For many years, neurology has instructed us that Alzheimer’s illness is brought on by poisonous proteins (amyloid plaques and tau tangles) that clog the mind. Pharmaceutical firms have poured billions into anti-amyloid medicine designed to clean them away. The outcomes? Repeated failures, high-profile disappointments, and a handful of marginal approvals with no significant enchancment in sufferers’ lives. Sound acquainted? In cardiology, we’ve constructed a whole business on decreasing LDL ldl cholesterol. Statins transfer the lab numbers impressively, but absolutely the profit is modest: in main prevention, possibly a 1 to 2 % absolute danger discount in occasions over 5 to 10 years, with an NNT usually within the 50 to 100 vary.
Now have a look at what occurs whenever you goal the possible trigger moderately than the downstream particles. In 2017, a nationwide Taiwanese research adopted greater than 33,000 sufferers with HSV an infection. Those that didn’t obtain antivirals had a dementia incidence of about 28.8 % over ten years. These handled with anti-herpetic medicine (acyclovir, valacyclovir, and famciclovir) had an incidence of simply 2.9 %.
- Absolute danger discount (ARR): A discount of 25.9 %.
- Quantity wanted to deal with (NNT): Roughly 4.
For each 4 HSV sufferers handled, one case of dementia was prevented over ten years. That’s staggering. Examine it to statins: NNT roughly 50 to 100 in main prevention. Right here, NNT is roughly 4. The sign is so sturdy that skeptics argue it have to be confounding, however even when solely partly true, the magnitude suggests we’ve been trying within the incorrect place.
Which brings us again to amyloid and tau. As an alternative of “poisonous junk,” these proteins often is the mind’s model of a granuloma: defensive constructions spun out to wall off microbes. Autopsies of Alzheimer’s brains have revealed herpesviruses, Chlamydia pneumoniae, spirochetes, fungi, and periodontal micro organism like Porphyromonas gingivalis. Completely different organisms, similar sample: persistent an infection, persistent immune activation, and walling-off responses that ultimately destroy host tissue.
We’ve seen this earlier than. In TB, granulomas defend however scar lungs. In reactive arthritis, antibiotics enhance outcomes as a result of they hit the motive force, not simply the irritation. In cardiology, arterial plaques can also be granulomas, walling off pathogens like C. pneumoniae. A current Japanese research discovered its DNA in each single plaque sampled. And but we preserve decreasing numbers: LDL, amyloid PET scans, and Lp(a). We polish the smoke whereas ignoring the hearth.
Granulomas in TB. Amyloid plaques in Alzheimer’s. Atherosclerotic plaques in coronary heart illness. Even reactive arthritis joints. Completely different tissues, completely different outcomes, however maybe the identical story: an infection sparking a maladaptive immune response that drugs errors for the illness itself.
It’s time to cease pretending biomarker discount is victory. We want the trial neurology has averted: a randomized antiviral research in early Alzheimer’s. And cardiology wants the identical braveness: a randomized antimicrobial trial in youthful sufferers with early atherosclerosis, utilizing a triple-drug routine for no less than six months. Previous antibiotic trials failed as a result of they gave one drug for per week to sufferers already too far gone. That’s like giving two aspirin to somebody with metastatic most cancers and declaring the drug class ineffective. If plaques are infectious granulomas, we have to deal with them with the identical seriousness infectious illness docs already use for TB, leprosy, and HIV. Till then, we’ll preserve congratulating ourselves for shifting numbers whereas leaving sufferers to endure the identical outcomes.
Larry Kaskel is an internist and “lipidologist in restoration” who has been practising drugs for greater than thirty-five years. He operates a concierge observe within the Chicago space and serves on the educating school on the Northwestern College Feinberg College of Drugs. As well as, he’s affiliated with Northwestern Lake Forest Hospital.
Earlier than podcasts entered mainstream tradition, Dr. Kaskel hosted Lipid Luminations on ReachMD, the place he produced a library of greater than 4 hundred applications that includes main voices in cardiology, lipidology, and preventive drugs.
He’s the writer of Dr. Kaskel’s Residing in Wellness, Quantity One: Let Meals Be Thy Drugs, works that mix evidence-based medical observe with accessible methods for enhancing healthspan. His present initiatives give attention to reevaluating the ldl cholesterol speculation and investigating the infectious origins of atherosclerosis. Extra info is offered at larrykaskel.com.
