Year: 2016
Type: article
Study design: Observational Study
Abstract: Anosognosia, or loss of insight of memory deficits is a common and striking symptom in Alzheimer's disease (AD). Previous findings in AD 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 (Perrotin et al. 2015). The present study aims at extending these findings by better understanding the neural correlates of anosognosia in the prodromal stage of AD. Thus, here we used regional brain metabolism [FDG-PET] to unravel the metabolic correlates of anosognosia in patients with amnestic mild cognitive impairment (aMCI) and subsequently resting state fMRI [rs-fMRI] to investigate the intrinsic connectivity disruption between brain regions. Thirty-one subjects (mean age: 74.1; CDR: 0.5) with aMCI were included. All subjects underwent resting state 18-F fluorodeoxyglucose positron emission tomography (FDG-PET) for glucose metabolism measurement and resting state fMRI for intrinsic connectivity measurement. An anosognosia index was obtained by calculating discrepancy scores between subjective and objective memory scores. Voxelwise correlations between anosognosia and neuroimaging data were conducted. All analyses were controlled for multiple comparison using pFDR =0.05. Anosognosia in aMCI patients correlated with reduced glucose metabolism in posterior cingulate (PCC) cortices and hippocampus (Figure 1). 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, Figure 2). (A) Voxelwise statistical map of the significant correlations between FDG uptake and memory awareness index in aMCI patients (pFDR < 0.05), controlling for age and Geriatric depression scale (GDS). (B) Plot of the correlation between FDG uptake in the posterior cingulate (PCC) cluster and the memory awareness index. Lower score on the memory awareness index indicates increased anosognosia. (A) Whole brain map of regression of memory awareness index on posterior cingulate (PCC) functional connectivity demonstrating significant correlations between the PCC (seed region) and medial orbitofrontal cortex (OFC) and bilateral inferior parietal lobes (IPL), pFDR=0.05 controlling for age and GDS. (B) Plot of the correlation of the PCC-OFC instrinsic functional connectivity and the memory awareness index. Lower score on the memory awareness index indicates increased anosognosia. These findings provide further evidence implicating cortical midline structures involved in awareness of memory deficits. MCI patients with anosognosia showed reduced metabolism as well as disconnection between OFC, PCC and hippocampus, brain regions vulnerable to changes in early Alzheimer's disease, and therefore could be at increased risk of developing dementia.
Source: Alzheimer s & Dementia
Language: English
Subfield: Psychiatry and Mental health
Field: Medicine
Domain: Health Sciences
Open Access status: bronze
OpenAlex ID: W4206462745