Altered resting state activity associated with anosognosia in Alzheimer's clinical syndrome: Findings from the DELCODE study

Abstract

AbstractBackgroundAnosognosia, or lack of awareness of cognitive impairments, is a common phenomenon in Alzheimer’s clinical syndrome (ACS). Not just patients with dementia(AD) but also patients with mild cognitive impairment(MCI) may have diminished awareness of their deficits. Previous studies have shown that anosognosia is associated with dysfunction and reduced connectivity in the default mode network of the brain and insula. However, less is known about the level of awareness and its neural correlations in individuals with subjective cognitive decline(SCD). This study investigated the underlying neural mechanisms of anosognosia at different stages of ACS.Method504 participants (59 AD, 88 MCI, 176 SCD and 181 healthy controls[HCs]) from the DELCODE, a longitudinal multicenter observational study, were included. Cognitive awareness was assessed with a discrepancy score between participants’ report about their own cognitive abilities and report provided by informants. Resting‐state fMRI data of all subjects were analyzed and the fractional amplitude of low frequency fluctuations(fALFF) were calculated as an index of regional spontaneous neural activity. Voxel‐ and clusterwise correlations were conducted using SPM12, controlling for multiple comparisons(GRF). Age, gender and site (9 sites total) were controlled for in each statistical model.ResultCompared to HCs, subjects with SCD showed heightened awareness for cognitive changes and on the contrary, MCI and AD subjects had higher anosognosia scores. Within‐group comparisons revealed that MCI subjects with anosognosia had reduced neural activity in the left anterior insula compared to MCI subjects without anosognosia (GRF corrected, p<0.005). Moreover, SCD subjects with heightened awareness showed reduced right amygdala activity(GRF corrected, p<0.005), whereas higher activity was observed in the dorsomedial prefrontal cortex (dmPFC) compared to SCD subjects without heightened awareness(GRF corrected, p<0.001).ConclusionThis is the first study evaluating the association between cognitive awareness at different stages of ACS and regional neural activity using fALFF. Consistent with prior findings, MCI subjects with anosognosia showed reduced neural activity in the anterior insula. Heightened awareness in SCD was associated with higher activity in the dmPFC. Future work should examine the interplay between amyloid pathology and fALFF measures for cognitive awareness, in order to specify neural correlates of cognitive awareness in the Alzheimer’s continuum.