Dataset Information

Frontal asymmetry in behavioral variant frontotemporal dementia: clinicoimaging and pathogenetic correlates.

ABSTRACT: We aimed to assess associations between clinical, imaging, pathologic, and genetic features and frontal lobe asymmetry in behavioral variant frontotemporal dementia (bvFTD). Volumes of the left and right dorsolateral, medial, and orbital frontal lobes were measured in 80 bvFTD subjects and subjects were classified into 3 groups according to the degree of asymmetry (asymmetric left, asymmetric right, symmetric) using cluster analysis. The majority of subjects were symmetric (65%), with 20% asymmetric left and 15% asymmetric right. There were no clinical differences across groups, although there was a trend for greater behavioral dyscontrol in right asymmetric compared with left asymmetric subjects. More widespread atrophy involving the parietal lobe was observed in the symmetric group. Genetic features differed across groups with symmetric frontal lobes associated with C9ORF72 and tau mutations, while asymmetric frontal lobes were associated with progranulin mutations. These findings therefore suggest that neuroanatomical patterns of frontal lobe atrophy in bvFTD are influenced by specific gene mutations.

SUBMITTER: Whitwell JL

PROVIDER: S-EPMC3404265 | biostudies-literature | 2013 Feb

REPOSITORIES: biostudies-literature

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Frontal asymmetry in behavioral variant frontotemporal dementia: clinicoimaging and pathogenetic correlates.

Whitwell Jennifer L JL Xu Jia J Mandrekar Jay J Boeve Bradley F BF Knopman David S DS Parisi Joseph E JE Senjem Matthew L ML Dickson Dennis W DW Petersen Ronald C RC Rademakers Rosa R Jack Clifford R CR Josephs Keith A KA

Neurobiology of aging 20120411 2

We aimed to assess associations between clinical, imaging, pathologic, and genetic features and frontal lobe asymmetry in behavioral variant frontotemporal dementia (bvFTD). Volumes of the left and right dorsolateral, medial, and orbital frontal lobes were measured in 80 bvFTD subjects and subjects were classified into 3 groups according to the degree of asymmetry (asymmetric left, asymmetric right, symmetric) using cluster analysis. The majority of subjects were symmetric (65%), with 20% asymme ...[more]

PMID: 22502999

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Project description:Antemortem behavioural and anatomic abnormalities have largely been associated with right hemisphere disease in behavioural-variant frontotemporal dementia, but post-mortem neuropathological examination of bilateral hemispheres remains to be defined. Here we measured the severity of post-mortem pathology in both grey and white matter using a validated digital image analysis method in four cortical regions sampled from each hemisphere in 26 patients with behavioural-variant frontotemporal dementia, including those with frontotemporal degeneration (i.e. tau = 9, TDP-43 = 14, or FUS = 1 proteinopathy) or Alzheimer's pathology (n = 2). We calculated an asymmetry index based on the difference in measured pathology from each left-right sample pair. Analysis of the absolute value of the asymmetry index (i.e. degree of asymmetry independent of direction) revealed asymmetric pathology for both grey and white matter in all four regions sampled in frontototemporal degeneration patients with tau or TDP-43 pathology (P ≤ 0.01). Direct interhemispheric comparisons of regional pathology measurements within-subjects in the combined tauopathy and TDP-43 proteinopathy group found higher pathology in the right orbitofrontal grey matter compared to the left (P < 0.01) and increased pathology in ventrolateral temporal lobe grey matter of the left hemisphere compared to the right (P < 0.02). Preliminary group-wise comparisons between tauopathy and TDP-43 proteinopathy groups found differences in patterns of interhemispheric burden of grey and white matter regional pathology, with greater relative white matter pathology in tauopathies. To test the association of pathology measurement with ante-mortem observations, we performed exploratory analyses in the subset of patients with imaging data (n = 15) and found a direct association for increasing pathologic burden with decreasing cortical thickness in frontotemporal regions on ante-mortem imaging in tauopathy (P = 0.001) and a trend for TDP-43 proteinopathy (P = 0.06). Exploratory clinicopathological correlations demonstrated an association of socially-inappropriate behaviours with asymmetric right orbitofrontal grey matter pathology, and reduced semantically-guided category naming fluency was associated asymmetric white matter pathology in the left ventrolateral temporal region. We conclude that pathologic disease burden is distributed asymmetrically in behavioural-variant frontotemporal dementia, although not universally in the right hemisphere, and this asymmetry contributes to the clinical heterogeneity of the disorder. The basis for this asymmetric profile is enigmatic but may reflect distinct species or strains of tau and TDP-43 pathologies with propensities to spread by distinct cell- and region-specific mechanisms. Patterns of region-specific pathology in the right hemisphere as well as the left hemisphere may play a role in antemortem clinical observations, and these observations may contribute to antemortem identification of molecular pathology in frontotemporal degeneration.

Project description:Emotional events gain special priority in how they are remembered, with emotionally arousing events typically recalled more vividly and with greater confidence than non-emotional events. In dementia, memory and emotion processing are affected to varying degrees, however, whether emotional enhancement of memory for complex ecologically-valid events is differentially affected across dementia syndromes remains unclear, with previous studies examining effects of emotion on simple visual recognition only. Here, we examined memory for an emotionally arousing short story and a closely matched, emotionally neutral story in behavioral-variant frontotemporal dementia (bvFTD) (n = 13) and Alzheimer's disease (AD) (n = 14), and contrasted their performance with healthy controls (n = 12). Multiple-choice recognition memory for specific details of the story was assessed after a 1-h delay. While AD and control groups showed enhanced memory for the emotional story, the bvFTD group recalled a similar number of details from the emotional and neutral stories. Voxel-based morphometry analyses revealed emotional enhancement of memory correlated with distinct brain regions in each patient group. In AD, emotional enhancement was associated with integrity of the bilateral hippocampus, parahippocampal gyri, temporal fusiform gyrus and frontal pole, regions typically implicated in memory processes. In contrast in bvFTD, integrity of emotion processing regions, including the orbitofrontal cortex, right amygdala and right insula, correlated with the extent emotion enhanced memory. Our results reveal that integrity of frontal and temporal regions determine the quality and nature of emotional memories. While emotional enhancement of memory is present in mild AD, in bvFTD emotion does not facilitate memory retrieval for complex realistic events. This attenuation of emotional enhancement is due to degradation of emotion processing regions, which may be important for modulating levels of arousal in response to emotional events in these patients.

Dataset Information

Frontal asymmetry in behavioral variant frontotemporal dementia: clinicoimaging and pathogenetic correlates.

Publications

Frontal asymmetry in behavioral variant frontotemporal dementia: clinicoimaging and pathogenetic correlates.

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