Alzheimer’s: Can It Be Stopped?

In February, my uncle was diagnosed with advanced Alzheimer’s disease (AD). He had spent the better part of the last few years trying to figure out what was wrong with him. He felt dizzy, which often resulted in fainting upon standing; when he walked, he appeared to be drunk; and his weight went from healthy to 120 pounds for his 5-foot-11-inch frame. Doctor after doctor failed to diagnose him, until he checked into the Mayo Clinic in Rochester, N.Y., in January. He remembers things from his past, but he can’t remember the name of the Mayo Clinic he went to or that it was in Rochester. He gets confused about what date and time it is, and he gets up in the middle of the night because he is confused. He can still converse, but others have to fill in words for him and remind him where he is in his story. The doctors say that he is incredible, as the average person with his loss of brain cells as shown on MRIs and cognitive tests would be unable to converse.

AD is named after German Dr. Alois Alzheimer, who described in 1906 the symptoms of a patient known as Auguste D that included memory loss, strange behavior and shrinkage in the patient’s brain. Psychiatrist Emil Kraepelin, Dr. Alzheimer’s colleague, coined the term “Alzheimer’s disease” in a 1910 medical book. In 1976, Dr. Robert Katzman, a neurologist, declared AD the most common form of dementia and a substantial public health challenge.¹

AD is the sixth leading cause of death in the U.S., and the fifth leading cause of death for those age 65 and older. In 2013, it was estimated that 5.2 million Americans of all ages have AD, which includes more than five million individuals age 65 and older and approximately 200,000 individuals younger than age 65 who have younger-onset AD. By 2025, it is predicted that the number of people age 65 and older with AD will reach 7.1 million (a 40 percent increase), and by 2050, that number may nearly triple (barring the development of medical breakthroughs to prevent, slow or stop the disease). Today, an American develops AD every 68 seconds; by 2050, an American will develop the disease every 33 seconds. In 2013, the cost of caring for individuals with AD in America is estimated at $203 billion, and the cost is predicted to increase to $1.2 trillion by 2050.²

AD is perhaps one of the most devastating and frightening diagnoses a person can receive. There is no cure, and the future is certain: a cognitive decline so great that the individual’s brain essentially dies, eventually rendering that person incapable of remembering anyone or anything or of having a simple conversation.

What Is AD?

AD is the most common form of dementia — a general term for loss of memory and other intellectual abilities serious enough to interfere with daily life — accounting for 50 percent to 80 percent of dementia cases. It is not a normal part of aging, despite the fact that age is the greatest known risk factor and the majority of people with AD are 65 and older. Only 5 percent of people with AD have early-onset AD, which usually occurs in people in their 40s and 50s.³

Scientists first linked amyloid plaques to AD more than 100 years ago, when Dr. Alzheimer documented unusual protein knots in the brain of his patient during an autopsy. By the mid-1980s, scientists determined that the plaques are made up of a protein they named beta-amyloid, which healthy neurons produce plenty of, but which the purpose of is still unknown. It is known that in the early stages of AD and other neurodegenerative disorders, beta-amyloid proteins begin to behave strangely by sticking together to form larger and larger clumps.⁴

These clumps (now called amyloid plaques) and tangled bundles of fibers (now called neurofibrillary tangles) are two of the main features of AD. The third is the loss of connections between nerve cells (neurons) in the brain. This damage to the brain starts a decade or more before problems typically appear. During the preclinical stage of AD, individuals are free of symptoms but toxic changes are taking place in the brain. Abnormal deposits of proteins form amyloid plaques and tau tangles throughout the brain, causing once-healthy neurons to begin to work less efficiently. Eventually, those neurons lose their ability to function and communicate with each other, and they die. After that, the damage spreads to a nearby structure in the brain called the hippocampus, which is essential in forming memories. And, as more neurons die, affected brain regions begin to shrink. By the final stage of AD, damage is widespread, and brain tissue has shrunk significantly.⁵

What Causes AD?

What causes AD is not known, but risk factors have been identified, including age, family history and heredity. Age is the greatest known risk factor, and after age 65, the likelihood of developing AD doubles about every five years. After age 85, the risk reaches nearly 50 percent. Those who have a parent, brother, sister or child with AD are more likely to develop the disease, and the risk increases if more than one family member has AD.

When diseases tend to run in families, it is believed that either heredity or environmental factors, or both, may play a role. Scientists know that genes play a role in AD. There are two types of genes that can affect whether a person develops AD: risk genes and deterministic genes. Risk genes increase the likelihood of developing AD, but don’t guarantee it. The risk gene with the strongest influence is E-e4 (APOE-e4), with estimates that this gene may be a factor in 20 percent to 25 percent of AD cases. Everyone inherits a copy of some form of APOE from each parent. While scientists aren’t certain how APOE-e4 increases risk, they do know that those who inherit the gene from one parent have an increased risk of AD, and those who inherit it from both parents have an even higher risk. In addition, the APOE-e4 gene may make AD symptoms appear at a younger age. Genetic tests are available for this gene, but they are not recommended.

Deterministic genes directly cause a disease. Anyone who inherits one of the three deterministic genes for AD — amyloid precursor protein (APP), presenilin-1 (PS-1) and presenilin-2 (PS-2) — will develop autosomal dominant AD (ADAD), also known as familial AD. Symptoms nearly always develop before age 60, and may appear in the 30s or 40s. It should be noted that deterministic AD variations have been found in only a few hundred extended families worldwide, accounting for less than 5 percent of cases.⁶

There are a few other theories about what causes AD that are being investigated. One theory centers on chemicals. Studies of AD patients’ brains have uncovered diminished levels of various neurotransmitters (the chemicals that allow white brain cells to communicate with one another) that are thought to influence intellectual functioning and behavior. An alternate chemical theory is aluminum since increased deposits of the metal have been found in AD brains.7 However, while aluminum emerged as a possible suspect in causing AD during the 1960s and 1970s, studies have failed to confirm any role.⁶

Other theories being studied are that AD is an autoimmune disease in which the body’s immune system attacks itself; a slow virus theory, which has been identified as a cause of some brain disorders that closely resemble AD; and a blood vessel theory in which there are defects in blood vessels supplying blood to the brain.⁷

Symptoms of AD

The Alzheimer’s Association has broken the symptoms of AD into seven stages. In stage one, there is no impairment and no symptoms. In stage two, there is very mild cognitive decline, which may be either normal age-related changes or early signs of AD, but no symptoms of dementia can be detected during a medical exam or by friends or family.

In stage three, there is mild cognitive decline (known as early-stage AD) that friends or family begin to notice, including noticeable problems coming up with the right word or name, trouble remembering names when introduced to new people, having noticeably greater difficulty performing tasks in social or work settings, losing or misplacing a valuable object, and increasing trouble with planning or organizing. At this stage, doctors may be able to diagnose AD in some people.

In stage four, there is moderate cognitive decline, also known as early-stage AD, and symptoms include forgetfulness of recent events, impaired ability to perform mental arithmetic, greater difficulty performing complex tasks (e.g., planning dinner for guests or paying bills), forgetfulness about one’s own personal history, and becoming moody or withdrawn. A careful medical interview should be able to detect clear-cut symptoms of AD at this stage.

In stage five, there is moderately severe cognitive decline, known as moderate or mid-stage AD. At this stage, individuals show noticeable symptoms, including the inability to recall their own address or telephone number, becoming confused about where they are or what day it is, trouble with less-challenging mental arithmetic, needing help choosing proper clothing and remembering significant details about themselves and their family. However, while they need help with day-to-day activities, they still require no assistance with eating or using the toilet.

In stage six, there is severe cognitive decline, known as moderately severe or mid-stage AD. At this stage, the individual’s memory begins to worsen, personality changes may take place, and they may need extensive help with daily activities. Symptoms include losing awareness of recent experiences and their surroundings, remembering their own name but having difficulty with their personal history, distinguishing familiar and unfamiliar faces but having trouble remembering the name of a spouse or caregiver, needing help dressing properly, experiencing major changes in sleep patterns, needing help handling details of toileting, having increasingly frequent trouble controlling their bladder or bowels, experiencing major personality and behavioral changes, and tending to wander or become lost.

Stage seven is the last stage in which there is very severe cognitive decline, known as severe or late-stage AD. This is the final stage of the disease during which individuals lose their ability to respond to their environment, carry on a conversation and, eventually, to control movement. At this stage, the individual may also lose the ability to smile, to sit without support and to hold their heads up. Their reflexes become abnormal, their muscles grow rigid, and their swallowing is impaired. In this final stage, the patient is bedridden.⁸

One symptom that is not listed in the seven stages and is being investigated as an early sign of AD is weight loss. In a study published in the Archives of Neurology, the researchers found that a subtle speeding up of weight loss that can accompany aging may be a very early warning sign of AD. Older people in the study who were followed for an average of six years lost twice as much weight in the year before the first signs of dementia appeared as people who did not develop Alzheimer’s-related dementias — 1.2 pounds compared with 0.6 pounds per year. While the study’s authors said the acceleration in weight loss was too small to help physicians identify AD earlier in individual patients, they did think the finding may help researchers better understand the disease.⁹

More recently, a study found that non-overweight individuals in their late 60s, 70s and early 80s who have no outward symptoms of Alzheimer’s are more likely than their heavier peers to have biological markers of AD. In the study, researchers looked at 101 people who underwent brain scans designed to identify the plaques and abnormal tangle of proteins thar are the hallmark of AD, and another 405 people whose cerebrospinal fluid was analyzed for fragments of the beta-amyloid peptide and tau proteins. Each group included some people with AD, some with mild cognitive impairment and some with no signs of mental deterioration. There was no connection between body mass index (BMI) and AD biomarkers in the patients who had AD. But, in the other two groups, lower BMI was associated with higher levels of biomarkers and a higher likelihood of having brain plaques and tangles. For instance, among people with mild cognitive impairment, 85 percent of non-overweight individuals had signs of these brain abnormalities compared with just 48 percent of those who were overweight or obese.

According to the researchers, the finding raises the possibility that weight loss or a low BMI later in life may be an early warning sign of mental decline. Jeffrey M. Burns, the lead author of the study and the associate director of the University of Kansas Alzheimer’s Disease Center, said that well before memory loss and other symptoms appear, AD may trigger metabolism changes that promote weight loss. “In general, we think of Alzheimer’s as a brain disease,” Burns said. “But, this is evidence that there are systemic problems throughout the body in the early stages of Alzheimer’s.”^10,11

Another symptom that also is not included in the seven stages and that is being investigated to identify AD patients at high risk of rapid cognitive decline is balance. In a study published in the Journal of Alzheimer’s Disease, 686 AD patients were evaluated by a geriatrician every six months for up to two years to measure their degree of cognitive impairment. At the same time, a “one-leg balance” test was given during which participants were asked to stand on one leg for as long as possible. The test was considered abnormal when the participant was unable to stand on one leg for five seconds or more. At the outset, roughly 15 percent of the study subjects had an abnormal one-leg balance test, and these patients were significantly older and had significantly more severe cognitive impairment. In analyses taking into account factors that might influence the results, the researchers found that subjects with an abnormal one-leg balance test had significantly greater decline in memory and thinking at 12 months, 18 months and 24 months. “Our results reinforce, in an Alzheimer’s disease population, the growing evidence suggesting a link between physical performance and cognitive decline,” said study chief Dr. Yves Rolland of the University of Toulouse III in France. “If these results are confirmed by other data, the one-leg balance test could be adopted in clinical practice to identify Alzheimer’s disease patients at risk of rapid decline.”¹²

Diagnosing AD

The only way to make a definite diagnosis of AD is to determine whether there are plaques and tangles in the individual’s brain tissue, which can only be done in an autopsy. Therefore, doctors must make a possible or probable AD diagnosis. Fortunately, at specialized centers such as the Mayo Clinic, doctors can correctly diagnose AD up to 90 percent of the time. To do this, they utilize several tools: a complete medical history, which includes information about the person’s general health, past medical problems and any difficulties the person has carrying out daily activities; medical tests such as tests of blood, urine and spinal fluid, which help discover other possible diseases causing the symptoms; neuropsychological tests that measure memory, problem solving, attention, counting and language; and brain imaging studies using magnetic resonance imaging (MRI) or positron emission tomography (PET). It’s important for physicians to rule out other possible causes of the person’s symptoms using information from the medical history and test results. For instance, thyroid problems, drug reactions, depression, brain tumors and blood vessel disease in the brain — all of which can be successfully treated — can cause AD symptoms.13

There are some new biomarkers that are being investigated for diagnosing AD. In the past 10 years, scientists have developed sophisticated brain scans that can estimate the amount of plaque in the brain while people are still alive. These scans have proved useful in studying the earliest stages of AD before overt symptoms appear. One such scan is called Amyvid, which was approved in 2012 by the U.S. Food and Drug Administration (FDA). Amyvid was built on an approach developed a dozen years ago at the University of Pittsburgh. In that approach, researchers injected patients with a small, benign amount of a radioactive dye they named Pittsburgh compound B, or PiB. The dye traveled through the blood to the brain and clung exclusively to clusters of amyloid protein. Scanning the brain with a PET machine then produced images that highlighted any plaques by detecting radiation in the form of gamma rays emanating from the dye. Scientists at Philadelphia-based Avid Radiopharmaceuticals then developed a longer-lasting dye that gave clinicians more time to scan their patients, and the result was Amyvid, which Eli Lilly bought in 2010 for $300 million. Today, the test is available in more than 450 imaging centers at a cost of $3,000 or more.

But, the use of Amyvid is under debate. Officially, the test has been approved primarily to exclude AD as a diagnosis for someone who already has cognitive impairment, which can be particularly helpful when causes are unclear. But, in January 2013, an expert task force convened by the Alzheimer’s Association and the Society of Nuclear Medicine and Molecular Imaging published guidelines that advised limiting the test’s use to patients with unexplained, persisting mild cognitive impairment and to those who either have developed dementia unusually early or have dementia with atypical symptoms such as hallucinations or delirium. It also advised against amyloid scans for people with no cognitive impairment. Because there is no treatment for AD, panelists worried that amyloid-positive results might send some vulnerable individuals into depression or perhaps suicide, and that it might make it harder for an individual to get long-term care insurance or renew a driver’s license. A clinical trial began last November to quell the controversy. The study at 60 U.S. medical centers aims to screen 3,000 healthy senior citizens to identify 1,000 amyloid-positive individuals who will receive either a drug therapy for AD called solanezumab or a placebo for three years. But, the study is accepting only participants who are “capable of handling uncertainty and, potentially, what could be construed as bad news if they learn that they are amyloid-positive on imaging.” The trial’s results are not expected until 2018.⁴

Blood tests are another new method being investigated for diagnosing AD earlier than the current brain scans and cognitive tests. In a recent trial at Saarland University and Siemens Healthcare, scientists compared and contrasted 140 microRNAs (non-coding genetic molecules) of a sample group of 202 people made up of AD patients and a healthy control group. They found that 12 of the microRNAs differed significantly between the AD patients and the healthy group. By using those 12 as biomarkers, the technique accurately identified the presence of AD 93 percent of the time. It also distinguished AD from similar neurodegenerative diseases such as Parkinson’s and early-onset dementia. Researchers now need to ensure the accuracy of the biomarkers and get the test approved for clinical use.¹⁴

Even better, in March, researchers at Georgetown University in Washington, DC, developed a blood test that identifies 10 chemicals in the blood associated with the disease two to three years before symptoms start, and it might be able to predict Alzheimer’s decades earlier. The researchers studied 525 people age 70 and older for five years who showed no signs of mental impairment at the start of the study. Each year, the team performed a detailed cognitive examination and took blood samples from all participants. During that time, 28 people developed Alzheimer’s or mild cognitive impairment, which is thought to be the earliest noticeable sign of dementia. An analysis of the participants’ blood highlighted 10 metabolites that were depleted in those with mild cognitive impairment who went on to get Alzheimer’s compared with those who didn’t. In subsequent trials, the team showed these chemicals could predict who would go on to get Alzheimer’s within the next three years with up to 96 percent accuracy. Once verified in a larger group, the test should provide a cheap and quick way of predicting Alzheimer’s. And, because the brain changes associated with Alzheimer’s begin many years before symptoms occur, “these metabolic changes might occur 10 or 20 years earlier,” says team member Mark Mapstone at the University of Rochester Medical Center in New York. “That would give us a real head start on predicting the disease.”¹⁵

Researchers at Georgetown University Medical Center (GUMC) and the University of Hong Kong also have found a new biomarker for possibly diagnosing AD by simply screening for changes in the eyes. In their study, the scientists showed how the thicknesss of a particular layer of retinal cells may serve as an indication of AD progression. They analyzed the thicknesses of the six layers of retinas in a group of mice that had been genetically engineered to develop AD. They found that there was significant loss in thickness to both the inner nuclear layer, which experienced an average 37 percent loss of neurons, and the retinal ganglion cell layer, which experienced an average 49 percent loss. “The retinas have neurons themselves that send projections straight to the brain,” said Dr. R. Scott Turner, director of the Memory Disorder Program at GUMC. “Those nerve cells are directly connected to the brain via the optic nerve.… So, when looking at the retina, it’s the easiest place to see the brain and its neurons.” The next step is to see if the biomarker translates to humans with AD. If similar changes in retinal thickness occur in people, then a simple, noninvasive procedure known as optical coherence tomography can be used to measure loss of neurons in these layers.¹⁶

Last, a new clinical test to confirm a diagnosis of early-stage AD is being examined at the University of Florida. In a small pilot study, patients who were coming to the university’s College of Medicine’s department of neurology to be tested for AD also sat down with a clinician who had 14 grams of peanut butter, which equals about 1 tablespoon, and a metric ruler. With the patients’ eyes and mouth closed and one nostril blocked, the clinician opened the peanut butter container and held the ruler next to the open nostril while the patient breathed normally. By moving the peanut butter up the ruler 1 cm at a time during the patient’s exhalation, the researcher was able to measure the distance at which the patient could detect the odor. The other nostril was tested after a 90-second delay. The scientists found that patients in the early stages of AD had a dramatic difference in detecting odor between the left and right nostril. The left nostril was impaired and did not detect the smell until it was an average of 10 cm closer to the nose than the right nostril. This was not the case in patients with other kinds of dementia; these patients had either no differences in odor detection between nostrils or the right nostril was worse at detecting odor than the left.

Of the 24 patients tested who had mild cognitive impairment, which sometimes signals AD and sometimes turns out to be something else, about 10 patients showed a left nostril impairment and 14 patients did not. The clinicians running the test did not know the patients’ diagnosis, which was con- firmed weeks after the initial clinical testing. It’s possible that this test could be used by clinics that do not have access to the personnel or equipment to run other, more elaborate tests required for a diagnosis.¹⁷

Treating AD

There are currently four medications approved by FDA to treat AD. The first was a result of a collaboration between the National Institute on Aging (NIA), the Alzheimer’s Association and the Warner-Lambert Pharmaceutical Company (now known as Pfizer) in 1987. Together, they started the first clinical trial of a drug, tacrine (Cognex), designed to treat the symptoms of AD, which was approved by FDA in 1993. Four more Alzheimer’s drugs were approved during the next decade.¹

Tacrine (now discontinued in the U.S. because of its serious side effects) is in a class of drugs called cholinesterase inhibitors, which are used to treat mild to moderate AD. Currently, the three FDA-approved drugs in this class are rivastigmine (Exelon), donepezil (Aricept) and galantamine (Razadyne, formerly Reminyl). Donepezil is the only cholinesterase inhibitor approved to treat all stages of AD, including moderate to severe. Cholinesterase inhibitors inhibit (block) the action of acetylcholinesterase, the enzyme responsible for the destruction of acetylcholine. Acetylcholine is one of several neurotransmitters in the brain, chemicals that nerve cells use to communicate with one another. Reduced levels of acetylcholine in the brain are believed to be responsible for some of the symptoms of AD. By blocking the enzyme that destroys acetylcholine, the drugs increase the concentration of acetylcholine in the brain, and this increase is believed to be responsible for the improvement in thinking, memory and speaking skills, and may help with certain behavioral problems.^18,19

Memantine (Namenda) is another drug approved by FDA to treat moderate to severe AD. Memantine is prescribed to improve memory, attention, reason, language and the ability to perform simple tasks. The drug regulates the activity of glutamate, a different messenger chemical involved in learning and memory; delays worsening of symptoms for some people temporarily; and can cause side effects, including headache, constipation, confusion and dizziness. And, it can be used alone or with other AD treatments. Individuals who are taking a cholinesterase inhibitor might also benefit by taking memantine.²⁰

It should be noted that none of the FDA-approved drugs has been directly compared with another, and while patients may respond better to one drug than to another, they work in a similar way, and it is not expected that switching from one to another will produce significantly different results. In addition, these drugs don’t change the underlying disease process. And, while they are effective for some but not all people, they may help only for a limited time.¹⁹

As with most diseases, there also are many alternative treatments. These include caprylic acid (Ketasyn), coenzyme Q10 (ubiquinone), coral calcium, ginkgo biloba, huperzine A, omega-3 fatty acids, phosphatidylserine and tramiprosate (ViviMind). However, claims about the safety and effectiveness of these products are based largely on testimonials, tradition and a small body of scientific research.²⁰

The Future of AD

Today, AD is at the forefront of biomedical research, and the future of the disease will depend on furthering our understanding of it, diagnosing it early and discovering ways to prevent, treat and even cure it.

Diagnosing it early and preventing it could be a matter of genetics. In a recent study, a research team divided 52 participants between the ages of 32 and 72 who were free of dementia into four groups: those who had either a mother with AD, a father with AD, both parents with AD or no family with AD. After participants underwent a series of brain scans, including an MRI and PET, researchers found that those whose mother and father both had AD showed 5 percent to 10 percent more brain plaques in specific brain regions and more severe brain abnormalities in brain volume and metabolism compared with people who had one parent or no family members with AD. They also found that those who have mothers with AD are more likely to develop the condition compared with people who have fathers with the disease.²¹ The hope is that the study will be helpful to future genetic investigations, one of which is currently ongoing. In 2003, the Alzheimer’s Association and the NIA started accepting people in the National Alzheimer’s Disease Genetic Study. Funded by the federal government, researchers take and store blood samples from people in families with more than one member with AD. The goal of the ongoing study is to find genes that may make someone more likely to get AD.¹

There are many studies that are focusing on development therapies for AD, many of which fall under the Alzheimer’s Disease Cooperative Study (ADCS), a large clinical trials consortium supported by the NIA with sites throughout the U.S. that is investigating both the cognitive and behavioral symptoms of AD. Some of the recent therapies being investigated are intravenous immune globulin (IVIG), resveratrol and nerve growth factor. IVIG contains naturally occurring antibodies against beta-amyloid. Preliminary studies have shown that it may improve cognition, increase levels of anti-betaamyloid antibodies in plasma, and promote clearance of betaamyloid from cerebrospinal fluid. Baxter conducted one NIA-supported IVIG study, known as the GAP study, which was a Phase III double-blind, placebo-controlled study to examine the safety, effectiveness and tolerability of IVIG in people with mild to moderate AD.22 Unfortunately, the study did not meet its co-primary endpoints of reducing cognitive decline and preserving functional abilities in patients with mild to moderate AD. Therefore, the company is reconsidering the current approach for the AD program, and will determine next steps after full data analyses.²³

Grifols also is currently undergoing its own study, the AMBAR (Alzheimer Management by Albumin Replacement) study, to determine whether plasmapheresis with infusion of human albumin combined with IVIG is able to modify cognitive, functional, behavioral and global domains in patients with mild to moderate Alzheimer’s disease. Begun in July 2012, the study is being conducted in hospitals in Spain and the United States and includes 350 Alzheimer’s patients at the mild to moderate stage of the disease, randomly grouped into three treatment groups and a fourth control group. The treatment groups consist of plasmapheresis with 20% albumin and IVIG high dose, plasmapheresis with infusion of 20% albumin and IVIG low dose and plasmapheresis with infusion of 20% albumin low dose. Patients will be treated with a propotype of a plasmapheresis machine developed by Fenwal that was specially adapted to make the treatment experience more pleasant for the patient and easier for the medical staff to administer, which the study also seeks to validate. The estimated duration of the study is two years.

In September 2009, Grifols published partial results (29 patients out of 42) of a preliminary trial conducted in two hospitals in Spain and two in the U.S., which showed a tendency for the treatment to stabilize the disease. “This study is the fruit of over five years of research that have produced encouraging results, with patients receiving prior treated maintaining cognitive stability through the study period and achieving positive ADAS-cog scores,” said Dr. Merce Boada, medical director of Fundacio ACE and clinical head of the Neurology Service of the Vail d’Hebron Hospital in Barcelona. “The AMBAR study opens up new prospects and hopes in dealing with an illness where success involves maintaining the quality of life of these patients.”²⁴

Resveratrol is an antioxidant compound found in grapes and red wine. Observational studies have shown that moderate consumption of red wine is associated with a lower incidence of AD, and animal studies have demonstrated resveratrol’s neuroprotective properties. The resveratrol in AD study is a Phase II double-blind, randomized, placebo-controlled trial that began recruiting 120 volunteers at 26 sites affiliated with the ADCS across the U.S. in early 2012. It is evaluating the impact of resveratrol treatment on biomarkers and clinical outcomes in people with AD.²²

Also currently underway is a Phase II clinical study of Ceregene’s CERE-110, a gene therapy product designed to deliver nerve growth factor (NGF) to the brain for the treatment of AD. The rationale behind the study is that NGF is known to promote survival of certain neurons, called cholinergic neurons, that degenerate in AD, and therefore may provide sustained functioning of these neurons. Direct delivery of CERE-110 into the brain aims to selectively target the Nucleus Basalis of Meynert (NBM), where cholinergic neuronal degeneration occurs in AD. The study will examine the safety and effectiveness of NGF on AD in 50 patients at 11 research sites affiliated with the ADCS across the U.S.²⁵

In 2011, President Obama signed into law the National Alzheimer’s Project Act (NAPA). NAPA is the first law to outline a national strategy for research and care of people with AD. The act also addresses support for people caring for AD patients. A year later, the National Alzheimer’s Plan was released, which set a goal of creating AD prevention methods by 2025.¹

It may be too late to find a treatment for my uncle. But, with so much research in progress and the dedication of so many groups to make progress in preventing this disease, it is certainly possible there may be hope for future generations.