> "Conclusions: The modern 'epidemic level' of advanced dementias was not described among ancient Greco-Roman elderly. The possible emergence of advanced ADRD in the Roman era may be associated with environmental factors of air pollution and increased exposure to lead. Further historical analysis may formulate critical hypotheses about the modernity of high ADRD prevalence."
"High-income North America" has the highest age-standardized incidence rate, whereas smog-shrouded South Asia has the lowest. East Asia, infamous for industrial and urban air pollution, is also fairly low on the list. From this data, there's apparently zero correlation between pollution and incidence rate.
Current air pollution levels isn’t indicative of lifetime or especially childhood exposure.
Leaded gas for example has seen a huge decline, but was still a thing when current 70+ year olds where young. Similarly, current developing economies where very different 50 years ago.
Sure, but even so it's not clear that air pollution is a factor. Some researchers recently compiled a "chronology of global air quality" which might be worth a review to see if any correlations can be uncovered. At a glance, it looks to me as though Europe and the USA cleaned up their act a long time ago -- so unless pollution exposure in early childhood is somehow especially bad, pollution still has no explanatory power: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7536029/
Not really [0], leaded gas was completely banned in the US in 1996 but really hadn’t been used since the early 80s and had start the phase out in 1996.
So you’d probably need to look at people in their 50s who really had an impact of lead from auto fuel.
Where "completely" in this case implies "for road-going vehicles". General aviation (largely small, piston-engine planes) still overwhelmingly run on 100 octane low-lead (100LL).
This is a very big deal if you spend time around small aircraft (hangar floors in particular sometimes have terrifyingly high lead levels.) But if you’re not spending time close to aircraft, the amount of lead you’ll be exposed to is negligible - at least compared to auto emissions, which were ubiquitous and extremely concentrated in residential neighborhoods. Unfortunately the lead remains in the soil, so there’s still exposure to it today.
Good point. I meant “completely” for consumer vehicles in the US. That’s what was pumping out all that lead into the air in the US. The other uses were much smaller.
On road use is banned. Also, the cost per gallon of leaded gas is at least $10/gallon now, which is a pretty large incentive enough for people not to use it :)
Basically most piston engine aircraft use Avgas 100LL (low lead solution). So the majority of the air traffic found at a typical municipal airport. Fortunately this is being phased out by the FAA in favor of unleaded.
Surely studies could get a good control group of people who grew up in rural Montana, or the Andes. Assume we can find groups with near-zero lifetime exposure to atmospheric (and/or waterborne) lead. What's their background rate of Alzheimer's?
>> "Conclusions: The modern 'epidemic level' of advanced dementias was not described among ancient Greco-Roman elderly. The possible emergence of advanced ADRD in the Roman era may be associated with environmental factors of air pollution and increased exposure to lead. Further historical analysis may formulate critical hypotheses about the modernity of high ADRD prevalence."
It's not as if they were doing detailed demographic studies back then, though. There's just certain things that can't be known, and this is one of them.
Indeed - it could equally be explained by dementia/Alzheimer’s being a contagious disease, such as a prion or similar protein malformation, which quite a bit of current research seems to suggest, and it simply had not become endemic at that point.
It disappoints me that something which severely impacts the lives of perhaps one third of humans isn't better understood.
If it were a prison disease, surely with ~2 billion data points of those with/without dementia, we would have isolated exactly what molecule causes it and how it gets transmitted from person to person.
Anyway, the cause seems to be nutritional. People used to consume vastly more copper than we do today. The modern recommended intakes were hastily made up for the need in the WW2, and never seriously revised.
Nullius in verba. You'd be well advised to take a skeptical view of every scientific paper -- especially those promoted by University PR departments.
Besides, "it's air pollution's fault" was a throwaway statement by those UCLA gerontologists. It wasn't the focus of their study; it was simply an unsupported notion of what might explain the supposedly higher rate of Alzheimer's disease in Rome as opposed to Ancient Greece. (I write supposedly because they don't really have enough for a statistically valid conclusion. What they have is: "In the writings that have survived, the Greeks mentioned something like Alzheimer's once. The Romans mentioned it four times. Now what could account for this presumptive discrepancy? We'll assume that it could have been lead or dirtier air.")
It has been MANY, MANY years since the alignment of academic institutions was solely meritorious, perverse incentives distort truth regardless of infomation source.
This might be interesting because here people with dementia were not classified as suffering from cognitive impairment but as witches. It went as far as considering dementia purely a white people disease that didn’t occur in Africa. Maybe the Greeks and Romans did similar mistakes (e.g. treating them as seers, oracles or such)?
Or maybe the people with dementia died off early in the cycle before it became pronounced enough for other people to truly notice and remark on it. Life is much safer nowadays and we tend to forget all the guardrails we have up for everyone
Honestly this seems to me to be much more likely a reason than industrial society environmental factors. My father was in his early 80s before he could no longer “fake away” the mental decline he was experiencing due to Alzheimer’s. At 86 and moving into stage 7 of the disease.
I have to think people reaching that advanced an age was relatively rare in pre industrial times, coupled with the fact that today Alzheimer’s affects only about 10% at age 65. You would need a large population reaching that age and beyond to the later stages where the disease becomes problematic before it would become noticeable in a society.
This complete fallacy that "people didn't live that long" can't die soon enough. Mortality numbers are horribly skewed by high birth and infancy mortality rates and a spike for military-aged individuals, but people that made it to forty didn't wait to turn fifty then keel over and die.
But still high infant mortality and spike in deaths of military aged people, as well as more primitive medical (lack of antibiotics etc.), There was not as many people that made it to the advanced ages where the results of dementia becomes particularly problematic for the people around them. Because of that smaller group, and a portion of that smaller group being affected, it might not be a widespread and noticeable societal issue. Couple that with a less complex lifestyle and you may not notice the dramatic differences as we do today of the afflicted.
For instance…my father about 4 years ago lost all ability to successfully use a TV remote, telephones (To call), to drive, etc. He could read, was able to eat, handle self hygiene needs, etc. Our society notices the decline sooner because of the tech we use. However, 2000 years ago, the decline may not have been as noticeable until it hit the most advanced stages. At the advanced stages, hygiene, eating, etc… become difficult to impossible and these later stages back then would likely bring quicker physical declines and death than they do today.
The "mortality was skewed by infant mortality" myth can't die soon enough. Yes the life expectancy being 35 didn't mean everyone died at 35, but your mortality at any given age was substantially higher than today. Whereas today living into your 70s is nearly a given and people have decent odds of remaining healthy into their 80s, in the past living to such ages was exceptional. Of course it happened on occasion, but if you look at the ages people actually died of natural causes, it was typically between 50 and 65. Even when people were noted for their incredibly long life, it was still rather short compared to today. Louis XIV, for example, was the longest reigning european monarch of all time, living to the ripe old age of 76, outliving his son (who died at 49) and grandson (dead at 29), to be succeeded by his great grandson who would live to be 64. The modern life expectancy in France is 82.
Not really. Ben Franklin died at 84, for example. Jefferson died at 83.
Being poor, however, has always sucked. Being wealthy always meant you lived longer.
The difference is that wealth concentration was much more strongly localized and concentrated in the past. And the famous people, who you have heard of, were generally the more wealthy people.
It seems odd to me that they would describe folks with impairments like dementia as witches or oracles. Do dementia patients make prognostications along with their problems with memory, incontinence, temper?
But I suppose if the dementia appears as an acquired condition then having some ominous description for the victim would help avoid the spread of whatever contamination or infection that could have been an explanation.
This article uses the example of the Tsimané people of Bolivia as a model for pre-industrial society, and notes that a very low percentage of older Tsimané experience measured dementia (something like 1% compared to 11% in North America). But it's also the case that the at-birth life expectancy of a Tsimané person is quite low compared to the rest of North America; a smaller percentage of Tsimané survive to the age at which Alzheimers becomes a major epidemiological issue in modern societies. How does a researcher account for that? It seems like it could be a confounder.
I often wonder what the effects of reduced infant mortality will be on the population. For all of human history before about 100 years ago, we were aggressively selected for survival at birth or shortly after. Now, we're not. All those people who would have died might not only suffer other health problems in their life but propagate the "die as a baby" genes to their offspring. Optimistically, it might mean that humans both become dependent on those medical technologies that save babies and mothers, and maintain the capability to provide them so we're fine. It could be a positive direction for evolution, like how we're already adapted to depend on ancient technologies like housing, clothing, and cooking. But maybe it's just bad and future generations will be generally get less and less healthy.
The head sizes of babies are actually getting larger over the past decades [1]. This might be because of better nutrition, but maybe it is by a large part because we can do caesarean sections in every hospital now and head size is not as limited as it was before anymore.
I doubt that infant mortality was mostly because of genetics, since natural selection would make it hard for that gene to spread unless there was some other benefit (e.g. how being a carrier for sickle cell anemia is good, even though having sickle cell anemia is bad). The main reason for high infant mortality was probably because of illnesses and famine, not genetic.
That's irrelevant to some extent. It still means that those who could better resist illness and famine had a better chance to live, which is likely to have some genetic correlation. Even when the famine is extreme, it still selects for the families cold hearted enough to be able to consciously feed only those who have a chance to survive instead of trying to spread their resources to all their children, which itself may have some genetic source that can be selected by this pressure.
Not that either of these are good or necessary for a healthy species, mind you. We will always adapt to our environment and the selective pressures that match it, even when it's one of our own making. If that means fewer children die young, that is an excellent outcome - evolution is never goal oriented anyway.
It could be partly due to normal harmful random mutations reducing the mother/baby's fitness, which are now being allowed into the gene pool more than before.
> a smaller percentage of Tsimané survive to the age at which Alzheimers becomes a major epidemiological issue in modern societies. How does a researcher account for that? It seems like it could be a confounder.
This would be an issue if Alzheimers is part of a phenotype that raises all-cause mortality in the young. I'm not aware of any research on this. Alzheimers is known to be correlated with certain lifestyle and immune factors, and these factors might be expressions of a common phenotype that also increases early mortality and is moderated by pre-industrial environments---e.g. increased risk-taking or decreased immunity.
A common phenotype hypothesis might explain some of the difference in Alzheimers incidence between Tsimane and Westerners, but it would be surprising if it were the main reason. Assuming the hypothesis only, an Alzheimers delta of 11x for those over 65 implies a mortality rate delta of 11x between the under-65 phenotype groups. That is a massive effect, and if it includes child mortality, we would expect to see genetic drift over time and a lower genetic predisposition to Alzheimers among Tsimane (has that been studied?).
Do you suspect a higher percentage of those of the Tsimane who died young would have developed dementia after 65 (which seems to be the cutoff they're using)? That would be an interesting result, but unless there's some reason to think it, it's just one of many potential hypotheses.
I don't know! I think the subtext of the article is that the Tsimané have, ceteris paribus, a lower incidence of dementia --- that if you could keep the lifestyle and environment constant and raise the at-birth life expectance of these people to modern standards, they'd still have low rates of dementia. I'm wondering if that's true, and how you'd go about investigating that.
In a study of all men of renown, living in the 5th and 4th century in Greece, we identified 83 whose date of birth and death have been recorded with certainty. Their mean +/- SD and median lengths of life were found to be 71.3+/-13.4 and 70 years, respectively.
Dementia starts to be noticeable in modern society after about 75. I haven't found a source showing the distribution of age at diagnosis.
Also the title is highly misleading: Alzheimers is only one form of dementia.
From another source:
A growing number of studies indicate that the prevalence 223.267.315-322 and incidence270.320-329 of Alzheimer's and other dementias in the United States and other higher income Western countries may have declined in the past 25 years,270,277.320-328.330-333 though results are mixed. 60.261.334-335 One recent systematic review found that incidence of dementia has decreased over the last four decades while incidence of Alzheimer's dementia, specifically, has held steady
It is estimated that about 12% of Romans that survived first 10 years of life (half of them died before that, but cest la vie if you don't have vaccines and antibiotics) lived to be 70 years or older.
Currently, this figure is 43% worldwide from birth. But fertility is also way lower as a response to low infant and child mortality.
So 3.5x increase in over-70 population seems a decent guesstimate. In developed countries even more.
Right, so the premise of the article is an inquiry into whether there is something neuroprotective about the lifestyle or environment of premodern civilization.
I'm curious about the day to day environment the Tsimané live in since I can see a relationship between dementia and increased accidental deaths in more dangerous environments. Let's say you need to walk 5 miles a day through a predator infested jungle for water. Getting lost one day due to an episode of dementia could easily kill you. Same for eating a poisonous plant or drinking water from the wrong source or even getting a simple cut that becomes infected due not paying attention. The study used 65 as a cutoff which is before most physical deteriorations so individuals are likely still self-reliant.
> with sedentary behavior and exposure to air pollution largely to blame.
Both of my grandpas worked manual labor their entire lives. One had Alzheimer's, the other started to develop dementia but is on medicine now.
Interesting thing to note, both were extremely intelligent. Seems like the more intelligent of my extended family were also more likely to have memory issues.
You edited out their jobs, but I saw before the edit. Without restating those jobs I'll say that one would have had exposure to emissions from 2-cycle mixed oil/gasoline engines. The other would have had exposure to lead solder fumes.
Upon further thought, the Romans were exposed to lead, their water pipes were made from lead (installed by plumbers), not to mention pewter and bronze objects.
And they were certainly breathing lots of smoke from their cooking fires. Although wood smoke is probably less hazardous than two stroke oil.
They also got a lot of copper from those. It's well documented that brains with Alzheimer's lack copper. It's probably all that it is. The fight against copper has no scientific basic, it's actually hard to overdose on it, our bodies can handle it very well.
Skimming a review article on this topic this appears to be the since at least partially discredited amyloid beta Alzheimer's hypothesis, and studies are divided on whether too much or too little copper is a problem.
: Scientific evidence has shown that metal ion binding to β-amyloid accelerates amyloid aggregation, which could finally damage the neurons in AD (Pithadia and Lim, 2012). The involvement of copper in AD is controversial, as some studies show copper deficiency in AD, and consequently a need to enhance copper levels (Borchardt et al., 1999; Kessler et al., 2005, 2008a,b; Exley, 2006; Jiao and Yang, 2007; Vural et al., 2010; Kaden et al., 2011; Exley et al., 2012), while other data point to copper overload and therefore a need to reduce copper levels (Cherny et al., 2001; Sparks et al., 2006; Hua et al., 2011; Luo et al., 2011; Ceccom et al., 2012; Eskici and Axelsen, 2012; Brewer, 2014; Squitti et al., 2014b; Yu et al., 2015). An aberrant copper homeostasis with an increase in the labile pool of copper and a decrease in the copper bound to protein is the main up-dated interpretation (Kepp, 2016; Squitti et al., 2016). In this paper, the role of metal ions, particularly copper, in AD is reviewed and discussed.
You are trying to impress with the number of sources, but it's all from animal models, or even speculative, while the data for its absence is from actual autopsies.
Also, it isn't something that is difficult or expensive to try.
I'm not trying to impress jack all. I literally just block quoted the text of the review article most relevant to the point.
I spot checked starting from newer to older the too much copper citations and the third one I checked, "Brewer, 2014", though it itself cites animal studies, was about copper in humans (specifically inorganic copper as a hypothesized problem, versus organic copper which he says is fine). The Brewer paper references "Squitti et al., 2005" which was a study of humans showing elevated copper (of inorganic origin? I didn't read further than the abstract) and a couple of other things in Alzheimer's patients.
So copper from food? Good. Copper from water pipes? Bad. Chelated copper from supplements? I don't know. Maybe further reading would show other results. Again, I just skimmed this.
There is literally no reason to believe this. Plus, the amounts leeched from pipes are nowhere near high enough to provide even the paltry RDA. People used to cobsume more. They used to use bronze or copper cookware. It's bullshit. You are only coming up with excuses why it isn't copper. Why? I suppose because the cure would be almost free.
I don't care. It's unreasonable. There is no such a thing as "organic copper". People used to use those much more. There is no good correlation between blood levels and copper status. The actual levels in the actual brains show the opposite in autopsies.
How was their sleep? I have sleep difficulty (including a non-24 hour circadian rhythm) and significant early memory issues. I also have a family history of dementia (I only know anything about the sleep of one family member with dementia, who did have significant sleep issues). I did a quick search and found there are some signs of a potential connection and this seems to be under more intense research at this point.
Also, manual labor isn't the same as cardiovasular exercise and it is possible (and likely much easier these days with all of the powered machinery and transport) to not get much cardiovascular exercise despite a physically intensive job. Although I'm guessing even today a logger would.
I'm convinced sleep has something to do with it. If sleep is an issue, then stress is likely also a factor so I imagine a racing mind with no rest is was does it.
Sleep issues can be stress related but aren't always (and aren't in my case, at least at this point). Stress does seem to make everything worse though and I could see it playing a role in my family members developing dementia. I could potentially see sleep issues and stress triggering a process. I was thinking more along the lines of circadian issues since the immune system works differently at night so I could imagine that confusion over if it should be in night mode or day mode could potentially cause serious trouble.
There is evidence that cardiovascular exercise results in neurogenesis which results in lower incidences of dementia in older adults.
This is speculation but it wasn't until the past 70 or so years that large amounts of people were able to be sedentary.
I know the "simple explanation for why everything is fucked up" answer is almost always wrong but I'm very convinced that lack of walking is a major contributor to all of this stuff.
Alzheimer's is a prion disease. Prions are proteins that cause other proteins to misfold. What's interesting is that most prion diseases are transmitted through ingestion or physical contact - possibly there's a correlation with population density and/or sanitation. It's also possible that there are low occurrences in ancient populations because most people died of other things. For example, 200 years ago bacteria diseases were the most common cause of death. Now that we have conquered most infection disease the primary cause of death now is cancer and cardiovascular issues.
The first part of Book 3 in Marcus Aurelius' Meditations has this description of "dementia".
... If dementia sets in, there will be no failure of such faculties as breathing, feeding, imagination, desire: before these go, the earlier extinction is of one's proper use of oneself, one's accurate assessment of the gradations of duty, one's ability to analyse impressions, one's understanding of whether the time has come to leave this life - these and all other matters which wholly depend on trained calculation. So we must have a sense of urgency, not only for the ever closer approach of death, but also because our comprehension of the world and our ability to pay proper attention will fade before we do.
as most dementia is found among individuals ≥ 75 years of age, the pyramid-shaped age structure of the Tsimane and Moseten populations means that the crude prevalence would be expected to be low.
Relatively low exposure to traffic and industrial sources of environmental pollution are offset to an unknown extent by cooking fires and biomass burning.
Evidence is converging as to the major modifiable risk factors for dementia and AD.5, [6] These include low formal education[7]; vascular factors, including midlife hypertension and diabete[8]; cardiovascular disease other than stroke[9]; physical inactivity[10]; and—a recently recognized addition—air pollution.[6] Higher coronary artery calcium (CAC) scores—a marker of atherosclerosis—is related to increased risk of dementia.[11] Evidence-based dietary recommendations for reducing risk of dementia and AD include regular consumption of fresh vegetables, fruits, and fish.[12] In addition, several microbial pathogens have been associated with AD.
In a study of all men of renown, living in the 5th and 4th century in Greece, we identified 83 whose date of birth and death have been recorded with certainty. Their mean +/- SD and median lengths of life were found to be 71.3+/-13.4 and 70 years, respectively.
The “green movement” is not setting research agendas or funding for Alzheimer’s. The vast majority of this research operates in the opposite direction, starting with patients and figuring out what they have in common.
I guess it has to do with the no social connections. I am introvert but not because of looking at the end of life I start to change myself. Internet devolopment are already taking toal on people's mental health. I got ridoff of Facebook and Instagram long back because of this as well
This article explores brain volume and aging in two indigenous societies. Whereas brain volume is lower with greater body mass index (BMI) in industrialized populations, the association of BMI and non-HDL cholesterol with brain volume is largely positive, only declining with high BMI and cholesterol. This discrepancy represents a form of evolutionary mismatch we call an “embarrassment of riches” due to recent changes in diet, activity, and other environmental exposures. The minimal dementia and coronary artery disease in Tsimane and Moseten, combined with these findings, imply that aging outcomes are optimized at intermediate lifestyle values. Future research should focus on how our evolved biology interacts with conscious goals in relation to eating, exercise, and physiology.
[Abstract]
Little is known about brain aging or dementia in nonindustrialized environments that are similar to how humans lived throughout evolutionary history. This paper examines brain volume (BV) in middle and old age among two indigenous South American populations, the Tsimane and Moseten, whose lifestyles and environments diverge from those in high-income nations. With a sample of 1,165 individuals aged 40 to 94, we analyze population differences in cross-sectional rates of decline in BV with age. We also assess the relationships of BV with energy biomarkers and arterial disease and compare them against findings in industrialized contexts. The analyses test three hypotheses derived from an evolutionary model of brain health, which we call the embarrassment of riches (EOR). The model hypothesizes that food energy was positively associated with late life BV in the physically active, food-limited past, but excess body mass and adiposity are now associated with reduced BV in industrialized societies in middle and older ages. We find that the relationship of BV with both non-HDL cholesterol and body mass index is curvilinear, positive from the lowest values to 1.4 to 1.6 SDs above the mean, and negative from that value to the highest values. The more acculturated Moseten exhibit a steeper decrease in BV with age than Tsimane, but still shallower than US and European populations. Lastly, aortic arteriosclerosis is associated with lower BV. Complemented by findings from the United States and Europe, our results are consistent with the EOR model, with implications for interventions to improve brain health.
Average life expectancy is a very bad number to compare across such vast amounts of time, especially when you're looking at a disease that only happens in advanced age.
Infant mortality rates were dramatically higher in the past and drag that average way down, for instance, say I have a 1 day old infant, and a 100 year old person and they both die, they have a combined 'average life expectancy' of 50 years old. But, once you made it out of the 'childhood illness' mortality stage, most folks could expect to see 70 years old.
All worth exploring. You forgot low sperm production. We are surrounded by manufactured molecules that mimic hormones from our bodies, an experiment with not much of a control group, and an experiment where the naive materialist model would lead one to expect effects.
Asthma, IIRC there was also a study that showed just living adjacent to roads with high truck traffic caused sizable increases in percent of children who developed asthma compared to other local neighborhoods.
>Alzheimer's is a side effect of a sugar rich diet.
Careful with those absolutes. That linked article overall discusses obesity as a likely risk factor for it. On the sugar point, "sucrose" only appears once in the piece and the referenced study involved mice, not humans.
Yes, but there are other studies that make this link. The link is apparently strong enough that some prefer the phrase “type three diabetes” as a way to describe Alzheimers.
“Currently, there is a rapid growth in the literature pointing toward insulin deficiency and insulin resistance as mediators of AD-type neurodegeneration, but this surge of new information is riddled with conflicting and unresolved concepts regarding the potential contributions of type 2 diabetes mellitus (T2DM), metabolic syndrome, and obesity to AD pathogenesis.”
That’s still far from established at the level to warrant the original expression of absolute certainty. Considering that people have been studying it for decades, and that it’s like 70% heritable, it’s unlikely that everyone missed something as simple as “they are eating too much sugar” – something like this is likely to involve multiple genetic and lifestyle risk factors. I would defer to the researchers who still characterize it as a hypothesis - for example, this article is recent but is still careful not to overstate the case:
Part of why that matters is that you will have no trouble finding people who ate little sugar and still developed it, or sweet fiends who didn’t, and presenting such a simple explanation can feel cruel to people who saw their loved ones die a pretty ugly death since it sounds like you’re saying it’s a choice.
and what was the life expectancy during these times? 20-30 years for the population as a whole, according to GPT-4. It did mention some wealthier folk might live longer if they can avoid the many other dangers like war, disease etc...
There’s lies, damned lies, and statistics quoted by AI. Average ancient life expectancy numbers are substantially lowered due to high infant mortality. Once this early danger had passed, most people lived to approximately the same age we do now: https://pubmed.ncbi.nlm.nih.gov/18359748/#:~:text=Their%20me....
> "Conclusions: The modern 'epidemic level' of advanced dementias was not described among ancient Greco-Roman elderly. The possible emergence of advanced ADRD in the Roman era may be associated with environmental factors of air pollution and increased exposure to lead. Further historical analysis may formulate critical hypotheses about the modernity of high ADRD prevalence."
Air pollution has near-zero explanatory power, though. See: "Global, regional, and national burden of Alzheimer's disease and other dementias, 1990–2019" at: https://www.frontiersin.org/articles/10.3389/fnagi.2022.9374...
"High-income North America" has the highest age-standardized incidence rate, whereas smog-shrouded South Asia has the lowest. East Asia, infamous for industrial and urban air pollution, is also fairly low on the list. From this data, there's apparently zero correlation between pollution and incidence rate.