Cardiovascular Health and Neurocognitive Function among US Latinos from Diverse Backgrounds.

Wassim Tarraf, PhDWayne State UniversityPresented at the ICAA, September 22nd 2017

Dementia Projections – The Americas

World Alzheimer's Report Alzheimer's disease International World health Organization, 2015

Background• Very few studies on Latino

cognitive function and disorders.

• Available studies (e.g. SALSA, NMAP) are geographically limited, not diverse, and limited considerations of MCI phenotype.

• Estimates of cognitive disorders vary widely.

SALSA Prevalence Estimates WHICAP Prevalence Estimates

Yearly Incidence Estimates*

Haan et al (2007). Prevalence of Dementia in Older Latinos: The Influence of Type 2 Diabetes Mellitus, Stroke and Genetic Factors http://onlinelibrary.wiley.com/doi/10.1046/j.1532-5415.2003.51054.x/fullGurland et al (1999). Rates of dementia in three ethno-racial groups https://www.ncbi.nlm.nih.gov/pubmed/10398359* Adapted from: Mehta, K. M., & Yeo, G. W. (2016). Systematic review of dementia prevalence and incidence in US race/ethnic populations. Alzheimer's & Dementia.

Why important?

• Better epidemiological data!• Better linkages to known risk

factors.• Better disease

characterization - likely “modifiers.”

• Better models for public health (comorbidities, death, quality of life) and health policy (health resource utilization) purposes.

http://onlinelibrary.wiley.com/doi/10.1002/ana.24897/full

Why HCHS/SOL & SOL-INCA?• Understanding diversity is fundamental to Latino public health

research

• Cardiovascular risk and disease variations• Factors that influence disease onset and course also vary

• Multisite, probability sampled, prospective cohort (n=16,415; ages 18-74 years) Representative of targetpopulations, not national.

• Oversampled (9,623) - 45-74 years• Diverse

• Central Americans, Cubans, Dominicans, Mexicans, Puerto Ricans, and South Americans

• Multimodular: Extensive cardiovascular data (e.g., ECG, Echo), biospecimens, genetics (e.g., GWAS; WES; WGS), medical histories, sociocultural, acculturation, etc…

Study of Latinos: Baseline years (2008-2011)

SOL Latino Cardiovascular Health: Obesity

Kaplan, R. C., et al. (2014). "Body mass index, sex, and cardiovascular disease risk factors among Hispanic/Latino adults: Hispanic community health study/study of Latinos." J Am Heart Assoc 3(4).

MF=29.8MM=29.0

Mean ~ 26

37 % ObeseM 42 % ObeseF

44 %

49 %

SOL Latino Cardiovascular Health: Diabetes

Schneiderman N* et al. Prevalence of Diabetes… (2014) Diabetes Care. 37(8):2233-2239

SOL Latino Cardiovascular Health: High Cholesterol

Rodriguez, C. J., et al. (2015). "High Cholesterol Awareness, Treatment, and Control Among Hispanic/Latinos: Results From the Hispanic Community Health Study/Study of Latinos." J Am Heart Assoc 4(7).

SOL Latino Cardiovascular Health: Hypertension

Sorlie PD, Allison MA, Avilés-Santa ML, et al. Prevalence of Hypertension Awareness Treatment and Control SOL Am J Hypertension. 2014;27(6):793-800.

SOL Latino Cardiovascular Health

Low Risk CVH

Daviglus, M. L., et al. (2016). "Prevalence of Low Cardiovascular Risk Profile Among Diverse Hispanic/Latino Adults in the United States by Age, Sex, and Level of Acculturation: The Hispanic Community Health Study/Study of Latinos." J Am Heart Assoc 5(8).

favorable levels of:Serum cholesterol, Blood pressure, Body mass index, No diabetes mellitus, Not currently smoking.

SOL Latino Cardiovascular Health: Hypertension

Sorlie PD, Allison MA, Avilés-Santa ML, et al. Prevalence of Hypertension Awareness Treatment and Control SOL Am J Hypertension. 2014;27(6):793-800.

Gardener, H. et al. (2015) Brain health and shared risk factors for dementia and stroke Nat. Rev. Neurol. doi:10.1038/nrneurol.2015.195

SOL Latino Cardiovascular Health: Life Simple 7

AHA LS7 Criteria

González, HM, Tarraf W et al. (2016) Cardiovascular health among diverse Hispanics/Latinos, Am Heart Journal 176, 134-144.

Background• Very few studies on Latino

cognitive function and disorders.

• Available studies (e.g. SALSA, NMAP) are geographically limited, not diverse, and limited considerations of MCI phenotype.

• Estimates of cognitive disorders vary widely.

SALSA Prevalence Estimates WHICAP Prevalence Estimates

Yearly Incidence Estimates*

Haan et al (2007). Prevalence of Dementia in Older Latinos: The Influence of Type 2 Diabetes Mellitus, Stroke and Genetic Factors http://onlinelibrary.wiley.com/doi/10.1046/j.1532-5415.2003.51054.x/fullGurland et al (1999). Rates of dementia in three ethno-racial groups https://www.ncbi.nlm.nih.gov/pubmed/10398359* Adapted from: Mehta, K. M., & Yeo, G. W. (2016). Systematic review of dementia prevalence and incidence in US race/ethnic populations. Alzheimer's & Dementia.

HCHS/SOL: Cognitive Function

Verbal learning & memory*

Phonemic verbal fluency*

*Higher is better

González HM, Tarraf W et al.(2015) Neurocognitive Function Among Middle-aged and Older Hispanic/Latinos…Archives Clin Neuropsych 30(1): 68-77.

❀Higher is worse

Six-Item Screener❀Cognitive Impairment

Low Mental Status

SOL-Investigation of neurocognitive aging (INCA)

Builds on the SOL platform (R01-AG48642 ; 2015-2020):1. Examine neurocognitive function &

identify MCI/AD* (n=6500+; ages 50-82y)

2. Examine midlife cardiometabolic risks (CmR) for MCI/AD

3. Examine genetic variants at loci known to influence dementias/neurocognitive disorders and CVD

Cardiovascular Risk Factors and Cognitive Health

Two manuscripts:

1) Ideal cardiovascular health links to cognitive function2) Compromised blood pressure as a risk factor for cognitive

dysfunction even in middle-age

Mechanism

Qiu, C. and L. Fratiglioni (2015). "A major role for cardiovascular burden in age-related cognitive decline." Nat Rev Cardiol 12(5): 267-277.

Risk accumulation Two hit hypothesis

Zlokovic, B. V. (2011). Neurovascular pathways to neurodegeneration in Alzheimer’s disease and other disorders. Nature reviews. Neuroscience, 12(12), 723.

Gardener, H. et al. (2015) Brain health and shared risk factors for dementia and stroke Nat. Rev. Neurol. doi:10.1038/nrneurol.2015.195

SOL Latino Cardiovascular Health: Life Simple 7

AHA LS7 Criteria

SOL LS7 (0-14) and Neuro-cognition

González, HM, Tarraf W et al. Life’s Simple 7’s cardiovascular health metrics are associated with Hispanic/Latino neurocognitive function: HCHS/SOL results, J Alzheimer’s Disease, July 2016

1 Unit ↑ in LS7

~0.65 (DSS) to 1

year (Verbal Learning and Memory) of

cognitive aging saved

By Sex

González, HM, Tarraf W et al. Life’s Simple 7’s cardiovascular health metrics are associated with Hispanic/Latino neurocognitive function: HCHS/SOL results, J Alzheimer’s Disease, July 2016

By Education

Sex and Education Modifications

Summary: o Higher neurocognitive function was associated with better

cardiovascular health.o Consistent across multiple domains of neurocognitive health

including mental status/orientation, episodic learning and memory, verbal fluency, and psychomotor speed.

o Substantial and consistent with mounting evidence on the importance of both behavioral and biomarkers specific CVH factors.

o Extends the implications of CVH to middle-aged and early older age, in Hispanic/Latino adults.

o Stronger associations between better neurocognitive function and LS7 scores among women compared to men.o Potentially more beneficial as intervention targets given that

women are at higher risk for Alzheimer’s disease relative to men.

o Strongest associations between neurocognitive measures of verbal episodic learning and memory and LS7s were among those at the lowest education levels (vs. Other groups).o Important since Low education is an important dementia risk.

Low education participants with the highest LS7s levels statistically “caught up” with performance of Hispanics/ Latinos with post-secondary education.

By A

ge

SOL Blood Pressure and Neuro-cognition

βage =-0.024

βage =-0.025

βage =-.006

βage =-0.04

βage =1.05

~ 3.2 - 5 years of cognitive aging

~ 4.5 -7 years of cognitive aging

SOL Blood Pressure and Neuro-cognition

Summary:

o Higher systolic, pulse, mean arterial, and, to a lesser extent, diastolic BP diffusely linked to cognitive performance net of social, behavioral, and cardio-metabolic adjustment.

o NO modification by age, sex, and Latino background.o Associations are apparent beginning in midlife and into older age.o Consistent mechanism across sex and Latinos groups.o Higher CVD risk subgroups Higher risk for dysfunction

o Unable to identify cognitively optimal or “protective” BP ranges among middle-aged and older Latinos (HIGHER IS WORSE). o True among hypertensives and noto True irrespective of threshold splines considered.o No quadratic no cubic functions.o Shape of associations might change as population ages (to be tested with Wave 2 data).

Future Directions• More focus on explaining Latino ancestry differences which we

have evidence to suggest are apparent in midlife.• Particular interest in genetic stratification (given the possibility of

differential risk and gene*environment interactions)• Mainlanders vs. Islanders• Genetically derived population groups based on continental-ancestry modeled and

estimated under the assumption of the three ancestral populations prevalent in SOL Hispanics (West African, European, Amerindian).

• Focus on in vascular heath and vascular health change and disease and cognitive change and clinical phenotypes (e.g. MCI).

• Focus on incident measures of vascular heath and disease and cognitive change and clinical phenotypes (e.g. MCI).

• Focus on MRI quantified biomarkers of brain disease and injury.

Disclosure & Acknowledgement

No conflicts to report.

Great thanks to the staff and participants of HCHS/SOL for their important contributions.

Investigators website—http://www.cscc.unc.edu/hchs/

Acknowledgment of Support: NIA - R21 AG056952 (PI – Ramos)NIA - R01 AG054548 (MPI – De Carli & Gonzalez)NIA - R01 AG48642 (PI – Gonzalez)NIA - P30 AG053760 (PI – Paulson)

Thank you!

Gardener, H. et al. (2015) Brain health and shared risk factors for dementia and stroke Nat. Rev. Neurol. doi:10.1038/nrneurol.2015.195

SOL Latino Cardiovascular Health: Life Simple 7

AHA LS7 Criteria

González, HM, Tarraf W et al. (2016) Cardiovascular health among diverse Hispanics/Latinos, Am Heart Journal 176, 134-144.

% 4+ Ideal LS7