Regional prefrontal cortical atrophy predicts specific cognitive-behavioral symptoms in ALS-FTD

Elena Ratti; Kimiko Domoto-Reilly; Christina Caso; Alyssa Murphy; Michael Brickhouse; Daisy Hochberg; Nikos Makris; Merit E Cudkowicz; Bradford C Dickerson

doi:10.1007/s11682-021-00456-1

Regional prefrontal cortical atrophy predicts specific cognitive-behavioral symptoms in ALS-FTD

Brain Imaging Behav. 2021 Oct;15(5):2540-2551. doi: 10.1007/s11682-021-00456-1. Epub 2021 Feb 15.

Authors

Elena Ratti^{1

2

3

4

5

6}, Kimiko Domoto-Reilly^{7

8

9

10}, Christina Caso^{7

10}, Alyssa Murphy^{11

12}, Michael Brickhouse⁷, Daisy Hochberg^{7

13}, Nikos Makris¹⁴, Merit E Cudkowicz^{11

12}, Bradford C Dickerson^{7

8

9}

Affiliations

¹ Neurological Clinical Research Institute (NCRI), Massachusetts General Hospital, 165 Cambridge Street, Suite 600, Boston, MA, 02114, USA. elena.ratti@alumni.harvard.edu.
² Frontotemporal Disorders Unit, Department of Neurology, Massachusetts General Hospital, 55 Fruit Street, Boston, MA, 02114, USA. elena.ratti@alumni.harvard.edu.
³ Amyotrophic Lateral Sclerosis Multidisciplinary Clinic, Department of Neurology, Massachusetts General Hospital, 55 Fruit Street, Boston, MA, 02114, USA. elena.ratti@alumni.harvard.edu.
⁴ Massachusetts Alzheimer's Disease Research Center (ADRC), 149 13th Street, Charlestown, MA, 02129, USA. elena.ratti@alumni.harvard.edu.
⁵ Athinoula A. Martinos Center for Biomedical Imaging, 149 13th Street, Charlestown, MA, 02129, USA. elena.ratti@alumni.harvard.edu.
⁶ Biogen, 300 Binney Street, Cambridge, MA, 02142, USA. elena.ratti@alumni.harvard.edu.
⁷ Frontotemporal Disorders Unit, Department of Neurology, Massachusetts General Hospital, 55 Fruit Street, Boston, MA, 02114, USA.
⁸ Massachusetts Alzheimer's Disease Research Center (ADRC), 149 13th Street, Charlestown, MA, 02129, USA.
⁹ Athinoula A. Martinos Center for Biomedical Imaging, 149 13th Street, Charlestown, MA, 02129, USA.
¹⁰ Department of Neurology, University of Washington Medical Center, 1959 NE Pacific Street, Seattle, WA, 98195, USA.
¹¹ Neurological Clinical Research Institute (NCRI), Massachusetts General Hospital, 165 Cambridge Street, Suite 600, Boston, MA, 02114, USA.
¹² Amyotrophic Lateral Sclerosis Multidisciplinary Clinic, Department of Neurology, Massachusetts General Hospital, 55 Fruit Street, Boston, MA, 02114, USA.
¹³ Speech and Language Pathology, Massachusetts General Hospital, 275 Cambridge Street, Boston, MA, 02114, USA.
¹⁴ Department of Psychiatry, Massachusetts General Hospital, 55 Fruit Street, Boston, MA, 02114, USA.

Abstract

Amyotrophic Lateral Sclerosis-Frontotemporal Dementia (ALS-FTD) may present typical behavioral variant FTD symptoms. This study aims to determine whether profile and severity of cognitive-behavioral symptoms in ALS/ALS-FTD are predicted by regional cortical atrophy. The hypothesis is that executive dysfunction can be predicted by dorsolateral prefrontal cortical (dlPFC) atrophy, apathy by dorsomedial PFC (dmPFC) and anterior cingulate cortical (ACC) atrophy, disinhibition by orbitofrontal cortical (OFC) atrophy. 3.0 Tesla MRI scans were acquired from 22 people with ALS or ALS-FTD. Quantitative cortical thickness analysis was performed with FreeSurfer. A priori-defined regions of interest (ROI) were used to measure cortical thickness in each participant and calculate magnitude of atrophy in comparison to 115 healthy controls. Spearman correlations were used to evaluate associations between frontal ROI cortical thickness and cognitive-behavioral symptoms, measured by Neuropsychiatric Inventory Questionnaire (NPI-Q) and Clinical Dementia Rating (CDR) scale. ALS-FTD participants exhibited variable degrees of apathy (NPI-Q/apathy: 1.6 ± 1.2), disinhibition (NPI-Q/disinhibition: 1.2 ± 1.2), executive dysfunction (CDR/judgment-problem solving: 1.7 ± 0.8). Within the ALS-FTD group, executive dysfunction correlated with dlPFC atrophy (ρ:-0.65;p < 0.05); similar trends were seen for apathy with ACC (ρ:-0.53;p < 0.10) and dmPFC (ρ:-0.47;p < 0.10) atrophy, for disinhibition with OFC atrophy (ρ:-0.51;p < 0.10). Compared to people with ALS, those with ALS-FTD showed more diffuse atrophy involving precentral gyrus, prefrontal, temporal regions. Profile and severity of cognitive-behavioral symptoms in ALS-FTD are predicted by regional prefrontal atrophy. These findings are consistent with established brain-behavior models and support the role of quantitative MRI in diagnosis, management, counseling, monitoring and prognostication for a neurodegenerative disorder with diverse phenotypes.

Keywords: Amyotrophic lateral sclerosis (4); Cerebral cortex (2); Frontal lobe (5); Frontotemporal dementia (3); Magnetic resonance imaging (1).

MeSH terms

Amyotrophic Lateral Sclerosis* / diagnostic imaging
Atrophy
Behavioral Symptoms
Cognition
Frontotemporal Dementia* / diagnostic imaging
Humans
Magnetic Resonance Imaging

Abstract

MeSH terms

Grants and funding