MRI cortical thickness biomarker predicts AD-like CSF and cognitive decline in normal adults - PubMed (original) (raw)

MRI cortical thickness biomarker predicts AD-like CSF and cognitive decline in normal adults

Bradford C Dickerson et al. Neurology. 2012.

Abstract

Objective: New preclinical Alzheimer disease (AD) diagnostic criteria have been developed using biomarkers in cognitively normal (CN) adults. We implemented these criteria using an MRI biomarker previously associated with AD dementia, testing the hypothesis that individuals at high risk for preclinical AD would be at elevated risk for cognitive decline.

Methods: The Alzheimer's Disease Neuroimaging Initiative database was interrogated for CN individuals. MRI data were processed using a published set of a priori regions of interest to derive a single measure known as the AD signature (ADsig). Each individual was classified as ADsig-low (≥ 1 SD below the mean: high risk for preclinical AD), ADsig-average (within 1 SD of mean), or ADsig-high (≥ 1 SD above mean). A 3-year cognitive decline outcome was defined a priori using change in Clinical Dementia Rating sum of boxes and selected neuropsychological measures.

Results: Individuals at high risk for preclinical AD were more likely to experience cognitive decline, which developed in 21% compared with 7% of ADsig-average and 0% of ADsig-high groups (p = 0.03). Logistic regression demonstrated that every 1 SD of cortical thinning was associated with a nearly tripled risk of cognitive decline (p = 0.02). Of those for whom baseline CSF data were available, 60% of the high risk for preclinical AD group had CSF characteristics consistent with AD while 36% of the ADsig-average and 19% of the ADsig-high groups had such CSF characteristics (p = 0.1).

Conclusions: This approach to the detection of individuals at high risk for preclinical AD-identified in single CN individuals using this quantitative ADsig MRI biomarker-may provide investigators with a population enriched for AD pathobiology and with a relatively high likelihood of imminent cognitive decline consistent with prodromal AD.

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Figures

Figure 1

Figure 1. The cortical signature of Alzheimer disease (AD)

A priori regions of interest composing the “AD signature” in which consistent thinning has been previously observed in multiple samples of patients with mild AD dementia. The MRI biomarker used in the present study is an average of the thickness of the cerebral cortex in all 9 of these regions of interest, obtained from each individual subject.

Figure 2

Figure 2. Expression of cortical signature of Alzheimer disease (AD) is associated with future cognitive decline

Participants who were cognitively normal at baseline but classified as high risk for preclinical AD on the basis of having low AD-signature cortical thickness were at markedly elevated risk of meeting the 3-year cognitive decline outcome (composite cognitive decline) as compared with participants with average or high AD-signature cortical thickness. Similar findings were present when the individual CDR–sum of boxes (CDR-SB) decline outcome or the neuropsychological performance decline outcome were examined.

Figure 3

Figure 3. Expression of cortical signature of Alzheimer disease (AD) is associated with AD-like spinal fluid

Cognitively normal participants who were classified as high risk for preclinical AD on the basis of having low AD-signature cortical thickness showed a trend toward being more likely to harbor abnormally low amyloid-β levels in CSF compared to participants with average or high AD-signature cortical thickness.

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