Would this be for an e3/e4 or just for an e4/e4? Also, is there any single journal article or study you’d share with an internist to convince them of the value of prescribing valacyclovir for this scenario?
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I found two papers that might be helpful:
R. F. Itzhaki, Herpes and Alzheimer’s Disease: Subversion in the Central Nervous System and How It Might Be Halted, Journal of Alzheimer’s Disease, 2016 Oct 18; 54(4):1273–1281. LINK
W. S. Tzeng et al., Anti-herpetic Medications and Reduced Risk of Dementia in Patients with Herpes Simplex Virus Infections – A Nationwide Population-Based Cohort Study in Taiwan, Neurotherapeutics, 2018 Apr; 15(2):415–416. LINK
There are also some related clinical trials. NCT03282916 VALAD and NCT04710030 VALMCI
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PYM
#283
An interesting thing is some studies show statins to be protective against AD, especially in apoE4 carriers. The theory being that apoE4 very poorly transports cholesterol between astrocytes and neurons, leading to cholesterol building up to toxic levels within the astrocytes+/- neurons. statins may thus protect the glia and neurons by preventing this toxic build up of cholesterol.
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This area may require a rethink. Especially this study which was prospective and in patients who statins were initiated, only a small benefit in non-ApoE4 carriers, and fairly sizeable 40% reduction in those with ApoE4’s. They didn’t seem to report effects on E4 hetero vs. homozygotes, and sadly didn’t as far as I can tell look at hydrophilic vs. lipophilic statins.
The theoretical approach Dr. Dayspring has taken, as did the preventive Neurologist on their discussion of this topic seem to be challenged by the study above.
It might be time for a rethink.
We’ve seen various associations with statins decreasing AD rates in the general population, but this is the first study I’ve seen that at least delineated on ApoE4’s and doing so prospectively.
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Beth
#285
As you know, this is all Greek to me, but I’ll share that my other doc said he is guessing the benefit is from cholesterol lowering in those with apoe4 and perhaps not from the statin. He said this because we already know that if lipids and bp are well managed, it offsets much of apoe 3/4 risk. In his opinion
He’d love to see this study with an arm that is taking repatha to compare to the statin. He did mention there was a study that made it seem statins can help, but that was with 80mg of crestor, that we don’t use in the US
What are your thoughts on if there is something inherent in the statins vs just the drastic benefit of lowering lipids?
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It’s a challenge and I’ll just put one study up that specifically looked at this issue – and lowering lipids didn’t seem to be an active ingredient. I’d certainly say that lipid management and BP management offsets the excess cardiac risk that those with ApoE4’s have.
A 2021 individual participant meta-analysis of 21,000 adults published in Dementia and Geriatric Cognitive Disorders I found no significant association between cholesterol reduction and reduced dementia risk in APOE4 carriers. The odds ratio for incident dementia was 1.01 (95% CI, 0.89–1.13), and results were consistent regardless of statin use or APOE genotype 1.
The data is complex and often times we are looking at and comparing slightly different things. I’d however say that we have no evidence to support just lowering lipids by any means is helpful. This study’s results also conflict with the studies showing benefit of statins in those with ApoE4’s.
I continue to gather more information as it looks like we have a modest amount of data on statins and AD and then specifically in those with ApoE4’s as in the trial I cited in a previous post.
I’d not be overly confident that there is nothing unique to statins and their benefit. I’d certainly not conclude that lipid lowering by other means is equivalent for AD risk - I’d say it is likely equivalent for CHD risk for the most part - although even then, there is an anti-inflammatory effect and plaque stabilization effect with them, that I don’t know is present in the other agents.
Anyway, I’m back on Rosuvastatin …j
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Maybe they didn’t live long enough…
| Ancient Greece and Rome |
510–330 BC |
20–35 years |
| Early Middle Ages |
476–1000 AD |
31 years |
| Pre-Columbian Mesoamerica |
1175–1520 AD |
24–32 years |
| Late Medieval Period |
1300–1500 AD |
30–33 years |
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blsm
#288
That’s exactly what I was thinking.
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fisher1
#289
I think those numbers are skewed because of infantile deaths which were very common up to the 20 century. My grandfather’s sibling’s (8 of them) average life expectancy was 32 years old. Five of them lived from 1 month to 10 months old and the rest (3 of them) lived one to 85, one 93, and one 91, and neither of the three had dementia nor AD. Clearly some of the diseases of today (i.e. AD, cancer, Diabetes) were much rarer in occurrence in times past.
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They considered records of people who were old, and there were several such people mentioned in ancient texts (some ancient Romans even lived into their 90s and even exceeded 100); though it’s possible their true age was distorted for whatever reason (e.g. to avoid military service).
In ancient Rome, people in the patrician class, if they survived childhood and young aduthood – say, past the age of 20 – they would have expected to live at least into their 50s, if not 60s or 70s. Also, here is a little something mentioned in the paper that I had forgotten about:
The city-states of Sparta and Athens required the registration of citizen children shortly after birth. These records gave official age thresholds for public duties: age 18, military service; 30, holding administrative office; 60 for termination of military duty. In Sparta, age 60 was also the threshold for election to the Gerousia or governing council, whose twenty-eight members served for life after election. While Greeks were fully aware of cognitive declines with age, elite elderly were valued for their civic wisdom.
They even anticipated some qualified “elders” to be alive to run the governing council.
…
It’s possible there is a kind of “health bias”, however, in these records, that affect the findings. People in ancient times who might have gotten Alzheimer’s in old age maybe tended to die younger, long before symptoms would have appeared; if so, they wouldn’t have been counted. Those people who survived into their 70s were perhaps much hardier than modern-day people who live into their 70s, that have access to modern healthcare.
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To me this shows people lived much longer than we are led to believe by looking at mere averages. I doubt they would have picked 60 as the threshold had they known that a 60-year-old (at the time) had only couple months or couple years to live.
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Neo
#292
What is the side effect profile you have seen from this, it is favorable?
Beth
#293
Also, @DrFraser, did you see this that Adssx posted? On Urolithin A possibly surprising hsv1
https://pubs.acs.org/doi/10.1021/acs.jafc.5c04281
Thoughts?
And hmmm, I’m willing to suffer a bit on statins if we are convinced it will help prevent ad… but because it would be a bit of a sacrifice, I would want it to be a good trade off.
The other alternative is that AD was under diagnosed in ancient times. Maybe everyone of an elderly age was a bit crazy or absent minded and that was considered normal.
You have to remember that the Roman population had extreme exposure to lead and toxic metals (plates, cutlery, water pipes, etc…) , so I would even venture to say that normal back then would be considered full onset demented now. Looking at health reports from antiquity is useless as diagnosis is too inaccurate.
Maybe dementia was considered normal back then and everyone had it so it was reported that no one did? I find that much more believable than there were low rates of dementia in the elderly.
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