Science and Research Questions

The arthritis medication Enbrel® (generic name: etanercept) is a TNF-alpha antagonist (TNF-alpha is an inflammatory cytokine). Studies suggest that brain inflammation may play a role in damage due to Alzheimer's disease and TNF-alpha secreted by glial cells in the brain may contribute to this damage. In a six-month pilot study in California, scientists found that perispinal injection (administration directly into the central nervous system) of etanercept produced significant cognitive improvements in all Alzheimer's disease patients (ranging from mild- to severe-Alzheimer's disease at the start of the study). Even more recently, these same researchers found that in one patient with late-onset Alzheimer's disease, perispinal injection of etanercept (i.e., injection into the fluid surrounding the spinal cord) induced significant cognitive and behavioral improvements within a matter of minutes.

These results are certainly encouraging, but additional testing will be necessary (such as much larger clinical trials and FDA approval) before any such treatment can be offered to the general public. Because etanercept is currently not approved for the treatment of AD, you can speak to a neurologist in your area but it is unlikely that he or she will be able to authorize this line of therapy. However, in the Resources section of our website you can search for Alzheimer's clinical trials in your area that you may be able to participate in.

Hallucinations can be caused by dementia itself, by drug interactions, or by a combination of both damage to the brain (such as is found with Alzheimer's dementia) and an adverse reaction to a drug or to combinations of drugs. A physician should be consulted to rule out drug interactions or other underlying medical ailments. Depending on the area of the brain affected by Alzheimer's, a patient may retain the bulk of their verbal capabilities until a late stage of the disease, or conversely, the patient may develop progressive difficulty in being able speak coherently or to comprehend verbal or written language. While in general the disease follows a progressively degenerative course, the specific symptoms of the disease and their severity are typically unique for each patient.

Bryostatin was originally developed as an anti-cancer drug, but it has shown great promise in the laboratory as a neuroprotective agent. Bryostatin is a protein kinase C (PKC) activator. PKC is a protein that is involved with synaptic signaling (the signaling connections between brain cells). Proper signaling at neuronal synapses is necessary to form and store memories. If these synaptic connections are lost or injured, such as in the case of Alzheimer's disease or other neurological disorders, then memory will deteriorate. Bryostatin is therefore thought to work by activating PKC in neurons, which helps to repair and restore synaptic connections, which has been shown to result in improved and enhanced memory in laboratory animals.

So far, test in animals have found that bryostatin can protect neurons from the damage caused by stroke, Alzheimer's disease (AD), and even normal aging. The drug even has been demonstrated to reduce the production of the AD-associated protein amyloid-beta within cells, which makes it even more valuable for the treatment of AD. The FDA recently approved phase II clinical trials for byrostatin, which were to commence in late 2009. The results of this trial are eagerly anticipated.

There is, however, one drawback to bryostatin: it is very difficult to obtain in large quantities. Bryostatin is produced naturally by tiny sea organisms called bryozoans, but it takes a vast quantity of bryozoans to make a small amount of the drug. Therefore, despite its complex structure, researchers have been trying to figure out how to produce bryostatin synthetically. In doing so, researchers have found less complex forms of bryostatin (called analogs) that are even more potent in terms of their neuroprotective effects. These synthetic forms of bryostatin may therefore prove useful clinically, though much laboratory testing needs to be completed before any clinical trials in humans using these analogs can take place.

What the doctors may be referring to is vascular dementia, which is distinct from Alzheimer's disease (AD) although the two diseases may have many common symptoms (such as memory and cognitive disturbances). After Alzheimer's disease, vascular dementia is the second most common cause of dementia in the elderly. It is caused by damage to the brain resulting from cardiovascular problems, such as a stroke. Sometimes, a person may have many small strokes that generally go unnoticed at the time. The cumulative effects of these mini-strokes, however, eventually damage enough brain tissue that symptoms become noticeable, sometimes within what seems to be a relatively short period of time.

This type of vascular dementia is called multi-infarct dementia (MID). There are also many other vascular disease problems that could cause vascular dementia, some less severe than others. Whether or not your mother’s condition will stay the same or deteriorate really depends upon the underlying vascular issues. If the MRI indicated mild vascular disease, it is possible that your mother suffered only a few minor strokes and her symptoms may stabilize, particularly with appropriate blood pressure or heart medications (if this is indeed the problem).

If however, your mother develops MID or another more progressive form of vascular disease, then her condition may worsen over time. Please try to speak to your mother’s doctor about her condition, and what her prognosis may be. Also, you can read more about the different types of dementia, including vascular dementia, through the National Institute of Neurological Disorders and Stroke (NINDS) website, which provides an informative guide to dementia.

Unfortunately, there is no rhyme or reason with this disease—some patients can go on for years with seemingly little decline, and others may progress much more rapidly. A traumatic life event—such as the death of a loved one—cannot in and of itself cause Alzheimer's disease or dementia in general, but it can exacerbate the symptoms of a patient who already has the disease. The death of your grandfather could have easily triggered a bout of depression in your grandmother, which could have worsened her memory problems, making them more noticeable to yourself and others. So it is possible that your grandfather’s death hastened the appearance of more severe memory deficits in your grandmother, but the disease itself would have already been present, albeit in a milder form. It is also possible that the death of your grandfather coincided with an unreported medical event in your grandmother, such as a small stroke, which also could have progressed dementia symptoms.

Mild forgetfulness and memory delays often occur as part of the normal aging process. Older individuals simply need more time to learn a new fact or to remember an old one. We all have occasional difficulty remembering a word, someone's name, or where they placed their car keys. Memory loss—particularly of short-term memory—will increase with age and it is all quite normal. A 50 year old will simply not be able to remember things as quickly or well as a person half their age.

Despite this discouraging news, there is evidence to suggest that exercising your mind as well as your body can help to reduce memory loss. A healthy diet and exercise can also help to reduce your risk of developing Alzheimer's disease. Your mother should therefore strive for diet that is low in saturated and trans fats, low in cholesterol, and high in antioxidants. Foods considered antioxidant-rich include blackberries, blueberries, spinach, strawberries, red bell peppers, walnuts, artichoke hearts, green tea, dark chocolate, red wine and tomatoes, among many others. Your mother can mentally exercise her brain by doing puzzles, word games, learning a new language, musical instrument, skill or technology—anything really that challenges the mind and really makes you think. But don't forget about the body. Physical exercise for your body is just as important because it can help to lower blood pressure, reduce body weight (or maintain a healthy weight), and decrease stress levels. Reducing stress will not only act to aid short-term memory, but can also improve overall emotional well-being, which is good for long-term cognitive health. Finally, be sure your mother gets enough sleep. Most adults need at least 7-8 consecutive hours of sleep each night in order for their memory functioning to be at its best.

Good quality and sufficient sleep are definitely both integral to proper cognitive functioning – chronic sleep deprivation can wreck havoc with a person’s ability to concentrate and remember. It has been commonly reported that patients with Alzheimer's disease have impaired rapid eye movement (REM) sleep. And current Alzheimer's disease treatments, such as donepezil (Aricept®) have been noted to enhance REM sleep in patients with Alzheimer's disease, which could contribute to the beneficial effects of the drug.

Alzheimer’s Disease Research is currently sponsoring researchers at Northwestern University who are investigating whether or not a connection exists between memory dysfunction and sleep in Alzheimer's disease. As part of the study, the researches will examine whether abnormalities in sleep patterns (which would include looking at REM sleep) have any bearing on memory functioning, such as in patients with mild cognitive impairment (MCI) or in patients having probable Alzheimer's disease.

Since the late 1990s, research has been developing on the use of immunotherapy to treat neurodegenerative diseases such as Alzheimer's. Immunotherapy of Alzheimer's disease involves the use of immune molecules, such as antibodies or other immuno-modulatory agents, to treat the disease by reducing or even preventing brain amyloid plaques.

Initial trials with a beta-amyloid protein vaccine in 2001 were halted when some of the participants in the study began to develop signs of brain inflammation. Although this was disappointing, a great deal was learned from the research. Autopsies of several participants who died of other causes revealed that a large amount of beta-amyloid had been cleared from their brains, their brain volume was lower, and lower levels of tau, another protein related to AD, were found in their spinal fluid. Further, for the living trial participants who developed antibodies, there was evidence of better memory, attention and concentration.

More recently, some pharmaceutical companies have begun further human trials using passive immunotherapy, in which antibodies to a protein (such as the beta-amyloid protein) rather than the protein itself are given to the recipient. There are basically two types of anti-amyloid antibody therapeutic approaches currently under investigation. The first type of anti-amyloid antibody attaches to already-present amyloid plaques and recruits the brain's own immune cells to aid in attacking and eliminating the plaques. The second type of antibody blocks the formation of new amyloid plaques by binding to beta amyloid protein and removing it from the brain and central nervous system before it has a chance to aggregate and form deposits. Both of these approaches have already demonstrated significant results in animal models of Alzheimer's disease, with considerable reductions in brain amyloid plaque burden as well as significant improvements in performance of memory tasks. Therefore, a combination approach using both types of anti-amyloid antibodies is also being considered for Alzheimer's treatment.

Great strides in protein and antibody engineering technology has also allowed researchers to develop safer and more effective therapeutic antibodies. For example, most experimental antibodies are initially made and tested in mice. These mouse antibodies cannot be given to humans because they can cause quite severe immune reactions, especially if used repeatedly. But through advances in antibody engineering, it is possible to “humanize” the mouse antibodies, making them safe for human use. This technique has already been successfully used to develop therapeutic antibodies for other diseases. So if the latest clinical trials go well, it looks promising that antibody-based therapies for Alzheimer's disease will be available within the next few years.