Cumulative Midlife Vascular Risk Factors Associated With Increased Brain Amyloid

[ru442]

I found this very interesting, and supportive of my efforts (which are primarily CVD related at this stage of my journey, but with an eye on LOAD). Would be interested in others thoughts with more knowledge than myself!

http://www.medscape.com/viewarticle/878591#vp_1

ETA: Link to the full text study

http://jamanetwork.com/journals/jama/ar ... ct/2616396

[Julie G]

I haven’t found full-text yet, but this is a well constructed prospective cohort study. Abeta deposition was measured at baseline along with a variety of vascular risk factors: BMI, smoking, hypertension, diabetes, and cholesterol. The same cohort (n=322) was checked approximately 24 years later evaluating the same parameters. From what I could glean from various press releases, high BMI at midlife had the strongest odds ratio (2.06.) The others had a cumulative effect, reported below:

In adjusted models, compared with 0 midlife vascular risk factors, the OR for elevated SUVR associated with 1 vascular risk factor was 1.88 (95% CI, 0.95-3.72) and for 2 or more vascular risk factors was 2.88 (95% CI, 1.46-5.69).

Risk factors at old age didn’t seem to affect abeta deposition. Interesting. If we’re very good now, we can be bad later APOE didn’t either; that’s huge. I’ll be on the lookout for full-text to see the strength of each vascular risk factor's odds ratio. The takeaway for me; being healthy at midlife is extraordinarily important. Having excess weight at midlife may be particularly dangerous.

[ru442]

Crud... full text is $$$...

"Having excess weight at midlife may be particularly dangerous"

This ^^^^..... so glad I found this place and my BMI is optimal at mid-ish life (well ok... more like 3/4 ish life!)

[TheresaB]

Just published on the role of ApoE4 and it's role in Vascular Dementia:
Apoε4 disrupts neurovascular regulation and undermines white matter integrity and cognitive function
https://www.nature.com/articles/s41467-018-06301-2

This is a mouse study but the data suggests that APOE4 increases the risk of dementia caused by vascular factors.
SVD = small Vessels Disease
WM = white matter
CBF = cerebral blood flow

The findings shed light into the association of ApoE4 genotype, SVD and WM damage11. ApoE4 could be involved both in the pathogenesis of SVD as well as in the resulting WM damage. On the one hand, ApoE4-related oxidative stress and endothelial dysfunction may promote small vessels atherosclerosis and lipohyalinosis, pathological hallmarks of SVD30,40. On the other hand, reduced baseline CBF and neurovascular dysfunction afforded by ApoE4 may exacerbate hypoperfusion and hypoxia in the highly vulnerable subcortical WM. The combined effect of these alterations is likely to act in concert to promote hypoxic-ischemic WM damage leading to cognitive impairment.

In conclusion, we have demonstrated that the ApoE4 genotype is associated with reduced resting cerebral perfusion, coupled with a marked impairment of the major factors responsible for maintaining an adequate blood supply to the working brain. Furthermore, in conditions of cerebral hypoperfusion, ApoE4-TR mice develop more severe WM damage and cognitive impairment. The findings, collectively, provide insights into the mechanistic bases for the increased susceptibility to SVD and WM lesions in ApoE4 carriers, and highlight the prominent role that genetic risk factors play in microvascular function and susceptibility to WM injury.