Common neurobiological mechanisms underlying anosognosia and neuropsychiatric symptoms across the Alzheimer’s disease spectrum

Abstract

AbstractBackgroundBoth loss of awareness for cognitive decline (a.k.a. anosognosia) and neuropsychiatric symptoms (NPS) are common symptoms in Alzheimer’s disease (AD) and have been associated with AD pathology. Recent studies have shown a co‐occurrence between these symptoms across the AD spectrum, suggesting shared underlying neurophysiological processes, especially within the default mode network (DMN). Here, we investigated the relationship between NPS and altered awareness and the structural integrity (as assessed with diffusion tensor imaging, DTI) of brain regions supporting the DMN in participants with and without amyloid pathology.MethodsThree‐hundred participants from the Alzheimer’s Disease Neuroimaging Initiative (ADNI) underwent an amyloid positron emission tomography (PET), using 18F‐AV45 (florbetapir), and were classified into two groups: amyloid‐positive (A+) and negative (A‐). Individual mean fractional anisotropy (FA) was calculated from tracts overlapping the DMN regions. An awareness index was computed using the discrepancy between Everyday Cognition questionnaire scores from participants and informants. The Neuropsychiatric Inventory Total Score was used to assess the informant‐reported NPS. We compared amyloid groups on demographics and our different measures of interest. Pearson correlations were used to determine associations between measures of interest in each amyloid group. A multivariate multiple regression (MMR) model was performed to determine whether structural brain integrity predicts altered awareness and NPS jointly.ResultsA+ participants were significantly older (74 ± 7 vs. 72 ± 7 for A‐), more impaired (CDR global), and showed lower awareness and diffusion, and greater NPS (all p<0.001, see Table 1). Significant correlations were found between the FA, NPS, and awareness measures in A+ participants, with decreased FA associated with decreased awareness and more NPS. The MMR confirmed these associations between FA, awareness and NPS (p<0.02, see Table 2). The Pillai test revealed that the DTI effect jointly contributed to both models. No significant relationships were observed in the A‐ group.ConclusionOur results show that, in amyloid‐positive individuals across the AD spectrum, decreased awareness and increased NPS were related to decreased structural integrity of the DMN. This supports the hypothesis of common neurobiological mechanisms underlying anosognosia and NPS in AD.