Active lifestyles moderate clinical outcomes in autosomal dominant frontotemporal degeneration

K B Casaletto, A M Staffaroni, A Wolf, B Appleby, D Brushaber, G Coppola, B Dickerson, K Domoto-Reilly, F M Elahi, J Fields, J C Fong, L Forsberg, N Ghoshal, N Graff-Radford, M Grossman, H W Heuer, G-Y Hsiung, E D Huey, D Irwin, K Kantarci, D Kaufer, D Kerwin, D Knopman, J Kornak, J H Kramer, I Litvan, I R Mackenzie, M Mendez, B Miller, R Rademakers, E M Ramos, K Rascovsky, E D Roberson, J A Syrjanen, M C Tartaglia, S Weintraub, B Boeve, A L Boxer, H Rosen, K Yaffe, ARTFL/LEFFTDS Study, K B Casaletto, A M Staffaroni, A Wolf, B Appleby, D Brushaber, G Coppola, B Dickerson, K Domoto-Reilly, F M Elahi, J Fields, J C Fong, L Forsberg, N Ghoshal, N Graff-Radford, M Grossman, H W Heuer, G-Y Hsiung, E D Huey, D Irwin, K Kantarci, D Kaufer, D Kerwin, D Knopman, J Kornak, J H Kramer, I Litvan, I R Mackenzie, M Mendez, B Miller, R Rademakers, E M Ramos, K Rascovsky, E D Roberson, J A Syrjanen, M C Tartaglia, S Weintraub, B Boeve, A L Boxer, H Rosen, K Yaffe, ARTFL/LEFFTDS Study

Abstract

Introduction: Leisure activities impact brain aging and may be prevention targets. We characterized how physical and cognitive activities relate to brain health for the first time in autosomal dominant frontotemporal lobar degeneration (FTLD).

Methods: A total of 105 mutation carriers (C9orf72/MAPT/GRN) and 69 non-carriers reported current physical and cognitive activities at baseline, and completed longitudinal neurobehavioral assessments and brain magnetic resonance imaging (MRI) scans.

Results: Greater physical and cognitive activities were each associated with an estimated >55% slower clinical decline per year among dominant gene carriers. There was also an interaction between leisure activities and frontotemporal atrophy on cognition in mutation carriers. High-activity carriers with frontotemporal atrophy (-1 standard deviation/year) demonstrated >two-fold better cognitive performances per year compared to their less active peers with comparable atrophy rates.

Discussion: Active lifestyles were associated with less functional decline and moderated brain-to-behavior relationships longitudinally. More active carriers "outperformed" brain volume, commensurate with a cognitive reserve hypothesis. Lifestyle may confer clinical resilience, even in autosomal dominant FTLD.

Keywords: cognitive activity; cognitive reserve; exercise; frontotemporal dementia; physical activity.

© 2020 the Alzheimer's Association.

Figures

Figure 1.
Figure 1.
Baseline levels of physical and cognitive activity are lowest in syndromic autosomal dominant FTLD mutation carriers (adjusted for age, sex, education).
Figure 2.
Figure 2.
Baseline levels of physical and cognitive activities do not differ across FTLD genotype (adjusted for age, sex, education, and FTLD-CDR sum of boxes).
Figure 3.
Figure 3.
Higher levels of baseline physical and cognitive activities are associated with significantly slower clinical decline over time in autosomal dominant FTLD mutation carriers (adjusted for age, sex, education). Bands represent 95% CI.
Figure 4.
Figure 4.
Baseline models illustrating the moderating effect of physical activity on the relationship between frontotemporal volumes and clinical outcomes in FTLD mutation carriers (adjusted for age, sex, education, and FTLD-CDR sum of boxes).
Figure 5.
Figure 5.
Baseline models illustrating the moderating effect of cognitive activity on the relationship between frontotemporal volumes and clinical outcomes in FTLD mutation carriers (adjusted for age, sex, education, and FTLD-CDR sum of boxes).
Figure 6.
Figure 6.
Baseline physical and cognitive activities significantly moderate the relationship between frontotemporal atrophy and longitudinal clinical outcomes in autosomal dominant FTLD mutation carriers (adjusted for baseline age, sex, education, and FTLD-CDR sum of boxes). Bands represent 95% CI.

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