Anosognosia in Amnestic Mild Cognitive Impairment Is Related to Diminished Hippocampal Volume Comparable to Alzheimer's Disease Dementia: Preliminary MRI Findings.

Juan Francisco Flores-Vázquez,Gabriel Ramírez-García,Ruth Alcalá-Lozano,Yaneth Rodríguez-Agudelo,Andre Aleman,Gilberto Isaac Acosta-Castillo,Oscar René Marrufo-Meléndez,Morten Peter Lietz,Ana Luisa Sosa-Ortiz,Remco J Renken,Stefanie Enriquez-Geppert

doi:10.3389/fnagi.2021.739422

Abstract

Although the presence of anosognosia in amnestic mild cognitive impairment (aMCI) may be predictive of conversion to Alzheimer’s disease (AD), little is known about its neural correlates in AD and aMCI. Four different groups were compared using volumetric and diffusion magnetic resonance imaging metrics in regions of interest (hippocampus and cingulum cortex gray matter, cingulum bundle white matter): aMCI subjects with anosognosia (n = 6), aMCI subjects without anosognosia (n = 12), AD subjects with anosognosia (n = 6), and AD subjects without anosognosia (n = 9). aMCI subjects with anosognosia displayed a significantly lower gray matter density (GMD) in the bilateral hippocampus than aMCI subjects without anosognosia, which was accounted for by bilateral hippocampal differences. Furthermore, we identified that the mean hippocampal gray matter density of aMCI subjects with anosognosia was not statistically different than that of AD subjects. The groups of aMCI and AD subjects with anosognosia also displayed a lower GMD in the bilateral cingulum cortex compared to subjects without anosognosia, but these differences were not statistically significant. No statistically significant differences were found in the fractional anisotropy or mean diffusivity of the hippocampus or cingulum between subjects with and without anosognosia in aMCI or AD groups. While these findings are derived from a small population of subjects and are in need of replication, they suggest that anosognosia in aMCI might be a useful clinical marker to suspect brain changes associated with AD neuropathology.

Highlights

Anosognosia is defined as the loss or decline in a subject’s awareness of problems in daily functioning, behavior, cognition, or mood (Starkstein, 2014)
In the amnestic mild cognitive impairment (aMCI) group, subjects with anosognosia had a lower gray matter density (GMD) in the bilateral hippocampus regions of interest (ROIs) (M = 0.55, Mdn = 0.54, interquartile ranges (IQR) = 0.06, and Rng = 0.48–0.60) than subjects without anosognosia (M = 0.64, Mdn = 0.65, IQR = 0.08, and Rng = 0.51– 0.73)
The group of aMCI subjects with anosognosia displayed a lower GMD in the bilateral cingulum cortex ROI (M = 0.47, Mdn = 0.47, IQR = 0.02, and Rng = 0.44–0.51) than subjects without anosognosia (M = 0.51, Mdn = 0.51, IQR = 0.11, and Rng = 0.43–0.60), but this difference was not statistically significant (W = 49.0, p = 0.25, and rrb = 0.36)

Summary

Introduction

Anosognosia is defined as the loss or decline in a subject’s awareness of problems in daily functioning, behavior, cognition, or mood (Starkstein, 2014). This condition is frequent throughout the trajectory of Alzheimer’s disease (AD), with a prevalence ranging between 20 and 80%, and its presence is linked to increased dependence, reduced adherence to treatment and risk behaviors in patients, increased caregiver distress, and a greater economic burden for families and societies (Turró-Garriga et al, 2013; Starkstein, 2014). The presence of anosognosia in aMCI has been associated with underlying brain changes characteristic of AD, and may have a predictive value for further worsening of cognition and progression to AD dementia (Scherling et al, 2016; Gerretsen et al, 2017; Therriault et al, 2018; Hanseeuw et al, 2020). The understanding of the neural changes associated with anosognosia is necessary for the adequate characterization of aMCI and the early stages of AD (Mondragón et al, 2021)

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