Alzheimer’s Disease

Treating Alzheimer’s

  • Treatment of Alzheimer’s disease (AD) requires not only pharmacotherapy (prescription medication), but also non-pharmacological interventions, including social and lifestyle strategies.


    ecause memory tends to be significantly affected in AD, one cannot rely as heavily upon it in taking care of one’s daily routine. Variations in daily routine require short-term memory to adapt to the changes. This means that for the AD patient, it is best to not vary a given day's routine. By keeping the routine of a particular day rigid and invariable-like that found in military establishments-there is less reliance on short-term memory, less confusion, and greater independence for the AD patient. An analogous situation is brushing one’s teeth in the morning. This is usually done every day and has therefore become a well-learned habit. It requires very little, if any, short-term memory to brush one’s teeth each morning. Similarly, if one sets up a schedule whereby certain activities are done at specific times each day, these activities will become habits over the course of about 3 months. As such, these habits will be easier to perform and be less susceptible to failure as the short-term memory of AD becomes more impaired. This phenomenon may be the reason why some patients can continue to play a large repertoire of piano pieces in spite of being severely demented and unable to tell you their name.

    Another key to maintaining one's functional abilities with AD is to exploit the physiological concept of brain function called “synaptic plasticity.” Synaptic plasticity refers to the fact that synapses--the connections of the brain-are like muscles; they get larger and stronger the more they are activated. Synapses on neurons located in specific parts of the brain are activated by specific activities. For example, the synapses on neurons in the hippocampus are activated by learning new things and recalling recent events and conversations. They get larger and function more efficiently with repeated use. Learning to play piano activates synapses on neurons in a different set of brain areas whose function is to learn new skills. Repeated practice on the piano reinforces the synapses in these skill learning brain areas, and they become more resistant to damage by a variety of diseases, or perhaps they simply continue to function in the presence of diseases such as AD. This principle of synaptic plasticity means that the skills and activities one maintains are the ones that will be preserved and function the best for much longer than skills and activities which are not used regularly by an AD patient. By combining synaptic plasticity principle with a fixed, invariable daily schedule of activity, an AD patient can preserve independent function across a broader range of abilities for much longer.

    A final key to maintaining one's functional abilities with AD is physical exercise. There is no getting around the fact that the neurons in the brain require fuel to function and require more fuel than normal aging individuals because the brain attempts to repair the damage caused by AD and other dementing disorders. This fuel comes from oxygen, glucose, nutrients and growth factors delivered by the blood to each brain area. The driving force that pumps this fuel to all brain areas is the muscle called your heart, and the only way to strengthen the heart muscle is to exercise it regularly. In most cases, it is actually easier to exercise every day at a specific time and in a specific way because the exercise done in this manner becomes a habit that is less dependent upon short-term memory. AD patients who exercise invariably maintain their functional independence longer, have better mood, fewer behavioral problems, and fewer medical problems.

    These principles have become embraced by organizations such as the Alzheimer's Family Services Center affiliated with Hoag Hospital. They incorporate physical and mental exercise, increase social interaction (a form of mental exercise itself), and do so in a structured way that helps bypass the functional impairment caused by the short-term memory loss of AD. Some professional caregivers who help take care of AD patients in their home have also learned to use these non-pharmacological principles of AD treatment to maximize functional independence through a structured daily schedule of physical and mental activity. Some supportive organizations such as the Alzheimer's Association and the Orange County Council on Aging provide invaluable education as to how to achieve these beneficial non-pharmacologic AD treatment approaches. The treatment effects of these non-pharmacological approaches to AD are every bit as large as the treatment effects achieved by medication, and they are complementary. Individuals and family who combine the proper combined medication therapy with the proper non-pharmacological therapy for AD patients have much better long-term outcomes and a better quality of life.


    Contrary to the notion that current AD treatments are ineffective, timely intervention with appropriate medications can have substantial benefits and, on the average, delay disease progression for 3-5 years. The best long-term clinical study of AD treatment came from the Massachusetts General Hospital Memory Disorders Unit, which showed that combined therapy with Namenda plus a cholinesterase inhibitor delayed AD progression by 33-60% over the 4 years of the study, regardless of the initial level of severity. Such a delay amounts to approximately 5 to 6 years of the 14-year course of AD, which is long enough to keep most people from being institutionalized, and substantially reduces the cost of care.

    Most AD patients however, are not treated with combined therapy because of the way these medications were approved by the FDA. In the same study, treatment with a cholinesterase inhibitor alone (Aricept®, Razadyne® or Exelon®) did not alter the functional decline over 4 years compared to no treatment at all.

    The perception that “no effective treatment for AD” has arisen from the fact that the majority of the time, AD patients are treated with cholinesterase inhibitors alone, which in fact does not delay AD progression. The perception of “no effective treatment for AD” is further compounded by the fact that the average AD treatment duration is less than 2 years, which is equivalent to 15% of the 14 year clinical course of AD. In other words, AD patients typically do not receive the proper medication treatment for an average of 85% of the clinical duration of their disease. The perception of “no effective treatment for AD” is further reinforced by the fact that AD is first diagnosed and treated after 9-11 years of symptoms (mild to moderately demented stage), which means that treatment is first applied to extensively damaged brains that have reached the end stages of the disease process. Initiating treatment of any disease at its end stage results in perceived inefficacy of the treatment. These different phenomena have reinforced the perception of “no effective treatment for AD” in spite of the best available clinical evidence that combined therapy with Namenda plus a cholinesterase inhibitor delays AD progression at all clinical stages.

    Today there are five FDA-approved medications for treatment of AD (e.g. Cognex® (tacrine), Aricept® (donepezil), Razzadyne® (galantamine), Exelon® (rivastigmine) and Namenda® (memantine). When Namenda plus a cholinesterase inhibitor (Cognex, Aricept, Razadyne, or Exelon) are used together, they delay progression, on the average, for all clinical stages of AD. This means that early detection, accurate diagnosis and proper combined treatment are needed to obtain the greatest benefits in treating each AD patient.


    Cognex® (Tacrine), Aricept® (donepezil), Razzadyne® (galantamine) and Exelon® (rivastigmine) belong to a class of medications called cholinesterase Inhibitors. Cholinesterase inhibitors increase the availability of acetylcholine, an important transmitter that helps control mood, behavior, memory and other cognitive abilities. Acetylcholine is markedly reduced in AD, Parkinson's disease, Lewy body disease and many other dementing disorders.

    Cholinesterase inhibitors reduce the production of beta amyloid, which may be their basis for delaying AD progression when used in conjunction with Namenda. Each of the cholinesterase inhibitors have published studies that have examined the effect of treatment for 3 years or longer. Ethically, these studies cannot be double-blind, randomized, placebo-controlled trials after about 12 months of treatment. These longer-term studies were added onto more rigorous clinical trials that ended at 12 months, and were extended to provide all trial patients the cholinesterase inhibitor for up to 5 years (open label extension study). They therefore are more difficult to interpret because there is no placebo group once the open-label extension part of the study begins. Each open label extension study compared the effect of the cholinesterase inhibitor to the projected course of the placebo group from the initial portion of the trial over the duration of the study. The findings must be interpreted with caution because more patients drop out from these open-label extension studies than they do during the initial double-blind, randomized placebo controlled phase of the study. However, they do provide a picture, albeit flawed, of the course of those AD patients who remained in the open label extension study compared to the estimated, or projected, course of how placebo-treated AD patients would have done. For these open label extension studies, there are 5-year data on Exelon®, 3-4 year data on Razadyne®, and 3-5 year data on Aricept®. In terms of these comparisons, the delays in AD progression for these studies were approximately 33% for 2-3 years on Aricept®, 33-50% for 2-3 years on Razadyne®, and 25-54% for 3-5 years on Exelon®.


    Namenda® (memantine) belongs to a class of medication called glutamate receptor modulators. Glutamate is the transmitter for 75% of all neurons in the gray matter on the surface of the brain (cerebral cortex). Excessive amounts of glutamate that can cause neuron death are released in a wide variety of brain disorders, including stroke, Parkinson's disease, multiple sclerosis, traumatic brain injury, and probably AD. The excessive release of glutamate triggers certain suicide genes in neurons to cause their self-destruction. Namenda® blocks this self-destruction plus allows normally released amounts of glutamate to exert their proper function in brain communication. Namenda® may also prevent the skeletal proteins of the neuron-called tau microtubules-from twisting into paired helical filaments and interfering with neuron and synapse function. If Namenda® has this effect, it would explain how Namenda® can delay neuron and synapse loss (a hallmark of AD pathology) to delay AD progression.