Abstract
BackgroundNormal 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 Findings75 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.ConclusionLoss 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.
Highlights
Accumulating evidence suggests that synaptic dysfunction precedes neuronal death in the earliest stages of Alzheimer’s disease (AD) [1,2,3]
Recent cross-sectional functional magnetic resonance imaging (fMRI) studies have extended these findings by showing that task-related functional posteromedial cortex (PMC) deactivation is reduced in AD and mild cognitive impairment (MCI) [14,19,20]
While most fMRI studies in dementia have focused on positive activations, or increases in task-related signal, recent studies in AD have examined task-related deactivations, defined as a decrease in signal during an active vs. passive task
Summary
Accumulating evidence suggests that synaptic dysfunction precedes neuronal death in the earliest stages of Alzheimer’s disease (AD) [1,2,3]. Functional magnetic resonance imaging (fMRI) studies during episodic memory encoding tasks in AD have demonstrated decreased medial temporal activation [7,8,9,10,11,12]. In normal younger subjects there is functional deactivation (decreased activation) in this network during a broad range of cognitively challenging tasks [17]. Recent cross-sectional fMRI studies have extended these findings by showing that task-related functional PMC deactivation is reduced in AD and MCI [14,19,20]. Recent cross-sectional functional magnetic resonance imaging (fMRI) data suggests that deactivation during memory tasks is impaired in Alzheimer’s disease (AD). 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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