Investigating the Relationships of Atrophy and Hypometabolism on Cognitive Decline in Frontotemporal Dementia
Salih Cayir1, Yanghong Yang1, Tommaso Volpi1, Faranak Ebrahimian Sadabad1, Takuya Toyonaga1, Jean-Dominique Gallezot1, Adam P. Mecca2, Arman Fesharaki-Zadeh3, David Matuskey1
1Department of Radiology and Biochemical Imaging, Yale University, 2Department of Psychiatry, Yale University, 3Department of Neurology, Yale University
Objective:

To relate neuroimaging biomarkers of atrophy and hypometabolism via structural MRI (T1w) and [18F]fluorodeoxyglucose ([18F]FDG) PET imaging, respectively, to cognitive performance assessed by Montreal Cognitive Assessment (MoCA) in frontotemporal dementia (FTD).

Background:

Few studies have examined cognition, hypometabolism, and gray matter (GM) atrophy in the same cohort of FTD patients. This is important to demonstrate possible associations and/or discrepancies between different neuroimaging modalities and clinically relevant cognitive scores in FTD.  

Design/Methods:

This retrospective study included 17 patients diagnosed with FTD (14 male,3 female;mean age:69.5±8.1 years old). Patients with FTD were included if they had T1w MRI, [18F]FDG PET, and MoCA global scores that could be obtained through medical records. Iterative-Yang partial volume correction was applied to [18F]FDG data to control for possible bias caused by volumetric differences. Whole-cortex GM volume and standardized uptake value ratio (SUVR) using the brainstem as the reference region were the primary outcome measures. Secondary analyses were performed for 12 brain regions of interest. Spearman’s correlations (ρ) were used to relate imaging variables and MoCA scores (p values uncorrected for multiple testing).  

Results:

We observed a significant positive correlation between whole-cortex GM volume and MoCA scores (ρ=0.539,p=0.026). There was no significant correlation between whole-cortex SUVR and MoCA (ρ=0.326, p=0.202). At the regional level, GM volumes of the frontal and parietal lobes, as well as the insular cortex and caudate (ρ=0.594, p=0.012; ρ=0.504,p=0.039; ρ=0.581,p=0.014; ρ=0.697, p=0.002, respectively) were significantly correlated with MoCA. When relating regional SUVRs with MoCA, only the frontal lobe was significantly correlated (ρ=0.486,p=0.048).

Conclusions:

Cortical GM atrophy, but not hypometabolism, was significantly associated with worse cognitive performance in patients with FTD. Regional analysis indicates that the associations between GM volume and cognition are stronger than the association between metabolism and cognition. These results may provide insight into the relationships between structural, metabolic, and cognitive changes due to FTD.

10.1212/WNL.0000000000204352