Resting-state connectivity is altered in hypernosognosia within the Alzheimer’s Disease continuum
Poster No:
1663
Submission Type:
Abstract Submission
Authors:
RICCARDO MARAMOTTI1, Daniela Ballotta1, Chiara Carbone1, Chiara Gallingani1, Giuseppe Pagnoni1, Giovanna Zamboni1, Manuela Tondelli1
Institutions:
1University of Modena and Reggio Emilia, Modena, Italy
First Author:
Co-Author(s):
Introduction:
Patients with Alzheimer's Disease (AD) may be unaware of their cognitive and behavioural symptoms ("anosognosia" or "impaired self-awareness"; Pringatano, 2009). However, recent findings suggest that an increased awareness of cognitive function ("hypernosognosia") may serve as a marker in the preclinical stage (Lopez-Martos, 2024). Recent evidence suggests also that anosognosia in the AD continuum is associated with a dysregulation of two large-scale brain networks, namely the Default-Mode (DMN), and the Salience (SN). Here, we further investigate if this functional connectivity dysregulation shows a different trajectory across the continuum between hypernosognosia and anosognosia.
Methods:
Sixty patients (27 females; mean age 75.4 ± 6.7 years; mean education 14 ± 3.5 years of school attendance) with MCI and AD dementia underwent fMRI and neuropsychological assessment including the Anosognosia Questionnaire Dementia (AQ-D; Migliorelli et al., 1995), a measure of anosognosia based on a discrepancy score between patient's and caregiver's judgments. Patients were classified in 3 groups according to AQ-D scores: hyperaware (hyAW) if AQ-D<-14, unaware (uAW) if AQ-D>14, aware (AW) if -14<AQ-D<14. Demographic, neuropsychological and clinical measures were compared between hyAW, uAW and AW patients. Functional data were acquired with a 3T scanner and an EPI sequence (TR=2000 ms; echo time, TE, 28ms; flip angle 89°; field of view 192mm; 180 volumes; 3x3x3.5 mm voxels; acquisition time 6:04min). fMRI preprocessing and analysis were performed using FSL tools. After having applied Independent Component Analysis using MELODIC, functional data were compared between the 3 groups considering DMN and SN functional connectivity. Age, Mini-Mental State Examination (MMSE) scores, and grey matter volumes were included as regressors of no interest in all the GLMs. Cluster-based thresholding was used to control for whole brain voxel-wise multiple comparisons, and FWE-corrected significance threshold of p<0.05 was applied to the suprathreshold clusters.
Results:
According to the established cutoff, 9 patients were hyperaware (AQ-D = -20 ± 5.4), 37 patients had preserved awareness of their cognitive deficits (AQ-D = -2 ± 7.1), whereas 14 patients had anosognosia (AQ-D = -22 ± 6.8). ANOVA performed on the total MMSE score showed a significant effect of group (F (2) = 5.5, p<0.05). Bonferroni post-hoc tests revealed a significant difference between hyAW patients (MMSE = 26) and uAW patients (MMSE = 22; p<0.05), and also between AW (MMSE = 25) and uAW patients (p<0.05). Cognitive impairment was comparable between hyAW and AW patients. No significant differences were found in age, years of education or gender between the three groups.
hyAW subjects had greater DMN functional connectivity in posterior cingulate cortex in comparison to uAW and AW subjects, and in midcingulate cortex in comparison to AW only. On the contrary, uAW subjects had greater salience functional connectivity in anterior cingulate in comparison to hyAW and AW, and in anterior insula, and basal ganglia in comparison to AW only (Figure 1).
hyAW subjects had greater DMN functional connectivity in posterior cingulate cortex in comparison to uAW and AW subjects, and in midcingulate cortex in comparison to AW only. On the contrary, uAW subjects had greater salience functional connectivity in anterior cingulate in comparison to hyAW and AW, and in anterior insula, and basal ganglia in comparison to AW only (Figure 1).
Conclusions:
Our results confirmed that awareness in the AD continuum is associated with an imbalance of the functional connectivity of two large-scale brain networks, namely the DMN and the SN. In addition, we demonstrated that the recruitment of these two functional networks follows a gradient according to the level of awareness.
Disorders of the Nervous System:
Neurodegenerative/ Late Life (eg. Parkinson’s, Alzheimer’s)
Modeling and Analysis Methods:
fMRI Connectivity and Network Modeling
Task-Independent and Resting-State Analysis 1
Perception, Attention and Motor Behavior:
Consciousness and Awareness 2
Keywords:
Aging
Computational Neuroscience
FUNCTIONAL MRI
Meta-Cognition
Other - Resting-State; Anosognosia; Alzheimer's
1|2Indicates the priority used for review
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Were any human subjects research approved by the relevant Institutional Review Board or ethics panel? NOTE: Any human subjects studies without IRB approval will be automatically rejected.
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Provide references using APA citation style.
Prigatano, G. P. (2009). The study of Anosognosia. Oxford, NY: Oxford University Press.