Risk Factor Question - Family History

[lindaelane]

My mother and maternal grandmother had dementia. I am 3/4. I know it is not certain, but I think the "4" was probably from grandmother/mother. (No dementia on father's side).

Both mother and grandmother were cognitively fine until age 80, at which point some decline set in. They were able to live alone for some years, and passed away before being in a state that today would be considered "in need of a memory care facility". (Though they were trying to put Mom in one at the end, and I will admit there were days when she was in need of it, but not the majority of days.)

Anyway...my question...I know being female raises my risk but being educated lowers it. Does the 80ish onset for my female relatives say I may at least have some reduced risk until I'm older? (This presumes they were both 3/4....I want to take that presumption and go from there.)

(Mom's dad's sister also had dementia, but her dad did not....hence my 3/4 presumption, but its possible she was a 4/4 who beat the odds. No known dementia in grandmother's parents, who died at ages 75 and 83).

[Plumster]

Yes, based on the 2018 guide from the Physicians for Responsible Medicine on AD and family history, "your risk is inversely proportional to the age of onset in a first-degree relative." In my case, my mother was diagnosed with AD at 65, which is bad news for me. My grandmother lived until 86 and definitely had memory problems in her 80s. So, it wasn't true in my mom's case. But I think my grandma lived a healthier life and there's always your father's genes to consider as well. But I'd say you're in a pretty good position based on family history.

[Fiver]

That is my understanding also. Not great for me, but good for you!

[mike]

Anyone can get AD, and age is the best correlation. One ApoE4 increases your risk a bit, but should be possible to lower your risk through likestyle changes.

[NF52]

My mother and maternal grandmother had dementia. I am 3/4. I know it is not certain, but I think the "4" was probably from grandmother/mother. (No dementia on father's side). ...
Anyway...my question...I know being female raises my risk but being educated lowers it. Does the 80ish onset for my female relatives say I may at least have some reduced risk until I'm older? (This presumes they were both 3/4....I want to take that presumption and go from there.)...

Hi lindaelane, what a great question!

Many of us have one or two copies of ApoE 4 (which is true for about 20-25% of the population with European ancestry), and many of us also have a family history of some kid of dementia. It's important to remember that what we sometimes assumed was Alzheimer's disease may well have been vascular dementia, linked to cardiac disease, high blood pressure and strokes, or other dementias such as Parkinson's with dementia or Lewy Body dementia. Given how little was known about the risk of high blood pressure in most of the 20th century, and how little was known about coronary artery disease in women, it's possible your mother and grandmother had risk factors you don't share and are unlikely to develop.

Here's a meta-analysis of four large studies (three of them population-based, following people for decades, one drawn from memory care center referrals). Their prediction of risk of either Mild Cognitive Impairment (MCI) or dementia to the age of 85 for people currently 60 and 75 is encouraging:

The Generation Study elected to disclose the following “lifetime” risks of MCI or dementia to its potential participants: 30%–55% for individuals with APOE-e4/e4; 20%–25% for individuals with APOE-e3/e4 and -e2/e4 (with a note that risk might be lower for those with APOE-e2/e4); and 10%–15% for individuals with APOE-e3/e3, -e3/e2, and -e2/e2 (with a note that risk might be lower for those with APOE-e2/e3 and -e2/e2). These values are consistent with our findings, but use round numbers for intelligibility, and broader ranges to reflect statistical and other sources of uncertainty. The regression models are insufficiently precise for “personalized medicine” incidence estimates based on sex, education, or other factors, but they do allow for qualitative adjustments to overall stratified risk estimates.

APOE-related risk of mild cognitive impairment and dementia for prevention trials: An analysis of four cohorts

[lindaelane]

Thanks! This looks really interesting. Looked promising for e4/e4, but in limitations they state that numbers of these cases were small.

However, for my concern (I'm e3/34) - as I drill down to the results in the charts, I see that the conflate e2/e4 with e3/e4 and do not break down the figures for simply e3/e4 (perhaps done elsewhere in the paper but I did not see it in the charts). I think the protective value of e2 could widely effect the results. Or...maybe there were so few e2e4 folks, comparet to the results were not that widely effected. I'd really like to see the e3/e4 results without the e2/e4 thrown in there. (Sorry to ignore e4/e4...right now i am a beginner at learning about this and so for now mainly focused on the condition I have....)

Finally, their conclusion discusses estimates are sensitive to variation in sampling, assessment, and modeling. So I am not sure yet...but I hope to see more studies like this. Thanks!

Btw, anything on whether risk is lowered if family history is present, but not until over age 80?

[DebbieG]

I wonder if risk changes over time. It seems like I (age 65 now) will be exposed to more toxins over my lifetime and more likely to get type 2 diabetes earlier than my 85 year old mom, whose MCI onset was diagnosed when she was 82. And in younger age groups there is so much obesity and much more exposure to toxins at a younger age. That is very worrisome to me.