Smarter than the average björn

# # # # Certain life-style and environmental factors may render individuals more vulnerable to Parkinson’s, and a better understanding of them could aid in effects to reduce the incidence of the condition. Some of these risk factors (such as smoking and drinking coffee – PLEASE DO NOT START SMOKING!) can reduce the risk of developing Parkinson’s, while others such as exposure to pesticides can increase the chances of PD. Recently, researcher in Sweden have made a rather curious association: High IQ is associated with Parkinson’s In today’s post, we will discuss the results of this new study and we will speculate a little with regards to what they could mean for Parkinson’s. # # # #

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Lund. Source: Copenhagen-travel

When I was younger and less beautiful, I spent half a decade of my life enjoying the charms of a small Swedish city called Lund.

I was there to do a PhD (the chance of a life time for a simple country boy from the back-waters of third world New Zealand), but I absolutely fell in love with the place (a quiet, cobble-stoned, academic town) and the local customs.

Source: Beaps

Life in Sweden was really good. They had a fantastic quality of life, but more importantly they encouraged a very strong sense of social consciousness, inclusion, and justice.

But there was one aspect of ‘svenska livet’ that surprised me.

Despite a strong military history, Sweden chose to adopt a policy of neutrality in 1815 and it has not taken part in any armed warfare since that time (with the exception of peacekeeping). And yet, the country has maintained mandatory military service (in Swedish: värnplikt) for men since 1901 (the practice was paused between 2010 and 2017, but has subsequently been restarted on a reduced level).

Interesting, but what does mandatory military service have to do with Parkinson’s?

Well, the Swedish military are careful with regards to who they teach to shoot a gun or drive a tank, and they conduct thorough investigations of their young recruits which involve treating them to the ‘Swedish Enlistment Battery’.

Over the years, the results of this cognitive assessment and the personal characteristics of the recruits have piled up, and this has evolved into a rather impressive database of young men in Sweden which can now be analysed.

And recently some Swedish researchers have conducted an analysis involving the Swedish Military Service Conscription Registry which suggested an interesting observation about Parkinson’s.

This is the report:

Title: High IQ in Early Adulthood Is Associated with Parkinson’s Disease
Authors: Fardell C, Torén K, Schiöler L, Nissbrandt H, Åberg M.
Journal: J Parkinsons Dis. 2020 Jul 21. Online ahead of print.
PMID: 32716321

In this study, the researchers collected data on from the Swedish Military Service Conscription Registry database. They looked at all of the young men who enlisted for military service between 1968-1993. This was a total of 1,319,235 individuals.

Once they had all of that data, they next looked at whatever happened to each of those individuals using the massive Swedish National Patient Register and the Swedish Cause of Death Register (these Scandinavians love their registries – and so do data analysts!).

Combined, they had a very thorough idea of what each individual was like at a young age and they could also determine what happened to each of them over time.

Next they went looking for associations.

In the patient and death registers, a total of 1,724 were identified as being diagnosed with Parkinson’s later in life. When they compared these individuals with everyone else, they noticed something really interesting:

“High scores on IQ tests were associated with an increased risk of being diagnosed with Parkinson’s later in life”

A 1.3 fold increase to be exact, and this result was hugely significant (p < 0.0001). The results of the analysis indicated that high education level at a young age was associated with increased risk of Parkinson’s at a later stage of life. And parental education level did not affect these results.

 

# RECAP #1:  Life in Sweden is good. The Sweds have mandatory military service, and the assessment of young men entering the armed forces has provided a very useful database for academic investigations. Recent analyses of the Swedish Military Service Conscription Registry database have indicated that high scores on IQ tests were associated with an increased risk of being diagnosed with Parkinson’s later in life. #

Intelligence is associated with a higher the risk of PD? How on Earth do we explain that?

Well, the researchers who conducted the study focused their discussion of possible explanations on smoking.

You see, smoking was inversely associated with Parkinson’s – by this I mean, people who smoke are less likely to develop Parkinson’s. And this is a well recognised relationship (Click here to read a very old SoPD post on this topic).

Source: MJFF

But the researchers also noted that smoking was inversely associated with IQ as well as. That is to say, the more intelligent you are, the less likely you are to smoke.

But there was one interesting detail in the study that deserves some consideration. In their report, the researchers wrote that:

“IQ at conscription was not associated with later diagnosis of PD. Due to the low number of PD cases in the 1969–1970 sub-cohort (n = 256), there is a lack of power and the precision of this analysis is limited”

This suggests that the association between IQ and really late onset Parkinson’s might not be as strong as the earlier onset PD cases. And this leads one to wonder (read: speculate) if there isn’t some kind of ‘evolutionary advantage’ effect going on here with Parkinson’s.

I’m sorry, did you suggest there’s an ‘evolutionary advantage’ to Parkinson’s?!?

Yeah.

Could you please explain?

About 20% of Parkinson’s cases are associated with genetic risk factors. Tiny errors in certain areas of our DNA that result in an increased risk of developing Parkinson’s. And as we have discussed in a recent SoPD post, there is the possibility that additional variations in our DNA might be acting as ‘genetic modifiers’ on top of the activity of any underlying risk factor (Click here to read that post).

Source: Evolutionnews

Mother nature is continually experimenting with us. Each generation is a lottery of genetic chance. A very subtle rearrangement of our parents DNA occurs when each of us was conceived, as mother nature rolled the dice to see if some novel, more desirable traits can be gained.

But could it be that a trait that might be beneficial at a young age, may not be so great to have at a later stage of life.

What do you mean?

Back in 2014, this research report was published:Title: Abnormal visual gain control in a Parkinson’s disease model.
Authors: Afsari F, Christensen KV, Smith GP, Hentzer M, Nippe OM, Elliott CJ, Wade AR.
Journal: Hum Mol Genet. 2014 Sep 1;23(17):4465-78.
PMID: 24718285                     (This article is OPEN ACCESS if you would like to read it)

In this report, the researchers wanted to investigate visual ability in flies that had been genetically engineered so that their dopamine neurons carried the human LRRK2-G2019S genetic variant (we have previously discussed this Parkinson’s associated risk factor – click here to read more about LRRK2). When the researchers looked at contrast sensitivity in the eyes of these flies, they found something really intriguing:

The presence of human LRRK2-G2019S in the dopamine neurons resulted the flies having faster and stronger visual responses in the young stages of life, but this effect was lost and eventually deteriorated as the flies aged.

That is to say, a genetic alteration (of adding in a Parkinson’s associated risk factor) resulted in a better visual response at an earlier age. But this heightened visual advantage was lost and possibly detrimental later in the fly’s life.

The investigators were so intrigued with their finding that they decided to investigate whether other Parkinson’s-associated genes could cause similar effects. They published this report a year later:

Title: Classification of Parkinson’s Disease Genotypes in Drosophila Using Spatiotemporal Profiling of Vision.
Authors: West RJ, Elliott CJ, Wade AR.
Journal: Sci Rep. 2015 Nov 24;5:16933.
PMID: 26597171                     (This article is OPEN ACCESS if you would like to read it)

In this study, the researchers compared flies with genetic mutations associated with early-onset forms of Parkinson’s (PINK1 and DJ-1) with the later-onset Parkinson’s-associated LRRK2. They also compared these results with normal control flies. What they found was that flies with the genetic mutations associated with early-onset forms of Parkinson’s also had elevated levels of visual responses in the young stages of life (a 2x increase in response amplitudes compared with controls).

So the effect was not unique to just LRRK2.

The investigators speculated that the increased level of neuronal activity would probably result in increased energy requirements for the cell (more activity = burning more energy). This need for energy would put pressure on the mitochondria (the power stations of the cell) to supply more energy (in the form of ATP). Increased ATP production, however, would result in the increased production of oxidative stress species, and – if this is not carefully controlled for – this could put a lot of stress on cells in the brain and potentially lead to cell death.

They tested this idea in another follow up study that was published in 2018:

Title: Abnormal visual gain control and excitotoxicity in early-onset Parkinson’s disease Drosophila models.
Authors: Himmelberg MM, West RJH, Elliott CJH, Wade AR.
Journal: J Neurophysiol. 2018 Mar 1;119(3):957-970.
PMID: 29142100                      (This article is OPEN ACCESS if you would like to read it)

In this study, the researchers took their flies with genetic mutations associated with early-onset forms of Parkinson’s and they generated additional neuronal stress by exposing those flies to randomly pulsating light for 7 days. This increased the level of activity for the cells would put extra pressure on the energy requirements of the cells. And the investigators found that this exposure to the pulsating lights resulted in a profound loss of vision at a later stage of life in all of the flies with genetic mutations associated with early-onset forms of Parkinson’s.

This result supports the idea of a ‘excitotoxicity theory’ of Parkinson’s in some of these genetic forms of the condition. It also supports the idea that these mutations may be linked to advantages (more sensitive neuronal signalling) in the early life, which may cause may not be so advantageous later in life.

And the idea of PD-associated genetic risk factors being potentially ‘advantageous’ could partly explain why some of these genetic mutations (which increase risk of developing Parkinson’s later in life) have lasted so long across human history (for example, the LRRK2-G2019S variant has existed for over 2000 years and has two distinct origins – click here to read more about this).

These results could also explain why high IQ in young Swedish arm recruits is associated with a higher risk of Parkinson’s later in  life. Supporting this concept, the investigators who conducted the fly research suggested that their findings could explain why we see a higher incidence of Parkinson’s in people with higher socioeconomic status jobs (Click here to read more about this).

 

# # RECAP #2:  Smoking is negatively associated with both IQ and Parkinson’s, which may explain the link between high IQ and Parkinson’s in Swedish army recruits. But genetic varitions in Parkinson’s associated regions of our DNA may provide an alternative interpretation. PD-associated genetic risk factors have been reported to infer beneficial properties at a young age in flies, which diminish over time. # #

What did you mean “we see a higher incidence of Parkinson’s in people with higher socioeconomic status jobs”?

In 2017, this research report was published:

Title: Mortality from Amyotrophic Lateral Sclerosis and Parkinson’s Disease Among Different Occupation Groups – United States, 1985-2011.
Authors: Beard JD, Steege AL, Ju J, Lu J, Luckhaupt SE, Schubauer-Berigan MK.
Journal: MMWR Morb Mortal Wkly Rep. 2017 Jul 14;66(27):718-722.
PMID: 28704346          (This article is OPEN ACCESS if you would like to read it)

In this study, the researchers used data from the CDC’s National Institute for Occupational Safety and Health (NIOSH) database called the National Occupational Mortality Surveillance (NOMS). NOMS is a US-based program that monitors work-related acute and chronic disease mortality among workers in 30 U.S. states. The database contains information associated with approximately 12.1 million deaths.

In total, there were 26,917 deaths associated with Amyotrophic Lateral Sclerosis and 115,262 deaths associated with Parkinson’s. The occupations of the deceased were grouped into 26 categories based on similarities of job duties and ordered roughly from high socioeconomic status (e.g., legal, finance, management) to lower socioeconomic roles (e.g., construction, transportation and material moving).

After accounting for age, sex, and race, the investigators found that occupations associated with higher socioeconomic status (such as computer and mathematical; Legal; Life, physical, and social sciences) were particularly elevated in people that passed away with Amyotrophic Lateral Sclerosis and Parkinson’s (Click here to see the full list).

And curiously, 11 occupation categories were significantly not associated with Parkinson’s. They were generally lower socioeconomically associated categories, and they included:

• Building and grounds cleaning and maintenance
• Protective service
• Food preparation and serving
• Transportation and material moving
• Installation, maintenance, and repair

And one in particular – called ‘extraction‘ [involving mining or oil and gas drilling] – was particularly not associated with Parkinson’s.

Interesting, but this was just one study right?

Actually no. This observation keeps popping up in other reports. For example:

Title: Occupational complexity and risk of Parkinson’s disease.
Authors: Valdés EG, Andel R, Sieurin J, Feldman AL, Edwards JD, Långström N, Gatz M, Wirdefeldt K.
Journal: PLoS One. 2014 Sep 8;9(9):e106676.
PMID: 25198429              (This article is OPEN ACCESS if you would like to read it)

In this study, the investigators used the Swedish Twin Registry that included 28,778 twins (born between 1886 and 1950 – what did we say about Scandinavians loving their registries!). They identified 433 cases of Parkinson’s. When they assessed occupations, they found that high occupational complexity (with data and people) was associated with increased risk of Parkinson’s, particularly in men.

And there are other previous research reports supporting the idea of more complex occupations being associated with an increased risk of Parkinson’s (Click here and here to see two other examples). So perhaps there is some evidence that people at risk of Parkinson’s have intellectual advantages in younger life while they are being educated and trained for a career in a high socioeconomic occupation. Maybe there is some sort of ‘evolutionary advantage’ to some of the genetic risk factors and modifiers that are associated with Parkinson’s.

Mother nature is still rolling her dice, but unfortunately somebody forgot to tell her that we are all living longer.

So what does it all mean?

Charles Darwin. Source: rmg

Charles Darwin didn’t teach us ‘evolution’.

Jean-Baptiste Lamarck can lay claim to that.

Nor did Darwin come up with “Survival of the fittest”. That classic belongs to Herbert Spencer.

No, what Darwin taught us is the importance of context.

It is only when the context of an organism’s situation changes that the full outcomes of certain traits become apparent, and either more or less desirable. So while it is possible that some of these Parkinson’s-associated genetic mutations may be resulting in faster and stronger neuronal signalling in the first half of a human life span – which could be advantageous – as we have gradually started to live longer (and the context changed), these traits have become less desirable. During the first centuries BC and the first centuries AD, the average life span was about 35 years, which meant that these the downside to these genetic variants which increase one’s risk of developing Parkinson’s were largely irrelevant.

It will be interesting to see if other research groups can replicate and expand on the genetic fly work discussed in this post (perhaps in other parts of the brain or body). In addition, it would be fascinating if the Swedish army IQ data can be replicated across other military databases.

There has been a bit of speculation in this post, but hopefully it has been of interest.

 

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