By Pamela M. Greenwood and Raja Parasuraman MIT Press, 2012 Review by Roy Sugarman, PhD on Sep 4th 2012
By now, most readers will have been bombarded with the popular and scientific literature on ageing and obesity, sedentary behavior and diabetes, the risks of these to the brain and body. Visits to primary care practitioners for all of us who are ageing is the standard response that we must accept that (1) ageing is inevitable and (2) that decline is inevitable. Clearly from studies such as Snowdon's on the teaching order of the nuns of Notre Dame, this is not necessarily the case even if you accept that (1) is true, which it is.
Your eye will thus be immediately drawn to the chapter headings which include evidence for the fact that cognitive decline at least is not inevitable, nor is it a universal experience anyway, which supports the evidence that it is not built into our genes necessarily. Not news: it may very well be a lifestyle factor. The whole idea is that cognitive reserve can be accumulated by doing the right things, and that preservation of cognitive capacity, i.e. speed and accuracy=efficiency, is a matter of building and maintaining cognitive resilience to physical ageing processes.
The major factors as you will suspect immediately if you read any newspaper health section on paper or on the internet is that of building brain banks of cells by continuing education and new learning, exercise, diet, positive approaches to life and ageing, socializing and the avoidance of loneliness and so on.
Science rather than anecdotal evidence separates out the expert from the charlatan, and it is well accepted that stem cells, and hence neuroprotection and neuroplasticity are a part of ageing brains, and thus can be stimulated via epigenetic systems such as lifestyle interventions. Certain types of mental and physical activity have the capacity, along with food choices, to prolong an efficient cognitive system, even in the face of apparent physical loss of brain tissue, as Snowdon showed with his famous Sister Beatrice.
Both authors are from George Mason University and hence approach the evidence from the basis of their years of academic experience, and the seeming contradictions between cross-sectional vs. longitudinal studies. The authors are quick to let us know that they are looking at healthy ageing vs. pathological ageing, eg. Dementia, but they do make occasional reference to the latter as you must when unable to tease out normal from natural from pathological changes in the brain and therefore cognitive capacity as well.
From the get go, the authors show that perhaps 70-90% of variance in testing scores across time is unrelated to age. That makes sense: people only enter aged care facilities in the most part for health and disability reasons, not their age. Chapter two presents the timescale of emerging research involving amongst other things research into songbirds such as the Zebra Finch, which demonstrated plasticity in response to environmental pressures. This would include preserving sharpness in brains by administering large amounts of nicotine, delaying pathological ageing by reversing changes in the synapses of the brain cells, as one can do with estrogen for instance, or exercise. Whilst cross sectional studies suggest ageing begins in the 30's, longitudinal studies project this decline only in the 60's. Now as we would all agree, I hope, between group studies say little or nothing about the individual, and so do not explain much about the individual trajectory across time nor the individual weighting of lifestyle factors in any one person, as their gene expression is altered by epigenetic factors such as those above.
The downward trend of a group thus may be entirely ignored by a specific individual, whose capacity across time may be highly variable even into the 90's where the trend would predict they are dysfunctional, which they are not, as with Snowdon's nuns or other researchers' songbirds. However, even for songbirds their will come a time when their need to add 1% of their brains each day to produce a new mating song will be overcome by a failure of the brain to be that plastic, making way for the younger male breeding birds to establish their song-bounded territory.
For humans, many of us at advancing age will still however compete with younger individuals on cognitive tasks, especially those with an emotional loading. Wilson, Shupf and others have shown that 25% may show no decline, 15% only slow decline across a few years. These longitudinal studies thus best demonstrate that decline is not universal. Cognition aside, brain volumes may decline, but may also improve in some. Decline in those that do fade are often related to health issues as I mentioned above, as with independence overall. So while the physical aspects of body and brain must decline with age, there are overall indicators that brain and cognitive decline are not inevitable, and may be strongly associated with factors beyond natural ageing.
Pasko Rakic set the world back a long way when he suggested in the 80's that we are born with just about all the neurons we will ever have, which we now know is false. Just as the body of an elderly person responds to resistance training, so does the brain, namely, shifting cognitive weights helps defend against age-related decline. As much as brain volume shrinks in ageing, it does so as children and adolescents go through periods of pruning and arborization, killing of vast amounts of neurons in a process we consider healthy. The loss of grey matter in childhood continues into adulthood in a linear fashion, with losses of grey and white matter from 30 to 90 years old in the vicinity of 14 and 26% respectively, with similar figures for the age bands 22-88 years. Regional changes are also evident as the brain does not shrink uniformly. The prefrontal areas are most vulnerable.
Everyone is in love with MRI technology, but Piguet was able to post-mortem brains from 46-92 and found no grey matter changes, and only white matter decline. So there is a discrepancy between MRI studies in living adults, which shows the grey matter decline first beginning in adolescent children and then onto adults, and autopsy studies (the dead but previously healthy adult) across the span that show this is not the case but show white matter decline instead. Linking grey matter decline to cognitive decline is however proving difficult. Grey matter studies across numerous papers show either weak or even negative correlations with cognitive capacity. If bigger is better in ageing, then Van Petten's study that showed a negative correlation between hippocampal size and memory is confounding, in children and adolescents, with mixed results in older adults. In older adults, Van Petten and colleagues found that prefrontal and temporal gyri sizes were again negatively correlated with good performances. Salat and others again showed that lower grey matter prefrontal volumes were associated with better cognitive performances, not worse. These were cross-sectional designs, with cohort effects depending on what group you are examining.
In longitudinal designs, only the entorhinal cortex, not the prefrontal or hippocampus as such, showed correlations between size and function in memory, as shown by Rodrigue and Raz. This was predictable: the entorhinal area is the one focused on by Alzheimer's researchers, not normal ageing studies.
These findings therefore suggest that regional brain shrinkage with healthy ageing is not associated with overall cognitive decline, although this can happen in apparently healthy older adults in the early stages of as of yet undiagnosed Alzheimer's-related pathology of the entorhinal cortices. The view that most old brains are irreversibly structurally impaired is thus weakened somewhat.
Older people use their brains differently, for instance using bilateral frontal activity as opposed to unilateral in the younger adult. The chapter continues on this vein, analyzing the changes in various cells and structures in the brain, and in the chemistry, e.g. glucose. Ageing effects are thus seen to be selective and subtle in terms of the biophysical properties of the neurons, and only seen in certain regions and for specific cell types. A change in neuron properties does not however necessarily lead to a changes in transmission or cognition. Synaptic changes are not seen unimpaired ageing adults. Chronic disease rather than natural ageing is thus the issue for the 50-60% of adults that do age abnormally in terms of brain function.
The next chapter focusses on ameliorating cognitive ageing, from a neurocognitive framework. Brain plasticity along with cognitive resilience and plasticity of the brain are the focus here, and aligning with most modern views, novel experiences in childhood, physical exercise, which fascinates John Ratey and others is reviewed, diet and nutrition are of course emerging as critical, estrogen and cognition enhancing medication, and learning and cognitive training involving challenging material, all play a role and are discussed. This leads to the next chapters, each of which addresses one of these factors.
Stern's view on cognitive reserve emerges here as it seems that the more one enriches one's education in childhood and early life, the more resilience the brain is in playing the number's game of later cognitive decline. Cognitive enrichment thus leads to cognitive reserve and a firewall against later decline.
Physical exercise evidence such as that from Colcombe and Kramer shows the differential effects of exercise on for instance executive function, spatial or speed capacity. The benefits of exercise on neurogenesis are discussed including the concept of synaptic plasticity and cerebral blood flow. Again, the benefits are discussed in terms of reversing the ageing effects in healthy adults, but not in those with some putative brain condition, despite what some may now say about Alzheimer's etc.
Diet and nutrition, including the effects of caloric restriction are of interest here as well. Changes to insulin sensitivity and body temperature, as well as DNA damage are also reduced by caloric deprivation, which is of small comfort to concentration camp survivors who of course have produced some surprising longevity post-war. Lean muscle mass, prevention of disease, and reduced atrophic changes in subcortical brain areas particularly basal ganglia and insula amongst a host of other benefits are noted in animal studies. More cogently, dietary restriction at the cellular level leads to increased cellular resilience, including resilience to the effects of the SIRT1 gene which has been associated with age related diseases.
It is unlikely though that humans can tolerate fasting alternate days, which may in fact have health risks; most manage however to follow calorie restricted diets. Bayer-Carter and her colleague looked at the role of high fat and high sugar diets, and as others have found, markers for Alzheimer risk were elevated, and in those on low fat and other controlled elements in their diet, cognition improved. Glucose regulation, plasticity, oxidative stress, and other neuroprotective mechanisms are implicated and discussed. Substances such as resveratrol appear to mimic the effects of dietary restriction. Quercetin, found in green tea, has a similar effect. So supplemental diets with red wine and green tea are thought to mitigate many of the effects of not only healthy ageing, but some of the markers for Alzheimer's are reduced, as they are with diets with fat restriction. Fatty acids on the other hand may have overall health benefits, whereas the effect on cognition is equivocal still. Most of us understand that high levels of homocysteine carry risk, and in theory Vit B supplementation should reduce this risk, but the results of supplementation are again equivocal.
If the ageing brain can be reorganized by cognitive demand, as is argued earlier in the book , and if this is dependent on underlying neural plasticity and health, then dietary restriction, resveratrol, and antioxidant foods play a role in keeping an elderly ageing healthy brain at a high level of function. As I have been pushing for years, and integrated approach, using insights from these past chapters, not in isolation, is required (page 126).
The role of estrogen and other cognition-enhancing drugs is then contemplated. Estrogen has both excitatory and neuroprotective and neurogenesis properties amongst other more corporeal effects. Pharmacological agents have been found to be of little value, stimulants such as caffeine more so, and the post-menopausal supplementation of women has to be further examined in respect of other health risks.
Retirement is therefore a double edged sword in terms of the probably loss of cognitive stimulation, and certainly a risk for post-menopausal women. Research in various countries with high versus low retirement age parallels cognitive decline in memory for these groups: use it or lose it applies it seems. The authors conclude here that cognitive training appears to change brain structure and physiology, and neurogenesis my play a role in the benefits of new learning. Training on executive training may be an essential element for training to transfer.
Putting all of the above together across the past chapters, chapter 10 examines the possibility of combinations of the above. Again, the need for an integrated approach is considered beneficial compared to isolated, siloed approaches, the combination of interventions considered much greater than the individual contributions (page 167). The literature on humans is however even smaller than the evidence from animal studies. Nevertheless the implication is clearly on the side of combining various lifestyle interventions to maximize the impact on the ageing brain.
Given the powerful effect of the environment at work and at home on the brain, changing home and work environs to accommodate the limitations of the ageing brain may help, adapting the setting rather than the brain.
No such work would be complete without a discussion of nature versus nurture in producing the ageing phenotype, and chapter 12 does just that, especially in regard to genetic vulnerabilities such as APOE e4 carriers.
So adapting the person via exercise, substituting PU fats for saturated, restriction of calories, learning new skills and acquiring knowledge, using estrogen supplement if female, taking cognitive enhancing medication, looking at lifestyle overall versus integration; also here is the idea of modifying the environment. Most highly valued is substituting fats, regular aerobic exercise, cognitive training, but motivating people here is another issue, especially in terms of diet.
A great first look at integrative approaches to healthy ageing brains, although a more pathology-focused approach would be exciting. However, as integration continues to look for a home, the healthy ageing adult is a great target, especially in terms of institutions such as the Alliance for Ageing Research and their focus both politically and in lifestyle terms. We know that certain of us are more resilient, but does that mean that we were always going to be more resilient and healthy in our choices, or do those choices independently alter anyone and everyone to combat both healthy ageing and abnormal ageing in dementing conditions?
A great resource from these two authors, and I hope we will see the pathology version some time in the future.