In his dystopian novel Fahrenheit 451, Ray Bradbury wrote of a future in which firemen were employed not to put fires out, but to start them—their job was to burn books. To keep the words and ideas of great books alive, some people would volunteer to learn a book in its entirety, which they could then recite by heart.
Bradbury’s cautionary tale reminds us that at the dawn of history, before writing was invented, people needed to memorize songs, stories, and legends in order to pass them on to the next generation. In India especially, some of the epics were so enormous that it could take days to recite them. How did ancient people manage such prodigious feats of memory? Some scholars believe they got help from an herb called Bacopa.
Bacopa, a Gift from Ayurveda
Bacopa monniera, also known as Brahmi, is a perennial, creeping marsh plant native to India that has long been part of the traditional Hindu practice of Ayurvedic medicine. Ayurveda is a form of holistic medicine that has persisted and thrived for several millennia, which leads us to suspect there may be something to it. It emphasizes the healthy unity of body, mind, and spirit.
Bacopa is used in Ayurveda for fever, inflammation, and pain, which is pretty much what plain old aspirin is good for. But Bacopa goes further: its nervous-system effects include sedation, seizure control, and, most notably, memory enhancement. The last property continues to be the focus of scientific investigation.
Memory is a complex phenomenon. When you first learn something, the knowledge of it goes into short-term memory storage. Then the memory enters a phase of consolidation, after which it is ensconced in long-term memory. These two kinds of memory are not the same—in fact, it’s not unusual for an elderly person to recall childhood events with crystalline clarity, yet be unable to say whether or not a family member visited earlier that day. In such cases, short-term memories have clearly not made it into long-term storage.
Dementia Is . . . uh . . .
It’s perfectly normal (we keep telling ourselves) to become a little forgetful as we age. Like many things biological, though, what’s “normal” is a matter of degree. When forgetfulness and fading mental prowess become significant (there are standardized tests to measure this), we call the condition mild cognitive impairment (MCI). When memory, judgment, and concentration have deteriorated to the point of serious functional impairment, it’s called dementia. (Dementia also has a secondary meaning of insanity, but we use it here strictly to mean impaired cognitive function caused by organic disease or injury to the brain.)
Alzheimer’s dementia is always preceded by MCI (even if the MCI went unrecognized as such), but MCI does not always lead to Alzheimer’s, let alone the many other types of dementia. Among these are Lewy body dementia (the second most prevalent type, after Alzheimer’s*), vascular dementia, and dementias associated with Parkinson’s disease, Huntington’s chorea (hereditary), Pick’s disease, Creutzfeldt-Jakob disease, motor neuron disease, alcoholism, AIDS, and head trauma.
It Must Be Something in the Water
Some patients undergoing hemodialysis (blood cleansing with the artificial kidney machine) used to be afflicted with a mysterious ailment whose protean manifestations included decreased concentration, disordered mood, impaired memory, personality changes, hallucinations, and, ultimately, death. The disorder was called dialysis encephalopathy, dementia dialytica, or dialysis-associated cerebral dyspraxia. (Dyspraxia means impaired or painful functioning in any organ. Got heartburn? Tell your friends you have gastroesophageal dyspraxia.)
The disorder was eventually traced to aluminum in the dialysis water, which is typically purified domestic tap water.1 The water in some parts of the country has a high aluminum content, and aluminum sulfate is commonly used in water-purification plants everywhere.† This was a recipe for trouble: while toxins in the patient’s blood were traversing the dialysis membrane to be flushed away with the water, aluminum ions from the water were passing in the other direction to enter the patient’s blood.
†Aluminum compounds enter our bodies through our mouth, nose, and skin. Significant amounts are present in certain antacids, antiperspirants, and food additives, making aluminum buildup a hazard of modern living.
Some researchers noted the striking similarity of dementia dialytica to Alzheimer’s dementia, so naturally they posited that aluminum toxicity might be the underlying cause of Alzheimer’s. This lent support to a conjecture that had first been made about a decade earlier. Several decades later, however, the conjecture remains unproved and still controversial. Aluminum might be only one link in a causal chain, and not necessarily a vital one.
The Aluminum Hypothesis of Alzheimer’s Disease
A recent paper in the Journal of Alzheimer’s Disease examines the evidence for the so-called aluminum hypothesis and finds that it’s still very much alive.2 Some epidemiologic evidence indicates an increased risk of Alzheimer’s disease where the drinking water has a high aluminum concentration, and there is biochemical evidence of aluminum’s effects on brain proteins associated with neurodegenerative diseases (for more on that, see the sidebar). There is also evidence, however, that implicates zinc, copper, and iron in Alzheimer’s or other neurodegenerative diseases.
What is not in dispute is that aluminum is neurotoxic. Aluminum compounds promote cell-damaging oxidative reactions. Aluminum binds to DNA, alters gene expression, interferes with enzymes in energy metabolism, disrupts the proteins forming the cells’ structural “skeleton,” induces peroxidation in the fatty insulating sheath on nerve fibers, disturbs the balance or activity of various brain chemicals, and induces apoptosis (cellular suicide) of nerve cells and their supporting cells.
A Seahorse to Remember
Deep inside your brain, on each side, there’s a little seahorse. That, anyhow, is what that part of the brain looked like, sort of, to early neuroanatomists. So, being educated gents who knew Latin, they named it the hippocampus. It turned out to be an important seat of memory, learning, and cognition.
Bacopa monniera is good for your hippocampus, as we reported in March 2003 (“Bacopa May Help Your Brain Cope with Stress”). We described research on rats that were stressed by exposure to cold (hypothermia) and low oxygen levels (hypoxia).3When they had been pretreated with Bacopa, these rats produced less than the expected amount of a type of protective protein, called a heat-shock protein, in certain brain areas, notably the hippocampus and cerebral cortex. Why? Because Bacopa had apparently made those brain areas less susceptible to hypothermic and hypoxic stress by increasing the brain’s available store of protective enzymes.
Bacopa—Antioxidant with Antiaging Potential
Researchers seemingly never tire of abusing the hippocampus. In a recent study, scientists at the Jawaharlal Nehru University in New Delhi reported on the protective effect of Bacopa against aluminum-induced oxidative stress in the hippocampus of rats.4They laced the rats’ drinking water with neurotoxic aluminum chloride and protected some of them with simultaneous administration of Bacopa extract or the anti-Parkinson’s drug L-deprenyl, more commonly known as selegiline (Carbex®). Like Bacopa, selegiline is an antioxidant and neuroprotectant; it is thought to have antiaging effects.
By itself, aluminum chloride produced evidence of oxidative stress in the form of lipid and protein oxidation products and lipofuscin (an age-related pigment), as well as necrosis-like changes in the cellular ultrastructure of the hippocampus. Not surprisingly, these results were accompanied by reduced levels of an important antioxidant—the enzyme superoxide dismutase (SOD)—that the researchers were also measuring.
Coadministration of Bacopa monniera or selegiline with the aluminum chloride, however, largely prevented the oxidative damage to the rats’ hippocampal cells and restored SOD levels to near normal. Necrosis-like changes in the cells were eliminated. The authors stated,
. . . Bacopa’s antioxidative effects appear to be similar to those of L-deprenyl [selegiline]. Oxidative stress … is thought to contribute to the aging process. Bacopa … could thus be considered as a potential antiaging substance. Furthermore, the similarity of Bacopa’s effects with those of L-deprenyl, which is a candidate [anti]aging drug, would also be indicative of its antiaging potential.
Bacopa Improves Learning and Memory
Thus, no matter what kind of stress was placed upon the hippocampus—cold and oxygen deprivation in the first case, aluminum toxicity in the second—Bacopa protected that key brain area from harm. (Sadly for the rats, the scope of Bacopa didn’t encompass protection from neurobiologists who wanted a peek at their brains.)
Obviously, experimental designs such as those used in the rat studies are unsuitable for humans. It’s relatively easy, however, to run neuropsychological tests on people taking Bacopa. A double-blind, placebo-controlled study of this type in Australia, which we reported on in October 2001 (“Bacopa Enhances Memory and Cognitive Functions”), strongly indicated that Bacopa may improve higher-order cognitive processes, such as learning and memory.5 A subsequent study of different design, using a combined extract of Bacopa monniera and Ginkgo biloba, did not show an effect, however, perhaps because it was of shorter duration.6 There are no published studies on Bacopa and Alzheimer’s disease.
Memory Hole, Memory Whole
Ray Bradbury wrote Fahrenheit 451 back in 1953, a time when nobody gave a hoot about what books you checked out at the library (so long as you returned them on time). As an exemplary “negative utopia,” it’s in the vein of George Orwell’s earlier 1984.
Orwell’s book had the ironically named “memory hole,” where politically incorrect information disappeared forever, and Bradbury’s book had ironically named firemen who burned socially unacceptable information. We don’t for a moment suppose that we will ever require a defense against firemen and memory holes. Of course not. But isn’t it comforting to know that if we did, we might very well have one in Bacopa?
One hundred years ago, Dr. Alois Alzheimer looked through his microscope at the brain tissue of a woman who had died after severe dementia. He observed and described ugly clumps of matter outside her neurons, and strange knots of matter within them. Today, we refer to the clumps as neuritic plaques and the knots as neurofibrillary tangles. Both are hallmarks of what came to be called Alzheimer’s disease.
The plaques are believed to form between neurons before the latter begin their slow march to extinction. They consist mainly of a protein called beta-amyloid (also called amyloid-beta), which is derived from a larger molecule called amyloid precursor protein (APP). The tangles usually appear later in the course of the disease than the plaques; their formation, in fact, is brought about in part (and indirectly) by the plaques.
Tangles consist of knots of a protein called tau (rhymes with wow), which, together with other proteins called tubulins, act as structural elements of the neurons’ architecture. Tau is vulnerable to a chemical process called hyperphosphorylation (excessive phosphorylation), which causes it to disengage from the tubulins and form paired helical filaments that get all tangled up with themselves.
There has long been a debate among neurologists as to whether hyperphosphorylated tau or beta-amyloid (abbreviated ßA or bA) was the more important element in the origin of Alzheimer’s disease. The two camps have been jokingly referred to as tau-ists and ba-ptists. The weight of evidence now seems to have swung toward the latter, especially with a recent discovery suggesting that tangled tau may play a less important role in Alzheimer’s than had previously been thought.*
One angle on the aluminum hypothesis of Alzheimer’s disease has to do with the fact that aluminum binds strongly to phosphorylated amino acids in proteins. This can cause the protein molecules to undergo various conformational changes (they’re literally bent out of shape) and to self-aggregate. Aluminum also induces phosphorylation of tau and inhibits its dephosphorylation. And it causes conformational changes in beta-amyloid. We might well refer to neurologists who are especially knowledgeable on these matters as the alum-inati.