Science and Research Questions

Whether or not to withdraw memory medications is often discussed during the course of Alzheimer’s disease, especially in the more advanced stages of the disease. Within weeks after withdrawal of the cognitive enhancing medications such as Namenda or Aricept, the benefits will mostly be gone. Earlier in the course of Alzheimer's disease, the result of medication withdrawal may be a cognitive decline. Later, cognitive decline may be more difficult to recognize but there is a possibility that functional or behavioral symptoms that were helped by the medication(s) might increase. It is not clear whether medication withdrawal shortens life. Determining the effect of medication withdrawal on the patient's quality of life is complicated, but in cases where behavioral symptoms increase there may certainly be a deleterious effect on both patient and caregiver quality of life. On the other hand, the cholinesterase inhibitors can produce gastrointestinal side effects and other medical symptoms that will go away if the medication is discontinued, and memantine (though typically associated with minimal side effects) can also produce side effects such as constipation or confusion that will subside with medication discontinuation. The decision to discontinue cognitive enhancers must be individualized, and should take into account the balance between the benefits of discontinuation (reduced expense, simplified management, elimination of side effects) and the drawbacks (potential for more rapid or severe cognitive and behavioral decline).

Alzheimer's disease (AD) is like frontotemporal dementia (FTD) in that both are dementias. Both affect memory and language among other cognitive faculties, and both can result in behavioral disturbances. These two dementias differ in important ways, including the following:

• Prevalence (AD is around six times as frequent as FTD among older adults)
• Etiology (the pathology of AD includes the famous "plaques and tangles," while a variety of other changes characterize FTD)
• Location of pathology (FTD is associated with very significant frontotemporal atrophy*, while brain atrophy in AD is located more in the temporoparietal areas)
• Age of onset (FTD starts at an earlier age)
• Effects on behavior (FTD is adversely affected earlier with such symptoms as disinhibition)
• Medication treatment (AD is treated with cholinesterase inhibitors and/or memantine, while FTD currently has no FDA-approved medications)

*atrophy is the wasting away or decrease in size of a body organ or tissue

You may be referring to a small pilot study performed by Dr. Alan B. MacDonald in 2006, who found DNA for Borrelia burgdorferi, the Lyme disease spirochete, in seven of ten autopsied Alzheimer's disease brains obtained from the McLean Hospital Brain Bank of Harvard University. Because of the similarity in pathology observed in the brains of patients with Alzheimer's disease patients and those having viral infections of the brain or central nervous system (CNS), Dr. MacDonald proposed a hypothesis that chronic infections caused by viruses or bacteria (as in the case of Lyme disease) may underlie Alzheimer's disease.

However, other studies with a larger number of subjects have not found a connection between Lyme disease and Alzheimer's disease. For example, one study found no evidence of Borrelia antibodies (antibodies are an indicator that the body has been exposed to a foreign pathogen, which in this case would be the Lyme disease pathogen) in patients with Alzheimer's disease. Clearly, further research needs to be performed in order to determine if spirochetes can in any way influence the development of Alzheimer's disease or other neurodegenerative disorders.

At present, the only way to truly confirm a diagnosis of Alzheimer's disease is through autopsy of a patient’s brain at death. Because the symptoms of Alzheimer's disease (AD)—including memory problems, cognitive deficits, and changes in mood or behavior—can occur in a number of other diseases and disorders, sometimes it is difficult to distinguish AD from other conditions. Some people in the medical community say that Alzheimer's disease may be over-diagnosed (or misdiagnosed), and that there are other, under-diagnosed dementias that have been lumped into the AD camp.

Particularly if your doctor did not perform extensive medical and psychological tests on you, it is possible that your diagnosis may be incorrect, but that does not mean that there is nothing wrong at all. You probably presented with at least some symptoms of AD for your doctor to have arrived at this diagnosis. So, you may either have AD and are very fortunate that it has not progressed very rapidly (perhaps you are on medications and they have helped to slow the progress of the disease symptoms?), or you may not have AD, but some other condition with symptoms very similar to it. It would be helpful to speak to your doctor and ask him how he came to the diagnosis of AD. In other words, what criteria were used to arrive at this diagnosis? Additionally, if possible, it wouldn’t hurt to obtain a second opinion.

While Alzheimer's disease has been reported in individuals as young as their late twenties, this is very atypical. Apart from persons having Down’s syndrome, it would be highly unusual for a non-Down’s syndrome teenager to develop Alzheimer's disease pathology. Because the disease is believed to be the result of an abnormal accumulation of amyloid deposits and tau tangles in the brain, and because this process generally takes years or even decades to develop, this would mean that a teenager would have to start developing such pathology as a child.

If, for argument’s sake, a teenager were to develop Alzheimer's disease, then the symptoms and treatment options would most likely be the same as for an older adult.

It's not possible to diagnose early Alzheimer's disease from your description of memory slips that could result from so many different possible causes. Normal aging is associated with some "senior moments" and these are worse and more frequent when people are stressed or depressed. Some antidepressant medications can affect memory, as can a thyroid imbalance or morphine. My suggestion is that you review your medications and conditions with the clinicians helping you, aim for consistency in your use of the proper medications, and ask your clinicians whether formal neuropsychological testing (in a memory clinic, for example) would be appropriate at this time.

Niacinamide, also called nicotinamide, was reported in 2008 to improve cognitive functioning in mice genetically engineered to have a disease similar to Alzheimer's disease. The nicotinamide was thought to work by inhibiting the hyperphosphorylation of tau protein that creates "neurofibrillary tangles" (one of the hallmarks of Alzheimer’s disease) and destroys the internal structure of brain cells. The results of human studies are still awaited. Though related to niacin, niacinamide doesn't produce the uncomfortable "flush" that niacin often does. On occasion, in high doses, it can sometimes cause liver toxicity.

Aricept (donepezil) is a well-known medication indicated by the FDA for treatment of mild, moderate, and severe Alzheimer's disease.

Lithium aspartate does not carry an "indication" for Alzheimer’s disease and lithium has potential side effects, but is also believed to have some chemical properties that might be "neuroprotective." The small dose of lithium aspartate you mention may be unlikely to cause harm but should (like all medications) be reviewed with the clinicians treating your wife.

Exelon (rivastigmine) is one of the cholinesterase inhibitors and is FDA indicated for treatment of mild to moderate Alzheimer's disease. Namenda (memantine) works on a different neurotransmitter system (glutamate) and is FDA indicated for use in moderate to severe Alzheimer's disease. It is common practice to combine any of the cholinesterase inhibitors with memantine and there are research findings to support that approach. Several studies have tried to look specifically at the combination of rivastigmine with memantine and most (but not all) support using both medications together. The likelihood of the combination being less tolerable than rivastigmine alone is small. Some studies have reported an additional benefit from adding memantine to rivastigmine, but these studies are of the type called "open label." That means both the subject and investigator knew what experimental drug was being taken, which is a potential source of bias. It would be more convincing to have "double blind" studies that compare subjects on rivastigmine with a placebo added, to subjects who are taking rivastigmine with memantine added, under conditions in which neither subjects nor investigators know who is taking which drug.