Association of Alzheimer disease pathology with abnormal lipid metabolism: the Hisayama Study.

[Hepoberman]

And the plaques can be eliminated by Vitamin D3 at the right levels, and turmeric and anti inflammatories as mentioned, so what if I am at 230 if I am eliminating them, the point is that 224 is not oh my God, I am a dead man number if the right compensatory things are done.

Good point. There may be ways to get away with it. I'm glad too because I've spent much of my life above 224 . The point is though that there is no other bio-marker that suggests a 25 fold more likelihood in Neuritic plaque. Not 25%, but 2500% more risk!?

I think we should get right down to business and figure out how us ~4's can reduce APOB but thats another thread. Hep

[Julie G]

I finally had an opportunity to read the full study (with tables!) thanks to Bulldog Stavia Because the cholesterol hypothesis is so pervasive, I always like to go back to raw data to see if my interpretation jives with the study conclusions and in this case with Dr. Michael Greger's interpretation that even "moderately elevated cholesterol increases dementia risk."

Using the demographic data from Table 1, it looks like Greger partially got it right. The modifiable risk factors that predisposed a participant to having neuritic plaques (NPs) are presented below in order of their significance.

-LDLC/HDLC, 25%
-TC/HDLC, 24.32%
-Fasting Insulin, 22.23%
-Exercise, 21.2%
-LDLC, Non-HDLC, TGs- 20%
-TC, 10.25%
-HDLC, 7%
-Blood Glucose, 5%
-BMI, .4%

Greger chose to focus on cholesterol, but it turns out (just using the data from this study) that the LDLC/HDLC and TC/HDLC ratios are MUCH bigger drivers of neuritic plaque that LDLC or TC alone. LDLC is in 5th place at 20% and TC is in 6th place at 10%.

What really caused my head to head to spin, was learning those with NPs lived on average seven years longer. And, higher systolic and diastolic BP as well as cigarette smoking protected against NPs. Huh?

I think we should get right down to business and figure out how us ~4's can reduce APOB but thats another thread.

Agreed, Hep! PLEASE start a thread on how to reduce LDLC/APOB, but let's make reducing cholesterol ratios & fasting insulin while increasing exercise an even bigger focus.

[RichardS]

I've just reviewed the study based on the OP quoting a risk "up to 25 times" for those with dyslipidemia.

There were only 147 subjects in the entire study which should give anybody pause for in figuring out how risk ratios of 25 to 1 make any sense. In fact, the largest risk ratios of up to 25 are based on a statistical model with 10 predictive factors. That many factors for only 147 subjects makes me think the researchers were doing excessive data mining for their Model 3.

Looking at the basic raw data, the first 3 quartiles of their favored lipid marker (total cholesterol) showed a consistent 62% (23/37 for each group) presence of neuritic plaques (NP's). For those with cholesterol over 225, it was 86% (31/36). But the really important point is that they did not actually assess the correlation between dementia and lipids. It was only NP's.

From the Results section: "After the clinical examination in 1988, 34.0% (n = 50) of subjects developed dementia; specifically, 17.7% (n=26) were Alzheimer-type dementia, 13.6% (n = 20) were vascular dementia, and 2.0% (n = 3) were mixed-type dementia.". This study attempted to squeeze clinical risk data out of a moderate sized pool of a general community and using a potentially relevant biomarker rather than the disease itself. In this study, there are no data relating initial lipid status with autopsy-confirmed dementia. Perhaps this Hisayama data has been published elsewhere, but it would still represent a fairly small sample size for the findings we are interested in.

Also remember that cerebrovascular disease in this group was widespread: "Prevalence of cerebrovascular disease at autopsy was 59.2% (n = 87), which included any type of infarction (n = 73), hemorrhage (n = 10), or Binswanger type change (n = 6)."

The number of APOE4 carriers was about 16%. In the end, I see little reason to get excited about this study from the APOE4 perspective.

Richard

[Stavia]

I've been thinking a lot about lipids. Without delving into subfractions, which I have no experience with and which only you USA denizens can access, the body of evidence consistently points to LDL (and TC/HDL ratio which we use in my country, this ratio incorporates TGs cos they correlate with VLDL) as bad for cardiovascular outcomes. The evidence is strong and consistent and has been replicated many times over the decades and only a handful of outlier (yet vocal) scientists dispute this. And bad cardiovascular outcomes correlate with increased AD. If we think there are multiple triggers for AD, this would be possibly one of them.
In my opinion it would be prudent to optimise these markers.

BUT - without a statin, how?????
Excercise can modestly raise HDL. Alcohol can too but we can't go there. Dietary measures are notoriously ineffective in reducing LDL. We are all already limiting saturated fat.
So thats what worries me...Im scared cos my LDL is 3.5, and dunno how to get it down because I believe its relevant.

Ps I'm not talking about TGs. They are carbohydrate driven. Im talking about LDL.

[Welcomeaboard]

Richard S nice play by play analysis.

[Julie G]

Welcome, Richard!

I agree with Hep & Stavia. Reducing LDLC/ApoB should be ONE of our goals in the context of a larger clinical picture of high HDLC/low TGs, no insulin resistance. I clearly found my upper end of dietary fat tolerance a la Dr. Gundry per my recent LDL-P . I've had luck in the past with a similar diet (HFLC) just more restrained EVOO. Tweaking.