Parkinson's, Alzheimer's, and the New Science of Hope

[MBAnderson]

"In the case of Parkinson's disease, a brand new review paper published this week by an international group of European neuroscientists argues that alpha-synuclein is nothing more than a red herring—an innocent bystander that only appears guilty by association.

How many people with Parkinson’s disease have insulin resistance?

A 2018 study of 154 non-diabetic Parkinson’s patients conducted at Cedars-Sinai Hospital in Los Angeles found that 58% of them had insulin resistance. All of these people had normal fasting glucose levels and—in many cases—normal hemoglobin A1C levels and normal body weight as well. In fact, a surprising 42% of normal-weight people with Parkinson’s had insulin resistance [determined by a HOMA index of 2.0 or above and/or a hemoglobin A1C of 5.7 or above]. These data underscore the fact that routine diabetes testing and body weight measurements often fail to detect insulin resistance, fooling people into thinking they are metabolically healthy and don’t need to make lifestyle changes.

Other studies have shown that people with Parkinson’s disease who also have insulin resistance are more likely to have severe symptoms, faster disease progression, and Parkinson’s-related dementia.

So, while insulin resistance is certainly not the only player in the development of Parkinson’s disease, it is clearly a force to be reckoned with in the majority of cases."

psychologytoday.com/us/blog...

How to Diagnose, Prevent and Treat Insulin Resistance [Infographic]

diagnosisdiet.com/how-to-di...

Reversing Type 2 diabetes starts with ignoring the guidelines | Sarah Hallberg | TEDxPurdueU

youtube.com/watch?v=da1vvig...(Not working as expected?)

[LAJ12345]

I think they are right!

[MBAnderson in reply to LAJ12345]

I agree. Steering clear of insulin resistance via very low-carb and intermittent fasting is right for me.

[WinnieThePoo]

Not sure about the alpha synuclein being a distraction though. I knew as soon as I posted that there was a lot of new smoking gun for A-syn there would be some contrary research published. I think it unlikely A-syn will turn out to be an innocent bystander, although Lewy bodies may turn out to be responses rather than causes.

As Dr Haroun Gajraj, a UK vascular surgeon, who has taken a stance against statins said "In my view, high total blood cholesterol or high LDL levels no more cause heart attacks than paramedics cause car crashes, even though they are present at the scene."

The same may turn out to be true of Lewy bodies and PD. But not I think A-syn. It is proposed as a biomarker in tears for early PD detection, among many links to the disease. Of the many recent A-syn reinforcers, the Guardian article I linked to in "I told you Parkinsons was poo" is very smoking gun.

I know its mice, but it's different. Importantly different. Typical mouse research (the Bristol GDNF trials would be a good example) take healthy mice and chemically damage parts of their brains to replicate the damage done to humans by PD. Usually destroy dopamine neurons in the substantia nigra. They then trial things on those modified mice, who have some features of PD but not the underlying engine of the disease. Transfer to humans with real PD and it doesn't work.

But this time, they didn't chemically damage their brains, they introduced "bad A-syn" to their bowels, near the vagus nerve, and watched bad A-syn migrate up the vagus nerve to the brain, and replicate the pathology of PD. (Sort of - there were differences like sequence of migration to olphactory bulb, but totally different from normal mouse PD experiments)

The psychology today article had some questionable interpretations on the core research

"Unfortunately, countless desperate dollars have fueled decades of sophisticated drug research taking aim at these and other potential culprits leading to exactly zero medications with the potential to make any meaningful difference in the course of these conditions thus far."

Really? I'm not aware of any drug research into A-syn medications until very recently. I can think of 4 current trials into brand new medications specifically targetting A-syn (covered by Simon in his Science of Parkinsons preview of the year), all in current phase 2 trials with no results published, but no such medications before. Lots of PD med trials which failed, but none targetting A-syn until now

I would be cautious. And optimistic.

[WinnieThePoo]

I have a wee issue with insulin resistance and PD too. Not that I question the association, but I wonder about another case of "it always rains when the pavements are wet". (That's sidewalks for our American chums).

30 million Americans have type 2 diabetes diagnosed, and by definition insulin resistance, but more than 29 million of them don't have and won't have PD.