Cerebral systems underlying anosognosia for memory loss in aging and Alzheimer’s disease

• Published in: Alzheimer's & dementia Vol. 19; no. S16
• Main Authors: Mimmack, Kayden J., Qiao, Krystal, Gagliardi, Geoffroy Pierre, Bueichekú, Elisenda, Cacciamani, Federica, Wang, Sharon, Udeogu, Onyinye, Marshall, Gad A, Sepulcre, Jorge, Vannini, Patrizia
• Format: Journal Article
• Language: English
• Published: 01.12.2023
• ISSN: 1552-5260; 1552-5279
• DOI: 10.1002/alz.080305

Background Loss of awareness of cognitive decline (a.k.a. anosognosia) is a common symptom of Alzheimer’s disease (AD) dementia and has also been observed in its predementia stages. Anosognosia is thought to be related not only to functional changes in individual brain regions, but also to a disturbance in functional connectivity (FC) between or within networks. This study aimed to investigate how memory awareness relates to resting‐state fMRI segregation (within‐network connectivity) and integration (between‐network connectivity) maps across the AD spectrum. Method We included 66 older adults divided in two groups: cognitively normal (CN, n = 49), and symptomatic (mild cognitive impairment or mild AD; n = 17). Memory awareness was measured as the discrepancy between the participant’s and study partner’s scores on the Cognitive Function Instrument. Positive values indicated heightened awareness and negative values indicated unawareness. We assessed whole‐brain connectivity with resting‐state fMRI and computed voxel‐level maps of segregation and integration. General linear models were used to relate the integration or segregation of each voxel to memory awareness (in the total sample and in the two groups separately), adjusted for age, sex, and education. Multiple comparison correction was performed using cluster‐wise Monte Carlo simulations. Result Demographics are presented in Table 1. Segregation maps showed that lower awareness was associated with increased connectivity within the frontoparietal network (FPN) and with decreased connectivity within the medial visual, default mode (DMN), and sensory‐motor networks (Figure 1A(i); Table 2A(i)). The relationship with the FPN persisted in the CN and symptomatic groups separately, and an additional negative association between awareness and FC in the salience network was found in the CN group (Figure 1B‐C(i); Table 2B‐C(i)). In integration maps, lower awareness was associated with increased between‐network connectivity of the dorsal attention and DMN, and decreased connectivity of the salience and sensory‐motor networks (Figure 1A(ii); Table 2A(ii)). In the CN group, the sensory‐motor relationship persisted, while the DMN relationship reversed (Figure 1B‐C(ii); Table 2B‐C(ii)). Conclusion Anosognosia is characterized by reduced FC patterns featuring disconnection between self‐referential networks (DMN and salience) to other networks and hyperconnectivity within the FPN. Future studies should investigate the pathological underpinnings for these functional changes.