Trajectories of cortical atrophy by cognitive phenotype in patients primary brain tumors
Poster No:
1731
Submission Type:
Abstract Submission
Authors:
Jiwandeep Kohli1, Anny Reyes1, Austin Hopper1, Natalia Menendez1, Kathryn Tringale1, Roshan Karunamuni1, Jona Hattangadi-Gluth1, Carrie McDonald1
Institutions:
1University of California, San Diego, San Diego, CA
First Author:
Co-Author(s):
Introduction:
Radiotherapy (RT) is standard of care for most patients with primary brain tumors (Nabors et al., 2020), but is often accompanied by cognitive side effects. These patients demonstrate heterogeneous patterns of cognitive impairment, due to multifactorial etiologies and variability in treatments. Cognitive phenotyping has shown utility for parsing this heterogeneity by identifying clinically meaningful groups of patients with similar neuropsychological profiles. Our prior work has demonstrated that unique cognitive phenotypes have distinct neuroanatomical profiles before RT (Kohli et al., 2024), but the extent of cortical vulnerability demonstrated by these phenotypes has not been tested post-RT. We investigated cortical atrophy longitudinally in patients with primary brain tumors before and after RT, hypothesizing those with more impaired cognitive profiles would show greater and more widespread atrophy post-RT than minimally-impaired patients.
Methods:
Patients with primary brain tumors were recruited for a prospective, observational study examining the effects of fractionated, partial brain RT on brain structure and cognition. Neurocognitive and structural MRI data were available for 85 participants at baseline. Follow up MRIs were performed at 3 (n=83), 6 (n=82), and 12 months (n=82) following completion of RT. Anatomical MRIs were acquired using a T1w sequence (TE/TR=2.8/6.5ms; inversion time=450ms; flip angle=8°; FOV=24cm). Scans were processed using FreeSurfer v5.3.0 (Dale et al., 1999) to extract cortical thickness (CT) measurements from 68 ROIs using the Desikan-Killiany atlas. Participants completed comprehensive neuropsychological testing prior to RT. Latent profile analysis was used for cognitive phenotyping of patients in a prior study (Reyes et al., 2024), resulting in three unique groups: generalized impairment (12.9%; impairment in three+ cognitive domains), isolated verbal memory impairment (18.8%), or minimal impairment (68.3%; no impaired domains). Atrophy rates were compared among cognitive phenotypes using multilevel models controlling for age and sex. P-values were adjusted using the false discovery rate.
Results:
There were no significant differences in age, education, race/ethnicity, history of surgery or seizures, use of antiseizure medications, or other tumor characteristics. Patients in the minimal impairment phenotype showed no significant decline in CT following RT. Those in the verbal memory impairment phenotype showed a decline in CT in the left superior temporal gyrus and superior parietal lobule (ps<0.005). The generalized impairment phenotype demonstrated a decline in CT in left frontal pole, inferior parietal, inferior temporal, lateral occipital, middle temporal, paracentral, precentral, precuneus, rostral middle frontal, and superior frontal ROIs (ps<0.01), as well as right caudal anterior cingulate, lateral occipital, and superior parietal (ps<0.007) ROIs. Atrophy patterns and regions of significant decline are depicted by cognitive phenotype in Figure 1.
·(A) Whole brain cortical atrophy patterns by cognitive phenotype (B) Regions demonstrating statistically significant decline in cortical thickness (CT) (C) Annualized atrophy rates by phenotype
Conclusions:
We found bi-hemispheric, multi-lobar atrophy in the year post-RT in patients with a generalized impairment profile. In contrast, patients with minimally impaired profiles showed minimal cortical atrophy, and those with an isolated verbal memory impairment showed focal atrophy in left temporoparietal cortex post-RT. Annualized cortical atrophy rates for the impaired phenotypes are concerning in that they are comparable to regional cortical volume loss reported in Alzheimer's Disease and frontotemporal dementia (Chan et al., 2001; Thompson et al., 2003). These findings suggest that a patient's cognitive profile prior to RT may inform their risk for RT-related cortical atrophy and the neuroanatomical regions at greater vulnerability for injury, and possibly additional cognitive decline following RT. These findings could provide a blueprint for tailoring interventions to prevent further cognitive decline for at risk patients.
Higher Cognitive Functions:
Higher Cognitive Functions Other 2
Modeling and Analysis Methods:
Multivariate Approaches
Neuroanatomy, Physiology, Metabolism and Neurotransmission:
Cortical Anatomy and Brain Mapping 1
Novel Imaging Acquisition Methods:
Anatomical MRI
Keywords:
ADULTS
Cognition
Cortex
Multivariate
Neoplastic Disease
Statistical Methods
STRUCTURAL MRI
1|2Indicates the priority used for review
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Provide references using APA citation style.
Dale, A. M. (1999). Cortical surface-based analysis: I. Segmentation and surface reconstruction. Neuroimage, 9(2), 179–194.
Kohli, J. S. (2024). Neuroanatomical profiles of cognitive phenotypes in patients with primary brain tumors. Neuro-Oncology Advances.
Nabors, L. B. (2020). Central nervous system cancers, version 3.2020, NCCN clinical practice guidelines in oncology. Journal of the National Comprehensive Cancer Network, 18(11), 1537–1570.
Reyes, A. (2024). Cognitive phenotypes: Unraveling the heterogeneity in cognitive dysfunction among patients with primary brain tumors receiving radiotherapy. Neuro-Oncology.
Thompson, P. M. (2003). Dynamics of Gray Matter Loss in Alzheimer’s Disease. Journal of Neuroscience, 23(3), 994–1005.