Better cardiovascular health is associated with slowed clinical progression in autosomal dominant frontotemporal lobar degeneration variant carriers

Anna M VandeBunte; Hyunwoo Lee; Emily W Paolillo; Ging-Yuek Robin Hsiung; Adam M Staffaroni; Rowan Saloner; Carmela Tartaglia; Kristine Yaffe; David S Knopman; Eliana Marisa Ramos; Katya Rascovsky; Andrea C Bozoki; Bonnie Wong; Kimiko Domoto-Reilly; Allison Snyder; Peter Pressman; Mario F Mendez; Irene Litvan; Julie A Fields; Douglas R Galasko; Ryan Darby; Joseph C Masdeu; Maria Belen Pasqual; Lawrence S Honig; Nupur Ghoshal; Brian S Appleby; Ian R Mackenzie; Hilary W Heuer; Joel H Kramer; Adam L Boxer; Leah K Forsberg; Brad Boeve; Howard J Rosen; Kaitlin B Casaletto; ALLFTD Consortium

doi:10.1002/alz.14172

Better cardiovascular health is associated with slowed clinical progression in autosomal dominant frontotemporal lobar degeneration variant carriers

Alzheimers Dement. 2024 Oct;20(10):6820-6833. doi: 10.1002/alz.14172. Epub 2024 Sep 6.

Authors

Anna M VandeBunte^{1

2}, Hyunwoo Lee³, Emily W Paolillo¹, Ging-Yuek Robin Hsiung³, Adam M Staffaroni¹, Rowan Saloner¹, Carmela Tartaglia⁴, Kristine Yaffe¹, David S Knopman⁵, Eliana Marisa Ramos⁶, Katya Rascovsky⁷, Andrea C Bozoki⁸, Bonnie Wong⁹, Kimiko Domoto-Reilly¹⁰, Allison Snyder¹¹, Peter Pressman¹², Mario F Mendez¹³, Irene Litvan¹⁴, Julie A Fields⁵, Douglas R Galasko¹⁴, Ryan Darby¹⁵, Joseph C Masdeu¹⁶, Maria Belen Pasqual¹⁶, Lawrence S Honig¹⁷, Nupur Ghoshal¹⁸, Brian S Appleby¹⁹, Ian R Mackenzie²⁰, Hilary W Heuer¹, Joel H Kramer¹, Adam L Boxer¹, Leah K Forsberg⁵, Brad Boeve⁵, Howard J Rosen¹, Kaitlin B Casaletto¹; ALLFTD Consortium

Affiliations

¹ Department of Neurology, University of California, San Francisco, Memory and Aging Center, San Francisco, California, USA.
² Department of Psychology, Palo Alto University, Palo Alto, California, United States.
³ Division of Neurology, UBC Hospital, University of British Columbia, Vancouver, British Columbia, Canada.
⁴ Tanz Centre for Research in Neurodegenerative Diseases, Division of Neurology, Department of Medicine, University of Toronto, Toronto, Ontario, Canada.
⁵ Department of Neurology, Mayo Clinic, Rochester, Minnesota, USA.
⁶ David Geffen School of Medicine at UCLA, UCLA Semel Institute for Neuroscience and Human Behavior, Los Angeles, California, USA.
⁷ Department of Neurology, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
⁸ Department of Neurology, University of North Carolina, Chapel Hill, North Carolina, USA.
⁹ Harvard Massachusetts General Hospital Frontotemporal Disorders Unit, Charlestown, Massachusetts, USA.
¹⁰ Department of Neurology, University of Washington, Seattle, Washington, USA.
¹¹ National Institute of Neurological Disorders and Stroke, Bethesda, Maryland, USA.
¹² Department of Neurology, University of Colorado School of Medicine, Aurora, Colorado, USA.
¹³ David Geffen School of Medicine at UCLA, Reed Neurological Research Center, Los Angeles, California, USA.
¹⁴ San Diego Department of Neurosciences, University of California, San Diego, La Jolla, California, USA.
¹⁵ Department of Neurology, Vanderbilt University, Nashville, Tennessee, USA.
¹⁶ Houston Methodist Neurological Institute, Houston, Texas, USA.
¹⁷ Department of Neurology, Irving Medical Center, Columbia University, New York, New York, USA.
¹⁸ Department of Neurology, St. Louis School of Medicine, Washington University, St. Louis, Missouri, USA.
¹⁹ Department of Neurology, Case Western Reserve University, Cleveland, Ohio, USA.
²⁰ Department of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, British Columbia, Canada.

Abstract

Introduction: Cardiovascular health is important for brain aging, yet its role in the clinical manifestation of autosomal dominant or atypical forms of dementia has not been fully elucidated. We examined relationships between Life's Simple 7 (LS7) and clinical trajectories in individuals with autosomal dominant frontotemporal lobar degeneration (FTLD).

Methods: Two hundred forty-seven adults carrying FTLD pathogenic genetic variants (53% asymptomatic) and 189 non-carrier controls completed baseline LS7, and longitudinal neuroimaging and neuropsychological testing.

Results: Among variant carriers, higher baseline LS7 is associated with slower accumulation of frontal white matter hyperintensities (WMHs), as well as slower memory and language declines. Higher baseline LS7 associated with larger baseline frontotemporal volume, but not frontotemporal volume trajectories.

Discussion: Better baseline cardiovascular health related to slower cognitive decline and accumulation of frontal WMHs in autosomal dominant FTLD. Optimizing cardiovascular health may be an important modifiable approach to bolster cognitive health and brain integrity in FTLD.

Highlights: Better cardiovascular health associates with slower cognitive decline in frontotemporal lobar degeneration (FTLD). Lifestyle relates to the accumulation of frontal white matter hyperintensities in FTLD. More optimal cardiovascular health associates with greater baseline frontotemporal lobe volume. Optimized cardiovascular health relates to more favorable outcomes in genetic dementia.

Keywords: Life's Simple 7; aging; cardiovascular health; frontotemporal dementia; genetic dementia; lifestyle behaviors; modifiable risk; neuropsychology.

MeSH terms

Aged
Brain / diagnostic imaging
Brain / pathology
Cognitive Dysfunction / genetics
Cognitive Dysfunction / pathology
Disease Progression*
Female
Frontotemporal Lobar Degeneration* / genetics
Frontotemporal Lobar Degeneration* / pathology
Heterozygote
Humans
Magnetic Resonance Imaging
Male
Middle Aged
Neuroimaging
Neuropsychological Tests* / statistics & numerical data
White Matter / diagnostic imaging
White Matter / pathology

Abstract

MeSH terms

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