Alzheimer’s disease | medical plaintalk

The arrival of the baby boom generation at the threshold of old age coincides with a technology boom that marries the appeal of computer and video games to updated views on the brain’s neuroplasticity– its capacity to rewire itself even in adulthood. This union has spawned mind game businesses in which clients exercise their brains with computerized games, quizzes and tests. Lumosity and other cognitive training companies (see a sampling below) claim success in improving clients’ mental flexibility, speed, focus, concentration and memory. Well over 60 million subscribers hope their brains benefit from mental workouts in virtual gyms. Is their money well spent?

What is neuroplasticity?

Neuroplasticity refers to the dynamic process of physical change in and between brain cells that occurs in response to experience. When an infant is born, there is ample space between the cells in the outer layer of his brain, where higher functions like seeing, thinking, speaking, planning and remembering will develop. By the time he is two years old, this space between brain cells is tangled with nerve fibers connecting them to each other and to new cells which have migrated in from deeper areas. These changes continue in response to experience and are accompanied by pruning away of some of the initial connections to maximize efficiency and conserve energy.

For years the dogma taught in medical school was that neural circuitry was complete by the early twenties, a concept that was hard to understand because learning is possible at all ages and learning must have some kind of physical basis. But new evidence gradually emerged to prove that the brain continues to rewire itself throughout life. Neuroplasticity persists. The developers of the tools used by the companies like Lumosity seized upon this concept and added to it a wealth of data obtained from cognitive testing by psychologists and neuroscientists about how people think, remember, organize, plan and act. The brain games they devised for mental workouts in virtual gyms call upon these functions in hope of strengthening the brain circuits they use.

Use the circuits or lose them

Unused brain circuits lose connections just like unused muscle loses size. Hard learned algebra disappears once there are no more tests to call it into use. But there are apparently some traces of initial learning left, because relearning is easier than first time learning. Rusty skills can be brushed up with less effort than their first development required. Brushing up a skill presumably involves a physical process within the networks of nerve cells called upon for the task. It is this process that the virtual brain gyms seek to stimulate and apparently succeed in doing according to at least some measures of improvement.

Virtual mental gyms vs. real life mental exercise

The mental skills exercised by cognitive training programs include memory, attention, mental speed and flexibility, mathematical skills and visual-spatial processing. There is no doubt that exercising these brain functions is beneficial and that, with enough time spent and effort expended, the exercise improves the ability to do the tasks involved. The question is whether or not the improvement in these tasks carries over into real-life reasoning, planning and problem solving abilities. Here the data are murky indeed. It appears that the positive effects of exercising in mental gyms, if measurable, are confined to the types of tasks involved in the exercise and are not sustained for long after the practice ends. Lifetime habits of mental activity have much more persistent influence as people age.

Most people know elderly individuals who have maintained robust minds. They are usually curious about life, resilient, adaptable and habitual seekers of information. These traits inform all of their interactions and activities. They spend their lives in mental gyms of their own construction and prefer active use of their minds over passive entertainment. Very often, they have also remained physically active long into older years.

The brain training programs popular today aim to provide a similar pattern of mental activity in an entertaining way, but the challenges are intermittent and short. If the participant has been on a lifelong course of high mental engagement with the world, and if he happens to enjoy the games and tests he is involved in and is committed to them, his test results after participation are likely to be better than those of someone who has been less active mentally in the past and who does not particularly enjoy the program.

Does mental exercise prevent Alzheimer’s disease?

Does an active, flexible and resilient mind resist Alzheimer’s disease? Since we do not know the cause of this devastating disorder, it is hard to speculate about what might make a brain resistant to the pathology that characterizes the disease – the amyloid plaques and neurofibrillary tangles that scar the brain. But it has long been known that the degree of mental deterioration in life in does not necessarily reflect the amount of scarring seen in the brain at autopsy of the patient with Alzheimer’s disease. Of two people with virtually identical diseased brains at autopsy, the one who had higher levels of mental activity over life – more reading, writing, educational achievement- will have suffered fewer and less severe disease symptoms. But even if this observation is coincidental and mental exercise has nothing to do with protection against the symptoms of Alzheimer’s disease, an actively lived life of the brain has its own rewards beyond preservation of health. And it does not require a virtual gym.

Other options

Though mind games don’t necessarily improve mental functions in daily life, there are no negative effects from engaging in brain training, except, perhaps, on the budget and on time better spent in physical and social activity. Regular modest aerobic activity like walking (preferably outdoors), resistance training such as weight lifting and Pilates exercises, adequate sleep and a supportive and enjoyable social network have all been correlated with better mental functioning in old age. For no fees there are always books, board games, crossword puzzles, jigsaw puzzles, hobbies, crafts, conversations and devotion to others’ needs.

A Sampling of Reputable Brain Training Programs

Lumosity, http://www.lumosity.com

Rosetta Stone Fit Brains www.fitbrains.com

Brain Fitness by MindSparke www.mindsparke.com

Brain Gymmer http://www.braingymmer.com

Like Willy Sutton, the bank robber famed for his explanation of why he robbed banks (because that’s where the money is), Alzheimer’s disease researchers have aimed most of their efforts at the well-known, visible pathology of the disease, the collections of debris scattered among the dying cells in the brains of patients suffering from the dementing illness. Made of a protein known called beta-amyloid, these plaques are the cause of the progressive death of brain cells and consequent loss of mental function – or so it has been thought. Research focus on amyloid plaques has been disappointing, though, yielding neither effective treatments nor preventive strategies. Moreover, the dramatic rise in the incidence of Alzheimer’s disease (AD), from 2% of people over age 85 in 1960 to 50% in 2000 indicates that something else is in play, something other than bad genetic luck that supposedly causes beta-amyloid to accumulate and nerve cells to die.

Energy production in the brain

As attention has turned to other potential causes of AD, older research findings seemingly unrelated to AD have assumed new importance, particularly discoveries related to brain energy metabolism. The preferred fuel for the brain is glucose. Until the 1980s, researchers thought that the brain, unlike other organs, did not need use the hormone insulin to allow glucose to enter its cells. But in the 1970s insulin receptors were discovered in brain cells and insulin was found in the spinal fluid, implying that the brain did indeed use the hormone. Because progressive resistance to insulin and difficulty getting glucose into cells to provide energy are the hallmarks of type 2 diabetes, and because the rise in AD incidence paralleled rising rates of type 2 diabetes in the last few decades, researchers began to wonder if AD might be rooted in insulin resistance and impaired energy production in brain cells. Insulin resistance in the brain might also explain the results of glucose metabolism studies in the brains of people at high genetic risk for AD, showing as much as 25% decrease in the use of glucose in areas concerned with memory and learning – long before any symptoms suggestive of AD have appeared.

Insulin resistance

By 2005, the idea that insulin resistance in the brain plays a significant role in the development of AD gained traction. Since not all type 2 diabetics get AD and not all AD patients have type 2 diabetes, insulin resistance cannot be the sole cause of AD. But a high blood insulin level is one of the two biggest risk factors for the disease. The other is a genetic factor – the gene for the E4 version of a protein called apolipoprotein B (apoB). Like insulin, apoB’s function is moving the building blocks for energy production into place in the various cells of the body. ApoB is like a delivery vehicle, packed with fats and cholesterol which are necessary for building the cellular machinery in the brain and providing fatty fuel for use when glucose is unavailable.

The tie between glucose, insulin and amyloid

Does impairment of glucose metabolism in the brain have any relationship to the classic pathological components of the disease – the amyloid plaques littering the brain, the destruction of nerve cell architecture, and the non-specific inflammatory changes? There are tantalizing clues. In the brain amyloid protein is a normal waste product. What is not normal is its accumulation in clumps around nerve cells. Beta-amyloid is usually broken down by an enzyme called IDE, insulin destroying enzyme. IDE breaks down insulin much more readily than it does amyloid proteins and when insulin is present in high amounts, the amyloid waits longer to be cleaned up and precipitates out of solution, forming clumps. Uncleared amyloid also prevents insulin from attaching to nerve cells to let more glucose in, depriving them of fuel.

Competition for IDE may not explain beta-amyloid accumulation completely, but it is a link between insulin, glucose metabolism and AD. In addition, high levels of glucose in all parts of the body prompt the development of abnormal collections of proteins/glucose combinations called advanced glycation products which trigger inflammatory damage to tissues in all organs. The brain is no exception.

A link between poor sleep and AD?

Sleep is another subject beginning to gain attention in the prevention and treatment of AD. Lack of good sleep contributes to the development of the metabolic syndrome, including type 2 diabetes, though disruption of normal hormonal rhythms. In normal people and in people with sleep apnea, sleep deprivation produces measurable impairments in working memory, thinking speed, attention, vigilance, and higher cognitive functions – the same functions affected by dementing illnesses such as AD.

Reasons for optimism

Do changing theories about AD have any practical consequences? Indeed. First, there is more reason for optimism about the future. If AD rates have risen because of changing dietary habits and lifestyles, we can change them again. The factors known to produce the metabolic syndrome are weight gain, lack of exercise and poor diet. Regular exercise is recognized as a deterrent to the development of AD. Some people are beginning to feel that the low fat dietary recommendations must also be changed since they have resulted in diets high in processed foods and carbohydrates, and low in foods with high amounts of antioxidants which counter inflammation. Fat metabolism, abnormal in the metabolic syndrome, is also important in the brain, which contains 25% of the body’s cholesterol. It needs sufficient healthy fats in the diet for normal function.

The second practical implication of the changing view of AD is the application of known drug treatments for type 2 diabetes, both for attempted prevention and for treatment of AD. Clinical studies in AD patients are already under way, using medications that improve insulin resistance. Intranasal insulin has also been tried. It is delivered directly into the brain, without fear of lowering body glucose levels and has shown some promise in improving AD symptoms. These approaches are entirely new and evidence of shifting focus in research. If Willy Sutton were an AD researcher he would be changing his targets.

Terminal Lucidity and Lucid Intervals

Caregivers of Alzheimer’s patients have long reported episodes of the patient returning briefly to “themselves,” for periods of hours to days. Some dramatic cases of such returns have been reported in the terminal phases of life. All of these cases have fallen into the “we don’t know why that happens” category of clinical observations. The concept of brain cells failing to function because of lack of energy is one that fits the appearance of lucid intervals better than a theory of the disease that implicates cellular destruction alone as the underlying cause of symptoms.

Arch Gerontol Geriatr. 2012 Jul-Aug;55(1):138-42. doi: 10.1016/j.archger.2011.06.031. Epub 2011 Jul 20. Terminal lucidity: a review and a case collection.

Nahm M¹, Greyson B, Kelly EW, Haraldsson E.

Posted by medical plaintalk

Posted by medical plaintalk