Nigerian Alzheimer's Paradox?

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cdamaden
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Nigerian Alzheimer's Paradox?

Post by cdamaden »

I came across this website recently that tries to explain why Nigerians have one of the highest occurrences of APOE4 but one of the lowest of Alzheimer's disease.
http://www.alzheimersweekly.com/2016/02 ... radox.html
Their take-away is that the Nigerian diet leads to lower total cholesterol and better blood pressure readings. The dietary suggestions are for low animal fat and higher grains, roots, and tubers.

Thoughts?
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Re: Nigerian Alzheimer's Paradox?

Post by Julie G »

I find it really interesting that ApoE4 prevalence is very high not only in Nigeria, but in all of Sub-Saharan Africa, while AD prevalence is low among those eating their native diets leading a traditional lifestyle. It's worth noting that traditional diets from the dozens of African countries that make up Sub-Saharan Africa are extremely varied with the Maasai (southern Kenya & northern Tanzania) representing the antithesis of the Nigerian diet, eating lots of animal-based fat & protein from milk, blood, and meat. I can't help but wonder if the slowly increasing rate of dementia in the area now is another Weston A. Price (Nutrition and Physical Degeneration) example of western influence polluting traditional diet & lifestyle leading to a deterioration of health. Maybe it's not "low cholesterol," but really a mixture of CR, physical exercise, and abstaining from processed Western food that protects our Sub-Saharan brothers & sisters :idea:.

FWIW, we previously discussed this video when Dr. Gregor first posted it in this thread. I'd love to hear others thoughts on this.
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Re: Nigerian Alzheimer's Paradox?

Post by Harrison »

I liked the message of the video, but it needs to be taken with a grain of salt.

The paper citing the high rate of APOE4 in Nigerians is from 1989. There have been many publications since, and there are countries with higher rates. Here is a more recent publication: http://www.researchgate.net/publication/6704176

The top countries in terms of percentage of E4 carriers also happen to have rather short life expectancy. So the vast majority of E4 carries won't hit age 65. Here is a list I made using the above paper and some worldwide life expectancy data:

Code: Select all

Country              ApoE4 Rate  Life Exp  AD rate
1. Central Africa    40.7%        48.4       9.4%
2. Burundi           38.5%        53         9.6%
3. New Guinea        37.5%        62.9       7.7%
4. Kenya             32%          59.7       8%
5. South Africa      32%          58.3       6.6%
6. Sudan             29.1%        61.8       2.2%
7. Nigeria           28.7%        53.2       9.1%
8. Ecuador           28%          76         1.6%
13. Trinidad         23.2%        70.8       6%
16. Finland          21.5%        80.7       34.9%
18. Sweden           20.5%        81.7       21.5%
The first country to have a life expectancy long enough to see a reasonable number of AD cases is Ecuador. The first "Western" country to make this list is Finland, with a 21.5% E4 rate, a life expectancy of 80.7 years, and a whopping 34.9% Alzheimer's rate.

If had to pick a country to look more closely, it would probably be Ecuador. When this topic came up previously, we also discussed what Finland does differently than Sweden. There was a comment that Finland has a very high rate of alcohol use, which could explain some of the difference.

There are likely other genes at play here as well. So as Julie noted, you may find many different diets across these populations, and a mixture of factors is helping to avoid Alzheimer's, if the population lives long enough to get it.
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Re: Nigerian Alzheimer's Paradox?

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Julie G wrote: Sun May 22, 2016 5:32 pm I can't help but wonder if the slowly increasing rate of dementia in the area now is another Weston A. Price (Nutrition and Physical Degeneration) example of western influence polluting traditional diet & lifestyle leading to a deterioration of health. Maybe it's not "low cholesterol," but really a mixture of CR, physical exercise, and abstaining from processed Western food that protects our Sub-Saharan brothers & sisters :idea:.

FWIW, we previously discussed this video when Dr. Gregor first posted it in this thread. I'd love to hear others thoughts on this.
Sorry to resurrect such an old thread, but of all posts returned by my searches, this one is most relevant to my question.

I seem to remember reading but can't seem to find mention of a study comparing the prevalence of dementia / AD between these ApoE homozygous ε4 populations to that of relatives who relocated to and embraced the diet & lifestyle of "western" countries. If I'm not imagining the study, then can someone please provide a citation? TIA!
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Re: Nigerian Alzheimer's Paradox?

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Julie G wrote: Sun May 22, 2016 5:32 pm I can't help but wonder if the slowly increasing rate of dementia in the area now is another Weston A. Price (Nutrition and Physical Degeneration) example of western influence polluting traditional diet & lifestyle leading to a deterioration of health. Maybe it's not "low cholesterol," but really a mixture of CR, physical exercise, and abstaining from processed Western food that protects our Sub-Saharan brothers & sisters :idea:.

FWIW, we previously discussed this video when Dr. Gregor first posted it in this thread. I'd love to hear others thoughts on this.
OfficeSpace wrote: Fri Apr 19, 2024 3:01 pm Sorry to resurrect such an old thread, but of all posts returned by my searches, this one is most relevant to my question.

I seem to remember reading but can't seem to find mention of a study comparing the prevalence of dementia / AD between these ApoE homozygous ε4 populations to that of relatives who relocated to and embraced the diet & lifestyle of "western" countries. If I'm not imagining the study, then can someone please provide a citation? TIA!
This may not be the article you were thinking of, but JAMA Neurology in November 2023 published an "original investigation" into APOE Genotype and Alzheimer Disease Risk Across Age, Sex, and Population Ancestry Below is some of the information from the article, which is available for free. The abbreviation OR stands for odds ratio, which in Alzheimer's research refers to someone's odds compared to the "neutral" ApoE 3/3 level of risk. "Survival analysis" in this use appears to refer to how long people of different racial groups survive without Alzheimer's.
Importantly, race and ethnicity are socially ascribed identities that capture risk related to epidemiologic factors and social determinants of health, while genetic ancestry relates to geographical origins and inherent biologic variation ...There was a general, stepwise pattern of ORs for APOE*4 genotypes and AD risk across race and ethnicity groups. Odds ratios for APOE*34 and AD risk attenuated following East Asian (OR, 4.54; 95% CI, 3.99-5.17),White (OR, 3.46; 95% CI, 3.27-3.65), Black (OR, 2.18; 95% CI, 1.90-2.49) and Hispanic (OR, 1.90; 95% CI, 1.65-2.18) individuals. Similarly, ORs for APOE*22+23 and AD risk attenuated following White (OR, 0.53, 95% CI, 0.48-0.58), Black (OR, 0.69, 95% CI, 0.57-0.84), and Hispanic (OR, 0.89; 95% CI, 0.72-1.10) individuals, with no association for Hispanic individuals....Within Black individuals, decreased global African ancestry or increased global European ancestry showed a pattern of APOE*4 dosage associated with increasing AD risk... It is particularly interesting that ancestry-specific haplotypes on APOE may carry ancestry-specific variants that specifically modulate the association of APOE*2 or APOE*4 genotypes with AD risk. An example is provided by Griswold et al in 2021, suggesting that African compared with European ancestry haplotypes on APOE*4 reduced expression of APOE*4, which in turn may explain attenuated effect sizes for APOE*44 and AD risk in individuals of African ancestry compared with those of European ancestry....the sex-by-age–specific association of APOE*3/4 with AD risk among White individuals (greater risk among women) was reproduced but shifted to ages 60 to 70 years and was additionally replicated among Black and Hispanic individuals. Fourth, survival analyses indicated no difference in AD risk associated with APOE*44 across Black and White individuals, suggesting that future studies should evaluate age-at-onset effects among racial and ethnic minority populations
My non-scientist reading of this, and listening to similar presentations, is that genetic, biological differences may be relevant, along with lifestyle and environmental conditions, to the risk differences between individuals whose genome shows 100% African ancestry and those who show more European ancestry, even if both individuals live in the U.S. Work is being done now on studying differences between people who identify as Hispanic but may have more Amerindian and African ancestry and those who have more European Hispanic ancestry because of observed differences in AD risk in groups often considered simply "Hispanic".

As an example of how it can be tricky to assume a population not exposed to a Western diet is avoiding Alzheimer's with ApoE4, is this sobering statistic about Apoe4 and risk of death from HIV in Africa, from a 2021 study in Frontiers in Genetics
Apolipoprotein E Genetic Variation and Its Association With Cognitive Function in Rural-Dwelling Older South Africans:
APOE ɛ4 has been linked to AIDS severity and increased mortality especially in ɛ4 homozygotes (Valcour et al., 2004; Burt et al., 2008; Chang et al., 2015; Wendelken et al., 2016). It has been associated with faster disease progression and higher viral load in seropositive individuals due to enhanced entry of the virus into T cells (Burt et al., 2008; Kuhlmann et al., 2010). This may explain why we see a higher proportion of ɛ3 in our HIV positive sample as faster disease progression and poorer prognosis may have resulted in earlier HIV-related mortality in ɛ4-carriers. The mortality profile of the community from which this cohort was recruited was subject to high levels of HIV-associated death, and increased all cause death
And this makes me feel that women in Nigeria, in particular, may be living in the eye of a storm of risk--not in an idyllic risk-free zone: Diabetes/Dementia in Sub-Saharian Africa and Nigerian Women in the Eye of Storm
Sub-Saharian Africa women have a disproportionately two-to-eight fold increased prevalence of dementia. In the eye of this storm, Nigeria holds the highest number of diabetics on the African continent, and its prevalence is rising in parallel to obesity, hypertension, and the population’s aging. The socio-economic impact of the rising prevalence of DM and dementia will be huge and unsustainable for the healthcare system in Nigeria, as has been recognized in developed economies... The complex interplay of factors involved in diabetes and dementia in Nigerian women include key biological agents (metabolic syndrome, vascular damage, inflammation, oxidative stress, insulin resistance), nutritional habits, lifestyle, and anemia, that worsen with comorbidities. In addition, restricted resources, lack of visibility, and poor management result in a painful chain that increases the risk and burden of disease in Nigerian women from youth to old ages
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Re: Nigerian Alzheimer's Paradox?

Post by OfficeSpace »

Thank you! I had read the Griswold paper (Increased APOEε4 expression is associated with the difference in Alzheimer Disease risk from diverse ancestral backgrounds) but not the Soo article, which is fascinating. The HIV and diabetes / dementia angles you referenced do appear sensitive to at least some factors over which people have some control, which is encouraging (or at least not discouraging).
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Re: Nigerian Alzheimer's Paradox?

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Harrison wrote: Mon May 23, 2016 10:32 am
The top countries in terms of percentage of E4 carriers also happen to have rather short life expectancy. So the vast majority of E4 carries won't hit age 65. Here is a list I made using the above paper and some worldwide life expectancy data:

Code: Select all

Country              ApoE4 Rate  Life Exp  AD rate
1. Central Africa    40.7%        48.4       9.4%
2. Burundi           38.5%        53         9.6%
3. New Guinea        37.5%        62.9       7.7%
4. Kenya             32%          59.7       8%
5. South Africa      32%          58.3       6.6%
6. Sudan             29.1%        61.8       2.2%
7. Nigeria           28.7%        53.2       9.1%
8. Ecuador           28%          76         1.6%
13. Trinidad         23.2%        70.8       6%
16. Finland          21.5%        80.7       34.9%
18. Sweden           20.5%        81.7       21.5%
I don't agree with this statement,
life expectancy (is just determination of an average, just numbers) it is short mainly due to very high infant mortality (lots of kids do not even reach adulthood), maternal death is 10x higher than in developed countries (lots of per-menopausal women die giving birth), and also very limited basic medical system access to antibiotics and basic surgeries, lots of folks die young or mid life on severe injuries (like open fractures, animal bites), bacterial infections and starvation, some get into old age.

Example:
1, 5, 35, 52, 70, 85, 90
avg = 48.29

70, 85, 90
avg = 81.67

Similar in Tsimane life expectancy is low, about 48 (from reasons described above), but they also have old people living into their 95 (with no APOE2, and no doctors, just shamans) with much better brain volume than developed countries.
In APOE4 Tsimane with even mild parasitic infection, cognition is even better than APOE3 folks without parasites.

Ecuador data is really encouraging.
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Re: Nigerian Alzheimer's Paradox?

Post by AnnieV »

It would be very interesting to somehow get the University of Indiana raw data from their Nigerian Paradox study, on both subject sets, that most likely includes detailed cholesterol, homocysteine, etc. numbers. Can anyone here get that original data from the University of Indiana? I fully agree with what Julie G suggests in her 2016 reply, it matches my gut sense exactly from my research on this particular subject.
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Re: Nigerian Alzheimer's Paradox?

Post by JNB »

AnnieV wrote: Fri Apr 26, 2024 5:24 pm It would be very interesting to somehow get the University of Indiana raw data from their Nigerian Paradox study, on both subject sets, that most likely includes detailed cholesterol, homocysteine, etc. numbers. Can anyone here get that original data from the University of Indiana? I fully agree with what Julie G suggests in her 2016 reply, it matches my gut sense exactly from my research on this particular subject.
Can you share your gut feeling?
I agree with Julie G about diet variety (and also genetic variety) in African population
I suspect that higher degree of gut parasites in wilder or pre-industrial environment can actually improve cognition in APOE4 :shock:

the little evidence here
For homozygous E3/E3 carriers, higher eosinophil counts are associated with poorer performance on all cognitive measures (Supplemental Table S2). However, adults with high eosinophil counts, indicative of a high parasite burden, who carried at least 1 copy of the E4 allele (E3/E4 or E4/E4) showed better cognitive performance than did noncarriers.
Parasites seem to be missing link for APOE4, in general parasites have immunosuppressing functions on our bodies.
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Re: Nigerian Alzheimer's Paradox?

Post by AnnieV »

I certainly have a gut feeling as to a main factor that appears to be protective, preventative, where research and testing has led me to hypothesize. I can share it but I believe it's best to discuss the path where I found it and allow discussion to affirm or refute it along the way.

I have read about the parasite theories but what exactly, in specific language do parasites do that supposedly help?
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