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Normal Aging and Alzheimer’s Disease

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Patricio Reyes

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Transcript

Normal Aging and Alzheimer’s Disease: Similarities and Differences

Similitudes y diferencias entre el envejecimiento natural y la enfermedad de Alzheimer

Interview with Patricio Reyes by Luis Figueroa

Alzheimer’s Disease and Related Dementias: Diagnosis and Treatment

Alzheimer’s Disease: “Past, Present and Future” for Physicians

00:22 |

Buenas noches a todos. In my academic carrier and medical carrier, I've never lost a patient in my office, but I've lost four caregivers in my office, all spouses ofn Alzheimer's disease.
00:40 |

So I learned it the painful way and I vowed after that experience that I would always give, at least once a year, an educational program for caregivers and laypeople.
00:56 |

Because this disease, Alzheimer's disease, is not a usual disease to treat, you end up treating the entire family. There's a lot of emotional, economic burden associated withn this disease.
01:15 |

So tonight, I will begin with a prayer, I was raised a Catholic, I work for a Catholic institution, St. Joseph Hospital and Medical Center, but I found this prayer forn caregivers that is Jewish. It´s very appropriate for this talk.
01:32 |

Tonight I will begin by distinguishing the features of normal aging versus Alzheimer's disease. The reason for that is many times the symptoms of Alzheimer's disease, In consider part and parcel of the normal aging process.
01:50 |

As a matter of fact, as part of my job we want to educate in the United State,s different ethnic groups, and one of the problems we have encountered among certain ethnicn groups, is the fact that they would consider the symptoms of Alzheimer's disease as, not a disease but part of the aging process.
02:16 |

We believe that that's one of the reasons why the Hispanic population in the United States do not seek medical attention early on. And there's evidence that there´s an significant number of Hispanic population who suffer from Alzheimer's disease, but they're not examined and treated timely.
02:41 |

So our objectives tonight are to provide caregivers a better understanding of the differences and similarities between normal aging, dementia, and Alzheimer's disease.
02:55 |

I hope that you will become familiar with the signs and symptoms of Alzheimer's disease, how we diagnose the disease, and now how we treat the disease. We want to assistn caregivers and their families cope with the emotional and physical stress of care giving.
03:16 |

And I hope that at the end, I will be successful in giving families and caregivers hope, that because of our work and research we are going to provide you with firm confidencen and hope that in the future we will be able to cure this disease.
03:37 |

During the past three decades, we have seen the graying of the world. This is how the world will look like in the years to come. In every corner of the world there will ben large influct of older people.
03:56 |

In the United States alone, during the next decade we expect more than 20 million Americans to enter the older age group. Normal aging is the term that we use to describe then natural changes in the absence of disease.
04:17 |

There are changes that occur in the brain such as shrinkage or atrophy, but in spite of these changes older individuals are able to socialize, and continue their workn professionally without interruption.
04:34 |

They are able to perform their activities of daily living independently, without assistance. Although they may have lapses of memory, they´re able to describe details of then events and the symptom is not evident to family members, friends, and co-workers.
04:56 |

Normal elderly individuals remember important events in conversations, so I'll be testing some of you later on. There may be some occasional word finding difficulty and thatn means that sometimes we are trying to find the right word but it won't come out right away.
05:18 |

But that is not Alzheimer's disease because after a minute or two you remember the right word. Patients do not get lost in familiar territories; they´re able to operaten appliances like the stove, the refrigerator, the oven; although I have problems with computers all the time and my ten-year old son always teaches me, he doesn't think I have hope. He hopesn that I would learn it.
05:49 |

He maintains or she maintains interpersonal social skills, so they´re able o socialize, and when we examine them in the clinic we do all this testing that is also usuallyn normal.
06:08 |

And our testing and mental testing should take into account the education or the status of the patient, as well as the level of education and occupation.
06:22 |

Now, in Alzheimer's disease this yellow part is called the limbic system, all these structures are target structures in Alzheimer's disease. And these structures, beginningn from here up to there, represent the system that is very important in memory, emotional expression and behavior.
06:52 |

And if a disease like Alzheimer's disease affects these structures, then the main symptoms would be memory loss, language problems, behavior problems, abnormalities inn emotional expressions, and difficulty carrying out activities of daily living.
07:13 |

Now let's look at the brain itself, the brain is made up of, at least twelve billion neurons, imagine twelve billion neurons, and we better take care of them.
07:29 |

Now, for many years and centuries, as a matter of fact, we were told that the neurons or the brain cells do not multiply after birth. That is no longer true; there isn regeneration and new neurons could be produced in adult life.
07:49 |

Now, each of this is a neuron communicating with other neurons. And imagine this, one neuron is estimated to have at least twelve million connections.
08:04 |

Imagine that, that is the most complicated computer system that has ever been made and I don't think there is a man that would be able to do that.
08:21 |

So, in Alzheimer's disease something happens in these neurons and in their connections, so the brain cells are not able to communicate. So when the patient is asked to don complex jobs or new information is offered, then the neurons are not able to transmit those impulses.
08:51 |

And this is how it looks in a cartoon. This is a neuron that is communicating with another neuron, and there´s a chemical here called neurotransmitter and in Alzheimer'sn disease this neurotransmitter is lacking or deficient.
09:13 |

And this neurotransmitter is called acetylcholine. This disease was first recognized in 1901 by the doctor Alois Alzheimer, a German neuropathologist and psychiatrist.
09:33 |

It was only, not too long ago, that this chemical abnormality was discovered. We first began the development of this new drug, in 1986 with very little information, and inn 1993, we and others, came up with the first medicine for Alzheimer's disease approved by the U.S. FDA, and now we have five.
10:04 |

I'll discuss them with you later, and we have more coming. So we are continuing to work on this day in and day out, because it does become a national epidemic, at least in then United States.
10:20 |

Let's go back and define certain terms; dementia refers to a group of symptoms, and it can be due to many medical conditions, Alzheimer's disease is one of the many causes,n although it is the most common cause of dementia in adults.
10:44 |

It generally affects senior citizens, late middle-age and older individuals. A person who has dementia becomes dependent on family members and friends, they are unable ton perform their activities of daily living, drive a car, balance checkbooks, and go shopping.
11:12 |

They repeat the same question, asking for the same answers and this constantly causes conflict between husbands and wives, because the wife or the husband will be answeringn the same question.
11:26 |

They have frequent word finding difficulty; they may not be able to call this a watch or this anteojos, they may not be able to recall instances, recent events inn particular.
11:47 |

They won't be able to tell us what they ate for breakfas,t but they know when they got married, when they entered the military service, their serial number in the militaryn service, but not recent events.
12:02 |

And the symptoms become noticeable to the family members because they´re progressive; patients with dementia get lost in familiar surroundings, they have difficulty operatingn appliances.
12:23 |

As a matter of fact, one of the dangers that we have seen in these patients is leaving the oven on for many hours causing fire, for instance, and burning or failing to closen the door at night and they become victims of bad people.
12:44 |

They may exhibit inappropriate behavior, all of a sudden a person who is so vibrant and happy, and then he becomes sad and doesn't want to socialize anymore, doesn't entertainn friends and relatives.
13:04 |

As a matter of fact, in the medical school, I told my dean that any faculty member who all of a sudden does not attend his faculty meetings should be examined in ourn clinic.
13:17 |

And when we examine these patients we do find abnormalities in their mental status. Initially, patients may deny their symptoms because they´re trying to cover up. Andn relatives should help us uncover the symptoms by not denying the symptoms.
13:36 |

To make this simple, because part of my job is to make my lectures easy to remember for young physicians and medical students, we tell them that when you have a patient withn dementia just remember the alphabet, ABC.
14:05 |

A stands for decline in activities of daily living; some patients come to us because they have three car accidents in three months, before that, they never had any accidents.n Is that really an accident or are they victims of disease?
14:25 |

That raises very serious philosophical issues that has economic and legal implications. Many times I've been asked to determine whether individuals who sold properties weren taken advantage of because of their symptoms of Alzheimer's disease.
14:51 |

I can tell you cases within and outside the United States, wherein the seller or the buyer needed some confirmation, medical assistance as to whether the sales were legitimaten or not.
15:09 |

The symptoms are chronic and the early symptoms are difficult to recognize, because many times the patients are late middle-aged and elderly.
15:25 |

In addition, because the victims of Alzheimer's disease are older individuals, they also suffer from other medical conditions, they have hypertension, they are victims ofn heart disease, lung disease, kidney disease.
15:43 |

ISo now, it makes it difficult to determine what is the symptom that is related to Alzheimer's disease, versus symptoms due to heart diesease, hypertension, strokes or livern disease.
15:58 |

So it is not an easy case, frequently, and so we have to do a very comprehensive assessment or examination of these patients. And hopefully we are able to see them early son that we can intervene early.
16:12 |

Like any other disease, if we are able to treat them early on, the response is usually better. What are the common causes, and these are just some of the common causes,n Alzheimer's disease, of course, accounts for 65 to 70% of cases.
16:32 |

We have strokes that can also cause dementia and in 35% of cases, we have a combination of strokes and Alzheimer's disease. Parkinson's disease is also associated withn dementia.
16:47 |

Several years ago we reported a new type of dementia, that we called Lewy body dementia, although initially we called it Alzheimer's disease with Lewy bodies.
16:59 |

And then we have another disease that can mimic Alzheimer's disease called frontotemporal dementia. These patients are usually younger and they have pronounced psychiatricn symptoms earlier, rather than memory problems.
17:12 |

There's an interesting condition called normal pressure hydrocephalus, wherein patients have excessive water in their brain, and we are able to treat this successfully,becausen we can shunt the fluid from the brain, into the stomach and the patient recovers.
17:30 |

Mad Cow disease can cause dementia as well, rapidly, very rapidly. It's one of the few conditions that usually begins and proceeds very rapidly. In three to six months, manyn of them, in many cases, the disease is fatal and there is no treatment.
17:53 |

And we have to be careful with this because it is transmissible. Head trauma, and we have just, we have a paper that was recently accepted to describe the different types ofn brain lesions in retired boxers.
18:18 |

I happen to be a ringside physicians and a member of the Association... of the Board of American Ringdde Physicians Association, so we try to train ringside physicians on hown to officiate during boxing matches. MS and AIDS can also cause dementia.
18:43 |

For medical students I have developed a sort of way of remembering these diseases. So I use the word DEMENTIOUS, and each letter denotes a group of diseases.
18:59 |

D stands for degenerative; E for psychiatric conditions, like depression and psychosis; M for metabolic disorders; E for endocrine; N for nutrition; we mention B-12 deficiencyn because it can mimic the signs and the symptoms of Alzheimer's disease.
19:16 |

And I can tell you, later on, that one of the reasons why patients with Alzheimer's disease develop B-12 deficiencies is because they change their diet. Many of our patientsn live alone, they don't buy the right food, they don't cook the right food, and many of them like to eat sweets.
19:40 |

I've done a research on that, we reported that, I actually observed that in the University of Texas, very early on in my career; and I was puzzled why they like to eat icen cream, pudding, cakes.
19:54 |

So now I will watch you eat your dinner and I will have a report of who eats the most pudding or ice-cream after this lecture. Head trauma is a cause or a risk factor forn dementia, infections, auto-immune disorders, and strokes.
20:13 |

These are just examples of patients with Alzheimer's disease, different stages of the disease.
20:23 |

So what is Alzheimer's disease? It is a form of brain degeneration. We don't know the cause, but we know now certain risk factors, we are working very hard and I think eachn day we are inching our way on what causes this disease.
20:40 |

The brain starts to shrink progressively, we call that atrophy, brain cells die and chemicals are lost. Then there are two lesions that increase as the disease progresses andn they are called senile plaques and neurofibrillary tangles.
20:59 |

There may be fluctuation of symptoms early on, that´s why some will families say: "yell me Dr. Reyes, how could he have Alzheimer's? Yesterday he was fine", the day beforen that he was not fine, so there is fluctuation early on.
21:19 |

It is indeed, the most common cause of dementia among people age 65 and older; we now have more than five million American suffering from this disease. And by 2050, we expectn between 13 to 16 million Americans, if we do not advance in our treatment of this disease.
21:45 |

And remember too, that 50% of caregivers for Alzheimer's Disease suffer from major depression and they have to be treated. I told you about caregivers who died in front of men all of heart attack.
22:02 |

We cannot afford, even in the United States, to have a nursing home in every street corner. The national cost to the United States for this disease alone, the direct cost isn 0 billion.
22:21 |

But we don't take into consideration the family members expenses, the treatment for depression, and the amount of salaries or monies that are lost when caregivers have ton resign from work to care for their loved ones.
22:43 |

Most patients with Alzheimer's disease, even in the United States, are cared for at home, and they require 24-hour care. What are the early symptoms? They forget recentn events.
22:57 |

We talked about this, there's lack of interest of things they used to like, their mood changes, depression and these emotional abnormalities can precede the memory problemsn and cognitive problems.
23:15 |

So many times they´re treated by psychiatrists, and they have to be, if they're depressed. But underneath, is a slowly evolving dementing process, so it's not easy earlyn on.
23:31 |

They have difficult balancing checkbooks, for the ladies shopping may be interrupted. I always tell my patients and caregivers that if my wife doesn't go to the mall fiven times a week, there's a problem.
23:51 |

They may have difficulty with directions, going to work and back from work, they get lost. So what happens then? Let me show you, this is the brain of a normal 75-year-old.n And this is a 75-year-old with Alzheimer's disease.
24:13 |

There is loss of brain tissue that's why you have these widened spaces between brain tissue called gyri, and this is the main target of this disease. It´s called then hyppocampus, a very small structure in the temporal lobe, which is the seat of memory.
24:34 |

And look at the patient with Alzheimer's, there is actually a whole, it's replaced by a whole and that's what happens.
24:43 |

Under the microscope, we know that cells die, that´s why the brain shrinks, chemicals are lost and numbers of senile plaques and this tangles occur and the connections we calln synapses, remember those twelve billion synapses we talked about are also damaged.
25:02 |

In a moment I'll show you how this evolves. And look at this blue colored part of the brain. Even before the symptoms begin, the brain starts degenerating.
25:19 |

But because we have reserve there are no symptoms yet, so the challenges we have to us in the medical field, in the scientific field is to diagnose this early, even before then symptoms begin, because in every type of brain degeneration the process begins years before or months before the symptoms begin.
25:49 |

As a matter of fact, I preach and I believe very deeply in my heart, that the aging process begins in the womb, before we are born. If you studied the biology of life, in then womb or in uterus, the pruning process, the aging process begins.
26:12 |

Everybody thinks that human growth occurs after birth. From an infant who is probably a foot size, to about seven foot five if you are in Texas.
26:23 |

But actually, the biggest growth occurs in the womb because it´s microscopic, so to see it with your eye it has to enlarge by so many million times.
26:41 |

We don't think about that, if something happens during pregnancy to mom, there´s no normal aging process, that´s why for aging process to occur, things should happen normallyn in uterus, in the womb, and it begins there.
27:03 |

And look at this, and that is the problem with brain degeneration, as the disease progresses the blue colored parts of the brain increases, increase in area, and look at then advanced stage of Alzheimer's disease, most of the brain is already involved, blue.
27:27 |

And that is a challenge to many of us who work in this field, how to prevent, how to diagnose and how to stop the process, and we´re working very hard worldwide.
27:45 |

I hope that my colleagues here in Guatemala, my friends and my new friends, particularly here at the University Francisco Marroquin, will join us in our collaboration.
28:04 |

This is what happens during life. These dots are called senile plaques, and look at this, the brain is filled up with these, and that's why it won't work. And this contains an protein called amyloid.
28:22 |

Now using our own technique in our laboratory, we isolate one of those and this is how it looks. The red is the amyloid, that's the one that's deposited all over the brainn tissue.
28:41 |

So we are trying now to find out how this is deposited and how to prevent this from forming. Another lesion is called neurofibrillary tangles, and look at this brain is nown replaced by these called tangles, for short.
29:00 |

And look at this, how can the brain cell survive with this amount of protein that is destroying its brain cells, and that´s called neurofibrillary tangles. Again, were tryingn very hard to develop medications that will prevent the formation of these tangles.
29:26 |

How do we diagnose Alzheimer's disease? We use a very comprehensive medical history, we have to look at how the symptoms evolve, what happens to family members, are theren medications involved, are there other conditions involved, occupation; has the patient been exposed to toxins, for instance.
29:51 |

We´re trying to, we´re like detectives, trying to detect what could have happened before or what could have predisposed this patient to Alzheimer's disease.
30:03 |

We do blood examinations, blood count, we examine the liver, the kidney, electrolite the thyroid, very important, patients with thyroid problems can mimic signs of then symptoms of Alzheimer's disease.
30:12 |

B-12 deficiencies, we also do CAT scans, MRI and, for research purposes, we do a PET scan. And if necessary, we take fluid from the back, we can do a spinal tap to analyze then fluid. We can get EEG and also genetic testing.
30:39 |

Today we have no specific test in vivo, during life, that will confirm the diagnosis of Alzheimer's disease, there is none. The only way to confirm the diagnosis is byn autopsy, unfortunately. That's why, when I began my academic career, many years ago, I always had a brain bank wherever I worked.
31:14 |

And I helped established the Rapid Brain Autopsy System in the United States. At one point, I was in charge of developing a brain bank that collects fresh brain tissue,n because in the past,when I was trained, we just dumped the brain in a fixative, and examined the brain probably two or three weeks later.
31:45 |

By doing that you lose a lot of opportunities, the chemicals are lost right away, the proteins are lost, they dissappear, so how can you find it three weeks later?
31:56 |

And as soon as we did the Rapid Brain Autopsy System, that's when we began to learn more about this disease. So now, we know the chemicals are lost, so we develop new drugsn that will replenish them or correct the deficiency.
32:15 |

This is an MRI scan, this is a normal brain, this is the amount of water that is in the brain and look the picture is filled with brain tissue. This is, the white space on topn of the brain represents atrophy, meaning there´s loss of brain tissue.
32:39 |

This is water, there´s is also a secondary increase in the amount of water but that is not necessarily abnormal. In a PET scan, in certain cases where it´s very difficult ton diagnose Alzheimer's disease, and for research purposes we do PET scan.
32:56 |

This is expensive but we have to do them sometimes. The red here represents good, meaning the brain cells are working, because we inject patients radioactive material liken glucose or sugars and the brain cells metabolize sugar and we scan the patient and look for the red activity, which is good.
33:20 |

And look at the patient with Alzheimer's disease, there´s nothing, indicating that there is no metabolism and that is a signal to us that the patient probably has Alzheimer'sn disease.
33:38 |

Now let me tell you some good news; we now have new tests where we inject patients another material that´s regulated, we label it, we scan the patient and we can now see then amount of amyloid protein in the brain.
34:02 |

And if this is proven safe and effective, it´s now being tested, but the preliminary results are very encouraging. If this is effective, the questions are, could we use thisn to diagnose patients who are at risk for Alzheimer's disease?
34:24 |

Could we confirm the diagnosis of Alzheimer's disease and then use it also to monitor progress of our treatment, if the patient truly has Alzheimer's disease, are we reducingn the amount of amyloid? So for those reasons, it´s very exciting, at least I know of two drugs that are being tried right now to do this.
34:50 |

How do we treat patients? Well, let me tell you, the treatment of Alzheimer's disease does not only include medications. There are techniques that do not use medicines but aren effective.
35:08 |

And I´ll show you examples of that. Let's begin by reviewing the medications that we use. As I told you before, many years ago when we met for the first time in Washington DCn in 1985, there was nothing to offer.
35:30 |

We had a joke many years ago, when I was in training, that anybody who came to us with Alzheimer's disease or suspected of having Alzheimer's disease, our diagnosis wasn Alzheimer's disease, and after that we called it n , because we had nothing to offer.
35:53 |

And nobody wanted that patient, the neurologist would say it is a psychiatric problem; the psychiatrist would say it is a neurologic problem, the internist would say it hadn nothing to do with the brain.
35:57 |

So who would take care of these patients; can you imagine that, if we didn't advance? We have more than five million Americans, young and old, who do not have a phycisian ton care for.
36:21 |

So in 1985, we met, in Washington DC, and in 1993 we came up with the first medicine ever, which was not perfect by any means, but that was the beginning of research inn Alzheimer's disease, intensive research.
36:45 |

Nobody wanted to invest in this disease because we didn't know anything, but right now, at any given time in the world, there are at least 10 billion dollars committed ton Alzheimer's research.
36:59 |

So in 1993, we came up with this disease, however 10% of our patients developed hepatitis. Our Japanese counterparts introduced Aricept or Donepezil, without liver toxicity.n Novartis pharmaceutical developed Rivastigmine or Exalon.
37:23 |

And a year and a half ago we helped develop the skin patch for Alzheimer's disease, no longer tablet or capsule, but Rivastigmine now is a skin patch. Galantamine is a productn of Johnson and Johnson; they're all designed to correct the chemical deficiency for acetylcholine
37:46 |

Another drug in 2004 was approved called Memantine or Namenda, this is a different class of drug. It prevents excessive stimulation of neurons or brain cells, so you cann prescribe one of these and this one together.
38:05 |

And right now, at least, in our center,we are testing at least three new more drugs that we think could help in the management of treatment of Alzheimer's disease. Manyn patients become depressed so we used certain antidepressants, antipsychotics, antianxiety, and sedatives to help them sleep.
38:30 |

How about the nonpharmacologic, diet and nutrition; we have now evidence that, at least in animals, if we feed animals or mice every other day rather than every other day, then animals that are fed every other day live longer and are smarter.
38:57 |

And that is probably one of the reasons why in certain countries, particularly the poorer ones, the less developed countries, the reported incidents on Alzheimer's disease isn lower.
39:12 |

And there are studies now going on to verify the effect of caloric intake on intellectual function and life span, also diet is very important.
39:31 |

I've been working with the U.S. Department of Agriculture, and we are committed to studying and determining which vegetables and fruits are good for the brain.
39:45 |

After all, most medicines are derived from fruits and vegetables, so here in Guatemala you have a lot of indigenous fruits and vegetables that we can study, develop our ownn compounds, determine what are good for the brain.
40:02 |

Now let me tell you my own theory about this, for instance there is evidence now that spinach has very good antioxidant properties, all green-leafy vegetables, fruits liken blueberries are good, avocado; because many times our diet in America, in the United States, has no color, it´s bland, cheeseburger, hamburger, we need to add color to our diet. And so alln those fruits and vegetables, and
40:39 |

I have this theory that, I cannot prove this, but if you look at nature, when we face the sun in the morning going to work, what do we do?
40:53 |

We use dark glasses right, sunglasses, to protect neurons in the eyes from damage, whoever made those plants and vegetables, the skins of the fruits and vegetables that aren dark prevent them from radiation from the sun, and many of those have high antioxidant properties.
41:22 |

That prevents damage to cells and that to me, may be the reason why these are effective or this may be important in preventing, or at least reducing damage to the brain cells.n Mental and physical exercises are very good.
41:41 |

We recommend at least three to four times a week physical exercises and mental exercises. Try to do things that are new for the brain, challenge the brain cells, there isn evidence that by mental exercises there may be some regeneration, it may promote regeneration.
42:04 |

Identify and prevent bothersome behavior; stress, reduce stress. Sleep hygiene, try to maintain sleep hygiene and always seek for more educational programs, particularly ifn you're a caregiver.
42:23 |

Let me tell you some examples. I had a patient who had Alzheimer's disease and I put her on an experimental drug, she came from the Midwest.
42:25 |

A month later she went to Colorado, rented a cabin, and painted beautiful, drew a painting for me of the surrounding in Colorado, after she had Alzheimer's disease.
42:54 |

I had a patient who gave her first piano concert after she was diagnosed with Alzheimer's disease. I have a couple of patients who are writing books for kids and they do notn involve medications necessarily. Now I'll show you some examples later on, real life examples.
43:17 |

So the future treatement for Alzheimer's disease will depend on the cause or causes we are able to identify, we now have known risk factors, and I'll discuss them latern on.
43:27 |

We will attempt to diagnose the disease as early as possible, and those who may develop the symptoms progressively and were not able to treat them right away, we´ll treat themn based on the type and severity of symptoms.
43:44 |

As physicians and scientists, I promise you, we will continue to do research to better understand what happens to the brain and unfortunately, if this is a complicatedn process, we may have to use more than one medication.
44:03 |

Risk factors, the number one risk factor for Alzheimer's disease is advancing age. At age 85 the risk increases to 50%. So, usually it does not occur before age 65, unless wen are dealing with genetic problems.
44:24 |

Genetics is important, that may account for about 5%. Thanks to God, it only accounts to 5%, the majority is not related to abnormalities in genes.
44:35 |

Head trauma, diabetes, hypertension and strokes, these are three diseases that happen to have a much higher incidence in Hispanic population in the United States.
44:50 |

Obesity, sedentary life, we are trying to educate many members of our Hispanic populations in Arizona, about the risks of diabetes, strokes, hypertension, with respect ton Alzheimer's disease, increased cholesterol and heart disease.
45:18 |

We're trying to study, for instance, the relationship between bypass surgery of the heart and brain function because we see patients after bypass surgery develop progressiven dementia, similar to what you see in Alzheimer's disease.
45:36 |

So in terms of prevention, try to stimulate the brain, make the brain cells happy, learn games, crossword puzzles, learn a new language or musical instruments.
45:56 |

Volunteer in civic organizations, religious organizations, maintain some amount of physical activity, and don't forget your food; add color to your diet, fish oil is veryn good.
46:12 |

Some of these, we have tested using genetically engineered mice. It's amazing because brain cells are like old married couples; as brain cells get older, they don'tn communicate anymore. My job is to make couples and brain cells talk to each other again.
46:42 |

And we can see this in animals. So we give the animals, for instance in animals, we feed them with fish oil, make them swim and give them tasks to do, and that's how, and thenn examine their brains.
46:55 |

Like we have to tweaked certain animals, because no animals develop Alzheimer's disease. So what we have done is we tweak the genes and the animals develop plaques andn tangles.
47:10 |

So by giving them the said fish oil, Omega 3 fatty acid, we test their behavior and then we examine their brains. We have evidence that omega oil reduces the amount of plaquesn and tangles, and the animals perform better, same thing with spinach and blueberry extract.
47:35 |

The question of estrogen treatment after menopause is really uncertain, before we used to prescribe estrogen after menopause. For menopause, we need to treat the obstetrician,n the ginecologist, would treat their patients who are undergoing menopause with estrogen and the symptoms usually are relieved.
47:55 |

But after that period, the use of estrogen is controversial. So, we no longer recommend estrogen necessarily to all patients. And then there is such a thing as MCI, not ATandTn but MCI, and we revived, MCI became bankrupt but now we revived it.
48:23 |

MCI stands for Mild Cognitive Impairment, these are people like many of us, we live in the community, they're able to socialize, they go to work, when they come to see me andn the say
48:35 |

"Dr. Reyes, I'm no longer the same, I have to write things now all the time, and I have this memory loss, but I'm able to drive with no accidents, I'm able to shop, I'm ablen to balance my checkbook, but I'm different now, I know I'm different"
48:51 |

So, we do some early testings, and there may be some mild problems with memory, maybe problems if you give them complex tasks they may break down in the middle.
49:01 |

They may have problems with looking at relationships of objects through space and we call them MCI. Patients with MCI have been known to have from 11 to 15% risk of convertingn to Alzheimer's disease every year.
49:23 |

In particular, those patients with MCI, whose problem is purely memory loss, what we call the amnesic type, has the highest rate of conversion. So we've sub-categorized thesen patients now.
49:39 |

And that is the sort of a recent advance in the diagnosis of Alzheimer's disease, and there is no treatment, unfortunately. But many of our patients elect to take one of then anticholinesterase inhibitors. Strokes like this one can cause Alzheimer's disease.
50:04 |

I mean, can cause dementia, and you can see there´s multiple strokes in the brain, and this is what we call vascular dementia. Recognize however, that 30% of patients withn dementia may have both strokes and Alzheimer's disease, so things can get complicated. Parkinson's disease, at least one third of them can develop dementia.
50:30 |

For many years, for many decades we have been teaching that Parkinson's disease is merely a problem of tremor, of shaking, of muscle rigidity and stiffness, shuffling, andn slowness of movement.
50:45 |

We now find out that a significant number of them have dementia as well. Remember the normal pressure hydrocephalus we talked about, there's water in the brain, and this isn how it looks.
51:00 |

So a simple CAT scan or MRI directs us in the proper diagnosis and treatment. And this is reversible, however, if we do not recognize this early, patients may have permanentn symptoms. So we need to recognize these early.
51:18 |

In particular, after patients have a history of head trauma, a history of infections of the brain, like meningitis, or patients who have had hemorrhages in the brain. Thosen patients if recognized earlier respond best.
51:34 |

What we call shunting, we put a tube here diverting the fluid into the stomach and the patient recovers. But many times these patients are diagnosed as Alzheimer's disease orn Parkinson's disease.
51:48 |

We happen to be one of the very few centers in the United States that is studying this disease.
51:58 |

All the temporal events that we mentioned about this, but let me, because you are caregivers and you are... we learn more about Alzheimer's, we should, do not ignore then symptoms, seek early medical attention.
52:13 |

If you have a loved one or a friend, ask questions during your loved one's evaluation, second opinion may be necessary, and other resources that are available to you.
52:29 |

The Alzheimer's Association here, maybe other civic organizations, this conference like this, try to take advantage, you have fine medical schools, take advantage ofn conferences like this, listen to professionals, and recognize caregiving risks.
52:47 |

You are at risk if you are a caregiver. There is no question, physical and emotional, and take care of yourselves, because if I lose my caregiver, I lose the patient. Who'sn going to bring him, or her, to the clinic, who's going to give them the medication, make sure the medication is the right dose and the right timing? And seek medical attention forn yourself.
53:14 |

The four caregivers who died in front of me told me they were fine, but they were not.
53:26 |

Now this slide is very dear to me. The first one was drawn by a patient of mine from Colorado, it is hanging in my office, it is an oil painting.
53:42 |

The second one is a patient from Arizona, 85 years old, no painting classes. This one is a patient who has MCI, who is now running for a national competition on wood carving.n This is a carved bird sitting in my office, 24 hours a day. Thank you very much.
54:15 |

Audience:Could you mention how sugar and carbohydrates affect the correct functioning of the brain?
54:26 |

Dr. Patricio Reyes:Yes, well, too low insulin and excess of insulin can be harmful to the brain, so we have to maintain a normal level of sugar in the brain; too low sugar,n will cause damage, and excessive sugar will cause damage, that's one.
54:45 |

And obesity, a sedentary life, heredity could predispose an individual to diabetes, type two diabetes. In terms of carbohydrates, it´s important to have carbohydrates, but ifn you only eat carbohydrates, like certain patients who eat sweets, pudding, flan, ice-cream, then you're missing on the important minerals and vitamins that you need for your brain.
55:15 |

And I think that´s one of the reasons why we find a lot of our patients with low B-12 level, because they are affected and they don't eat the right food. Yes?
55:28 |

Audience:Dr. Reyes, I read an article of the National Academy of Science saying that insulin has a positive effect on Alzheimer's and what really interested me as a diabetic,n I've been diagnosed for over 35 years, is that they´re considering Alzheimer's as a new form of diabetes, now that´s very confusing to me, could you spread a little light on this please.
56:05 |

Dr. Patricio Reyes:Well the risk factor involves type 2 diabetes, not type 1 diabetes. Now, in two weeks I will be visiting the center that did a study on insulin.
56:17 |

There's a theory that there is low insulin level in the brain, and so, some of my friends have done some studies showing that patients with Alzheimer's disease are givenn intranasal, through the nose, insulin and they improve.
56:37 |

So we will be pursuing that. And I´m being asked to look at that experiment and we hope that we can answer that question definitively in a year or two.
56:56 |

Audience:But what is the idea of Alzheimer's being another form of diabetes?
56:57 |

Dr. Patricio Reyes:We don´t know that yet, that's speculation at the present time. But there´s no question that some people have produced data by giving through the nose,n intranasal, insulin the patient's symptoms improve. But I will be looking at that personally in two weeks.
57:22 |

Audience:What is the treatment with mega cells; I don't know how it is called in English, stem cells...?
57:30 |

Dr. Patricio Reyes:The problem with this is, actually it´s very controversial, we... there is one presumably treatment now approved by the FDA, stem cells as spinal cordn injury, this was released the day before I left the United States.
57:48 |

But the stem cells are with us; in our institutions the stem cells...we do not have any research on stem cells. But actually, if you look at stem cells, there are differentn types of methodologies and there are about ten.
58:05 |

Nine of them are not controversial, the one that is controversial is the one that requires killing an embryo, but the rest actually,you can use stem cells, and the church hasn no objection to that.
58:24 |

But there is one technique, if you have to destroy life to treat a patient that is the one that is not approved by certain religious faiths. And I happen to agree with that,n because there are actually, many other ways to use stem cells. Yes?
58:53 |

Audience:I have two questions actually, one is, would you rather start patients on one medication and then add up, or step up with medications if you see no clinicaln improvement, or have you seen more benefit using the NMDA antagonist and the anticholinesterase inhibitors since the beginning?
59:10 |

Dr. Patricio Reyes:What´s your second question?
59:12 |

Audience:My second question is, are there any other counter indications to Rivastigmine used as a patch beside the patients who already have like a recent mitochondrialn infraction or unstable angina?
59:25 |

Dr. Patricio Reyes:Thank you Ana. Ana will be working with me hopefully, in the near future. If she applies she will be in. Well, it is always important to go slow, start slown and go slow.
59:41 |

As a physician, it is very hard to start a patient in two medications, unless it´s an emergency problem. Because if something happens you don't know which one did it, son waiting for a week to introduce another medicine would be more systematic and safer.
01:00:01 |

After all, we're trying not only to be effective, but we are trying to give something that is safe and effective. So I'm very much against starting patients on twon medications, more than one medication, if the case is not an emergency. For emergency cases we may need to add two to three more.
01:00:24 |

But that is life saving, Alzheimer's disease that is not, it is a chronic process. And the second question is could you combine it or actually the third...three questions,n could you combine two medications?
01:00:42 |

Yes, you can combine, as I mentioned NMDA receptor, I begin them with cholinesterase inhibitor and then combine them with Namenda, say about two weeks later, if there aren no side effects.
01:00:55 |

And the third question, I forgot. (Laughter)
01:01:10 |

All of these drugs, the cholinesterase inhibitors can have side effects, because each class of drugs can have side effects. You look for nausea, vomiting, diarrhea,n abdominal cramping.
01:01:24 |

Some of them, patients may complain of vivid dreams, increased runny noses, and increased urinary frequency. So we need to follow up these patients.
01:01:37 |

And the reason I like to use Rivastigmine more is because it has a stronger action, it acts on two enzymes, whereas the others, act only on one enzyme. And now I can usen the pads easier, once a day, and I do not have to use pills or capsules that go to the stomach and may cause local irritation.
01:02:01 |

Audience:Does Alzheimer's disease without medication always lead towards physical decline?
01:02:10 |

Dr. Patricio Reyes:Actually, many patients are physically normal and the problem is intellectual behavioral in activities of daily living and that is why it is very puzzlingn because everything works, seems to me and in many cases but the brain doesn't.
01:02:26 |

So there´s something that happens and that is the key to understanding what really triggers this and when did it begin, so we can start treating these patients. Yesn ma'am?
01:02:42 |

Audience:Does the ginkgo biloba cause a benefit?
01:02:47 |

Dr. Patricio Reyes:I don´t have very good news for you on that, the second major study indicated there´s no effect. We actually did a four-year study on that too, and we usedn the purest type of ginkgo biloba from Germany.
01:03:04 |

Ginkgo biloba has been approved for the treatment of dementia in Germany for more than two decades, so many of my patients in Philadelphia were on that for many years. Butn they don't have any effects, and the last study was published about a week or two ago confirming that.
01:03:21 |

And let me tell you, by the way, about food supplements and alternatives, because many of my patients in the past, denied that they were taking them, hid their foodn supplements from me, and they would tell my nurse they were taking them but not me, because they're embarrassed.
01:03:47 |

But let me tell you about the problem that we have, many of these may have problems with purity. If you investigate the amounts of gingko biloba it may vary, it is possiblen that you can have zero to 100 percent, but nobody tests them, because all food supplements are not under the supervision of the FDA.
01:04:14 |

They can claim whatever they want, but we have seen complications, as a matter of fact ginko biloba can cause bleeding. So if you have problems with bleeding you can bleedn more with gingko biloba.
01:04:33 |

And so be careful with these food supplements, there are many, many. I just came back from Asia, and also there are problems there, because some drugs that are banned atn the United States are available there.
01:04:49 |

And you know, part of our obligation to our patients and their families, is not to take advantage of those families and patients who are desperate.
01:05:03 |

We need to accept many times, that we have limitations, that perhaps in my lifetime, medicine will not be able to explain everything. The guy up there may know, but In don't.
01:05:18 |

So let us be careful with those food supplements, there are claims that the brain is healthier after this and that but there is no proof. The fruits and vegetables In mentioned to you have been studied well,
01:05:37 |

at least, in animal experiments and we are doing that in humans now. For instance, the Mediterranean diet that uses more fish, fruits, and vegetables, including the Indiann diet from east India that uses kokumen or curry.
01:05:55 |

We have experiments doing there right now in the United States, to verifyng it's beneficial effects, because India reports low incidents of Alzheimer's disease.
01:06:06 |

So we are covering every field, and we expect that in the near future we will be able to answer the questions that you have raised tonight.
01:06:19 |

Audience:One question, my mother is 84 years old and ten years ago she started with Parkinson's and trembling, and she was taking medicine for that, but she likes drinking beern and she takes about one liter a day.
01:06:44 |

So she cured from Parkinson's but now she has some degree of Alzheimer's, do you think, I cannot take the beer out from her, but do you think I could brainwash more,n because a physician...
01:07:04 |

Dr. Patricio Reyes:Please don't...
01:07:07 |

Audience:But there is nothing, the social security the only medicine they gave her for Alzheimer's were brain vein dilators, artery dilators for the brain, arteryn dilators...
01:07:24 |

Dr. Patricio Reyes:Vasodilators, they're called vasodilators.
01:07:27 |

Audience:That's the only thing they gave her but she doesn't take them either.
01:07:31 |

Dr. Patricio Reyes:She's smart.
01:07:33 |

AudienceBut, what can I do?
01:07:38 |

Dr. Patricio Reyes:Let me tell you the dementia that occurs in Parkinson's disease. There are different possibilities, one is that after Parkinson's disease develops, after twon years or more, the patients may become forgetful, that's called Parkinson's disease dementia.
01:07:55 |

And the approved treatment for that in the United States is Exelon, the patch, the capsule will be eliminated pretty soon, so it will only be available the Exelon capsule,n wil be available in skin patch.
01:08:14 |

That is the approved treatment, Exelon, for dementia that occurs in Parkinson's disease. Because the patient is a senior citizen, we do not use the word older now, to ben politically correct, and I'm guilty of using that word today, it should be senior citizens.
01:08:37 |

She is a senior citizen, it is possible that one can have two diseases, like Parkinson's disease and Alzheimer's disease, it doesn't give you immunity when you haven Alzheimer's disease or Parkinson's disease that you don't develop Alzheimer's disease, you can still develop.
01:08:59 |

The third is....there´s a disease that we described many years ago in Philadelphia, we call it Alzheimer's disease with Lewy bodies. And this is a unique disease, and then first patient we saw was a very prominent scientist in the United States, and he was giving a talk and all of a sudden he forgot.
01:09:21 |

And I didn't forget your talk, okay, but when we examined his brain a few years later, we found out that the brain had lesions consistent with Parkinson's disease andn Alzheimer's disease, so we called it Alzheimer's disease with Lewy bodies.
01:09:46 |

And they hallucinate and they have problems with mood fluctuation, so that is another possibility. And again, we believe that in those cases, the treatment also, the bestn drug is Rivastigmine, the skin patch.
01:10:06 |

So those are the three possibilities and please don't take away the beer from her.
01:10:15 |

Thank you very much.
01:10:16 |

Sometimes I tell them to share that with their doctors in the office.
01:10:19 |

Audience:Dr. I have a question, is it possible that somebody in the family, has had, like became forgetful, Alzheimer's I presume, can we inherit that? Is there more chancen for.... It was my mother, let's put it... is it easier for us to get...?
01:10:43 |

Dr. Patricio Reyes:Your mother, how old was she when she started to have the symptoms?
01:10:47 |

Audience:I think about three years before she passed away, all of a sudden she...
01:10:49 |

Dr. Patricio Reyes:But how old was she?
01:10:52 |

Audience:75.
01:10:54 |

Dr. Patricio Reyes:75, okay, good. Let me tell you, usually we divide Alzheimer's disease into early onset versus late onset, having said that, when the symptoms began at agen 60 in particular, we call it early onset.
01:11:11 |

And we worry about abnormalities in three genes, mutations in chromosome 1, 14, and 21. If that mutation is present it is almost always guaranteed that the patient willn have Alzheimer's disease before age 60.
01:11:35 |

Now if, the Alzheimer's disease symptoms begin 65 and beyond, we call it adult onset and it is usually not hereditary. And the early onset, genetically-linked- type, onlyn accounts for about 3 and a half to 5 % the most. It is a rare condition.
01:11:59 |

Now having said that, there is another gene we have studied, and we look for it all the time, and that is the ApoE gene; ApoE4. The presence of ApoE4 merely increases then risk for Alzheimer's disease.
01:12:19 |

It doesn't mean that the patient will develop Alzheimer's disease, but if you have one or two copies of the gene, then the risk of developing the disease is significantlyn increased. Thank you.

00:01 |

Initial credits
22.2 |

Introduction
- Blessing for caregivers (Jewish)
- Overview
- Objectives
03:39 |

The graying of the world
- Normal aging
- Changes in the brain
- Ability to perform activities of daily living
- Capacity to describe details of events
- Occassional word-finding difficulty
- Orientation in familiar territories
- Maintenance of interpersonal social skills
- Normal performance on mental status exams
06:22.80000000000001 |

Structure of the brain
- Limbic system
- Effects of disease on these structures
- Neurons
  - Neuron regeneration
  - Neuron connection
  - Neuron connections in Alzheimer's disease
    - Neurotransmitter deficiency, Acetylcholine (ACh)
    - Development of new drugs
10:26 |

Dementia
- Symptoms
  - Dependency
  - Difficulty performing daily activities
  - Repetition of questions
  - Frequent word-finding difficulty
  - Lack of short-term memory
  - Progressive symptoms
  - Disorientation
  - Difficulty operating appliances
  - Inappropriate behavior
  - Abnormalities in mental status
- Characteristics
  - A, B and C
  - Chronic symptoms
  - Other medical conditions
- Common causes
  - Alzheimer's disease
  - Vascular dementia
  - Parkinson's disease
  - Lewy body dementia
  - Frontotemporal dementia
  - Normal pressure hydrocephalus
  - Mad cow or prion disease
  - Head trauma
  - MS and HIV-AIDS
- Medical conditions that can cause dementia
- D-E-M-E-N-T-I-A-S
20:15 |

Alzheimer's disease
- Characteristics
  - Brain degeneration
  - Atrophy of the brain
  - Senile plaques and neurofibrillary tangles increase
  - Fluctuation of symptoms
- Facts
  - The most common cause of dementia
  - Depression in caregivers
  - Economic cost
- Early symptoms
- Changes in the brain
  - Brain shrinks
  - Senile plaques, tangles and synapses
- Progression
  - Brain degeneration before the symptoms begin
  - Early diagnosis
  - Aging process begins in the womb
  - Senile plaques
  - Beta-amyloid protein
  - Neurofibrillary tangles
- Alzheimer's diagnosis
  - Medical history
  - Blood tests
  - CAT, MRI and PET scan
  - Spinal tap, EEG and genetic testing
  - No specific test to diagnose Alzheimer's during life
  - MRI scan
  - PET scan
  - Amyloid protein scan
34:51 |

Treatment for Alzheimer's disease
- Pharmacologic treatment
  - First medicine
  - Tacrine (Cognex)
  - Donepezil (Aricept)
  - Rivastigmine (Exelon)
  - Skin patches
  - Galantamine (Razadyne)
  - Memantine (Namenda)
- Non-pharmacologic treatment
  - Diet and nutrition
  - Mental and physical exercises
  - Identification and prevention of bothersome behavior
  - Sleep hygiene
  - Caregiver education
- Future of Alzheimer's treatment
- Risk factors
  - Advancing age
  - Genetics
  - Head trauma, diabetes, hypertension and strokes
  - Relationship between bypass surgery and brain function
- Prevention of Alzheimer's
  - Importance of fish oil
  - Uncertainty regarding estrogen treatment after menopause
  - Mild cognitive impairment (MCI)
50:01 |

Non-Alzheimer's causes of dementia
- Vascular dementia
- Parkinson's disease
- Normal pressure hydrocephalus
- Frontotemporal dementia
52:0.5 |

Recommendations for caregivers
53:25 |

Final words
54:14 |

Question and answer period
- How do sugar and carbohydrates affect brain function?
- How are Alzheimer's and diabetes related?
- Is there a treatment involving stem cells?
- Would you rather start patients with one medication and change it if there is no improvement or combine the NMDA antagonist and the anticholinesterase inhibitors from then beginning?
- Are there other contraindications to Rivastigmine skin patches besides the patients who have had a myocardial infarction or unstable angina?
  - Slow treatment
  - Combination of two medications
  - Side effects
- Does Alzheimer's disease without medication lead toward physical decline?
- Are there any benefits to taking Ginkgo biloba?
  - Food supplements and alternatives
  - Fruits and vegetables
- Parkinson's dementia
  - Exelon skin patches
  - Development of two diseases
  - Alzheimer's disease with lewy bodies
  - Best treatment
- Is Alzheimer's hereditary?
  - Early-onset Alzheimer's
  - Mutations in chromosomes 1, 14 and 21
  - Late-onset Alzheimer's
  - ApoE4 gene
01:12:42 |

Final credits

Colección

Normal Aging and Alzheimer’s Disease

Normal Aging and Alzheimer’s Disease: Similarities and Differences

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