Contributions
Abstract: 188
Type: Oral
Abstract Category: Pathology and pathogenesis of MS - 21 Imaging
Background: Substantial work has measured total whole brain and grey matter volume loss in MS, but the relative contributions of normal aging and MS-specific atrophy, and whether these contributions change with age, have not been examined. We hypothesize that most of the atrophy in young patients is disease-related, but the contribution of normal aging increases with age.
Objective: To estimate the relative contributions of normal aging and MS-specific atrophy to whole brain and deep grey matter volume across adulthood.
Methods: 601 total subjects (2741 MRIs) were analyzed: 520 relapse-onset MS subjects across the disease duration from a single-center prospective cohort with annual 3T MRIs, including standardized 1mm3 3D T1-weighted images (3DT1s; 2483 MRIs), and 81 healthy controls (HC) with longitudinal 3T MRIs (258 3DT1s). 3DT1s were processed using FreeSurfer's longitudinal pipeline (v5.3) and SIENA. Rates of change in deep grey matter regions and percent brain volume change (PBVC) from SIENA were estimated in MS and HC with linear mixed effects models. Age was tested as an effect modifier in the relationship between MS-related atrophy and time by adding a 3-way interaction term to the model (age*MS*time). Point estimates for MS-specific atrophy (total atrophy in MS - atrophy in HC) were obtained at ages 30, 40, 50 and 60.
Results: For SIENA, the relative contributions of MS and normal aging differed as age increased (p-value for βage*MS*time =0.01). Normal aging increased from 0.007%/year at age 30 to -0.31% at age 60, while MS-specific atrophy decreased from -0.38%/y at age 30 to -0.12% at age 60. A similar pattern was observed in the thalamus, where normal aging increased from -0.15%/y at age 30 to -0.62% at age 60, while MS-specific atrophy decreased from -0.59%/y at age 30 to -0.05% at age 60 (p=0.04). In the putamen and caudate, the contributions of normal aging and MS-specific atrophy did not vary by age (p=0.66 and 0.48, respectively).
Conclusions: For SIENA and thalamic atrophy, the relative contribution of normal aging increases with age, whereas it does not change with age in the putamen and caudate. This work emphasizes the need to understand the contribution of normal aging in different brain regions in MS. This may impact sample size calculations, as only the MS-specific atrophy is presumably amenable to therapeutic intervention, and may help our understanding of treatment effects on brain atrophy in older populations.
Disclosure:
Dr. Azevedo has served on advisory boards for Genentech, Biogen and Genzyme.
Dr. Pelletier has received consulting and/or speaking fees from Novartis, Roche, Sanofi Genzyme, and Vertex.
Drs. Cen, Zheng, and Jaberzadeh have nothing to disclose.
Abstract: 188
Type: Oral
Abstract Category: Pathology and pathogenesis of MS - 21 Imaging
Background: Substantial work has measured total whole brain and grey matter volume loss in MS, but the relative contributions of normal aging and MS-specific atrophy, and whether these contributions change with age, have not been examined. We hypothesize that most of the atrophy in young patients is disease-related, but the contribution of normal aging increases with age.
Objective: To estimate the relative contributions of normal aging and MS-specific atrophy to whole brain and deep grey matter volume across adulthood.
Methods: 601 total subjects (2741 MRIs) were analyzed: 520 relapse-onset MS subjects across the disease duration from a single-center prospective cohort with annual 3T MRIs, including standardized 1mm3 3D T1-weighted images (3DT1s; 2483 MRIs), and 81 healthy controls (HC) with longitudinal 3T MRIs (258 3DT1s). 3DT1s were processed using FreeSurfer's longitudinal pipeline (v5.3) and SIENA. Rates of change in deep grey matter regions and percent brain volume change (PBVC) from SIENA were estimated in MS and HC with linear mixed effects models. Age was tested as an effect modifier in the relationship between MS-related atrophy and time by adding a 3-way interaction term to the model (age*MS*time). Point estimates for MS-specific atrophy (total atrophy in MS - atrophy in HC) were obtained at ages 30, 40, 50 and 60.
Results: For SIENA, the relative contributions of MS and normal aging differed as age increased (p-value for βage*MS*time =0.01). Normal aging increased from 0.007%/year at age 30 to -0.31% at age 60, while MS-specific atrophy decreased from -0.38%/y at age 30 to -0.12% at age 60. A similar pattern was observed in the thalamus, where normal aging increased from -0.15%/y at age 30 to -0.62% at age 60, while MS-specific atrophy decreased from -0.59%/y at age 30 to -0.05% at age 60 (p=0.04). In the putamen and caudate, the contributions of normal aging and MS-specific atrophy did not vary by age (p=0.66 and 0.48, respectively).
Conclusions: For SIENA and thalamic atrophy, the relative contribution of normal aging increases with age, whereas it does not change with age in the putamen and caudate. This work emphasizes the need to understand the contribution of normal aging in different brain regions in MS. This may impact sample size calculations, as only the MS-specific atrophy is presumably amenable to therapeutic intervention, and may help our understanding of treatment effects on brain atrophy in older populations.
Disclosure:
Dr. Azevedo has served on advisory boards for Genentech, Biogen and Genzyme.
Dr. Pelletier has received consulting and/or speaking fees from Novartis, Roche, Sanofi Genzyme, and Vertex.
Drs. Cen, Zheng, and Jaberzadeh have nothing to disclose.