Neuroanatomical substrates of depression in dementia with Lewy bodies and Alzheimer's disease

Abstract

Dementia with Lewy bodies (DLB) and Alzheimer's disease (AD) are often associated with depressive symptoms from the prodromal stage. The aim of the present study was to investigate the neuroanatomical correlates of depression in prodromal to mild DLB patients compared with AD patients. Eighty-three DLB patients, 37 AD patients, and 18 healthy volunteers were enrolled in this study. Depression was evaluated with the Mini International Neuropsychiatric Interview (MINI), French version 5.0.0. T1-weighted three-dimensional anatomical images were acquired for all participants. Regression and comparison analyses were conducted using a whole-brain voxel-based morphometry (VBM) approach on the grey matter volume (GMV). DLB patients presented a significantly higher mean MINI score than AD patients (p = 0.004), 30.1% of DLB patients had clinical depression, and 56.6% had a history of depression, while 0% of AD patients had clinical depression and 29.7% had a history of depression. VBM regression analyses revealed negative correlations between the MINI score and the GMV of right prefrontal regions in DLB patients (p < 0.001, uncorrected). Comparison analyses between DLB patients taking and those not taking an antidepressant mainly highlighted a decreased GMV in the bilateral middle/inferior temporal gyrus (p < 0.001, uncorrected) in treated DLB patients. In line with the literature, our behavioral analyses revealed higher depression scores in DLB patients than in AD patients. We also showed that depressive symptoms in DLB are associated with decreased GMV in right prefrontal regions. Treated DLB patients with long-standing depression would be more likely to experience GMV loss in the bilateral middle/inferior temporal cortex. These findings should be taken into account when managing DLB patients.

Keywords: Alzheimer’s disease; Antidepressant; Dementia with Lewy bodies; Depression; Prefrontal cortex; VBM.

Fig. 1

Brain regions correlated with the MINI (Mini International Neuropsychiatric Interview, French version 5.0.0) score in dementia with Lewy bodies (DLB) patients. Negative correlations were found between MINI scores and two clusters in the right middle frontal gyrus: BA 10 (a) and BA 46 (b). Results were significant at p < 0.001, uncorrected, with a cluster threshold of 50 voxels, and with total intracranial volume (TIV), educational level (EL), and antidepressant treatment as covariates

Fig. 2

Brain regions correlated with the MINI (Mini International Neuropsychiatric Interview, French version 5.0.0) score in Alzheimer’s disease (AD) patients. Negative correlations were found between MINI scores and one cluster in the right temporal pole (BA 38). Results were significant at p < 0.001, uncorrected, with a cluster threshold of 35 voxels, and with total intracranial volume (TIV), educational level (EL), and antidepressant treatment as covariates

Fig. 3

Comparison of grey matter volume (GMV) between depressed dementia with Lewy bodies (dDLB) patients and non-depressed dementia with Lewy bodies (ndDLB) patients. We found a significant GMV loss in four clusters, including the right middle frontal gyrus (BA 10) (a), the right middle frontal gyrus (BA 46) (b), and the posterior cingulate gyrus (BA 31) extending to the precuneus (BA 7) (c). Results were significant at p < 0.001, uncorrected, with a cluster threshold of 50 voxels, and with total intracranial volume (TIV), educational level (EL), antidepressant treatment, and handedness as covariates

Fig. 4

Comparison of grey matter volume (GMV) between treated dementia with Lewy bodies (tDLB) patients and non-treated dementia with Lewy bodies (ntDLB) patients. Top: regions showing significant GMV loss in tDLB patients compared to ntDLB patients, i.e., the bilateral middle/inferior temporal gyrus BA 21/20 (a). Bottom: regions showing significantly higher GMV in tDLB patients compared to ntDLB patients, i.e., the left cuneus (BA 19) extending to the precuneus (BA 7) (b), the bilateral supplementary motor area (BA 6) and the right supplementary motor area (BA 6) (c), the right superior/middle frontal gyrus (BA 6) (d), the left middle frontal gyrus (BA 10) (e), and the right posterior cingulate (BA 31) (f). Results were significant at p < 0.001, uncorrected, with a cluster threshold of 50 voxels, and with total intracranial volume (TIV), educational level (EL), and age as covariates

Fig. 5

Overlap of the regression analysis in dementia with Lewy bodies (DLB) patients (Fig. 1), and the comparison analysis between depressed dementia with Lewy bodies (dDLB) patients and non-depressed dementia with Lewy bodies (ndDLB) patients (Fig. 3). The yellow colour represents the comparison analysis, the red color the regression analysis, and the orange colour represents voxels where the two analyses overlap. The two clusters in the right middle frontal gyrus, BA 10 (a) and BA 46 (b), are largely superposed in the two analyses