD," has been reported at the stage of dementia, MCI, and even in clinically normal (CN) older individuals predicted to develop AD. Despite multiple lines of evidence for each of these findings, the relationship between this structural marker of AD-related neurodegeneration and this functional marker of the integrity of the episodic memory system has not yet been elucidated. We investigated this relationship in 34 nondemented older humans (CN, N = 18; MCI, N = 16). Consistent with previous studies, we found evidence of hippocampal hyperactivation in MCI compared with CN. Additionally, within this MCI group, increased hippocampal activation correlated with cortical thinning in AD-signature regions. Even within the CN group, increased hippocampal activity was negatively correlated with cortical thinning in a subset of regions, including the superior parietal lobule (r = -0.66; p < 0.01). These findings, across a continuum of nondemented and mildly impaired older adults, support the hypothesis that paradoxically increased hippocampal activity may be an early indicator of AD-related neurodegeneration in a distributed network.

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Conflict of interest statement

Conflict of Interest: Dr. Sperling has consulted for Avid (unpaid), Bayer, Bristol-Myers-Squibb, Eisai, Elan, Janssen, and Pfizer, but not in a manner directly relevant to this manuscript.

Figures

Figure 1.

Figure 1.

AD signature of cortical thinning. A, Medial temporal lobe; B, inferior temporal gyrus; C, temporal pole; D, angular gyrus; E, superior frontal gyrus; F, superior parietal lobule; G, supramarginal gyrus; H, precuneus; I, inferior frontal sulcus.

Figure 2.

Figure 2.

In MCI, memory test performance (percentage high confidence hits) is (a) negatively related to hippocampal activation (r = −0.43, p = 0.09) and (b) positively related to AD signature cortical thickness (r = 0.38, p = 0.03). Additionally, (c), Hippocampal activation is negatively related to hippocampal volume (r = −0.53, p = 0.04).

Figure 3.

Figure 3.

CN (CDR 0) versus MCI (CDR 0.5) describing (a) hippocampal activation percentage signal change (t = 2.05, p = 0.04) and (b) medial temporal lobe cortical thickness in millimeters (b). * indicates a significant difference between the means.

Figure 4.

Figure 4.

Relationships by clinical subgroup between average hippocampal activation (percentage signal change) and cortical thickness in the (a) AD signature region summary measure (in millimeters) and (b) superior parietal lobule cortical thickness (in millimeters).

Figure 5.

Figure 5.

ROI-restricted vertex-based thickness correlation map of hippocampal activation and cortical thickness (p < 0.01, uncorrected) with an AD signature mask applied in the whole sample.

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