Inflammation links ageing to the brain.

Gabuzda et al. do a nice review of work by Zhang et al., that suggests that manipulation of hypothalamus regulation, and especially levels of the hormone GnRH (gonadotropin-releasing hormone) might abrogate some effects of ageing.  I want to pass on several clips from their summary:

One of the least-understood aspects of ageing is its coordinated and stereotyped progression in all organ systems. Although researchers have long suspected that the brain orchestrates systemic ageing, compelling evidence of this in mammals has been lacking. Furthermore, we have had no clear understanding of how ageing is affected by inflammation, which is a hallmark of age-related diseases such as diabetes, cardiovascular disease, arthritis and Alzheimer's disease. Zhang et al. help to make this connection by documenting the integration of inflammatory responses with systemic control of ageing by the hypothalamus — a part of the brain that controls growth, reproduction and metabolism.

FIGURE - Zhang et al. report that inflammation leads to activation of the signalling molecule NF-κB in the hypothalamus of the brain, and suggest that this contributes to the control of systemic ageing. They show that NF-κB activation in hypothalamic cells called microglia results in production of TNF-α, which, in turn, stimulates NF-κB activity in nearby neurons. This signalling results in epigenetic repression of the gene that encodes gonadotropin-releasing hormone (GnRH), leading to reduced GnRH release from the neurons, which is associated with multiple physiological changes related to ageing, including bone loss, skin atrophy, muscle weakness and memory loss. This pathway might also mediate the effects of a variety of environmental and physiological stressors.

'Inflammageing' describes the close relationship between low-grade chronic inflammation and ageing that has been linked to a wide spectrum of age-related disorders in various organs, including the brain6. Healthy ageing and longevity could relate, in part, to reduced levels of inflammation or strong protective mechanisms that guard against adverse effects of chronic inflammation. Conversely, genetic and environmental factors that promote inflammation or disrupt the mechanisms involved in reducing inflammation seem to confer increased susceptibility to 'accelerated ageing' and age-related disorders such as insulin resistance, metabolic disorders and cardiovascular disease7. Accelerated ageing typically involves multiple organ systems, although the effects in some organs might not be seen as clinical symptoms.

In addition to the classical activity of GnRH in regulating the release of sex steroids involved in development and reproduction (oestrogens and progesterone in females and androgens in males), the hormone might also mediate other functions12. Notably, Zhang et al. found that when mice were administered GnRH, it abrogated ageing effects and increased the production of new neurons in the hypothalamus and hippocampus (a part of the brain that regulates memory). By contrast, sex steroids did not have these anti-ageing effects. A decrease in gonadal sex steroids is a well-established marker of ageing, but many other hormonal changes occur as well; and some of these age-regulated hormones (such as dehydroepiandrosterone) also regulate inflammation and other immune responses. Thus, interplay between the hormonal and immune systems occurs at multiple levels.

How might hypothalamic regulation of ageing have evolved? Chronic inflammation arises from many kinds of insult, from acute infection to genomic instability. The concept that the hypothalamus can sense inflammation through immune pathways is a new one; just as the hypothalamus responds to nutrient status, its response to inflammation may enable the organism to rapidly adapt to physiological perturbations. Turning down the hypothalamic release of modulators such as GnRH to prevent reproduction and reduce growth may be evolutionarily advantageous during acute infection, injury or deprivation. Although this would have been adaptive for our shorter-lived ancestors, it may accelerate ageing in older individuals and have become apparent now that we live longer. This idea also raises the intriguing possibility that hypothalamic regulation could be therapeutically manipulated to have broad effects on the ageing process and age-related pathology.

A spiritual home for atheists.

For many of us secular humanists, agnostics, or atheists, life after our alienation from conventional religious congregations that offer prayers to an anthropomorphic god (or gods) ends up feeling a bit rye-crispy. We lose also the sense of belonging and community that was part of the experience of being in a church congregation. Thus I was struck by this article about a former Pentecostal minister who has started in Baton Rouge, LA., to offer atheist services with impassioned sermons, singing and light swaying, exhortations to service, etc., everything but God! Jerry DeWitt, who was raised as a pentecostal and served 25 years as a minister, now offers an emotional counterpoint to more academic atheist exponents like Richard Dawkins and Christopher Hitchens. While other non-deistic spiritual congregations now exist, especially in many larger urban areas ( usually with some mix or mysticism, new age rituals, or religious-scientific components) I doubt that many of them get quite as close to reproducing the gut-wrenching intensity of DeWitt’s pentecostal service minus God!

Linking brain imaging to our subjective experience - focused attention versus mind-wandering

An interesting study from Garrison et al at Yale:

Recent advances in brain imaging have improved the measure of neural processes related to perceptual, cognitive and affective functions, yet the relation between brain activity and subjective experience remains poorly characterized. In part, it is a challenge to obtain reliable accounts of participant's experience in such studies. Here we addressed this limitation by utilizing experienced meditators who are expert in introspection. We tested a novel method to link objective and subjective data, using real-time fMRI (rt-fMRI) to provide participants with feedback of their own brain activity during an ongoing task. We provided real-time feedback during a focused attention task from the posterior cingulate cortex, a hub of the default mode network shown to be activated during mind-wandering and deactivated during meditation. In a first experiment, both meditators and non-meditators reported significant correspondence between the feedback graph and their subjective experience of focused attention and mind-wandering. When instructed to volitionally decrease the feedback graph, meditators, but not non-meditators, showed significant deactivation of the posterior cingulate cortex. We were able to replicate these results in a separate group of meditators using a novel step-wise rt-fMRI discovery protocol in which participants were not provided with prior knowledge of the expected relationship between their experience and the feedback graph (i.e., focused attention versus mind-wandering). These findings support the feasibility of using rt-fMRI to link objective measures of brain activity with reports of ongoing subjective experience in cognitive neuroscience research, and demonstrate the generalization of expertise in introspective awareness to novel contexts.

Enhanced emotion regulation persists after meditation training.

Desbordes and collaborators have looked at the effects of training in both mindful attention meditation and compassion meditation in two groups of subject with no previous experience meditating enrolled in 8-week training courses in both. 12 participants from each group reacted to images of people in situations with positive, negative, or neutral emotional content during fMRI measurements made during three weeks before or at three weeks after the training sessions. From the review in The Harvard Gazette:

In the mindful attention group, the after-training brain scans showed a decrease in activation in the right amygdala in response to all images, supporting the hypothesis that meditation can improve emotional stability and response to stress. In the compassion meditation group, right amygdala activity also decreased in response to positive or neutral images. But among those who reported practicing compassion meditation most frequently outside of the training sessions, right amygdala activity tended to increase in response to negative images, all of which depicted some form of human suffering. No significant changes were seen in the control group or in the left amygdala of any study participants.

The Harm-Made Mind

Here is a fascinating bit from Daniel Wegner and his collaborators. (I cite Wegner extensively in my "I-Illusion" web-lecture in introductory lectures sections of the left had column of this web page.)

People often think that something must have a mind to be part of a moral interaction. However, the present research suggests that minds do not create morality but that morality creates minds. In four experiments, we found that observing intentional harm to an unconscious entity—a vegetative patient, a robot, or a corpse—leads to augmented attribution of mind to that entity. A fifth experiment reconciled these results with extant research on dehumanization by showing that observing the victimization of conscious entities leads to reduced attribution of mind to those entities. Taken together, these experiments suggest that the effects of victimization vary according to victims’ preexisting mental status and that people often make an intuitive cognitive error when unconscious entities are placed in harm’s way. People assume that if apparent moral harm occurs, then there must be someone there to experience that harm—a harm-made mind. These findings have implications for political policies concerning right-to-life issues.

Are you married? Did you meet on-line or off-line?

Interesting bit from Cacioppo et al.

Marital discord is costly to children, families, and communities. The advent of the Internet, social networking, and on-line dating has affected how people meet future spouses, but little is known about the prevalence or outcomes of these marriages or the demographics of those involved. We addressed these questions in a nationally representative sample of 19,131 respondents who married between 2005 and 2012. Results indicate that more than one-third of marriages in America now begin on-line. In addition, marriages that began on-line, when compared with those that began through traditional off-line venues, were slightly less likely to result in a marital break-up (separation or divorce) and were associated with slightly higher marital satisfaction among those respondents who remained married. Demographic differences were identified between respondents who met their spouse through on-line vs. traditional off-line venues, but the findings for marital break-up and marital satisfaction remained significant after statistically controlling for these differences. These data suggest that the Internet may be altering the dynamics and outcomes of marriage itself.

Brain science backlash, throwing out the baby with the bathwater.

A recent NYTimes Op-Ed piece by David Brooks' ("Beyond the Brain") references the recent book "“Brainwashed: The Seductive Appeal of Mindless Neuroscience.” a book that appropriately notes some of the limitations of zealous over interpretation of brain imaging data but also includes some facile straw man arguments. Brooks kind of loses it in his comment:

It is probably impossible to look at a map of brain activity and predict or even understand the emotions, reactions, hopes and desires of the mind...there appears to be no dispersed pattern of activation that we can look at and say, “That person is experiencing hatred."

These sentiments are simply wrong, and I thought, rather than rambling on myself, I would point interested readers to two cogent commentaries on the recent anti-brain science surge, one in The New Yorker blog posted by Gary Marcus, the other in The Neurocritic blog.

Paternal stress changes stress axis in offspring

A study from Bale and colleagues shows that stress on preadolescent and adult male mice induces an epigenetic mark in their sperm that reprogramms their offspring's hypothalamic-pituitary-adrenal (HPA) axis, the brain regions that governs responses to stress. Offspring from paternal stress groups displayed significantly blunted levels of the stress hormone corticosterone -- in humans, it's cortisol -- in response to stress. It is curious that both male and female offspring had abnormally low reactivity to stress. Perhaps this reduced physiological stress response may reflect some adaptive evolutionary benefit passed on to offspring to ensure survival in what is expected to be a more stressful environment.

Neuropsychiatric disease frequently presents with an underlying hyporeactivity or hyperreactivity of the HPA stress axis, suggesting an exceptional vulnerability of this circuitry to external perturbations. Parental lifetime exposures to environmental challenges are associated with increased offspring neuropsychiatric disease risk, and likely contribute to stress dysregulation. While maternal influences have been extensively examined, much less is known regarding the specific role of paternal factors. To investigate the potential mechanisms by which paternal stress may contribute to offspring hypothalamic–pituitary–adrenal (HPA) axis dysregulation, we exposed mice to 6 weeks of chronic stress before breeding. As epidemiological studies support variation in paternal germ cell susceptibility to reprogramming across the lifespan, male stress exposure occurred either throughout puberty or in adulthood. Remarkably, offspring of sires from both paternal stress groups displayed significantly reduced HPA stress axis responsivity. Gene set enrichment analyses in offspring stress regulating brain regions, the paraventricular nucleus (PVN) and the bed nucleus of stria terminalis, revealed global pattern changes in transcription suggestive of epigenetic reprogramming and consistent with altered offspring stress responsivity, including increased expression of glucocorticoid-responsive genes in the PVN. In examining potential epigenetic mechanisms of germ cell transmission, we found robust changes in sperm microRNA (miR) content, where nine specific miRs were significantly increased in both paternal stress groups. Overall, these results demonstrate that paternal experience across the lifespan can induce germ cell epigenetic reprogramming and impact offspring HPA stress axis regulation, and may therefore offer novel insight into factors influencing neuropsychiatric disease risk.

Paper is not dead...

Sorry to spam you, but particularly after yesterday's post about smartphone apps I thought this was hysterical.

More on smartphone brain training apps.

This post is just a quickie pointer to update the series of posts I have done on smart phone or PC apps that give your brain a workout.  It reviews several current products.  I try each new iteration for a bit,  but then fade because I am phobic about "competing" with myself or anyone else and also get concerned that my scores are not improving fast enough.  I didn't grow up in a video game playing world, and they feel too much like hard work - I like things that feel easy with the skills I have,  like learning a new piano score. 

Neuroimaging our self esteem - be happy!

There are more papers coming out on brain correlates of whatever aspect of our behaviors you care to name than anyone could possibly keep up with. I have the ‘my eyes glaze over’ experience in just scanning tables of contents of the relevant journals. Occasionally an item pops out that grabs my attention, such as this one (open access) on imaging brain correlates of self esteem. The drums continue to beat (see this book review) on how important a positive self image and an "Up" attitude are for health and longevity. Maybe someone will develop some kind of magnetic zapper that we can shoot ourselves up with whenever whenever we are feeling like a piece of …... 

Although neuroimaging studies strongly implicate the medial prefrontal cortex (ventral and dorsal), cingulate gyrus (anterior and posterior), precuneus and temporoparietal cortex in mediating self-referential processing (SRP), little is known about the neural bases mediating individual differences in valenced SRP, that is, processes intrinsic to self-esteem. This study investigated the neural correlates of experimentally engendered valenced SRP via the Visual–Verbal Self-Other Referential Processing Task in 20 women with fMRI. Participants viewed pictures of themselves or unknown other women during separate trials while covertly rehearsing ‘I am’ or ‘She is’, followed by reading valenced trait adjectives, thus variably associating the self/other with positivity/negativity. Response within dorsal and ventral medial prefrontal cortex, cingulate cortex and left temporoparietal cortex varied with individual differences in both pre-task rated self-descriptiveness of the words, as well as task-induced affective responses. Results are discussed as they relate to a social cognitive and affective neuroscience view of self-esteem.

.... stimulus presentations were blocked in terms of the conditions Reference (Self vs Other, i.e. photographs) and Valence (words), creating four trial types: self-negative (S-N), self-positive (S-P), other-negative (O-N) and other-positive (O-P). Participants were not instructed that they ‘should try to press the buttons as fast as possible’ as is often done in social cognition experiments. In contrast, participants were instructed only to press the buttons ‘so that we can assess afterwards whether you are paying attention to and completing the task’. This passive orientation was intended to focus attention towards introspection and interoception with participants reminded repeatedly of the importance of ‘paying close attention to how you are feeling throughout the different parts of the task’.

Young blood makes younger hearts (and brains) - also, aging resistant brains

I've previously mentioned work showing that providing young blood to an older brain can be beneficial, and now want to note work by Loffredo et al. that shows that exposure to a young circulation reverses age-related cardiac hypertrophy, which is a prominent feature of age-related diatolic heart failure. The TGFβ family member GDF11 appears to be the crucial circulating factor that declines with age; restoring GDF11 to youthful levels reverses age-related cardiac hypertrophy. 

Also, relevant to aging, I might note a longitudinal study by Pudas et al. comparing MRI data from elderly people most successful in preserving episodic memory and ability on paired association tasks with measurements on average contemporaries. The results suggest that successful cognitive aging is associated with preservation of the responsiveness of the hippocampus and prefrontal cortex.

Heart rate variability, ANS aging - a new device from "Phyode" - therapeutic agent or scam??

I want to put in this post a comment by reader "Andre" on my June 11 post ("Changes as an autonomic nervous system ages 11 years - The "Wild Divine" is a bit less wild.", along with my response.

Last week I backed a Kickstarter project from Phyode called the W/Me (http://goo.gl/en1Ea), a smartwatch that uses HRV and "ANS Age" as its primary markers for assessing the user's "mental state". I couldn't find a research precedent for using ANS aging for this purpose until your post came up in a Google search. Do you think Phyode's methodology is valid?

My response on looking at the website:

This is a very slick presentation, and looks like a potentially interesting product...If it were not for the fact that its development appears to be limited to Android products (i.e. no iPhone App)[NOTE! 10/22/13 - comment below says I'm wrong, it is for iPhone, not Android, my bad..] I would probably try it out when it is sold (There are, by the way several iPhone apps that do heart rate, HRV, etc.).....BUT, there are no pointers to basic scientific references on heart rate variability, ANS age, how it can be therapeutically altered in a beneficial way, or how his device would be used to do that. The FAQ section at the end of the web page with what look like links to such items as "What is HRV?" don't link to anything!! The Phyode "Full bio and links" doesn't yield anything significant! I would be interested in seeing something a bit more substantial from the people in the flashy video presentations (all appear to be 20-somethings, by the way). I don't want to play the complete nasty guy here, because a lot of effort went into the slick videos and description, and they look plausible, but what assures us that the fund raising "Back this project" (minimum donation $1.00) is not a scam? Does the Kickstarter cloud funding site that hosts this webpage have any quality controls or review criteria?? The "report this site to Kickstarter" link takes you to a page that requires you to join or be member of Kickstarter, and I'm not inclined to take that much time on this....

Carrying human (and mouse) babies reduces their crying and heart rate.

Esposito et al. present some really nice observations. They demonstrate for the first time that the infant calming response to maternal carrying is a coordinated set of central, motor, and cardiac regulations and is a conserved component of mammalian mother-infant interactions. You should watch the video.


-Maternal carrying reduces crying, body movement, and heart rate of infants
-In mice, a similar set of calming responses is observed during carrying
 -Mouse calming response requires proprioception and somatosensation
 -The calming responses in infants function to increase maternal carrying efficacy

Here we show a novel set of infant cooperative responses during maternal carrying. Infants under 6 months of age carried by a walking mother immediately stopped voluntary movement and crying and exhibited a rapid heart rate decrease, compared with holding by a sitting mother. Furthermore, we identified strikingly similar responses in mouse pups as defined by immobility and diminished ultrasonic vocalizations and heart rate. Using pharmacologic and genetic interventions in mouse pups, we identified the upstream and downstream neural systems regulating the calming response. Somatosensory and proprioceptive input signaling are required for induction, and parasympathetic and cerebellar functions mediate cardiac and motor output, respectively. The loss of the calming response hindered maternal rescue of the pups, suggesting a functional significance for the identified calming response.

Our memory can be selectively rewritten during its reconsolidation.

Chan and LaPaglia make an interesting observation in humans that had previously only been reported in animal studies. We can mess with an existing declarative memory of an event after that memory has been reactivated, if during its reconsolidation we are presented with changes that target and change some details of the original memory. Reactivated memories are vulnerable only to interference that specifically targets the existing memories. This work provides yet another example of how eye witness testimony of the sort used in legal proceedings can become unreliable.

During the past decade, a large body of research has shown that memory traces can become labile upon retrieval and must be restabilized. Critically, interrupting this reconsolidation process can abolish a previously stable memory. Although a large number of studies have demonstrated this reconsolidation associated amnesia in nonhuman animals, the evidence for its occurrence in humans is far less compelling, especially with regard to declarative memory. In fact, reactivating a declarative memory often makes it more robust and less susceptible to subsequent disruptions. Here we show that existing declarative memories can be selectively impaired by using a noninvasive retrieval–relearning technique. In six experiments, we show that this reconsolidation-associated amnesia can be achieved 48 h after formation of the original memory, but only if relearning occurred soon after retrieval. Furthermore, the amnesic effect persists for at least 24 h, cannot be attributed solely to source confusion and is attainable only when relearning targets specific existing memories for impairment. These results demonstrate that human declarative memory can be selectively rewritten during reconsolidation.

Antonin Scalia Does Not Believe in Molecular Biology

Thanks to my son Jon for pointing this out to me.

Private behaviors from public records...

The exposure of the PRISM surveillance system by Edward Snowden gave me a sort of "So what else is new?" reaction... I thought we knew this unfortunate stuff was happening, particularly in view of numerous academic articles in the vein of the following from Kosinski et al.:

We show that easily accessible digital records of behavior, Facebook Likes, can be used to automatically and accurately predict a range of highly sensitive personal attributes including: sexual orientation, ethnicity, religious and political views, personality traits, intelligence, happiness, use of addictive substances, parental separation, age, and gender. The analysis presented is based on a dataset of over 58,000 volunteers who provided their Facebook Likes, detailed demographic profiles, and the results of several psychometric tests. The proposed model uses dimensionality reduction for preprocessing the Likes data, which are then entered into logistic/linear regression to predict individual psychodemographic profiles from Likes. The model correctly discriminates between homosexual and heterosexual men in 88% of cases, African Americans and Caucasian Americans in 95% of cases, and between Democrat and Republican in 85% of cases. For the personality trait “Openness,” prediction accuracy is close to the test–retest accuracy of a standard personality test. We give examples of associations between attributes and Likes and discuss implications for online personalization and privacy.

Changes as an autonomic nervous system ages 11 years - The "Wild Divine" is a bit less wild.

Just after I retired from being a Univ. of Wisconsin department chair in 2001 I bought a set of finger sensors that fit on one's three middle fingers to report skin conductance and heartbeat to a PC or MAC via an A/D converter. These were part of a package with several CDs that installed a new age game on the computer that lead you through a rich environment of classical greek temples and waterfalls, attended by soothing music, that presented tasks in which you dinked with your own heart rate variability and sympathetic (arousing)/parasympathetic (calming) balance, going alternatively through periods of calm and arousal. I thought it was a hoot, and took the time to go through the "Journey to Wild Divine: passage" and "Journey to Wild Divine: Wisdom Quest."

Some of the current incarnations of these programs have moved to web browsers. Over the years a number of heavy weight new age gurus have signed on with their wares - Deepak Chopra, Dean Ornish, and Andrew Weil (Weil was in my Harvard graduating class...I'm tempted, but I won't burden you with my jaded opinion of this class of entrepreneurs, particularly Mr. Chopra.)

The main point of this post is note my experience on pulling out the finger sensors after 11 years trying the same exercises in their new presentation. What's the difference when this 71 year old tries the same manipulations of calm and arousal that the 60 year old played with with 11 years earlier? In a nutshell, I have less command over heart rate variability, which is lower, as the swings between calm and arousal have less amplitude.

And indeed, this fits with the literature on changes in the autonomic nervous system that occur on aging. If you simply do a google search for "autonomic nervous system and aging" numerous references appear that document how healthy aging is associated with lowered heart rate variability, elevated basal sympathetic nervous activity, and reduction of overall autonomic reactivity of sympathetic and parasympathetic nervous systems. Here is a very recent review, from which I pass on one figure:

Schematic of proposed features associated with the imbalance in the autonomic nervous system during aging. During aging there is a shift in the balance of the autonomic nervous system (ANS) towards the sympathetic nervous system (SNS). This may be influenced by circulating or local brain levels of angiotensin (Ang) II and leptin. The lower activity of the parasympathetic nervous system (PSNS) is proposed to result at least in part from an age-related decline in Angiotensin-(1–7). Lower Angiotensin-(1–7) and higher Ang II or leptin in the brain medulla would predispose to a decline in baroreceptor reflex sensitivity (BRS) for control of heart rate and heart rate variability (HRV), both of which are associated with aging. Moreover, impairments in BRS and HRV can contribute to target organ damage, including metabolic dysfunction, with or without an increase in blood pressure. 

If you're inclined, like Mr. Dylan Thomas, to not "go gently into that good night" you can find numerous sources (example here) on slowing these aging changes, usually by some sort of physical movement or stimulation.

Preventing Alzheimer’s associated brain cell atrophy with B vitamin treatment.

I pass this on because it seems like a very striking result. Douaud et al. find that high-dose B-vitamin treatment (folic acid 0.8 mg, vitamin B6 20 mg, vitamin B12 0.5 mg) causes a 7-fold decrease in cerebral atrophy of nerve cell areas most vulnerable to the Alzheimer's process over a 2-year period in a group of elderly subjects with increased dementia risk. (For comparison, Centrum Silver 50+ has Folic Acid 0.4 mg, Vitamin B6 3 mg, and Vitamin B12 0.025 mg.) The supplements decrease plasma levels of one of the bad players in the Alzheimer's story, homocysteine. (Homocysteine is a homologue of the amino acid cysteine,and can be recycled into methionine or converted into cysteine with the aid of B-vitamins.) Here's the abstract:

Is it possible to prevent atrophy of key brain regions related to cognitive decline and Alzheimer’s disease (AD)? One approach is to modify nongenetic risk factors, for instance by lowering elevated plasma homocysteine using B vitamins. In an initial, randomized controlled study on elderly subjects with increased dementia risk (mild cognitive impairment according to 2004 Petersen criteria), we showed that high-dose B-vitamin treatment (folic acid 0.8 mg, vitamin B6 20 mg, vitamin B12 0.5 mg) slowed shrinkage of the whole brain volume over 2 y. Here, we go further by demonstrating that B-vitamin treatment reduces, by as much as seven fold, the cerebral atrophy in those gray matter (GM) regions specifically vulnerable to the AD process, including the medial temporal lobe. In the placebo group, higher homocysteine levels at baseline are associated with faster GM atrophy, but this deleterious effect is largely prevented by B-vitamin treatment. We additionally show that the beneficial effect of B vitamins is confined to participants with high homocysteine (above the median, 11 µmol/L) and that, in these participants, a causal Bayesian network analysis indicates the following chain of events: B vitamins lower homocysteine, which directly leads to a decrease in GM atrophy, thereby slowing cognitive decline. Our results show that B-vitamin supplementation can slow the atrophy of specific brain regions that are a key component of the AD process and that are associated with cognitive decline. Further B-vitamin supplementation trials focusing on elderly subjets with high homocysteine levels are warranted to see if progression to dementia can be prevented.

Here is one figure from the paper:

B-vitamin treatment significantly reduces regional loss of gray matter. (A) Brain regions in blue demonstrate where B-vitamin treatment significantly reduces GM loss over the 2-y period. All blue areas correspond to regions of significant loss in placebo and known to be vulnerable in AD. (B) Percentage of GM loss for the 156 participants over the 2-y period, averaged across those brain regions that showed significant effect of B vitamins: placebo group (red triangles) had an average loss of 3.7% (±3.7), whereas the B-vitamin group (green circles) showed a loss of 0.5% (±2.9).

Visions of our high-tech future: Julian Assange, Jaron Lanier, et al. on Google, Siren servers and the banality of ‘Don’t Be Evil’

The book by Google's Eric Schmidt and Jared Cohen, "The New Digital Age" is a rosy scenario of our high-tech future that many have found a bit creepy and chilling. Since our techie surround will anticipate and take care of our every movement, it seems like we can just sign off and go along for the ride (turning in mental vegetables in the process? …and letting the rule of 'use it or lose it' do it's work on our poor brains?). Also, is it more than a coincidence that at roughly the same time as Schmidt's messianic book is appearing, the movie “The Internship,” a two-hour commercial for GoogleWorld masquerading as an aspirational buddy comedy, also appears in the movie theaters? (You might note this caustic review of the movie.)

Trying to set aside my bias, generated by extensive negative press comments on the behaviors of Wiki-Leaks' Julian Assange, I found his piece in the New York Times on the Schmidt and Cohen book to have some savory and choice screeds. A partial sampling:

“The New Digital Age” is, beyond anything else, an attempt by Google to position itself as America’s geopolitical visionary — the one company that can answer the question “Where should America go?” It is not surprising that a respectable cast of the world’s most famous warmongers has been trotted out to give its stamp of approval to this enticement to Western soft power. The acknowledgments give pride of place to Henry Kissinger, who along with Tony Blair and the former C.I.A. director Michael Hayden provided advance praise for the book.

…“Progress” is driven by the inexorable spread of American consumer technology over the surface of the earth. Already, every day, another million or so Google-run mobile devices are activated. Google will interpose itself, and hence the United States government, between the communications of every human being not in China (naughty China). Commodities just become more marvelous; young, urban professionals sleep, work and shop with greater ease and comfort; democracy is insidiously subverted by technologies of surveillance, and control is enthusiastically rebranded as “participation”; and our present world order of systematized domination, intimidation and oppression continues, unmentioned, unafflicted or only faintly perturbed.

This book is a balefully seminal work in which neither author has the language to see, much less to express, the titanic centralizing evil they are constructing. “What Lockheed Martin was to the 20th century,” they tell us, “technology and cybersecurity companies will be to the 21st.” Without even understanding how, they have updated and seamlessly implemented George Orwell’s prophecy. If you want a vision of the future, imagine Washington-backed Google Glasses strapped onto vacant human faces — forever. Zealots of the cult of consumer technology will find little to inspire them here, not that they ever seem to need it. But this is essential reading for anyone caught up in the struggle for the future, in view of one simple imperative: Know your enemy.

If you want to read what I think is one of the best articles I have seen so far on the unfortunate consequences of our digital universe and possible cures, check out Jaron Lanier's article "Fixing the Digital Economy." It describes the concentration of power and income in the small sliver of the population that designs and runs the massive servers (Siren servers) that analyze different sectors of our lives to minimize their risk and maximize their profits.

Even friendly, consumer-facing Siren Servers ultimately depend on spreading costs to the larger society. Siren Servers can function profitably only if people aren’t paid for the data that is used to calculate their statistical schemes.

Siren Servers drive apart our identities as consumers and workers. In some cases, causality is apparent: free music downloads are great but throw musicians out of work. Free college courses are all the fad, but tenured professorships are disappearing. Free news proliferates, but money for investigative and foreign reporting is drying up. One can easily see this trend extending to the industries of the future, like 3-D printing and renewable energy.

Lanier suggests that we need to nurture a middle class that can thrive even in a highly automated society. One approach:

Institute a universal micropayment system. Keep track of where information came from. Pay people when information that exists because they exist turns out to be valuable, no matter what kind of information is involved or whether a person intended to provide it or not. Let the price be determined by markets.

Person-to-person information markets might lead to a simpler and clearer online world. Because our information systems are designed to initially forget who provided information, services like Google and Bing must constantly scrape the global network to reconstitute the context of data. Siren Servers know who links to your data, but you don’t.

EVEN today’s titanic Siren Servers would benefit from a more monetized information economy, because it would be a healthier-growing economy. The information economy cannot exhibit the long-term growth it ought to if information coming from ordinary people is forever declared to be off the books.

Skeptics sometimes reveal hidden and unfounded wells of elitism. These surface in comments like: “Most people wouldn’t contribute very much.” But there are already empirical hints to counter such pessimism.

In networks with a central point of control, like YouTube or the Apple Store, we do see a Horatio Alger pattern in the distribution of outcomes, where there are very few viable winners and an unbounded number of hopefuls. But in more directly and thickly connected networks like Facebook, we see people typically exposed to a large number of other people, rather than just a few stars. Therefore, if Facebook users paid one another, they would see a less elite distribution of economic benefits.

Another potential benefit of monetized information is to balance the power of government. When information is free, there is no cost to gathering information about citizens. I would like the government, or anyone else, to pay each person each time that person is tracked by a camera. The government should be able to use cameras for security purposes, but in a limited, not unbounded way. Similarly, candidates should not be able to win elections by having the best Siren Servers, but that’s only a problem if the information is free. Citizens should not lose the power of the purse.

As a final note, this Douthat piece regarding the recently revealed NSA snooping on citizens mentions the fact that the problem isn’t that the Internet has been penetrated by the surveillance state; it’s that the Internet, in effect, is a surveillance state.