Hydroxychloroquine lowers Alzheimer's disease and related dementias risk

Note that this is an article making huge claims about Alzheimer's but is published in Molecular Psychiatry. Given that signal, I'm just going to look at the abstract and not read the full text.

Here, the study population is patients with rheumatoid arthritis. This tells you up front that we don't have a typical population, but a highly selected one.

The use of HCQ is observational, not randomly assigned.

So, how could HCQ look protective even if it had no effect on Alzheimer's biology?

1. Maybe more rheumatoid arthritis patients should be on HCQ. It's a disease-modifying drug, after all. So it may be the case that people with better care, or more wealth, are more likely to be on HCQ. And that could be associated with other lifestyle factors that are never fully accounted for in an observational analysis.

2. Or it could be the case that people with dementia are less likely to have their HCQ prescriptions renewed, so the arrow of causation could even be reversed.

Additionally, one could imagine that HCQ might actually protect against Alzheimer's disease in people with rheumatoid arthritis—but not in a general population. That would be very big news, but would require further study.

And sure, it could be the case that HCQ reduces Alzheimer's risk in everyone. But you'd need a lot more evidence to buy that.

If Hydroxychloroquine reduces inflammation and reduces immune responses damaging connective tissue I could see it generally useful for incidents where the body damages itself (such as Alzheimer or dementia)

Generally hydroxychloroquine is used in mild rheumatoid, whereas methotrexate is used in moderate-severe disease.

Inflammation in rheumatoid (and other inflammatory diseases) contribute to atherosclerosis and plaque buildup. Rheumatoid increases the risk of coronary disease by 1.5-2x.

That difference alone could account for the difference in dementia, particularly vascular dementia.

The largest effect size I know of, predicting incidence of real dementia in real people (46,000 people over 70), is that a recent Tdap booster predicts a 40% reduction. Nobody knows how or why, or isn't saying. Apparently treatment for herpes has a large effect size, too.

It is easy and safe to get both.

Being obese in your 30s-50s increases your chance of developing dementia or Parkinson's later in life by somewhere between 500 and 800 percent.

Losing the weight is such an OBVIOUS intervention for things like diabetes and CVD risk, but it affects risk factors for nearly every other chronic disease on the list, including something like half of all cancers.

And yet, we're researching the type of micro-optimizations indicated in this article.

Don't be fat from 30 to 60. That's it. That's the solution. And yet, all I see is:

Medically: Masking the symptoms with medication, with not even a cursory nod to improving lifestyle factors.

Societally: Wild adoration of Lizzo and "Health At Any Size" ridiculousness.

Not drinking water or eating food leads to lower risk of choking to death, but...

It is not a miracle drug and it is not useless for all medical purposes. It is a relatively mild anti-malarial drug with some anti-inflammatory properties. It is prescribed for autoimmune disorders in addition to malaria. Its anti-inflammatory/immune regulation effects are probably not that strong but its safety profile is well understood.

There are remarkably fewer demented people as a result of people taking Hydroxychloroquine.