The Science of Brain Aging

Research into brain aging is remarkable: we know so much, yet basic questions remain unanswered. In this overview, we'll look at what we understand about the brain's aging process, and how it can go awry and result in dementias like Alzheimer's disease.

It is discouraging how much we don't know. For instance, there is no general agreement on whether Alzheimer's is an extreme case of normal aging, or a disease; if it is a disease, whether it's one, or several; and what one or several things cause it.

Even so, researchers have a rough understanding of what is happening in aging brains, and what actions people can take to improve their odds of maintaining their brain health into old age.

Help! My Brain is Changing!

While the definition of "normal" brain aging is much debated, there are areas of agreement. Virtually all brains change with age, and for some the changes begin at about 30.

There are two primary processes at work. The first is the accumulated damage that comes with age. This can be from oxidation, injury, stress, and / or accumulated errors in the brain's DNA.

The second is the pruning of synapses. This seems to be a normal process, as the body focuses on maintaining and repairing the most important ones.

There are other physical changes as well. One that is the focus of significant research attention is the development of senile plaques (SPs) at about age 25 and of neurofibrillary tangles (NFTs) at about age 40. Early studies of the brains of deceased Alzheimer's sufferers seemed to implicate SPs and NFTs in some way with that disease; however, recent work shows that healthy brains develop them too.

One process that does not occur is brain cell loss. This notion was a textbook staple for years; but now, says neuroscientist Caleb Finch of USC, "it is really clear that if you don't have a specific disease that causes loss of nerve cells, then most, if not all, of the neurons remain healthy until you die.” Earlier researchers were thrown off by a reduction of water content in the brain that begins at about age 50.

To make matters even more interesting, studies of cognitively challenged rodents have shown that brain cells can even be replaced.

While accumulated damage and the brain's own maintenance routines account for most of the changes to a normal brain, that damage has an unequal impact on different brain functions

Multifunction Brain, Multiple Changes

People have a tendency to conceptualize the brain according to the dominant engineering model visible in their everyday life. At various times it has been modeled as a hydraulic system, a mechanical device, and now as a super-CPU. But it's a biological organ that -- while similar in some ways to each of these constructs -- has unique characteristics and problems. The brain doesn't just "think;" key functions include:

• learning & memory
• visio-spatial abilities
• executive function abilities (concept formation and abstract thought)
• language
• visual-motor processing
• sustained attention (the ability to focus and perform a simple task)
• speed of cognition

As accumulated damage and synapse pruning change the brain, these brain functions are affected differently.

In "normal" brain aging, fluid intelligence is likely to decline. That's the ability to handle new information or "think outside the box." This also includes memory of lists or geometric designs, spatial reasoning, word retrieval, and problem solving. (Has anyone retaken the SAT lately?)

The older brain also processes information slower than when it was young, and multitasking is harder.

But there's some (relatively) good news. "Crystallized intelligence" is likely to be preserved. The facts and experiences that one repeatedly refers to -- vocabulary, practical skills, and general information -- will be maintained, and performance may even be improved. This is likely the result of the pruning process in which the brain strengthens the most important synaptic links.

These aging effects are normal and most people find they can adapt to them. However, things can and do go wrong. And the results can be tragic.

The Brain In Trouble

When an aging brain deviates from this "normal" path the result can be dementias, such as Alzheimer's, or other severe problems.

Two things usually go wrong, and they often go wrong in the same brain.

First, the brain may be deprived of the energy it needs. The biggest problem is the failure to deliver enough oxygenated blood to the brain's neurons. This, in turn, is driven by poor heart function or constricted arteries -- the reason why a healthy diet and regular exercise are as good for your brain as for the rest of your body.

Problems with glucose delivery also impact energy delivery. Diabetes sufferers have been shown to do worse on brain performance tests than control groups. With today's greater understanding and broader definition of diabetes, many more people may realize they are at risk for brain aging problems from the disease.

The second major abnormality is misfolded proteins in the brain, caused by DNA damage, errors in brain chemistry, or too few enzymes to fight them. This is a major area of research with many unanswered questions, but researchers are pursuing several promising leads. Among the effects may be

• too many SP (senile plaques), which could cause dangerous levels of calcium, free radical attacks, inflammation, and 'neuronal suicide.'
• too many NFT (neurofibrillary tangles), which may kill neurons
• inflammation of brain tissue as the organ fights SP and NFT
• errors when information is moved from short to long term memory

Others believe that this research into misfolded proteins will not pan out.

The result of either reduced energy delivery or misfolded proteins is straightforward: dead brain cells and poorer connections between the remaining ones.

There may be other causes of worse-than-expected brain aging. An open question is the role of free radicals. Researchers are investigating whether mutations in mitochondrial DNA can shoot out free radicals, which could destroy neurons. If that's happening, it's still unknown how much of a contributor the process is to cell death.

Whose Brain Ages Abnormally?

The lack of complete understanding of what happens in brains that don't age "right" means we can't yet identify specific problems, only effects.

However, studies of Alzheimer's patients can at least provide a broad understanding of what contributes to the problem. Using twin studies, genetics seems to cause about 50% of Alzheimer's risk. Given that, the other 50% must be from environmental, lifestyle, or other health factors.

There are known risk factors for Alzheimer's and other dementias. Given what we suspect are the processes involved in abnormal brain aging, some seem obvious; others will certainly be understood better in years to come. The most common non-genetic risk factors are:

• age
• anything restricting blood flow, such as high blood pressure. This is correlated to poor physical health, including smoking, excess weight, or high cholesterol. Stress is also correlated to restricted blood flow.
• sex: men are more at risk than women
• diabetes
• possibly low education level or a low level job
• others include any head injury, depression, and others.

What do these risk factors add up to?

The "standard model" of brain health used by clinicians says that a brain is in one of three states: normal, mild cognitive impairment, or dementia. Dementias affect 5% of the 65+ population, but that escalates with age. Alzheimer's is the most common dementia, representing more than 50% of cases. At 65, 1-3% of the population suffers from it; at 75 the victims are 12% of age group, and half of all 85 year olds have the disease.

Some argue that the standard model presents a false division of what is really a continuum, with most people healthy and some suffering from various degrees of cognitive impairment, up to and including dementias such as Alzheimer's.

Whichever is right, longer lives and an aging baby boomer generation mean that in the U.S. alone, the Alzheimer's population may grow from 4.5m today to 12m by 2040. Recent research suggests that other types of dementias may not increase so dramatically, perhaps due to increased health, new medications, or lower risk factors such as education.

Stay Healthy

Because the exact mechanisms of unusual brain aging are not yet understood, the linkages between cause, effect, and treatment recommendation do not exist yet. What we're left with is association and correlation. As the science proves out over the coming years, we're likely to learn more about the contributions of the different problems physicians will be able to recommend more finely tuned treatment regimens.

What is known is that several behaviors are correlated with reduced risk of dementia in older brains:

• cognitive challenges: taxing the brain with a variety of difficult activities may help; doing the same puzzle -- think Sudoku -- day after day probably does not
• regular exercise: at least 45 minutes, three times per week
• positive emotions and relationships: the emerging science of positive psychology will help here
• limited exposure to chronic stress: stress doesn't just increase heart disease and stroke risk, it has long-term negative effects on the brain
• diet: a healthy diet rich in antioxidants and anti-inflammatories seems to help maintain brain health
• rest

Other associations that aren't especially changeable include a flexible personality style and a spouse with a "high intellectual status."

Health is health

The most important lesson from the evolving science of brain aging is that good health helps every part of the body, including the brain. What's good for the heart -- diet and exercise -- also reduces risk of severe brain health problems later in life. Take care of yourself and you could still be working crossword puzzles at 90.

"Saving Your Brain," by Dr. Jeff Victoroff
"The Aging Brain," by Lawrence Whalley
Aging and Cognition. Hassing LB, and Johansson B. 2005. Nordisk Psykologi 57(1):4-20.
Declining Prevalence of Dementia in the U.S. Elderly Population. Manton KG, Gu X, and Ukraintseva SV. 2005. Adv Gerontol 16:30-7
Virtual Hospital: Memory in the Aging Brain
USC Ageworks: Dementia Overview
Society for Neuroscience: Brain Facts
National Institute on Aging: The Healthy Brain
USC Health: Aging Changes
Senior Journal: Aging Brain Changes Not Necessarily Alzheimer's