Thursday, July 28, 2011

The Incredible Shrinking Human Brain

Thanks to Tim who sent me the link to this Wall Street Journal article:

Brain Shrinkage:  It's Only Human

Yup.  Many parts wither as we age, our brains among them.  Octogenarians are liable to have brains 15% smaller than Justin Bieber's brain.  Imagine that!  Humans it seems are unique among primates in that we are longest-lived with the largest brains, and are also susceptible to neuropathology in the late stages of life, such as dementia.

There are several types of dementia, but even normal human aging is characterized by neural deterioration and cognitive impairment to some extent.  Various pathologies are common - amyloid beta deposits, neuron trees dying off, reduced synapse numbers, loss of specific receptors… these seem to occur specifically in areas that are part of learning, memory, and executive function.  Some of these same changes occur in other primate species whose members (rarely) get, well, senile.  There have been case reports of elderly gorillas or chimps with Alzheimer's like plaques and tangles.  So for a long time, scientists apparently assumed that as a large extended family, our big primate brains kinda sputter out at the end, especially humans, with the biggest and longest-lived brain.

The (free for now) WSJ  article reports on a new study done by Sherwood et al in PNAS, called Aging of the cerebral cortex differs between humans and chimpanzees.

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Sherwood and his compatriots had the bright idea to get brain MRIs of a bunch of humans (87) and a bunch of chimps (69) spanning a wide age range - in chimps, ages 10-51, in humans, ages 22-88.  And, sure enough, among the humans, there was significant shrinkage in every area of the brain measured.  But, surprisingly, no significant shrinkage among the chimps.   Boom.  Humans are very vulnerable to dementia (except, of course, the famous Kitavans - and I will get back to that later).  Chimps don't seem to be.

Now there are a few wrinkles to understand here. The age ranges of both humans and chimps were chosen for the study by how long humans and chimps are expected to live (if they don't get killed in an accident or illness) in the wild - about 45 for chimps, and into the 80s for humans.  But, when the human data for this study were parsed out by age, it seems that all the major shrinkage occurred in the 7th and 8th decades of life, not before, and other human studies show there is minimal shrinking between ages 25 and 50, with accelerated shrinking thereafter.   This age is well above the age of any known chimpanzee in the wild.  One post-mortem study of captive chimps had a very minimal decline of brain size with age - the oldest captive chimp was 59.  Another study involving macaque monkeys (some 30 million years removed in lineage from humans, I believe) also showed no brain degeneration with age.

So… it would appear that humans are relatively unique in that our brains self destruct into a smokey inflammatory puddle of shrunken senility.  And we can't just say the chimps didn't get as old as we do - relatively speaking - they do.  Chimps start to slow down and become more physically frail with worn teeth in the 30s, though the females are fertile until nearly the end of the normal chimp lifespan.  Humans have a longer childhood and are generally still quite robust through the 30s and 40s, and women obviously hit menopause around age 50, followed by (generally) 2-3 more decades in a normal lifespan.  It is clear, then, that humans age more slowly than chimps.

Now, evolutionarily speaking, the authors of this paper throw out the grandmother hypothesis - humans clearly live long because there was a survival advantage among the grandchildren who had grandmothers around collecting food and passing on cultural knowledge.   But does that longevity have a cost unknown to other, grandmother-less primates?

As we well know, dementing brains have a build-up of protein aggregates and rely on the shoddy energy production of poorly functioning, reactive oxygen species-producing damaged mitochondria.  As we get older, our oxidative stress protection gene expression is upregulated - until I suppose it can be upregulated no more, and the cost of being a human with our big, energy hogging brains for so long is too high, and everything goes to hell in a hand basket.

The sticking point I have with this study?  Well, none of the subjects were "wild-type."  All the chimps were captives from the Yerkes National Primate Research Center in Atlanta.  The humans were volunteers, all right-handed, about equal numbers men and women, and all were healthy, with no psychiatric disorders, heart disease, hypertension, or diabetes.   I'm fairly convinced that Staffan Lindeberg did not take an MRI machine with him to Papua New Guinea.  So I don't know if the dementia-free Kitavans in the last century had shrinking brains.

So is dementia a human thing, the direct cost of being the brightest and longest-lived of all primates, design specs maxed out at a biochemical level?  Or is it a modern, industrial human thing, wrought from micronutrient deficiencies, infection, chronic hyperglycemia, and mucking around with our capability to produce cholesterol?  What do they feed those chimps in the Yerkes center, anyway?

I know what I think - what makes sense is that we aren't meant to become senile and a long-term survival burden as we age.  Okay, so maybe our big glorious brains are derived in part from sexual selection - thus an expensive ornament like a peacock's tail, meant to woo women, with a survival cost and not just survival benefit.  And yet… why evolve grandmothers just to have them get senile? The grandmother hypothesis would be completely backwards if our brains are just designed to slowly sputter out.  I don't have the proof - but my speculation is that true wild-type humans, even the very old, have robust brains too, like old chimps or gorillas.

A couple of other things before we go - today my podcast with Jimmy Moore came out - you can listen to it here (I remember saying I eat 18 eggs a week, which isn't true - my family eats about 18 eggs a week.  I eat about 12 of those :-) ) In any case it was a lot of fun talking to Jimmy.  He has an infectious enthusiasm.

And I have a couple new articles up at Psychology Today.  Please give them a click!

Sleep, Hyperactivity, and Behavior in Children

A Case of Scratchy Mice


  1. I definitely agree that we need to look at very healthy people to see if they have as much shrinkage. It is certainly possible to stay sharp for the entirety of a long life and we already know many ways to do it. After the bare essentials (like vanity!) I am mostly in this health thing for improvements in cognition and long-term brain health. All of that nasty neurodegenerative stuff scares me so I'm pulling out all the stops to avoid it.

    My grandmother is 91 and has dementia, but she has actually improved since seeing a nutritionist. Not sure if it was a paleo nutritionist but she is more like her old self.

    That interview with Jimmy was great. He sure knows how to pry the best out of people. The part about vitamin deficiencies causing mental illness was chilling.

    Will check out the Psychology Today posts too. Cheers.

  2. Your blog absolutely rocks! Keep posting so interesting articles as this one, I think you and the other guys out there are going to change the status of the scientific knowledge in a few years, investigating things like the connections between nutrition, diseases, aging and the brain. :-)

  3. I think the Yerkes chimps are fed Emory grad students. ;-)

  4. Time to pack up the MRI scanner and head for the South Pacific.

  5. Great post, Emily! My great-uncle is currently suffering from dementia, which is very sad to me. What to do once they are already suffering from dementia?

  6. This reminds me of a study that found less brain shrinkage in people taking a supplement of three common B vitamins. Study subjects had mild cognitive impairment at baseline. Here's a link to my blog post on it, if you don't mind:

    Unfortunately, the researchers didn't report whether cognitive function improved with vitamin therapy.

    Re: brain shrinkage of wild-type humans. I wonder if Paleolithic man tended to die off quicly after age 60. If so, they wouldn't have any adverse selection pressure linked to demented and shrunken brains. Modern humans live much longer thanks to better sanitation, medicine, surgery, technology, etc.

    -PS: I never knew you had a book published. I'm heading to STAT!

  7. Hi Steve - I think there are a lot of unknowns. I'm no anthropologist but a number of different lines of evidence come together to suggest a normal lifespan of around 80 - for example, the age at which humans get their adult molars (I think - maybe it's the first molars?) - anyway, that age, in primate species, has a direct ratio to ultimate lifespan. So I don't see why a human brain would start to shrink after 50 (accelerating at 70) and leave a bunch of demented elders wandering about. Sure, in the hard-living old days they might have been euthanized by the tribe or something - but I'm (obviously) very much struck by Staffan Lindeberg's descriptions of Kitavan elders being pretty strong and bright and useful right up until a few days before death, when they get tired and quietly die in their sleep - suggesting to me a central brainstem apnea mechanism that we see in Western humans too (when heart disease and cancer don't get you). Also no one on the island could remember anyone they knew who died, or descriptions of anyone who died, who had symptoms of dementia. Maybe it is a special Kitavan island thing - as Jaminet suggests, they might not have exposure to some of the long-term infections that hasten inflammatory damage, like chlamydia pneumonia or some of the herpes viruses. Or maybe it is all that coconut :) But I think your point is an important one and selection pressure would reasonably be less for grandparent health as opposed to parent health.

    Also, my book was written with my fabulous mentor Dr. Arthur Barsky back in 2003 and is about Health Anxiety, not about any of the stuff I write about on my blog. The nutrition chapter (I wrote) is something I no longer agree with. I should get in touch with my agent though. Maybe I have enough stuff now for a new book :) However - my old book is useful if you have patients or family members who need help coping with chronic symptoms.

  8. Nice to listen to you again Emily.

    You mention eating 12 eggs/week not 18.

  9. What about eating brains for omega3 and cholesterol instead of fish and fat?
    I hate the taste and texture of cow brain.
    Does cooking affect the nutrients?
    Also, I know in some places they prepare lysades.

  10. I did? Honestly the first thing I thought after finishing the interview was… did I say I eat 18 eggs a week? I don't do that… hah. I haven't had a moment to listen to it yet, but I will tonight!

  11. Gobbeldy - I think brains are a great source of a lot of nutrients, but I've never eaten them.

  12. About vitamins B: do you consider folic acid inadequate? I rad that one should use methylfolate

    Why L-Methylfolate Rather Than Folic Acid for Depression?

  13. Sorry, minute 29:59 you say: a dozen and a half = 18 Ididn´t hear "and a half".

  14. Gobbledy - my next project is folate. At issue is the fact that many of us do not have the enzymes (or have reduced capacity) to add the methyl groups we need to make active methylfolate. And excess folic acid itself may be toxic. There is a prescription vitamin methylfolate called deplin - as far as I am aware it has never been tested head to head vs folic acid. I do have some patients who have done much, much better on methylfolate (and a regular vitamin didn't do squat)

  15. What to make of this for brain health? Arachidonic Acid and mood (@4m48s neuroinflammation). I remember hearing about AA in Transcend

  16. Dr Deans, your interview with Jimmy Moore was excellent. Your medical background and willingness to share what you have learned is fantastic.
    On a egg note, I'm glad you clarified the 12-18 eggs per week comment! I thought 18 seemed "abut" high.
    Keep up the good work and I thoroughly enjoy your blog!

  17. Hey there,

    I've enjoyed your coverage the changing human brain. I recently just finished working on an infographic that looks at the shrinking human brain and explores interesting questions and statistics on the topic. I thought I would share it with you in the hopes you might make some use of it. Here's the link:

    Best Wishes,