"ApoE4 does not influence brain function at young age"

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NF52
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"ApoE4 does not influence brain function at young age"

Postby NF52 » Fri Jul 31, 2020 9:09 am

Here is some good news for young carriers of ApoE4 from a poster session by Lara Mentink of the Netherlands at the Alzheimer's Association International Conference today. Study size matters--especially when drawing conclusions about all young people with ApoE4 from a decade-old study of a few dozen.
Background: Filippini et al. [2009] reported an increased default mode network (DMN) co-activation during rest in young APOE ε4-carriers... However, this study only assessed a small sample.

Here, we aimed to replicate their finding in a substantially larger sample from the Human Connectome Project (HCP).
Method: We included participants from the HCP S1200 dataset...we assessed gray matter volume with FreeSurfer. To test for differences in [default mode network]DMN co-activation and gray matter volume between APOE ε4-carriers and non-carriers, we used Permutation Analysis of Linear Models (PALM). PALM controls for biases induced by the family structure of the HCP sample. Results were family-wise error rate corrected at p < 0.05.

Result: We included 167 APOE ε4-carriers and 419 non-carriers for the DMN analysis. In contrast to [Filippini], we did not find significant differences in DMN co-activation between carriers and non-carriers. For the morphometric analyses, 243 carriers and 544 non-carriers were included. No differences in brain volume were found between carriers and non-carriers. For both analyses...different combinations of age, sex, education level, head motion, did not alter the results.

Conclusion: We could not replicate the early findings of [1] in a large sample. Our results suggest that solely APOE ε4-carriership does not influence brain function at a young age. Future work will focus on the use of polygenic risk scores to study whether any genetic predisposition for AD influences brain function in young adults. Still, genetic predisposition for AD might not have any measurable effect decades before clinical expression of AD. Therefore, repeating the analysis in a healthy, middle-aged cohort could inform us whether the influence of genetic predisposition for AD increases over time.
Patterns of default mode network co-activation in young APOE ε4-carriers: an HCP replication study
4/4 and still an optimist!

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Re: "ApoE4 does not influence brain function at young age"

Postby Tincup » Fri Jul 31, 2020 10:21 am

NF52 wrote: Our results suggest that solely APOE ε4-carriership does not influence brain function at a young age.


My personal experience and observation of known ε4 carriers early in life would agree with this statement.

One anecdote, my mother was a very bright woman. She died with dementia at 87. I have no idea if she is the parent I got my ε4 from. She got a degree in theoretical physics in 1948. Went on soon after graduation to supervise the military's early use of computers to track missiles (she wryly would comment - they gave the job to a woman because they expected it to fail and they could pay her half as much). When she was around 60, she went back to school and picked up a degree in computer science. She was always setting the curve, competing with students in their teens and early 20's. She would comment to me that her brain worked so much slower than when she was 19. I wasn't very sympathetic, saying, "but mom, you are setting the curve, how slow can you be?" Knowing what I know now about ε4's and glucose metabolism would validate her statement. Her ability to set the curve came not just from IQ (which may have been diminished), but her organization, focus, motivation, grit and so on.
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Re: "ApoE4 does not influence brain function at young age"

Postby NF52 » Fri Jul 31, 2020 10:27 am

Tincup wrote:
NF52 wrote: Our results suggest that solely APOE ε4-carriership does not influence brain function at a young age.


My personal experience and observation of known ε4 carriers early in life would agree with this statement.

One anecdote, my mother was a very bright woman. She died with dementia at 87. I have no idea if she is the parent I got my ε4 from. She got a degree in theoretical physics in 1948. Went on soon after graduation to supervise the military's early use of computers to track missiles (she wryly would comment - they gave the job to a woman because they expected it to fail and they could pay me half as much). When she was around 60, she went back to school and picked up a degree in computer science. She was always setting the curve, competing with students in their teens and early 20's. She would comment to me that her brain worked so much slower than when she was 19. I wasn't very sympathetic, saying, "but mom, you are setting the curve, how slow can you be?" Knowing what I know now about ε4's and glucose metabolism would validate her statement. Her ability to set the curve came not just from IQ (which may have been diminished), but her organization, focus, motivation, grit and so on.


Thanks for sharing her inspiring story! One of the presentations I saw at AAIC (virtual conference; free to register with all presentations online for the next 30 days) included this statement (in my words) "Maybe people with elevated amyloid and tau who stay cognitively healthy into their 90's just have so many darn brain connections developed from capacity and use that their resilience is endless."
4/4 and still an optimist!


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