Prognostic value of posteromedial cortex deactivation in mild cognitive impairment - PubMed (original) (raw)

Prognostic value of posteromedial cortex deactivation in mild cognitive impairment

Jeffrey R Petrella et al. PLoS One. 2007.

Abstract

Background: Normal subjects deactivate specific brain regions, notably the posteromedial cortex (PMC), during many tasks. Recent cross-sectional functional magnetic resonance imaging (fMRI) data suggests that deactivation during memory tasks is impaired in Alzheimer's disease (AD). The goal of this study was to prospectively determine the prognostic significance of PMC deactivation in mild cognitive impairment (MCI).

Methodology/principal findings: 75 subjects (34 MCI, 13 AD subjects and 28 controls) underwent baseline fMRI scanning during encoding of novel and familiar face-name pairs. MCI subjects were followed longitudinally to determine conversion to AD. Regression and analysis of covariance models were used to assess the effect of PMC activation/deactivation on conversion to dementia as well as in the longitudinal change in dementia measures. At longitudinal follow up of up to 3.5 years (mean 2.5+/-0.79 years), 11 MCI subjects converted to AD. The proportion of deactivators was significantly different across all groups: controls (79%), MCI-Nonconverters (73%), MCI-converters (45%), and AD (23%) (p<0.05). Mean PMC activation magnitude parameter estimates, at baseline, were negative in the control (-0.57+/-0.12) and MCI-Nonconverter (-0.33+/-0.14) groups, and positive in the MCI-Converter (0.37+/-0.40) and AD (0.92+/-0.30) groups. The effect of diagnosis on PMC deactivation remained significant after adjusting for age, education and baseline Mini-Mental State Exam (p<0.05). Baseline PMC activation magnitude was correlated with change in dementia ratings from baseline.

Conclusion: Loss of physiological functional deactivation in the PMC may have prognostic value in preclinical AD, and could aid in profiling subgroups of MCI subjects at greatest risk for progressive cognitive decline.

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Conflict of interest statement

Competing Interests: Dr. Doraiswamy has received research grant support and/or honoraria for consulting or speaking from several pharmaceutical or diagnostic companies and owns stock in Sonexa Therapeutics. Duke University and Dr. Doraiswamy hold a use patent for an unrelated treatment indication in children; that patent is unlicensed and he derives no income from it. Dr. Petrella has received research support from Eisai/Pfizer and AVID for other pilot studies. Dr. Wang and Ms. Hellegers have received salary support from several pharmaceutical companies for other studies. Dr. Prince has no conflicts to disclose.

Figures

Figure 1

Figure 1. Posteromedical cortex (PMC), denoted in red and overlaid on a canonical T1-weighted brain template image in three orthogonal views, was used as an apriori functional region of interest.

In this region parameter estimates for activation magnitude showed a lesser-to-greater activation from Control, to MCI, to AD subjects.

Figure 2

Figure 2. Bar graph demonstrates the proportion of activators and deactivators among the four diagnostic groups.

The proportion of deactivators was significantly different (p<0.05) across diagnostic groups after adjusting for age, education and baseline MMSE score, with significantly fewer deactivators with increasing cognitive impairment grouping.

Figure 3

Figure 3. Bar graph demonstrates activation magnitude parameter estimate in the PMC region (taken from Figure 1), demonstrating a continuum from control, to MCI-Nonconverter, to MCI-Converter, to AD.

There were statistically significant (p<0.05) differences between all groups with the exception of the control and MCI-Nonconverter group, and the AD and MCI-Converter group. Note the overall pattern of negative activation magnitude in the Control and MCI-Nonconverter groups, and positive activation magnitude in the AD and MCI-Converter groups.

Figure 4

Figure 4. Scatterplots demonstrate activation magnitude parameter estimate in the PMC region (on the y-axis) significantly (p<0.05) correlated with longitudinal change in cognitive measures (increase in CDR-SOB, decrease in MMSE) in the MCI group.

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References

    1. Tanzi RE. The synaptic Abeta hypothesis of Alzheimer disease.[comment]. Nature Neuroscience. 2005;8:977–979. - PubMed
    1. Selkoe DJ. Alzheimer's disease is a synaptic failure. Science. 2002;298:789–791. - PubMed
    1. Palop JJ, Chin J, Mucke L. A network dysfunction perspective on neurodegenerative diseases. Nature. 2006;443:768–773. - PubMed
    1. Jack CR, Jr, Dickson DW, Parisi JE, Xu YC, Cha RH, et al. Antemortem MRI findings correlate with hippocampal neuropathology in typical aging and dementia. Neurology. 2002;58:750–757. - PMC - PubMed
    1. Jack CR, Jr, Petersen RC, Xu YC, O'Brien PC, Smith GE, et al. Prediction of AD with MRI-based hippocampal volume in mild cognitive impairment. Neurology. 1999;52:1397–1403. - PMC - PubMed

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