The Alzheimer’s Association-Rhode Island Chapter recently held its 14th annual research symposium, featuring Benjamin Wolozin, professor of pharmacology and neurology at the Boston University School of Medicine.
Wolozin subscribes to the philosophy that “heart health is brain health.” He authored a research methodology for studying U.S. Veterans over the age of 65 with cardiovascular disease who were taking cholesterol medication. The results showed a significant reduction in the incidence and progression of Alzheimer’s disease and dementia among this population.
Seifert Systems Invests in Energy Efficiency to Strengthen Operations
For manufacturers, energy is more than just another operating expense. It plays a critical role…
Learn More
The causes of dementia and Alzheimer’s are complex but evidence increasingly points to three main risk factors: age, the accumulation of amyloid in the brain, and the deterioration of the cardiovascular system.
PBN: How has recent research – looking both at genes and memory – changed the way in which Alzheimer’s disease is treated?
WOLOZIN: We increasingly understand that vascular health plays a major role in brain health, and that prevention should begin early to maximize beneficial outcomes. Many studies indicate that factors that promote vascular disease also lead to dementia, but only over the long term.
Mid-life vascular risk factors (diabetes, hypertension, high cholesterol, obesity) are associated with dementia later in life. Conversely, some of the medications that reduce vascular risk factors appear to reduce the incidence and progression of dementia.
These medications include cholesterol-lowering medicines, such as simvastatin (brand name: Zocor), rosuvastatin (Crestor) or atorvastatin (Lipitor), as well as angiotensin receptor blockers, such as candesartan (atacand), Irbesartan (avapro) and losartan (cozaar). The public needs to be aware, though, that the data on these medications are still controversial.
Epidemiological studies suggest benefits, but the controlled clinical trials on patients who actually have dementia have yet to show a benefit. Nevertheless, I think that the data are sufficiently strong that we can confidently state that heart health promotes brain health.
Another major change has been in diagnostics and in the therapeutic development pipeline. Medical centers that have a particular imaging device, termed a PET scanner, can actually see the amyloid as it accumulates in the brains of subjects at risk for Alzheimer’s disease. Several centers in Rhode Island have the ability to do PET scanning. This is important for multiple reasons. First, PET scans that measure a beta-amyloid imaging agent, termed PiB reactivity, can definitely rule out Alzheimer’s disease for the first time if subject lacks PiB activity. Second, imaging facilitates clinical trials by potentially reducing the number subjects needed for clinical trials.
Research has also moved out of the lab and into the clinic based on basic science research. The pipeline is full of truly innovative therapies, and we are all very excited about being able to have an impact on Alzheimer’s disease. The first clinical results are admittedly disappointing, but if you think about other diseases, such as cancer, the benefits of clinical research accrue slowly, but steady. I think the results for Alzheimer’s disease will show similar but faster progress.
PBN: Is there enough money flowing into Alzheimer’s research? What are the kinds of resources needed?
WOLOZIN: Funds for research are particularly an issue this year because one of the main sources of funding of Alzheimer’s research, the National Institute on Aging, has a severe budget shortfall and has had to cut back dramatically on funding.
This year we expect them to fund only one out of every 30 grant applications sent in. Organizations like the Alzheimer’s Association play a large role in moving research forward. Resources are needed to move the work on diagnostics, to facilitate the expensive clinical trials, and to continue the outstanding work on molecular genetics. Basic science continues to identify new targets for pharmacotherapy that need to be validated in animal models and through biomarkers. Only by maintaining this broad front of research will we ultimately identify the optimal strategy for preventing Alzheimer’s disease. And make no mistake: our ultimate goal is prevention!
PBN: A new neurosciences institute has been created in Providence, the Norman Prince Neurosciences Institute. The new clinical research institute will create an interdisciplinary, collaborative approach to brain research, tying together clinical and applied research efforts in neurosurgery, neurology and psychiatry. Is this the kind of collaborative approach that is best suited to address Alzheimer’s?
WOLOZIN: Absolutely. The buzz word these days is translational research, which means taking discoveries from bench to bedside. Researchers these days have incredible resources available to them, but every new resource demands interaction with someone who has expertise in using that resource.
This means that translational research demands interdisciplinary collaboration – for instance, between a chemist, a psychologist with expertise in imaging, a neurologist and a geneticist. The Norman Prince Neuroscience Institute takes advantage of the broad range of outstanding expertise already available through the neuroscience community at Brown, Rhode Island Hospital and other institutions, and then will add additional experts in the field of dementia research and neuroscience research. This is exactly the type of approach that can produce the breakthroughs of tomorrow.
PBN: What do you recommend as the best combined treatments today for Alzheimer’s?
WOLOZIN: The treatment depends on the stage of disease, and requires both pharmacological and behavioral interventions.
Patients with Alzheimer’s disease are typically started on a anti-cholinersterase inhibitor, such as donepezil (Aricept) or galantamine (Reminyl). If the medication is well tolerated, then mementine (Namenda) can be added on. These medications help patients by improving the symptoms of memory loss. Unfortunately, in many patients the benefits are marginal.
Many patients also experience problems related to mood and/or behavior. Patients with Alzheimer’s disease can feel depressed or anxious. If this is the case, patients should really consider taking an anti-depressant. The disease process can reduce levels of the neurotransmitter, serotonin. The low levels of serotonin produce the feelings of depression or anxiety (both behaviors are regulated by serotonin).
This is an important point because caregivers might assume that the depression results only from the existential depression that occurs as patients observe their cognitive function wane. However, a large component of the depression or anxiety is the actual disease process (i.e., loss of neurons that make serotonin),
Caregivers also need to be aware of the value of non-pharmacologic treatments. It seems that exercise helps patients with Alzheimer’s disease – possibly by increasing cerebral blood flow. As cognitive function declines, art can become an important mechanism to allow self-expression and promote relaxation. Art is particularly valuable for patients who are having difficulties with language because art, such as painting, accesses a different part of the brain and because the results of artwork are easily seen.
PBN: Recently, concerns have been voiced about the overuse of antipsychotic medications for nursing home residents with dementia, often Alzheimer’s? What questions should caregivers ask about medications?
WOLOZIN: Use of anti-psychotics can be helpful for both the patient and the caregiver, but over-medication can render patients somnolent. Patients with Alzheimer’s disease can become very upset, particularly at dusk, but more than generally as the disease progresses. An anti-psychotic medication such as Quetiapine (Seroquel) calms patients down, reduces the amount of wandering and promotes sleep. This can be good for the patient and help staff or caregivers to obtain their own much-needed rest during the nighttime.
However, every medication has side effects. Too much anti-psychotic can cause a tremor and can increase the risk of heart problems (cardiac events). Seroquel is frequently used because it has a very wide dose range over which it can be given. The caregivers should strive to use a dose that is as low as possible, and they should ask the staff to understand the degree of behavioral dysfunction and whether there are side effects, with the goal of identifying the lowest dose of medication that can be used.
