Dementia is one of the most frightening diseases that inflicts my patients. Approximately 2 million Americans suffer from dementia, and that number is increasing as more people are aging. Dementia is not merely memory loss; in fact, most elderly people suffer from memory loss as they age, and few of them actually become demented.

Dementia Is Not Just Memory Loss

Rather, dementia is deterioration of the thought process. While people with memory loss may forget someone's name or not remember where they put their keys, people with dementia cannot follow a conversation and often become confused about simple tasks. Most dementia also progresses through seven stages; the symptoms worsen with time at variable rates, and can often lead to total disability and dependency. While many forms of dementia exist, from Alzheimer's Disease to Pick's Disease, the deterioration in thinking and reasoning is similar in all of them.

What causes dementia? Put simply, we do not know. We do know that something (we think it is an abnormality of a certain protein in the brain) triggers a cascade of brain cell destruction that we have no capacity to prevent or stop. Very little of dementia is genetic; most cases occur in people who have no family history of the disease. The primary locations of brain cell destruction define what type of dementia, and consequently what symptoms, patients have. Some people with the disease hallucinate, some become agitated and violent, some become more passive and lethargic; there are probably many more forms of dementia than medical science has described, and most people have a combination of symptoms that change over time. Many dementia patients remain physically strong and live a long life, others stop eating or are prone to illness due to disability. In all cases, we can treat the symptoms, but not the disease.

There are drugs being tested that may impact disease progression by altering the protein malfunction, but these are in very preliminary trials. There are also several conditions that mimic dementia and can potentially be treated, but these are rare; of 1000 people who are screened for a reversible cause of dementia, only 3 are found to have reversible disease, and most of those are discovered by a basic set of tests that can be done by a primary care doctor. Seeing neurologists and doctors who are memory experts has not been shown to provide any benefit to dementia patients.

There Is No Cure; Just Mitigation

It is very important to realize that we currently have no treatment for dementia. While a host of medicines are offered to dementia patients, none of them alter the course of the disease. At best they can mitigate symptoms for a very brief period of time before they become ineffective. Still, that does not stop doctors and pharmaceutical companies from pushing these drugs, both individually and in combination, as a potent treatment for dementia. Unfortunately, as many of these drugs have side effects and interactions, and many of the newer ones are very expensive, their wide spread use has not made a significant dent in the lives of demented patients while often leading to untoward effects and escalating cost. The reliance on such drugs has also moved resources and focus away from more reliable ways to help control dementia, such as exercise, diet, and daycare programs.

Primary Dementia Drug Types

There are two primary types of dementia drugs. One has been around for several decades and has been well studied—the cholinesterase inhibitors (CI's)—which work by altering a brain chemical that may improve mental function temporarily. Most studies on these drugs have been done on Aricept (donepezil), one of the earliest versions, and studies of the other drugs in this class have produced similar results. Essentially there are two ways to ascertain the efficacy of these drugs. One is to use a 70 question screening survey called the ADAS-Cog, and see if a patient's score improves on a certain drug. An increase in 4 points is considered significant and is used to prove a drug's success. A second measure is the CGIS, which measures both doctor and caregiver impression as to whether a patient improved with treatment. Most studies rely on the ADAS-Cog to reach their conclusions.

A Placebo Effect

The most remarkable finding in dementia drug trials, and something rarely brought up, is that there is a tremendous placebo effect. In fact, of 1000 people who receive a placebo, approximately 300 of them will improve by 4 or more points on their ADAS-Cog. How can a person with dementia improve on an objective test by taking a placebo? It seems to make no medical sense, and is not something discussed extensively in the medical literature. Perhaps the hope that a drug can work can cause patients to release brain chemicals, such as serotonin or acetylcholine, which can improve mental capacity. If that is so, then perhaps other methods of increasing beneficial brain chemicals may have a similar effect, whether exercise or acupuncture or simply stress reduction. This is certainly something that should prompt further study, although currently no large studies to examine this are in the works.

Compared to placebo, CI's like Aricept help 90 out of 1000 demented patients improve by 4 or more points on the ADAS-Cog, meaning that 910/1000 people derive no benefit. There is no consistent improvement on clinical scales such as the CGIS in patients who take CI's compared to those who take placebo, and thus it is uncertain if these drugs produce benefit that are clinically relevant; they increase test scores, but not in a way that caregivers or doctors can notice. Also, the duration of improvement, and extent of it, both are very small. The treatment effect usually persists for 18-30 weeks, and after that patients on these drugs mirror those taking placebo. After a year most studies are stopped, and there is some concern that by that time all the positive effect from these drugs has evaporated - which is possibly why the pharmaceutical companies that sponsor such studies do not continue them beyond a year. There is a very small dose-related benefit, but the higher dose of Aricept (21mg) has not been shown to be more effective than lower doses. Also, approximately 70/1000 people who takes these drugs suffer side effects that cause them to stop the drugs when compared to people taking placebo, and approximately 2-13/1000 suffer serious side effects such as hip fracture and complete heart block. A recent study has shown that 100/1000 people who take these drugs suffer significant weight loss. Most significantly, it is important to realize that these drugs do not impact the disease itself; like with placebo, they can increase a brain chemical that may help some people function better for a short period of time, but the disease progression continues as it would if someone was not on the drug.

A second class of drugs called NMDA antagonists (Namenda being the most widely used of these drugs) has also been studied, and has not been proven to be consistently beneficial on either assessment scale. It seems to have its primary benefit in late stage dementia, and has virtually no impact in the earlier stages. Also, when it is combined with CI's, it offers no additional benefit. Still, Namenda (memantine), a glutamate inhibitor, is widely used by doctors in all stages of dementia, and is frequently combined with CI's despite a complete lack of efficacy in either scenario.

Ultimately, drug treatment of dementia has done very little to help patients live a better or longer life, although many patients and doctors rely on it as an effective treatment strategy. In the next article we will discuss non-pharmacological ways to address this devastating disease.