Abstract
Anosognosia, or loss of insight of memory deficits, is a common and striking symptom in Alzheimer's disease (AD). Previous findings in AD dementia patients suggest that anosognosia is due to both functional metabolic changes within cortical midline structures involved in self-referential processes, as well as functional disconnection between these regions. The present study aims to extend these findings by investigating the neural correlates of anosognosia in the prodromal stage of AD. Here, we used regional brain metabolism (resting state 18-F fluorodeoxyglucose positron emission tomography (FDG-PET)) to unravel the metabolic correlates of anosognosia in subjects with amnestic mild cognitive impairment (aMCI) and subsequently resting state functional magnetic resonance imaging (rs-fMRI) to investigate the intrinsic connectivity disruption between brain regions. Thirty-one subjects (mean age: 74.1; Clinical Dementia Rating (CDR) global score: 0.5) with aMCI, and 251 cognitively normal (CN) older adults (mean age: 73.3; CDR: 0) were included as a reference group for behavioral and FDG data. An anosognosia index was obtained by calculating a discrepancy score between subjective and objective memory scores. All subjects underwent FDG-PET for glucose metabolism measurement, and aMCI subjects underwent additional rs-fMRI for intrinsic connectivity measurement. Voxel-wise correlations between anosognosia and neuroimaging data were conducted in the aMCI subjects. Subjects with aMCI had significantly decreased memory awareness as compared to the CN older adults. Greater anosognosia in aMCI subjects was associated with reduced glucose metabolism in the posterior cingulate (PCC) cortices and hippocampus. Intrinsic connectivity analyses revealed a significant association between anosognosia and attenuated functional connectivity between the PCC seed region and orbitofrontal cortex (OFC) as well as bilateral inferior parietal lobes (IPL). These findings provide further evidence that implicates cortical midline structures and hippocampus in the awareness of memory deficits. Investigating neuroimaging changes that co-vary with memory awareness may improve our ability to identify the cause of anosognosia and ultimately increase our chances for its treatment.
Highlights
Impaired awareness of memory deficits, a.k.a. anosognosia, is a challenging manifestation of Alzheimer's disease (AD) that adversely affects the patient's safety and decision making and often imposes a negative impact on caregiver quality of life
No significant differences were found between cognitively normal (CN) and amnestic mild cognitive impairment (aMCI) subjects on all demographic variable, except for mini-mental state exam (MMSE) scores (Table 1)
In the aMCI subjects, no significant relationship was found between the memory awareness score and age (p = 0.7); gender (p = 0.4), or education (p = 0.7)
Summary
Impaired awareness of memory deficits, a.k.a. anosognosia, is a challenging manifestation of Alzheimer's disease (AD) that adversely affects the patient's safety and decision making and often imposes a negative impact on caregiver quality of life. The most common and consistent finding across these studies is the association between anosognosia and dysfunction in prefrontal, including dorsolateral and orbitofrontal regions, as well as in the temporoparietal regions, inferior parietal cortex, posterior cingulate cortex and precuneus. The observation that these findings overlap with brain regions which have been implicated in self-referential processing in normal individuals (Johnson and Ries, 2010; Northoff and Bermpohl, 2004; Northoff et al, 2006; Schmitz and Johnson, 2007), has led to the proposal that anosognosia may be caused (in part) by the alteration of internally oriented self-related processes (Ott et al, 1996a)
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