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. 2006 May;129(Pt 5):1229-39.
doi: 10.1093/brain/awl089.

Familial risk for Alzheimer's disease alters fMRI activation patterns

Susan Spear Bassett  1 , David M Yousem, Catherine Cristinzio, Ivana Kusevic, Michael A Yassa, Brian S Caffo, Scott L Zeger
Affiliations

Familial risk for Alzheimer's disease alters fMRI activation patterns

Susan Spear Bassett et al. Brain. 2006 May.

Abstract

Alzheimer's disease poses a looming crisis for the health care system as well as society in general. The low efficacy of current treatments for those already affected with this disease has prompted the suggestion that interventions might be more successful if they were applied before the development of significant pathology, that is, when individuals are clinically asymptomatic. Currently, the field requires a sensitive and specific diagnostic tool for identifying those individuals destined to develop this disease. As a first step, we present here an analysis of cross-sectional data for 95 asymptomatic offspring (50-75 years of age) of autopsy-confirmed late-onset familial Alzheimer's disease cases and 90 age-matched controls, studied with functional magnetic resonance imaging (fMRI) to investigate brain activation patterns. Analysis of activation in response to a paired-associates memory paradigm found significantly different patterns in these groups. At-risk individuals showed more intense and extensive activation in the frontal and temporal lobes including the hippocampus during memory encoding, an increase unrelated to the APOE epsilon4 allele. They also showed decreased activation particularly in the cingulum and thalamus during both the encoding and recall phases of the task. These results demonstrate that asymptomatic individuals, at genetic risk for development of late-onset Alzheimer's disease by virtue of familial clustering, show functional activation patterns distinct from those without such risk more than a decade before their parent's onset age. While longitudinal study is needed to determine whether these patterns, or a subset of them, are predictive of disease onset, these findings suggest that functional neuroimaging holds promise as a method of identifying pre-clinical Alzheimer's disease.

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Figures

Fig. 1
Fig. 1
Auditory word-pair-associates paradigm. During the encoding blocks, words are presented in pairs. During the cued recall blocks, subjects are asked to silently recall the second word in the pair, when cued with the first word.
Fig. 2
Fig. 2
Maximum intensity projections of selected activation differences between groups, mapped on a single-subject template (SPM99 MNI). (A) Locations of increased activation in at-risk subjects versus controls during the encoding phase of the task; (B) locations of decreased activation in at-risk subjects versus controls during the encoding phase of the task; (C) locations of increased activation in at-risk subjects versus controls during the cued recall phase of the task; (D) locations of decreased activation in at-risk subjects versus controls during the cued recall phase of the task. (Review the activation tables for the complete listing of all significant activation differences.)
Fig. 3
Fig. 3
Three-dimensional volume-rendered displays of activation differences between groups (SPM99 MNI). A shows differences in activation between groups during verbal encoding, while B shows differences in activation during recall.
See this image and copyright information in PMC

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