Latent profile analysis in frontotemporal lobar degeneration and related disorders: clinical presentation and SPECT functional correlates

Abstract

Background: Frontotemporal Lobar Degeneration (FTLD) thus recently renamed, refers to a spectrum of heterogeneous conditions. This same heterogeneity of presentation represents the major methodological limit for the correct evaluation of clinical designation and brain functional correlates. At present, no study has investigated clinical clusters due to specific cognitive and behavioural disturbances beyond current clinical criteria. The aim of this study was to identify clinical FTLD presentation, based on cognitive and behavioural profile, and to define their SPECT functional correlations.

Methods: Ninety-seven FTLD patients entered the study. A clinical evaluation and standardised assessment were preformed, as well as a brain SPECT perfusion imaging study. Latent Profile Analysis on clinical, neuropsychological, and behavioural data was performed. Voxel-basis analysis of SPECT data was computed.

Results: Three specific clusters were identified and named "pseudomanic behaviour" (LC1), "cognitive" (LC2), and "pseudodepressed behaviour" (LC3) endophenotypes. These endophenotypes showed a comparable hypoperfusion in left temporal lobe, but a specific pattern involving: medial and orbitobasal frontal cortex in LC1, subcortical brain region in LC2, and right dorsolateral frontal cortex and insula in LC3.

Conclusion: These findings provide evidence that specific functional-cluster symptom relationship can be delineated in FTLD patients by a standardised assessment. The understanding of the different functional correlates of clinical presentations will hopefully lead to the possibility of individuating diagnostic and treatment algorithms.

Figure 1

Maps of significant voxels representing regions of hypoperfusion in FTLD patients according to clinical diagnosis, superimposed to reference T1-weighted MRI image. bvFTD: behavioural variant of Frontotemporal Dementia (first row), SD: Semantic Dementia (second row), PNFA: Progressive Non-Fluent Aphasia (third row), PSP: Progressive Supranuclear Palsy (fourth row), and CBD: Corticobasal Degeneration (fifth row) patient subgroups are reported. Statistical threshold, P < 0.001, T ≥ 3.99, minimum cluster size = 50 voxels. Neurological convention: left is on the left side and vice versa.

Figure 2

Scatter-plot of FTLD patients labelled according to generated three Latent Classes. y axis: values of behavioural disturbances (measured by Frontal Behavioural Inventory Scale, FBI-A plus FBI-B,); x axis: values of cognitive deficits (cognitive sum, i.e. the sum of Equivalent Scores of all the neuropsychological tests included in the assessment, the higher the value the better the performance; see Table 4). The centroid (0;0) represents the overall mean profile; compared to the average value of the whole sample, LC1 patients have higher cognitive sum values (i.e. less severe cognitive impairment); while LC2 and LC3 patients have lower cognitive sum values (i.e. more severe cognitive impairment); vice versa the behavioural deficit values are higher in the LC1 than in the LC2 and LC3 patients.

Figure 3

Maps of significant voxels representing regions of hypoperfusion in FTLD patients according to the three Latent Classes, superimposed to reference T1-weighted MRI image. LC: Latent Class. LC1 (first row), LC2 (second row), and LC3 (third row) patient subgroups are reported. Statistical threshold, P < 0.001, T ≥ 3.40, minimum cluster size = 50 voxels. Neurological convention: left is on the left side and vice versa.

Figure 4

Proportion of each clinical diagnosis across the three Latent Classes. LC: Latent Class; bvFTD: behavioural variant of Frontotemporal Dementia, SD: Semantic Dementia, PNFA: Progressive Non-Fluent Aphasia, PSP: Progressive Supranuclear Palsy, and CBD: Corticobasal Degeneration.