Science and Research Questions

Previous studies using a rat model of Alzheimer's disease indicated that the active compounds found in marijuana, called cannabinoids, could protect the rats from the damaging effects of amyloid deposits in the brain. A synthetic cannabinoid called delta-9-tetrahydrocannabinol, or THC, was given to the rats and was found to reduce the toxicity of amyloid plaques as well as promote neurogenesis (the growth of new neurons) in the brains of the rats.

Hoping to reproduce these findings, investigators at the University of British Columbia and Vancouver Coastal Health Research Institute recently re-tested the hypothesis using a different animal model of Alzheimer's disease (AD). The transgenic mice used in these studies carry human genetic mutations associated with AD and develop pathology more similar to that which is seen in human AD patients.

Thus, the mice represent a more accurate model of the disease. Using two different doses of a synthetic cannabinoid called HU210 (which is many times more potent than the naturally-occurring cannabinoids found in marijuana), the mice were treated for several weeks and then assessed on memory and final brain pathology. Unfortunately, the researchers found no beneficial effect whatsoever for mice treated with HU210, and in fact there seemed to be a slight worsening of their condition. For example, the mice given the lower dose of HU210 had worse memory test scores than non-treated control mice, and the mice given the higher dose had slightly fewer neurons overall than control mice. Additionally, there was no difference in the number or extent of amyloid plaques between treated and untreated mice, regardless of the dose of drug administered.

The researchers therefore indicated that additional studies would need to be performed before much hope could be placed on using medical marijuana as a potential treatment for—or preventative measure against—Alzheimer's disease.

While the symptoms you list are could all be very early indications of a memory problem or dementia (with Alzheimer's disease being the most common form of dementia), many other conditions could account for these symptoms. For example, infections, drug interactions, a metabolic or nutritional disorder, brain tumors, stroke, depression or another progressive disorder like Parkinson's disease can all cause memory impairments, mood swings, and even disturbances in a person’s sleep-wake cycle.

At this point, the person you describe might have a condition called mild cognitive impairment (MCI). Individuals with “amnesic” MCI, the most common form, have memory impairment (for example, difficulty remembering names and following conversations and pronounced forgetfulness), but are able to perform routine daily activities without assistance. These MCI patients generally have normal judgment, perception and reasoning skills. Many people with MCI are at risk for further cognitive decline, usually caused by Alzheimer’s disease. However, while all patients who develop some form of dementia go through a period of MCI, not all patients exhibiting MCI will develop Alzheimer’s disease.

Symptoms of MCI may include:

• Memory problems that are noticed by others
• Poor performance on cognitive tests
• Depression
• Irritability, anxiety and sometimes aggressive or apathetic behavior

If any of the symptoms you mention become more pronounced in frequency or severity, or if the behaviors begin to interfere with daily activities (for example, employment tasks, social interactions and family chores), the person you refer to would definitely benefit from seeking qualified professional advice and evaluation by a physician with extensive knowledge, experience and interest in dementia and memory problems.

The two main neurochemical changes that have been demonstrated to occur in Alzheimer's disease (AD) are a decrease in the neurotransmitter acetylcholine (ACh) and alterations in N-methyl-d-asparate (NMDA) receptors (i.e., cell surface "docking sites"). In the first instance, ACh is known to be important for memory processing and learning. So decreased ACh levels, along with a decrease in the number of cholinergic neurons (the neurons which utilize ACh for signaling) are thought to underlie many of the memory and cognitive deficits seen in Alzheimer's disease patients. Cholinesterase inhibitors, such as Aricept® (donepezil), Exelon® (rivastigmine), Razadyne® (galantamine), and Cognex® (tacrine), work by slowing the metabolic breakdown of acetylcholine, and therefore make more of this neurochemical available for communication between nerve cells. This helps slow the progression of cognitive impairment and can be effective for some patients in the early to middle stages.

In the second instance, due to deficiencies in glutamate reuptake and metabolism, NMDA receptors are believed to be continuously activated, which leads to overstimulation of neurons and eventual cell death. This is where NMDA receptor antagonists such as Namenda® (memantine) come into play. Memantine appears to protect the brain's nerve cells against excess amounts of glutamate, a messenger chemical released in large amounts by cells damaged by Alzheimer's (and some other neurological disorders). When glutamate attaches to NMDA receptors, this permits calcium to flow freely into the cell, which in turn may lead to cell degeneration. Memantine may prevent this destructive sequence by adjusting the activity of glutamate.

Beyond these neurotransmitter systems, the destructive pathology of Alzheimer's disease, which mainly involves amyloid-beta plaques and neurofibrillary tau tangles, is associated with inflammation, oxidative damage, and a whole repertoire of immune cells and inflammatory molecules (such as cytokines, chemokines, free radicals, etc.) Because of this, scientists have investigated whether drugs that can reduce inflammation or oxidative damage, such as non-steroidal anti-inflammatory drugs (NSAIDs) and antioxidants, respectively, could also potentially help in the treatment of AD. Conflicting results in multiple studies on both NSAIDs and antioxidants means that further research is clearly needed.

By far, the single biggest risk factor for developing Alzheimer's disease (AD) is age. The risk of AD increases progressively with every decade of life, such that a person in their 80s is at a much higher risk for developing AD than a person in their 60s (assuming all other life factors are equivalent).

The majority of AD cases are late-onset, usually developing after age 65, and this form of the disease shows no obvious inheritance pattern. However, in some families, clusters of cases are seen. The gene called Apolipoprotein E (ApoE) appears to be a risk factor for the late-onset form of Alzheimer's disease. There are three forms of this gene: ApoE2, ApoE3 and ApoE4. Roughly one in four Americans has the ApoE4 gene and one in twenty has ApoE2. While inheritance of ApoE4 increases the risk of developing the late-onset form of Alzheimer's disease, inheritance of ApoE2 substantially protects against the disease. Some current research is focused on the association between these two forms of ApoE and Alzheimer's disease. Several other genes also appear to influence the development of Alzheimer’s disease, and more detailed information is available in the Heredity and Alzheimer's Disease section.

Familial Alzheimer’s disease (FAD) or early-onset Alzheimer's is an inherited, rare form of the disease, affecting less than 10 percent of patients. FAD develops before age 65, in people as young as 35. It is caused by one of three gene mutations on chromosomes 1, 14 and 21.

In addition to age and genetics, there are several other lifestyle and/or environmental factors that may contribute to a person’s overall risk of developing AD. For example, risk factors associated with cardiovascular disease and stroke, such as high blood pressure and high cholesterol, may also increase one’s risk of developing AD. Type II diabetes, traumatic brain injury, and even lower education levels have also all been linked with a higher associated risk of Alzheimer's disease.

Typically, Alzheimer's disease (AD) is divided into roughly three stages: mild, moderate and severe. Based upon what you describe, your wife appears to be in the moderate stage of the disease, which is generally the longest. During this stage, it is not uncommon for a person with AD to have difficulty following conversations. They even may invent words or else have other speech-related problems. As your wife becomes more disconnected from reality, she may forget how to use everyday objects such as comb, fork, or pencil, she may have difficulty recognizing familiar people (even you), and she may even at times not recognize her own reflection in the mirror. This is all a part of the disease.

Now may be a good time to start working on alternative means of communicating with your wife. As language may be confusing at times, touch can sometimes be a comforting means of communicating with a loved one, particularly in the later stages of the disease. Try just holding her hand, stroking her arm, or gently brushing her hair. When you do speak to her, try to speak clearly—use fewer or simpler words whenever possible. If you feel like she is losing interest or is confused about what you are saying, try redirecting her attention to a different activity, such as singing along to her favorite music, looking through a photo album, or looking at a book of artwork or pictures you know she’ll enjoy, etc. Or just take a walk with her if she seems restless. You can also ask the staff at the retirement home for suggestions about activities you could to together.

The most recent foods to receive attention by the medical community as being potentially beneficial for protecting against cognitive decline caused by Alzheimer's disease include coconut oil (also in fresh coconut and canned coconut milk), curcumin (the yellow pigment in the curry spice called turmeric), and apple juice. Foods rich in antioxidants may also be beneficial for slowing cognitive decline. Foods considered antioxidant-rich include blackberries, blueberries, spinach, strawberries, red bell peppers, walnuts, artichoke hearts and tomatoes, among many others. Green tea, dark chocolate and red wine all contain antioxidants too. Further research is required before definitive statements can be made with regard to the efficacy of using these food products for either the prevention or treatment of Alzheimer’s disease symptoms.

Any therapy that can help to reduce stress in the patient suffering from Alzheimer's disease is also good. Physical exercise (to the best of the patient’s capability), massage or relaxation therapy, music therapy and art therapy have all been reported as being helpful to AD patients.

Another lesser known alternative therapy is doll therapy, which involves giving a lifelike doll baby or teddy bear to a dementia patient and allowing them to interact with the doll. It has been observed that dementia patients given dolls to “care for” tend to be more communicative with caregivers and staff and less prone to negative behaviors, such as agitation or anxiety. Doll therapy seems to bring out the nurturing instinct in many dementia patients, particularly females, who may be reliving memories of being a parent of an infant, a time in their lives when they were very much needed and useful.

Non-formal observations by caregivers recommend that the doll be as lifelike as possible, and be introduced to the patient while he or she is still in the early stages of the disease to allow time for bonding with the doll. Given in the later stages, the doll may be less effective.

High levels of chronic stress, an incidence of head injury, and a close family member with Alzheimer's disease are all factors that have been associated with a greater risk of developing Alzheimer's disease (AD). So based upon these aspects, your overall risk of developing AD is higher than that of a person in the general population with none of these factors. However, this does not mean that you will definitely get the disease. There are a number of other genetic and environmental factors that can influence a person’s overall risk of getting AD - some of these are known (as are the 3 noted above), and some still have yet to be determined.

On the other hand, you can take some measures to help lower your overall risk as well. For example, 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 help to reduce your risk of developing Alzheimer's disease. You should strive for diet that is low in saturated and trans fats, low in cholesterol, and high in antioxidants.

You can mentally exercise your brain by doing puzzles, word or number games, or by 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 your 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 to get enough sleep. Most adults need at least 7-8 consecutive hours of sleep each night in order for memory functioning to be at its best.

Scientists have been aware for some time that electroconvulsive treatment (ECT) can promote adult neurogenesis (the formation of new brain cells or neurons) in the hippocampus, an area of the brain associated with memory. ECT has successfully been used as a treatment for patients with major depression who are non-responsive to conventional antidepressant drug therapy. Coincidentally, the hippocampus is also known to be subject to deterioration and loss of neurons caused by Alzheimer's disease (AD). Enhancing neurogenesis in general has been suggested as a therapeutic strategy for the treatment of AD. So it would seem obvious, as you suggested, to determine if ECT could be used to enhance neurogenesis in AD patients.

Surprisingly, however, there have been relatively few studies that have looked at the effects of ECT in the elderly, and in dementia patients in particular. Despite the positive effects seen in younger patients with depression, ECT has also sometimes been reported to worsen memory problems following treatment in depressed patients. Therefore, most of the studies on ECT in older persons have focused on the safety and efficacy of treatment, particularly to determine if ECT exacerbates memory deficits in older patients. When administered under optimal means, ECT has been found to be safe and relatively well-tolerated in the elderly.

A handful of studies have looked at whether or not ECT can be used to treat major depression in patients with dementia. Here too, ECT was reported to be safe and effective for the treatment of depression in dementia patients. Interestingly, these studies found that not only did ECT improve symptoms of depression in these dementia patients, but it also improved cognition. However, it was noted that about half of the patients developed short-term (1-3 days) delirium as a result of the procedure, but this side-effect did not negate the cognitive improvements observed in these patients. Unfortunately, this was a relatively small study (only about 30 patients), and there were no formal controls for comparison (such as non-depressed dementia patients or depressed age-matched non-AD patients), so it is difficult to draw many conclusions based on this report alone.

To date, there have not yet been any formal, controlled studies to directly test the hypothesis that ECT may be a potential treatment for AD. Until such research has been performed and verified, it is unlikely that ECT will be used as therapy for a non-depressed patient having AD.