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83 Neurobic Exercises to Help Prevent Memory Loss & Increase Mental Fitness Over 40? Getting forgetful? Having trouble learning new things, or remembering that actress's name without reaching for your smartphone? Neurobics is a unique brain exercise program that can be done anywhere, anytime. Based on the latest neuroscience, these deceptively simple exercises stimulate brain nutrients to help new brain cells grow. The key to keeping your brain strong and healthy is to break routines in unexpected ways.

Order Now 83 Neurobic Exercises to Help Prevent Memory Loss & Increase Mental Fitness


Over 40? Getting forgetful? Having trouble learning new things, or remembering that actress's name without reaching for your smartphone? Neurobics is a unique brain exercise program that can be done anywhere, anytime. Based on the latest neuroscience, these deceptively simple exercises stimulate brain nutrients to help new brain cells grow. The key to keeping your brain strong and healthy is to break routines in unexpected ways.

Nothing so easily stimulates the brain as breaking routines and using the five senses in new and unexpected ways. So if you're right-handed, wake up tomorrow and brush your teeth with your left hand. Or close your eyes before you get in the car and insert the key into the ignition. Every time you open a new circuit in your brain, it's like doing a round of mental sit-ups.

Keep Your Brain Alive is repackaged in a trim, tote-able format that makes it an ideal gift. Offbeat, fun, and easy, these 83 exercises will result in a mind fit to meet any challenge - whether remembering a name, learning a new app, or staying creative in your work.

Ordered. 5 Oct 2017 Now

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© 2017 Tufts University Health & Nutrition Letter. All rights reserved.

"Keep your brain alert". Cebria --- 83 Neurobic Exercises to Help Prevent Memory Loss & Increase Mental Fitness Over 40? Getting forgetful? Having trouble learning new things, or remembering that actress's name without reaching for your smartphone? Neurobics is a unique brain exercise program that can be done anywhere, anytime. Based on the latest neuroscience, these deceptively simple exercises stimulate brain nutrients to help new brain cells grow. The key to keeping your brain strong and healthy is to break routines in unexpected ways.

Ordered Now 5th Oct 2017 83 Neurobic Exercises to Help Prevent Memory Loss & Increase Mental Fitness


Over 40? Getting forgetful? Having trouble learning new things, or remembering that actress's name without reaching for your smartphone? Neurobics is a unique brain exercise program that can be done anywhere, anytime. Based on the latest neuroscience, these deceptively simple exercises stimulate brain nutrients to help new brain cells grow. The key to keeping your brain strong and healthy is to break routines in unexpected ways.

Nothing so easily stimulates the brain as breaking routines and using the five senses in new and unexpected ways. So if you're right-handed, wake up tomorrow and brush your teeth with your left hand. Or close your eyes before you get in the car and insert the key into the ignition. Every time you open a new circuit in your brain, it's like doing a round of mental sit-ups.

Keep Your Brain Alive is repackaged in a trim, tote-able format that makes it an ideal gift. Offbeat, fun, and easy, these 83 exercises will result in a mind fit to meet any challenge - whether remembering a name, learning a new app, or staying creative in your work.

Order Now

You are currently subscribed to Tufts University Health & Nutrition Letter as: Lilyanwhite@yahoo.com. Send this e-newsletter to a friend: Click here To read e-newsletter in your browser: Click here To Unsubscribe or manage the e-mails you get from us Click here Manage your Profile: Click here

© 2017 Tufts University Health & Nutrition Letter. All rights reserved.



p72 The New Memory Advantage

Products to Preserve Memory from the Effects of Aging, Stress, Brain Insult and Disease

There are two basic categories of dietary supplements, also called “nutraceutical” products, sold for memory improvement. The first is composed of products that are really not intended to improve memory in days, weeks, or months, but are intended to nourish the brain and protect it from damage as we grow older and face stresses and insults that contribute to brain aging. These products include omega-3 free fatty acids (FFAs). There is a growing body of sound evidence that omega-3 supplementation is important for the developing brains of fetuses and children and also the brains, as well as hearts, of mature adults. There are three omega-3 FFAs and these are ALA (alpha linoleic acid), EPA (eicosapentaenoic acid), and DHA (docosahexaenoic acid). ALA can be converted to EPA and DHA, although the process is inefficient, and it is derived from flaxseed, nuts and various oils. EPA and DHA are most commonly derived from oily fish such as tuna, salmon and mackerel, although DHA can be derived from marine algae. Because it is free of contaminants that may be found in fish, this form is now used in most infant formulas. Although DHA is the primary structural component of brain tissue, and DHA supplementation alone is probably adequate for the fetus, infant, and toddler, the mature adult brain probably benefits from EPA supplementation as well. I believe that daily supplementation with a fish oil product is beneficial, but care must be exercised in selecting a product that is not likely to be contaminated with mercury or other metals. Such contaminants are most likely to be found in farmed salmon or other fish rather than free ranging cold water fish. In addition to an omega-3 product, it is worthwhile to make sure that your multivitamin contains an adequate amount of natural Vitamin E. That powerful antioxidant can inhibit the destructive effects of oxidation in the brain and elsewhere in the body. If your daily vitamin does not contain at least 250 IU (international units),

Drugs and Dietary Supplements to Improve Memory 73
you may want to switch to another product or add a separate vitamin E capsule to your daily regimen. We strongly recommend 400 IU of a natural form of Vitamin E, that is “d” alpha (α) tocopherol— not “dl” alpha tocopherol, which is the much less active synthetic form. It may be absorbed just fine, but it may not get to the tissues as well to protect you!

Also, it is important to remember that the supplements containing these ingredients are good for brain health but they are not memory specific. Beyond these dietary supplements, and with one exception, I would be wary of the many, many products that are said to protect the brain from aging and insult. Products to Improve Memory

Drugs: Rather than being designed simply to protect the brain and limit further memory loss, there are also both supplements and drugs designed to improve memory in hours, days, weeks, or months. No such drugs are approved by the Food and Drug Administration (FDA) in the United States for AAMI. However, drugs that are approved in the United States for medical conditions other than memory loss are sometimes taken for that purpose “off-label.” By the way, don’t believe the stories you may read about the remarkable drugs for memory that are available overseas but blocked from sale in the U.S. by the FDA. There are no such drugs. The drugs approved for memory loss in European countries are mainly the so-called “nootropic” (toward the mind) drugs of which piracetam is the prototype. There are many published studies with these drugs and my colleagues and I studied a number of them for the treatment of AAMI in the late 1980s and the1990s. Despite substantial sales in Europe, then and now, we were unable to confirm any benefit of these compounds in healthy older subjects with age-related memory loss. That is also true of, literally, dozens of drugs designed by the

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leading multi-national pharmaceutical companies to treat AAMI or related disorders. This is true, even though most of these drugs were designed on a sound theoretical basis and did improve learning and memory in aged animals.

Among drugs approved in the United States for medical or psychiatric conditions that may be prescribed by physicians “off-label” to improve memory are the stimulants, amphetamines and methylphenidate (Ritalin), approved to treat attention deficit hyper-activity disorder (ADHD) and modafanil (Pro-Vigil), which is approved for excessive daytime sleepiness and narcolepsy. These drugs have the capacity to maintain cognitive performance and temporarily offset the effects of fatigue. There are likely arenas, such as the battlefield, where they can be useful, but I know of no evidence that they are useful in improving memory abilities diminished by age, stress, neurological disease, or the many other factors previously discussed that can cause memory loss. Stimulants also have physiological and psychological side effects that argue strongly against their use, except in conditions for which such use was approved by the FDA.

Dietary Supplements:

In contrast to drugs, there are many dietary supplements, or nutraceuticals, that are sold with a claim that they improve memory, or more generally, mental performance. This is possible because the principal federal law governing the sale of such products—the Dietary Supplement Health and Education Act (DSHEA), passed in 1994—limits the FDA control over dietary supplements and allows producers to make “structure and function claims” (e.g., improves memory) on the basis of far less evidence than is required in the case of a drug. Indeed, no approval is needed to bring a product to market and evidence to support efficacy must be provided only if a supplement maker is challenged, usually by the Federal Trade Commission (FTC) rather than the FDA.

Often, as is the case with too many products on the market, there is limited, or only early suggestive evidence to back up their overly:

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bold health claims. Some products are mixtures of various individual dietary supplement ingredients and usually any evidence of efficacy cited comes from studies of one or more of the components, not the actual mixture itself. And, far too often we have seen that the dosage of each component making up the nutritional product is far lower than the dosage, and frequently in a different form, than what was actually tested in the studies that are cited for back up.

Most importantly though, is that there is usually insufficient scientifically sound evidence to support the efficacy of each component in the product, even if it were administered in the dose said to be shown effective. Let us look at the most common substances sold alone or in combination and consider the evidence of efficacy in AAMI or comparable populations.

• Ginkgo Biloba. Sales of various ginkgo products soared in the United States during the mid and late 1990s and may have reached total sales of $400 million dollars. Since then, a number of studies have been published that did not find ginkgo products effective in AAMI or similar populations. Partly as a result, sales have declined dramatically. Ginkgo extracts appear to affect blood flow in the brain, but the preponderance of evidence suggests they are not useful in treating AAMI or related conditions. These conditions do not appear related to decreased blood flow in the brain and neither drugs nor supplements such as ginkgo would be expected to be beneficial. The usual dose of the standard extract (Egb 761) is 120 to 240 mg. per day divided into two or three doses. Combination products may contain much less.

• Phosphatidylserine (PS). PS is a phospholipid like PC, and a critical part of the cell membrane in every cell of every living organism. As cells in the brain (and elsewhere else in the body) age, they can become rigid as cholesterol replaces the normal phospholipids. PS administration is thought to improve brain cell fluidity and improve transmission across the cell wall. PS

76 The New Memory Advantage
also increases the availability of acetylcholine and affects other neurotransmitter systems that may be implicated in AAMI. It is particularly concentrated in brain cell membranes in mammals and, in fact, the PS compound my colleagues and I first studied in AAMI was derived from the brains of cattle slaughtered for human consumption. PS was first chemically isolated from the brains of cattle in 1948 and was approved as a drug in Italy and other European countries for treating what we now call AD and other generally ill-defined brain disorders. My colleagues at Stanford and Vanderbilt Universities and I conducted a very carefully controlled study in AAMI in 1989 through 1990 and reported our findings in the journal Neurology in 1991. We found statistically significant differences on a battery of neuropsychological tests when subjects administered 300 mg. PS daily for 12 weeks were compared with those given placebo for the same period. We did not find improvement in self-reported memory abilities, however. Subjects treated with PS performed better on memory tests, but did not perceive the improved performance. Soon after our paper was published, all PS research in humans abruptly ended because it was discovered in England, and later Europe, that humans who consumed tissue (particularly brain) from cattle with Bovine Spongiform Encephalopathy, mad cow disease, could develop a variant of a normally very rare and fatal dementing disorder known as Creutsfeld–Jakob Disease. It was not until the mid-1990s that PS products developed from vegetable sources came to the U.S. market and, whereas we had studied PS as a drug, the DSHEA legislation had been passed and it could be sold as a dietary supplement for memory loss. We conducted a study of one of these products, in which PS was derived from soybeans and reported, in 1998, results comparable to those seen with the bovine cortex-derived formulation. In animal experiments PS shows it can protect the receptors for nerve growth factor (NGF) against
Drugs and Dietary Supplements to Improve Memory 77:
age-related memory loss. PS also preserved the already established neural circuitry. These functions are highly prized for revitalizing the brain. PS can be a key ally in supporting brain health, but a couple caveats are necessary. First, we did not find that PS improved people’s assessment of their own memory abilities. In other words, they did not think their memory had improved. This could obviously be a problem, in that people may not continue to take a product if they do not feel improvement. It may be, however, that people taking PS do recognize improvement after an extended period of administration. Our studies lasted only 12 weeks. And secondly, and probably most important, the dosage we found effective was 300 mg per day. PS is expensive and the vast majority of PS or combination products on the market contain far less than the 300 mg daily dose.

While there are many other ingredients promoted as solutions for AAMI, in many cases there is little to no research supporting their efficacy in improving short term memory. Also, while some ingredients have been shown to have a positive effect on memory, many products that claim to improve memory do not contain the clinically tested amounts of these ingredients.

Twenty First Century Supplement Development for AAMI and Related Conditions:

We are not surprised that dietary supplement companies continue to introduce products that are said to be new and exciting when they are, in fact, simply rehashed mixtures of the same old, often centuries-old, compounds. The recognized need is high, but the qualified contenders are few. Just take a look at products in your health food store or on the web and you will see the same products discussed above reappearing, too often with inflated, unproven claims, usually at doses that would be ineffective even if the product actually worked.

78 The New Memory Advantage

In fact, too many products use poorly absorbed forms of nutrients, or synthetic antioxidants, and these are not recommended for brain or body health either.

The good news now is, in 2003, a novel neuropeptide compound was identified. The parent compound is a mixture of 85% amino acids and 15% neuropeptides of low molecular weight. Neuropeptides (NP) are short chains of amino acids, the twenty molecules that form proteins under direction of our genetic coding. NPs play diverse roles in the brain. They can influence cellular activity at the DNA level by altering gene structure to increase or decrease gene expression. Several neuropeptides, notably vasopressin (which is under the control of acetylcholine) and ACTH (adreno- corticotropic hormone), have been shown to play a role in learning and memory in animal studies and a few human trials. However, they are quite difficult to deliver exogenously to the brain and the magnitude of their effects in clinical trials has been small.

The parent drug, Cerebrolysin (CL), is sold in thirty-five countries for the treatment of a variety of brain insults and diseases, including AD. A severe limitation on CL use, though, that would preclude its use in AAMI, is that it must be delivered through intravenous infusion. Standard CL treatment consists of an infusion of 30 ml. CL mixed with 100 ml. saline for twenty minutes. This treatment is repeated fives day per week for four weeks, followed by an eight-week period off treatment, followed by a repetition of the four-week treatment period. This treatment regimen has been shown in large, multi-center trials to have significant benefits for as many as three months following treatment in AD and other neurological disorders. CL has been studied by leading teams of neuro- science researchers around the world and shown to have diverse effects that are associated with both acute improvement in learning and memory and in neuroprotection. In terms of acute improvement in memory, glucose is the most important source of energy in the brain and available glucose is diminished in AAMI, and further diminished in AD and other

Drugs and Dietary Supplements to Improve Memory 79:

brain disorders. Oral or intravenous administration of glucose can improve cognitive performance but very high doses must be administered, driving blood glucose dangerously high and, thus, this is not a practical treatment for memory disorders. CL, though, can raise glucose levels in the brain by facilitating glucose transport across the blood brain barrier (BBB). This is accomplished because CL up-regulates, or increases the expression, of a gene (GLUT-1) that partially controls the passage of glucose across the BBB. Because of this effect on glucose availability, CL has an immediate and pronounced effect on aerobic neuronal metabolism. This, in turn, may lead to improved learning and memory. In addition to the effects of CL on glucose transport, effects of the compound relate to a remarkable and fascinating story that began developing in the later years of the twentieth century. This is the story of brain plasticity (or neural plasticity) that has, heretofore, had no influence on the development of dietary supplements for memory and is only beginning to influence the development of pharmaceutical products for neurological disorders such as AD.

It was believed only a few years ago that when a neuron died it could not regenerate. It was further believed that memories were formed largely through neurochemical events rather that the actual growth of new dendrites and even new neurons in critical areas of the brain such as the hippocampus. We now have excellent evidence that dendrites sprout to develop millions of new connections among neurons, that new neurons can grow and form millions of interconnections and that this growth may represent the formation of new memories. We know too that CL can facilitate these processes. Evidence published in international neuroscience journals demonstrates that CL enhances synaptic density and neuronal transmission in the hippocampus and entorhinal cortex (an area important for memory). It also increases the density and expression of glutamate (an important neurotransmitter) receptors in the hippocampus and elsewhere in the brain, increases neuronal connectivity in critical brain areas and counters decreased neuronal plasticity in aged rats.

80 The New Memory Advantage:

In young rats, CL improves dendritic arborization (sprouting of branches, much like a tree in Spring), effects dendritic length and synaptic density, and improves neuronal plasticity by inducing neurite (immature neuron) growth and synapse formation. Many of the effects of CL mimic those of endogenous nerve growth factor (NGF) which, as one would expect, diminishes with advancing age. NGF is synthesized in the hippocampus and transported to neurons in the basal forebrain where it stimulates cholinergic activity and facilitates learning and memory. Exogenous NGF cannot be administered because it does not cross the BBB, but CL does cross and mimics NGF. On the neuroprotective side, CL protects cholinergic neurons from the neurotoxic effects of chemicals (glutamate) and lesions (fimbria-fornex) that would normally destroy them. It has anti- apoptic effects (that is, it protects against programmed cell death), it promotes cholinergic fiber regeneration, and it reduces the beta amaloid plaque (a hallmark of AD) burden in the aged brain. CL also reduces microglial activation and exerts a neuro-immunotrop ic activity that reduces the extent of inflammation and accelerated neuronal death that occurs under various pathologic conditions.

CL is produced by biotechnological methods, using a proteolytic breakdown of purified porcine proteins. All production is done to international pharmaceutical standards. Recognizing the limitations of a compound that must be delivered through intravenous infusion, and recognizing that a less potent version of CL might suffice in AAMI rather than in AD and other dementing disorders, The research scientists turned their research and product development technology to developing a faithful, but less potent version of CL, that could be orally administered. The product that emerged in 2003 was CebriaTM and my colleagues and I had the privilege of conducting the first clinical trial of Cebria’s neuropeptides in AAMI.

A very careful, fully randomized, placebo-controlled trial among fifty-four healthy persons over the age of fifty with “normal” age- related memory loss (i.e., AAMI). The average age of study subjects

Drugs and Dietary Supplements to Improve Memory 81

was sixty eight years old, and the duration of the trial was thirty days, with standardized cognitive testing and both clinical and self evaluations conducted prior to dosing and, again, at the conclusion of treatment. The tests used include more difficult versions of the same tests used by pharmaceutical companies to obtain approval for the AD drugs on the market in the U.S.

The vast majority of the clinical trials I have conducted have been negative and, so, I never expect positive results, even when the idea behind the trial is sound. I was particularly cautious in this case because the treatment period was only one month. With the drugs currently approved in the U.S. for AD, for example, no differences between drug and placebo are seen until at least three and often six months of treatment.

Nevertheless, we did find highly statistically significant differences between active- and placebo-treated subjects on memory test scores. This was the first time, in my experience, that a nutraceutical product for memory had succeeded in a clinical trial since my colleagues and I found PS effective in 1991. (We confirmed that finding in 1998.) With PS, though, we found improvement only on test scores and study subjects did not report that their memory had improved. With CebriaTM we found evidence of efficacy on self and clinical evaluations, as well as memory tests. We published our findings in the journal International Psychopharmacology in 2005 and, since then, we and other investigators have published electrophysiological and other evidence that the effects of CebriaTM are substantial.

Today, this patented blend of neuropeptides is available in the US as CebriaTM. I had the opportunity recently to interview a number of people taking CebriaTM and following is a representative interview.

Jane M. was a sixty-two-year-old woman who complained about memory loss affecting her performance in her job as a commercial real estate broker. She complained that she would confuse conversations she had with different real estate brokers, tenants, or land-lords. She had confused, for example, a rate given to one prospective tenant with a rate given to another in an entirely different building.

82 The New Memory Advantage:

Jane’s mother died in her mid-eighties, having suffered profound memory loss, probably due to Alzheimer’s disease, in the last several years of her life. Thus, it was not too surprising that Jane began to worry that she was at an early stage of Alzheimer’s disease. I explained to her the magnitude of “normal” memory loss that can occur by age sixty-two, suggested that she have a thorough medical evaluation and agreed to provide her with CebriaTM’s neuropeptides after the evaluation was completed. The interview that follows occurred three months after she began taking the compound.

T.C.: Would you be kind enough to describe the memory problems that led to the concern you had at the time you came in for an evaluation?

J.M.: Well, I had always had a really outstanding memory. I graduated in the top ten percent of my college class, and right out of college I took a job in the securities industry. At that time, there weren’t many women in the industry, except in secretarial or low level administrative roles—at least that was true in the part of the industry where I worked in New York. I was very concerned that I had to be every bit as sharp as my male colleagues and probably sharper if I hoped to get ahead. In the first month or two, I was a nervous wreck and very concerned that I would make a costly mistake, but as time went on, I became very comfortable that I could do mental calculations and make decisions as quickly as anyone I worked with. My memory for numbers became really phenomenal and I could think on my feet as quickly as anyone. I worked in the industry for seven years and left only after I had been married for a year and a half and became pregnant with my first daughter. Over the next five years, I had two other children and became a “stay at home mom.” I did not go back to work until my youngest daughter went off to college, although all the years I was home, I was actively involved in all sorts

Drugs and Dietary Supplements to Improve Memory 83:
of activities related to the kids’ school and many extracurricular activities. I also remained as I am now, an avid reader. I tried to keep up with technical advances and that was actually not too difficult since my husband and all three of my kids are sort of “computer geeks.” In going back to the workplace, I first took a course to get my commercial real estate license. I surprised myself by doing very well in the course, even though I was well into my fifties and, although there were people of all ages, some of the students were fresh out of college. I began work with a firm that was very informal and I really enjoyed my work. However, it seemed to me they had too many agents for the amount of business conducted and I sometimes came home at the end of the day having accomplished nothing. So, after eighteen months, I joined the firm I work for now and, boy, was that different. From the start, it was a go-go atmosphere where the phone never stopped ringing and I was dealing with dozens and dozens of people everyday. I use to be amazed at how quickly the day passed. I really enjoyed the work and I actually began to make enough money that my husband was impressed. Even though the job was pretty stressful and very fast paced, it was not nearly as difficult as my job trading securities. Still, I was having some problems remembering all the information on different accounts, all the people associated with different accounts and different brokers, and just remembering “who said what to whom, and when they said it.” I don’t think anyone noticed any problems, but I began worrying that maybe there was something wrong because I think my mother had Alzheimer’s disease and, I am not sure, but I think one of her sisters had it as well. I didn’t say anything to anyone, even my husband, and I was getting along okay, but I continued to feel that my memory was
84 The New Memory Advantage:
getting worse even though I must have read two dozen books on how to improve your memory. I also tried gingko biloba, which I bought and kept in the glove compartment of my car so that no one at home or at work would know I was taking it. I learned a number of helpful memory tricks and I still use those today but the gingko didn’t seem to help, so I stopped taking it after about six or seven months. I still had the feeling that my memory was getting worse, but I was doing fine at work until just a couple weeks before I met you when I had just a terrible week. I called one broker who I know very well Elaine when her name is Eileen, and entirely confused a quote I was given on one account with a quote I was given on another. This led to a very embarrassing situation in which, for the first time, my boss looked at me as if he had serious doubts about my abilities. I went home in tears that day and told my husband what had happened and told him that I really thought I was developing Alzheimer’s disease like my mother. My husband told me that he thought that was ridiculous and that it was I who was continuously reminding him of everything from appointments to the names of our friend’s children. I actually felt better after I talked to him and when you told me that memory loss is normal, even in the forties and fifties, I felt even better. As we agreed, I had a really, really complete physical examination and the doctor found nothing wrong with me that he thought had anything to do with memory.

T.C.: So, now, what has been your experience over the past three months taking the product that I gave you?

J.M.: Well, I really think it has helped alot. I feel that my memory is sharper or quicker and I think my problem in confusing accounts and people with one another has almost vanished. I think I also feel happier and more confident because I am not always doubting myself or questioning

Drugs and Dietary Supplements to Improve Memory 85

myself. Before, if I picked up the phone and someone said hello, I would be very hesitant to use that person’s name for fear that I’d be confusing him with someone else. I think other people in the office began to think that I was unfriendly because I would not immediately call them by name. I had to sort of rehearse the name in my head a cou- ple of times before I spoke to be sure I wouldn’t call some- one by the wrong name. I also am more confident with information on each of my accounts and don’t feel I have to read a reread and then reread again, all documents to be sure I am not making a mistake. So, I don’t know if am doing a lot better because of the neuropeptides or some- thing else, but I certainly feel that my memory has improved and I feel much more confident now.

T.C.: So, do you intend to keep taking the product?

J.M.: Oh my goodness, yes. In fact, I have gotten to the point where I am kind of hoarding boxes to be sure I don’t run out. T.C.: Well thanks so much for telling us about you rexperience. I think there are many people who can relate to the sort of memory problems that you experienced.

CebriaTM stands alone against so many of the products for AAMI that are of greater historic than current interest.