Aims

To assess longitudinal patterns of atrophy shown by magnetic resonance imaging (MRI) in the cortical and subcortical GM of patients affected by different clinical variants of the FTLD spectrum.

Methods

Fifty-nine patients, including 26 with behavioral variant of frontotemporal dementia (bvFTD), 10 non-fluent/agrammatic variant of primary progressive aphasia (nfvPPA), 12 semantic variant of PPA (svPPA), and 11 MND, in the absence of known pathogenic mutations, underwent MRI on a 3T scanner at 6-month intervals for one year. Thirty-three healthy controls underwent the same protocol. 3D T1-weighted MRI sequences were analyzed using voxel-based morphometry to assess the longitudinal evolution of GM atrophy in patients, compared with HC.

Results

At baseline, severe diffuse atrophy of frontotemporal cortical regions and basal ganglia was found in bvFTD, nfvPPA and svPPA groups, whereas MND did not show significant GM atrophy. At 6-month follow-up, bvFTD and PPA showed progression of atrophy in the insular (bvFTD, nfvPPA and svPPA) and anterior cingulate cortices (bvFTD and nfvPPA), bilaterally, as well as in the left caudate nucleus and middle temporal cortex (svPPA). At 12-month follow-up, similar patterns of atrophy progression were found, with the additional involvement of the superior frontal cortical gyri in nfvPPA, and right hippocampus in svPPA. No significant progression of atrophy was found in MND.

Conclusions

Atrophy of insular and anterior cingulate cortical regions closely reflects the progression of neurodegeneration across the behavioral and linguistic presentations of FTD, in contrast with a substantial sparing of GM in MND.

Supported by: European Research Council (StG-2016_714388_NeuroTRACK).

Aims

The aim was to unravel structural/functional MRI connectomic features of motor neuron disease (MND) and behavioral variant of frontotemporal dementia (bvFTD).

Methods

115 MND (including amyotrophic lateral sclerosis [ALS] and primary lateral sclerosis), 35 bvFTD patients and 61 controls underwent clinical/cognitive and MRI evaluations. MND patients were divided in 79 pure-motor (MNDpm), 36 cognitive/behavioral impaired (MNDci/bi). A sub-analysis was performed on ALS patients only (54 ALSpm, 21 ALSci/bi and 8 ALS-FTD). Graph analysis and connectomics assessed structural/functional topological network properties at global, lobar and regional level.

Results

Globally, bvFTD showed altered structural and functional network properties compared to all other groups. Particularly, bvFTD showed altered structural and functional network properties within the frontotemporal and basal ganglia areas relative to all groups. Structural alterations in the parietal lobe discriminated bvFTD from controls and MNDpm only. MND groups showed altered graph metrics within the sensorimotor and basal ganglia areas relative to controls. At regional level, bvFTD showed widespread structural damage and decreased functional connecivity (FC) relative to all groups. MND showed disrupted structural architecture and enhanced FC within sensorimotor, basal ganglia and frontotemporal areas relative to controls. Structural and functional patterns have been replicated in ALS sub-analysis.

Conclusions

The disruption of the structural architecture in MND worsens in relation with cognitive deficits. Functional changes are characterized by enhanced FC in presence of exclusive motor impairment that intensifies with the occurrence of cognitive impairment in MND. The comorbidity of ALS and FTD leads to decreased FC similarly to bvFTD.

Funding:The Italian Ministry of Health(GR-2011-02351217;GR-2013-02357415;RF-2011-02351193) and AriSLA(ConnectALS).