Korsakoff's Syndrome and Alzheimer's Disease-Commonalities and Specificities of Volumetric Brain Alterations within Papez Circuit

Abstract

Background: Alzheimer's disease (AD) and Korsakoff's syndrome (KS) are two major neurocognitive disorders characterized by amnesia but AD is degenerative while KS is not. The objective is to compare regional volume deficits within the Papez circuit in AD and KS, considering AD progression. Methods: 18 KS patients, 40 AD patients (20 with Moderate AD (MAD) matched on global cognitive deficits with KS patients and 20 with Severe AD (SAD)), and 70 healthy controls underwent structural MRI. Volumes of the hippocampi, thalami, cingulate gyri, mammillary bodies (MB) and mammillothalamic tracts (MTT) were extracted. Results: For the cingulate gyri, and anterior thalamic nuclei, all patient groups were affected compared to controls but did not differ between each other. Smaller volumes were observed in all patient groups compared to controls in the mediodorsal thalamic nuclei and MB, but these regions were more severely damaged in KS than AD. MTT volumes were damaged in KS only. Hippocampi were affected in all patient groups but more severely in the SAD than in the KS and MAD. Conclusions: There are commonalities in the pattern of volume deficits in KS and AD within the Papez circuit with the anterior thalamic nuclei, cingulate cortex and hippocampus (in MAD only) being damaged to the same extent. The specificity of KS relies on the alteration of the MTT and the severity of the MB shrinkage. Further comparative studies including other imaging modalities and a neuropsychological assessment are required.

Keywords: Alzheimer disease; Korsakoff’s syndrome; MRI; cingulate cortex; hippocampus; mammillary bodies; mammillothalamic tract; thalamus.

Figure 1

Volumetric comparisons between healthy controls (HC), patients with Korsakoff’s syndrome (KS), moderate Alzheimer disease (MAD) and severe Alzheimer disease (SAD) in several regions of the Papez circuit. In the upper right corner of the figure, regions of the Papez circuit considered in the analysis. Yellow: anterior and posterior cingulate gyri. Red: Thalamus. Blue: Hippocampus. Brown: Mammillary bodies. Green: Mammillothalamic tract. We used a generalized linear model (GLM): estimated marginal means are shown in green with vertical lines showing 95% Confidence Intervals. When F-tests were significant (p < 0.001, corrected for multiple comparisons), post-hoc tests were carried out (Tukey, unequal sample size). Statistically significant post-hoc tests between groups are shown with an overhead horizontal black line and associated p-value shown on the plots. Raw data are also illustrated via boxplots and volumes are expressed in mm³.