Neuroanatomical correlates of behavioural disorders in dementia

Abstract

Neurodegenerative diseases are associated with profound changes in social and emotional function. The emergence of increasingly sophisticated methods for measuring brain volume has facilitated correlation of local changes in tissue content with cognitive and behavioural changes in neurodegenerative disease. The current study examined neuroanatomical correlates of behavioural abnormalities, as measured by the Neuropsychiatric Inventory, in 148 patients with dementia using voxel-based morphometry. Of 12 behaviours examined, 4 correlated with tissue loss: apathy, disinhibition, eating disorders and aberrant motor behaviour. Increasing severity across these four behaviours was associated with tissue loss in the ventral portion of the right anterior cingulate cortex (vACC) and adjacent ventromedial superior frontal gyrus (vmSFG), the right ventromedial prefrontal cortex (VMPC) more posteriorly, the right lateral middle frontal gyrus, the right caudate head, the right orbitofrontal cortex and the right anterior insula. In addition, apathy was independently associated with tissue loss in the right vmSFG, disinhibition with tissue loss in the right subgenual cingulate gyrus in the VMPC, and aberrant motor behaviour with tissue loss in the right dorsal ACC and left premotor cortex. These data strongly support the involvement of the right hemisphere in mediating social and emotional behaviour and highlight the importance of distinct regions on the medial wall of the right frontal lobe in regulating different behaviours. Furthermore, the findings underscore the utility of studying patients with dementia for understanding the neuroanatomical basis of social and emotional functions.

Figures

Fig. 1

Study design matrix including two conditions and four behavioural covariates with condition by covariate interactions modelled.

Fig. 2

Boxplots of F × Sprod scores for four behaviours in FTD, semantic dementia and other neurodegenerative diseases. Horizontal grey lines mark the median score, the ends of each box mark the first and third quartiles, and the outer lines represent the range of scores or 1.5 box-lengths from the median. Circles mark scores >1.5 box-lengths from the median, and asterisks mark scores >3 box-lengths from the median.

Fig. 3

Regions of grey matter tissue loss associated with diagnosis and behaviour. (A) Average effects across four behaviours: apathy, disinhibition, aberrant motor behaviours and eating disorders in the FTD/semantic dementia group. (B) Tissue loss in FTD or semantic dementia versus any other dementia diagnosis. (C) Tissue loss in FTD versus semantic dementia. Slice thickness is 1 mm.

Fig. 4

Regions where individual behaviours showed unique associations with focal regions of tissue loss.

Fig. 5

Relationships between adjusted voxel intensity and NPI F × Sprod score at the four peaks where individual behaviours showed unique relationships with tissue loss.