Genetic Ancestry: Implications for Cognitve Decline in AD - Jorge J Llibre Guerra. MD, MSc.
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Genetic Ancestry: Implications for
Cognitve Decline in AD
DC2
Jorge J Llibre Guerra. MD, MSc.
Cognitive and Behavior Research Unit
National Institute of Neurology, Cuba
Senior Fellow at GBHI
Slide 1
DC2 Does this need to have quotes?
Deborah Costello, 01/02/2018
DisclosuresDC3
Dr. Jllibre’s research is approved and supported by Cuban
Ministry of Health.
Dr. Jllibre’s research is supported with funding from The
Alzheimer’s Association (ALZ-18-544305) and the Global Brain
Health Institute.
No personal financial relationships with commercial interests
relevant to this presentation.
Slide 2
DC3 I think this is what you mean in English
Deborah Costello, 01/02/2018
Overview: DC21 Evidence for disparities in cognitive aging and Alzheimer’s disease (AD) The challenge of studying AD disparities among minorities groups. Cuban’s genetic admixture studies. Effects of genetic admixture on cognitive performance and dementia rates. Effects of admixture as a modifier of the relation between ApoE, Dementia and cognitive decline.
Slide 3
DC21 I think this is what you mean in English
Deborah Costello, 01/02/2018
DC20
Are racial and ethnic minorities at greater risk of
developing Alzheimer’s and other dementias?
Slide 4
DC20 It is very crowded to have both of these on the same page. I suggest either one- see option next page or if you need both, use two pages
Deborah Costello, 01/02/2018
DC18
Are racial and ethnic minorities at greater risk of
developing Alzheimer’s and other dementias?
Mayeda et al., 2016
Slide 5
DC18 It is very crowded to have both of these on the same page. I suggest either one- see option next page or if you need both, use two pages
Deborah Costello, 01/02/2018DC4
Confounding of race with socio-economic status.
Health status varies by socioeconomic status.
Racial segregation creates different exposures to
community resources that enhance health.
“Race and Class”
or “Race or Class”
Adapted from Marden et al.,2016Slide 6
DC4 It is very crowded to have both of these on the same page. I suggest either one- see option next page or if you need both, use two pages
Deborah Costello, 01/02/2018Aging and Dementia In Cuba
Prevalence 6.4 - 10.2 %
Incidence rate 21.7 per 1000/year
28 670 new cases every year.
One new case every 5
minutes.
Main cause of disability.
No difference across ethnic groups.
Cuban Admixture Studies
Study Design:
Populations of mixed African and Caucasian ancestry DC5
(60 SNP markers of individuals admixture)
200 dementia cases
300 controlsSlide 7
DC5 It is nice to use an image but it is hard to know from this image what you are trying to show. Old people?
Deborah Costello, 01/02/2018APOE and Admixture Study in the Cuban Population A Population-Based Study
Population structure - Caribbean and neighboring populations
The average African ancestry in those self-reporting
to be:
“blanco” , 7.8%,
“mestizo”, 25.5%
“negro”, 65.5%.
Self-declared race and skin color are were poor
biological classifiers.
Native American Admixture
was under- represented
(3%).
Moreno-Estrada A, Gravel S, Zakharia F, McCauley JL, Byrnes JK, et al. (2013) Reconstructing the Population Genetic History of the Caribbean.
PLOS Genetics 9(11): e1003925.African Admixture by Case/Control Group and
Cognitive Status.
One-way ANOVA, p = 0.138 comparing percent admixture by groupsCognitive Performance:
Zahodne et al. MAY 2016–VOL. 64, NO. 5
(A and B ) Washington Heights-Inwood Columbia Aging Project (WHICAP)
(C and D National Survey of Midlife Development in the United States (MIDUS)African Admixture by Case/Control and mean Cognitive Score.
African admixture was not associated
with the prevalence of dementia.
Cognitive Status
Cognitive Performance:
Average Scores in
Episodic MemoryRisk Factors: Aging and Dementia Study
Habana y Matanzas (n= 2944)*
Exposure Odds Ratio 95% CI
APOE ε4 2.6 (2.0 - 4.0)
Stroke 2.8 (2.2 - 3.6)
Age (c/5años) 2.2 (1.9 - 2.5)
Alcohol 1.8 (1.2 - 2.6)
FHD 1.7 (1.3 - 2.1)
Ethnicity 1.08 (0.84-1.63)
* Adjusted for age, sex and education
There is a robust association between APOE genotype and AD in people of European
(Farrer et al., 1997) and south Asian descent (Ganguli et al., 2000).The U.S. and Nigeria Study
Clear association between apoE e4 and AD in African
Americans in Indianapolis, U.S.
» (Hendrie - Ann Neurol 1995)
No association between apoE e4 and AD in Yoruba in
Ibadan, Nigeria
» (Osontokun - Ann Neurol 1995)APOE and Incidence of Dementia (SHR) in Cuba
(n= 2 520) CI 95%
4 3.51
AD risk by ApoE4
3
APOE by African ancestry
interaction term
2
suggested that the effect
1.22 of any APOE e4 allele
1 would vary continuously.
80+ 80 60 40 20 20-
0
% of African Admixture
• Strong trend toward attenuated effect e4 in those with greater African ancestry ¹
Llibre, et al. , Incidence of dementia and association with Apoe genotype in older Cubans. Dementia
&Neuropsychologia , 20141. African ancestry is associated with lower odds ratio to develop
amyloid plaques.
Subjects with significant African ancestry showed lower prevalence of
neuritic plaques (OR 0.43, 95% CI 0.21–0.89, P = 0.02)*
* adjusted for age, sex, APOE genotype and environmental risk factors.
2. In individuals having at least one ApoE4, Caucasian ancestry
interacts with Braak stage resulting in worse cognitive status.Summary • The mean African admixture proportion for the three ethnic groups was 5.8% for ‘white’, 28.6% for ‘mixed’ and 49.6% for ‘black’. • African admixture, controlled for age, sex and education, was not associated with the prevalence of dementia. • A model including an APOE by African ancestry interaction term suggested the effect of APOE e4 is substantially attenuated among those with a greater proportion of African ancestors.
Racial and ethnic disparities reflect disparities based on
features of the communities where people live and may
be driven mostly by place, access to health care,
education and socio-economic status.
Future Directions
Develop better ways of defining and accurately measuring
“ethnicity” in the context of Health and Social Disparities.
Effects of admixture and ApoE genotype on cognitive decline rate
and median survival in patients with AD?
Effects of admixture on atrophy rate and other biomarkers?Acknowledgements
Bruce Miller, MD
Juan J Llibre Rodriguez, MD.PhD
Isabel Allen, PhD
Dra. Lea Greinburg, MD.PhD
Dr. Victor Valcour , MD.PhD
Llibre J is an Atlantic Fellow at the Global Brain Health Institute (GBHI) and thanks GBHI and the
Alzheimer’s Association for supporting his work (GBHI_ALZ-GBHI_ALZ-18-544305)You can also read
