Alzheimer's Risk Similar for Both Sexes Carrying APOE4

[TheBrain]

Here's the full title of the article: Alzheimer's Risk Similar for Both Sexes Carrying APOE4 — But women with one copy of APOE4 have higher risk at ages 65-75

https://www.medpagetoday.com/neurology/ ... ease/67551

The investigators performed a meta-analysis of 27 studies of 31,340 non-Hispanic white individuals between ages 55 and 85, working directly with each data set provider to classify each patient into categories of normal, mild cognitive impairment, and Alzheimer's disease. They excluded patients with a clinical history of stroke, cerebrovascular disease, Lewy bodies, amyloid precursor protein or presenilin gene mutations, or comorbidity with any other known neurological disease.
...
They discovered that, contrary to long-held views, men and women with the APOE ɛ3/ɛ4 genotype had nearly the same odds as developing Alzheimer's disease from 55 to 85 years. At ages 65 to 75, however, women with one copy of APOE4 were at increased risk of Alzheimer's disease.
...
Though individuals with APOE ɛ4/ɛ4 had increased risk compared with individuals with ɛ3/ɛ4, the researchers saw no significant differences between men and women with ɛ4/ɛ4.

The actual study was published online in JAMA Neurology on August 28, 2017, with the title "Apolipoprotein E Genotype and Sex Risk Factors for Alzheimer Disease: A Meta-analysis." Authors: Scott C. Neu, PhD1; Judy Pa, PhD1; Walter Kukull, PhD2; et al.

You can see the full text here: http://jamanetwork.com/journals/jamaneu ... le/2649260

[circular]

Wow, important update to consider. Be careful of what you think you know huh?

[TheBrain]

So true, circular. This reminds me of some scientists and doctors I listened to recently in a documentary, who all agreed: "There's no such thing as 'settled' science."

[WhatNext]

They discovered that, contrary to long-held views, men and women with the APOE ɛ3/ɛ4 genotype had nearly the same odds as developing Alzheimer's disease from 55 to 85 years. At ages 65 to 75, however, women with one copy of APOE4 were at increased risk of Alzheimer's disease.

Reading this, I started to think "Yay!" but then got curious. It's saying that if you look at all people between the ages of 55 and 85, equal percentages of 3/4 men and women have AD. If more women than men develop AD between the ages of 65 and 75, there must be an age range in which the percentage of men with AD "catches up".

I downloaded the supplement to the article and looked at Table 1, which shows the odds ratios for developing AD in 3/4 men and women during 3 different age ranges: 55-65, 65-75, and 75-85. The results are from five different sub-analyses of the data and I typed them into a spreadsheet and averaged them for the overall ORs.

The overall risk is slightly higher for women: OR = 3.18 vs 2.83; certainly a much smaller discrepancy that we've thought. If you look at the ORs at different age ranges you see when the men "catch up": in all five sub-analyses the risk for men increases with age. In all five sub-analyses the risk for women is highest in the 65-75 age range, after which it drops off. In the 75-85 age range the risk for women is less than the risk for men in 4 of the 5 sub-analyses. Averaged over the five sub-analyses, the risk for women in the three age ranges is 1.85, 4.43, and 3.25. The averaged ORs for men are 1.71, 3.09, and 3.67.

The good news for men is that onset tends to be later. The good news for women is that if we make it to 75 our risk drops somewhat.

[TheBrain]

I downloaded the supplement to the article and looked at Table 1, which shows the odds ratios for developing AD in 3/4 men and women during 3 different age ranges: 55-65, 65-75, and 75-85. The results are from five different sub-analyses of the data and I typed them into a spreadsheet and averaged them for the overall ORs.

The overall risk is slightly higher for women: OR = 3.18 vs 2.83; certainly a much smaller discrepancy that we've thought. If you look at the ORs at different age ranges you see when the men "catch up": in all five sub-analyses the risk for men increases with age. In all five sub-analyses the risk for women is highest in the 65-75 age range, after which it drops off. In the 75-85 age range the risk for women is less than the risk for men in 4 of the 5 sub-analyses. Averaged over the five sub-analyses, the risk for women in the three age ranges is 1.85, 4.43, and 3.25. The averaged ORs for men are 1.71, 3.09, and 3.67.

The good news for men is that onset tends to be later. The good news for women is that if we make it to 75 our risk drops somewhat.

WhatNext, thanks for doing this analysis. It's great that you found some good news in all this for both men and women.

[WalterW]

I read the study and it grouped males and females separately. Thus, males with ApoE4/3 were about 3 times a likely to develop Alzheimer disease as males with ApoE3/3. Similarly, over the same age range (55 to 85), females with ApoE4/3 were about 3 times as likely to develop Alzheimer disease as females ApoE3/3. Compared with those of their own sex, both faced three times the odds. However, the paper did not investigate whether the risks were similar for both sexes. For example, for ApoE3/3s, males may have had, at any given age, only half the risk as females, thus at all ages, it can be inferred for ApoE4/3 males (using the odds of 3 for both) that they have half the risk of females. To illustrate, poodles and collies both may be able to jump half their height but collies, being taller, would on average jump higher than poodles (note: I am making this up to make a point.). Is there evidence that males and females with ApoE3/3 have similar risks of getting Alzheimer disease? (This is not an easy question to answer as the paper showed that the odds vary over time between males and females). If not, I cannot see how the data supports the paper's conclusion (which is basically "risk similar for both sexes carrying APOE4"). Instead, it compared men with men and women with women.

[floramaria]

I r For example, for ApoE3/3s, males may have had, at any given age, only half the risk as females, thus at all ages, it can be inferred for ApoE4/3 males (using the odds of 3 for both) that they have half the risk of females. To illustrate, poodles and collies both may be able to jump half their height but collies, being taller, would on average jump higher than poodles (note: I am making this up to make a point.).

Good point, Walter, and I appreciate the dog analogy! Will leave it to someone with more understanding of the study to answer your question.

Meanwhile, Welcome to the Forums! Thank you for participating, and raising this question. Since you are relatively new to the site, if you have not found it already, you might like to check out the PRIMER, viewtopic.php?f=33&t=1418, which offers an overview of important factors for maximizing health and minimizing risk from ApoE4 .

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