Dementia Colleague Interview (Continued from page 11)
How does Early Onset Alzheimer’s disease differ from the more common occurrence in the elderly? Early onset AD is defined as cases that are diagnosed before age 65. Most patients are diagnosed in their 40s and 50s and have familial AD, with an autosomal dominant inheritance (i.e. a child has a 50% chance of inheriting the gene if one parent had the gene). About 5% of all AD cases are early onset, or about 200,000 cases. Many readers may be familiar with the ongoing NIH-funded clinical trial of a new amyloid antibody, crenezumab, in a large extended Colombian family with early onset AD, led by Eric Reiman M.D. and his group at the Banner Institute in Arizona.
Are there reliable genetic tests to disclose the probability of an asymptomatic young person eventually developing dementia? The APOE genotype on chromosome 19 is the most commonly tested genotype for Alzheimer’s disease. About 20% of the general population carries the APOE ε4 allele, which increases the risk of AD. (The APOE ε2 allele is protective, and the ε3 allele appears to be neutral). Although the ε4 allele increases one’s risk of developing AD, it is still not a reliable predictor of who will get Alzheimer’s disease. Previous studies have shown that even in people diagnosed with AD, up to 30% do not carry an APOE ε4 allele. Thus it is not generally recommended to get APOE genotype testing in an asymptomatic individual without a history of familial AD. However, it is has been shown that having one copy of the ε4 allele increases the risk of AD by about 2-3 fold (depending on whether the other allele is an ε2 or ε3 allele), and 2 copies of the ε4 allele increases the risk up to 15 fold.
When caring for patients with dementia — how should providers handle history-gathering, decisionmaking, informed consent, especially in situations where the patient has limited insight into their own impairment? Providing care for dementia patients is at once challenging and rewarding — I find dementia patients fascinating. However, it is not possible to obtain an accurate history or informed consent for release of information or a research study unless the primary caregivers or an informant are present. It is not advisable for dementia patients to attend a clinic visit without a caregiver or reliable informant, who in some cases may be a nurse from a nursing home or assisted living. Tracking down critical information regarding a new symptom or behavior problems by follow-up phone calls is much less effective and very time consuming, and most clinics don’t have the luxury of a nurse with dedicated time to conduct such phone calls.
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November/December 2016
Are there differences in treatment approaches depending upon which type of dementia exists — e.g. Alzheimer’s vs. Atherosclerotic (bilateral lacunar) vs. Frontotemporal? Yes, but the bottom line is that no medication has been identified that is effective in preventing or reversing dementia long-term. Donepezil and memantine are commonly used medications that may slow the symptoms of AD and vascular or combined AD/ Vascular dementia for one to two years. However, there are many ongoing national clinical trials with a broad range of medications and vaccines designed to either prevent or slow cognitive decline and dementia. Nasal insulin may prove beneficial in improving memory and is undergoing clinical trials nationally and here in the Twin Cities. Neurologist Dr. Mike Rosenbloom and Leah Hanson, Ph.D., are leading this study and currently enrolling eligible patients with mild cognitive impairment or early AD at HealthPartners Center for Memory and Aging (651-254-7936). In addition, the ongoing ASPREE (ASPirin in Reducing Events in the Elderly) trial sponsored by the National Institute on Aging, is measuring whether low dose aspirin 100 mg daily vs. placebo may decrease the risk of dementia, disability or death in 19,000 people 70 and older over about five years in the U.S. and Australia. I am the U.S. principal investigator for the ASPREE study, and the Berman Center for Clinical Research and Outcomes at HCMC is the U.S. coordinating center. ASPREE is in its fifth year of follow up, and we estimate the trial will end in 2018. It would be tremendously exciting if it turns out that a low cost simple aspirin a day could decrease the risk of dementia. The most effective lifestyle preventive intervention for everyone however appears to be regular exercise! Exercising including aerobic or strength-training for at least 30 minutes/day has been found to decrease risk of cognitive decline in multiple studies, and in one study regular walking slowed the rate of hippocampal shrinkage. Adhering to a Mediterranean or similar diet also decreases the risk of cognitive impairment. Early lifestyle intervention is key: the most effective time period to decrease or modify risk factors for cognitive decline is in middle age. Such modifiable risk factors include exercise, blood pressure, blood sugar/diabetes, abdominal obesity and a healthy diet. There are currently several ongoing European trials measuring the effect of multiple lifestyle interventions on cognitive decline; e.g., exercise, nutrition and blood pressure management.
What are the benefits of conducting dementia clinical research within the auspices of a facility such as HCMC’s Berman Center for Clinical Research? The Berman Center has a 25-year history of conducting clinical trials (ALLHAT, WHI, ACCORD Memory in Diabetes-MIND studies) and observational studies, and is fortunate to have the strong support of the Minneapolis Medical Research Foundation (MMRF), based at HCMC. We have the tremendous advantage of being located at HCMC with its diverse patient population MetroDoctors
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