INS NYC 2024 Program

Poster	Poster Session 02 Program Schedule 02/15/2024 08:00 am - 09:15 am Room: Majestic Complex (Posters 61-120) Poster Session 02: Aging \| MCI \| Neurodegenerative Disease - PART 1 Final Abstract #101 Disentangling the Neurobiological Pathways of Systemic Cardiovascular Health Anna VandeBunte, UCSF Memory and Aging Center, San Francisco, United States Brandon Chan, UCSF Memory and Aging Center, San Francisco, United States Julio Rojas, UCSF Memory and Aging Center, San Francisco, United States Argentina Lario-Lago, UCSF Memory and Aging Center, San Francisco, United States Shannon Lee, UCSF Memory and Aging Center, San Francisco, United States Coty Chen, UCSF Memory and Aging Center, San Francisco, United States Valentina Diaz, UCSF Memory and Aging Center, San Francisco, United States Lana Callies, UCSF Memory and Aging Center, San Francisco, United States Savannah Hallgarth, UCSF Memory and Aging Center, San Francisco, United States Miwa Tucker, UCSF Memory and Aging Center, San Francisco, United States Rowan Saloner, UCSF Memory and Aging Center, San Francisco, United States Joel Kramer, UCSF Memory and Aging Center, San Francisco, United States Kaitlin Casaletto, UCSF Memory and Aging Center, San Francisco, United States Emily Paolillo, UCSF Memory and Aging Center, San Francisco, United States Category: Neurodegenerative Disorders Keyword 1: cardiovascular disease Keyword 2: brain function Keyword 3: aging (normal) Objective: Systemic cardiovascular health is a modifiable factor important for prevention and mitigation of neurodegenerative diseases. However, mechanism(s) underlying the heart-to-brain connection are unclear given that systemic vascular health is multifaceted and cardiovascular indicators may affect neurodegenerative processes either directly, or through indirect pathways that are dysregulated in general brain aging. We therefore examined how molecular markers of astrocytic activation (GFAP), neuronal axon breakdown (NfL), and Alzheimer’s disease (AD) pathology (pTau181) in plasma map onto several major indicators of cardiovascular health in older adults along the AD continuum. Participants and Methods: 206 older adults (Meanage=72.8; Meaneducation=17.4; 59% female sex; 87% clinically normal; 13% MCI due to AD) completed 30-day FitbitTM Flex2 monitoring (average daily steps), in-lab blood pressure (BP) and heart rate quantification, and a blood draw with plasma analyzed for GFAP, NfL, and pTau181 (Quanterix Simoa). Linear regression models evaluated associations among indicators of cardiovascular health (systolic BP, objective physical activity, resting heart rate) and plasma markers of interest (GFAP, NfL, pTau181). We also examined interactions between cardiovascular health metrics and diagnostic status or sex on plasma biomarkers. Finally, to better understand our initial results, we tested a post-hoc mediation model (1000 bootstrap resampling) evaluating whether BP mediated the association between physical activity and plasma NfL levels. All models adjusted for age, sex, and body mass index. Results: Elevations in systolic BP were associated with higher plasma pTau181 (β =0.17, p=0.04) and NfL levels (β =0.19, p<0.01) and approached significance with higher GFAP levels (β =0.12, p=0.055). In contrast, greater average daily steps associated with lower plasma levels of GFAP (β =-0.15, p<0.05) and NfL (β=-0.15, p<0.05), but not pTau181 (β=-0.11, p=0.22). Resting heart rate did not meaningfully associate with plasma GFAP, NfL, or pTau181 levels (βrange=-0.007-0.02, ps>0.50). Interaction models suggested that these associations did not differ based on sex or clinical diagnosis (ps >0.5). In a post-hoc mediation model, systolic BP fully mediated the relationship between daily steps and plasma NfL (Indirect Pathway: β=-0.04, p=0.04; Direct Pathway: β=-0.12, p=0.15). Conclusions: While lower systolic BP associated with lower levels of AD pathology (ptau181), greater physical activity associated with lower markers of astrocytic activation. Both lower BP and greater step count associated with a marker of neuronal axon degeneration; however, the association between physical activity and axon degeneration was driven by systolic BP, one of the strongest indicators of overall cardiovascular state. Optimizing facets of cardiovascular health may provide an opportunity to bolster brain reserve and reduce risk of neurodegenerative disease, regardless of clinical diagnosis. Deeper understanding of the biological pathways involved in the heart-to-brain connection is still needed to inform more precise recommendations and interventions for healthy brain aging.

Poster

02/15/2024
08:00 am - 09:15 am
Room: Majestic Complex (Posters 61-120)

Poster Session 02: Aging | MCI | Neurodegenerative Disease - PART 1

Final Abstract #101

Disentangling the Neurobiological Pathways of Systemic Cardiovascular Health

Anna VandeBunte, UCSF Memory and Aging Center, San Francisco, United States
Brandon Chan, UCSF Memory and Aging Center, San Francisco, United States
Julio Rojas, UCSF Memory and Aging Center, San Francisco, United States
Argentina Lario-Lago, UCSF Memory and Aging Center, San Francisco, United States
Shannon Lee, UCSF Memory and Aging Center, San Francisco, United States
Coty Chen, UCSF Memory and Aging Center, San Francisco, United States
Valentina Diaz, UCSF Memory and Aging Center, San Francisco, United States
Lana Callies, UCSF Memory and Aging Center, San Francisco, United States
Savannah Hallgarth, UCSF Memory and Aging Center, San Francisco, United States
Miwa Tucker, UCSF Memory and Aging Center, San Francisco, United States
Rowan Saloner, UCSF Memory and Aging Center, San Francisco, United States
Joel Kramer, UCSF Memory and Aging Center, San Francisco, United States
Kaitlin Casaletto, UCSF Memory and Aging Center, San Francisco, United States
Emily Paolillo, UCSF Memory and Aging Center, San Francisco, United States

Category: Neurodegenerative Disorders

Keyword 1: cardiovascular disease
Keyword 2: brain function
Keyword 3: aging (normal)

Objective:

Systemic cardiovascular health is a modifiable factor important for prevention and mitigation of neurodegenerative diseases. However, mechanism(s) underlying the heart-to-brain connection are unclear given that systemic vascular health is multifaceted and cardiovascular indicators may affect neurodegenerative processes either directly, or through indirect pathways that are dysregulated in general brain aging. We therefore examined how molecular markers of astrocytic activation (GFAP), neuronal axon breakdown (NfL), and Alzheimer’s disease (AD) pathology (pTau181) in plasma map onto several major indicators of cardiovascular health in older adults along the AD continuum.

Participants and Methods:

206 older adults (Meanage=72.8; Meaneducation=17.4; 59% female sex; 87% clinically normal; 13% MCI due to AD) completed 30-day FitbitTM Flex2 monitoring (average daily steps), in-lab blood pressure (BP) and heart rate quantification, and a blood draw with plasma analyzed for GFAP, NfL, and pTau181 (Quanterix Simoa). Linear regression models evaluated associations among indicators of cardiovascular health (systolic BP, objective physical activity, resting heart rate) and plasma markers of interest (GFAP, NfL, pTau181). We also examined interactions between cardiovascular health metrics and diagnostic status or sex on plasma biomarkers. Finally, to better understand our initial results, we tested a post-hoc mediation model (1000 bootstrap resampling) evaluating whether BP mediated the association between physical activity and plasma NfL levels. All models adjusted for age, sex, and body mass index.

Results:

Elevations in systolic BP were associated with higher plasma pTau181 (β =0.17, p=0.04) and NfL levels (β =0.19, p<0.01) and approached significance with higher GFAP levels (β =0.12, p=0.055). In contrast, greater average daily steps associated with lower plasma levels of GFAP (β =-0.15, p<0.05) and NfL (β=-0.15, p<0.05), but not pTau181 (β=-0.11, p=0.22). Resting heart rate did not meaningfully associate with plasma GFAP, NfL, or pTau181 levels (βrange=-0.007-0.02, ps>0.50). Interaction models suggested that these associations did not differ based on sex or clinical diagnosis (ps >0.5). In a post-hoc mediation model, systolic BP fully mediated the relationship between daily steps and plasma NfL (Indirect Pathway: β=-0.04, p=0.04; Direct Pathway: β=-0.12, p=0.15).

Conclusions:

While lower systolic BP associated with lower levels of AD pathology (ptau181), greater physical activity associated with lower markers of astrocytic activation. Both lower BP and greater step count associated with a marker of neuronal axon degeneration; however, the association between physical activity and axon degeneration was driven by systolic BP, one of the strongest indicators of overall cardiovascular state. Optimizing facets of cardiovascular health may provide an opportunity to bolster brain reserve and reduce risk of neurodegenerative disease, regardless of clinical diagnosis. Deeper understanding of the biological pathways involved in the heart-to-brain connection is still needed to inform more precise recommendations and interventions for healthy brain aging.