Behavioural changes in frontotemporal dementia and their cognitive and neuroanatomical correlates

Abstract

Behavioural changes are a central feature of frontotemporal dementia (FTD); they occur in both behavioural-variant (bvFTD) and semantic dementia (SD)/semantic-variant primary progressive aphasia subtypes. In this study, we addressed two current clinical knowledge gaps: (i) are there qualitative or clear distinctions between behavioural profiles in bvFTD and SD; and (ii) what are the precise roles of the prefrontal cortex and anterior temporal lobes in supporting social behaviour? Resolving these conundrums is crucial for improving diagnostic accuracy and for the development of targeted interventions to treat challenging behaviours in FTD. Informant questionnaires to assess behavioural changes included the Cambridge Behavioural Inventory-Revised and two targeted measures of apathy and impulsivity. Participants completed a detailed neuropsychological battery to permit investigation of the relationship between cognitive status (including social-semantic knowledge, general semantic knowledge and executive function) with behaviour change in FTD. To explore changes in regional grey matter volume, a subset of patients had structural MRI. Diagnosis-based group comparisons were supplemented by a transdiagnostic approach that encompassed the spectrum of bvFTD, SD and 'mixed' or intermediate cases. Such an approach is sensitive to the systematic graded variation in FTD and allows the neurobiological underpinnings of behaviour change to be explored across an FTD spectrum. We found a wide range of behavioural changes across FTD. Although quantitatively more severe on average in bvFTD, as expected, the item-level analyses found no evidence for qualitative differences in behavioural profiles or 'behavioural double dissociations' between bvFTD and SD. Comparisons of self and informant ratings revealed strong discrepancies in the perspective of the caregiver versus the patient. Logistic regression revealed that neuropsychological measures had better discriminative accuracy for bvFTD versus SD than caregiver-reported behavioural measures. A principal component analysis of all informant questionnaire domains extracted three components, interpreted as reflecting: (i) apathy; (ii) challenging behaviours; and (iii) activities of daily living. More severe apathy in both FTD subtypes was associated with: (i) increased levels of impaired executive function; and (ii) anterior cingulate cortex atrophy. Questionnaire ratings of impaired behaviour were not correlated with either anterior temporal lobe atrophy or degraded social-semantic knowledge. Together, these findings highlight the presence of a wide range of behavioural changes in both bvFTD and SD, which vary by degree rather than quality. We recommend a transdiagnostic approach for future studies of the neuropsychological and neuroanatomical underpinnings of behavioural deficits in FTD.

Keywords: behavioural-variant frontotemporal dementia; semantic dementia; social behaviour; social-semantic knowledge; transdiagnostic.

Figure 1

Voxel-based morphometry results. Rows display regions of reduced grey matter volume in each patient group in comparison to age-matched controls. The bottom row shows regions of reduced grey matter volume in SD compared with bvFTD. Groups were compared using independent t-tests, with age, intracranial volume and scanner site included as covariates. Images are thresholded using a cluster-level threshold of P(FDR) < 0.05 (after an initial voxel-level threshold of P < 0.001). Significant clusters are overlaid on the MNI avg152 T1 template. Co-ordinates are reported in MNI space. bvFTD = behavioural-variant frontotemporal dementia; FDR = false discovery rate; FTD = frontotemporal dementia; MNI = Montreal Neurological Institute; SD = semantic dementia.

Figure 2

Scores across each CBI-R domain. (A) Average total scores across each CBI-R domain in each group. (B) The percentage of bvFTD and SD participants impaired on each CBI-R domain. bvFTD = behavioural-variant frontotemporal dementia; CBI-R = Cambridge Behavioural Inventory Revised; SD = semantic dementia.

Figure 3

Association between self and informant ratings of apathy. Data points represent scores on the self-rated AMI plotted against scores on the AMI-CG for each AMI domain. AMI = Apathy-Motivation Index; AMI-CG = Apathy-Motivation Index-Caregiver version; bvFTD = behavioural-variant frontotemporal dementia; SD = semantic dementia.

Figure 4

PCA loadings and factor scores. (A) Factor loadings for each informant questionnaire domain. Dashed vertical lines indicate the factor loading cut-offs (>0.5). (B) PC1 (apathy) plotted against PC2 (challenging behaviours). (C) PC2 (challenging behaviours) plotted against PC3 (ADLs). (D) PC3 (ADLs) plotted against PC1 (apathy). The dashed lines indicate the factor score of a hypothetical participant scoring 1.96 standard deviations below the control average on each task, and the shaded regions show the regions of preserved performance. ADLs = Activities of Daily Living; AMI-CG = Apathy-Motivation Index-Caregiver version; bvFTD = behavioural-variant frontotemporal dementia; CamQUAIT = Cambridge Questionnaire for Apathy and Impulsivity Traits; CBI-R = Cambridge Behavioural Inventory Revised; PCA = principal component analysis; SD = semantic dementia.

Figure 5

Receiver operating characteristic curves distinguishing between bvFTD and SD using the neuropsychological and behavioural components. ADLs = Activities of Daily Living; bvFTD = behavioural-variant frontotemporal dementia; FTD = frontotemporal dementia; SD = semantic dementia.

Figure 6

Regions of grey matter volume associated with factor scores. Multiple linear regression models were fitted with each factor as the main effect and with age, intracranial volume and scanner site included as covariates. Images are thresholded using a cluster-level threshold of P(FDR) < 0.05 (after an initial voxel-level threshold of P < 0.05). Significant clusters are overlaid on the MNI avg152 T1 template. Co-ordinates are reported in MNI space. FDR = false discovery rate; MNI = Montreal Neurological Institute; PC = principal component.