Don’t Forget…

Submitted by Michael Valente, DO, Augusta Health Shenandoah Valley Neurology

True disease modifying treatments for Alzheimer’s disease are on the near horizon – possibly being released for clinical use in the next 3 to 5 years! Several novel molecules and compounds are being actively developed. One agent, a recombinant human monoclonal antibody which targets the aggregated beta-amyloid plaques in the aging brains of persons with Alzheimer’s, has just entered into Phase III clinical trials. If ultimately approved by the FDA, this will not be a “simple” treatment, as it will be delivered by IV infusion every 28 days, and is destined to be among the most expensive of therapies.

Though not reversing the underlying pathology, currently we have treatments that have demonstrated benefit in potentially modifying the clinical course of the disease. Specifically there are the inhibitors of centrally acting acetylcholine esterase, which go by the trade names of Aricept, Exelon and Razadyne. As an example of their putative benefit, one of the early studies in 2001 showed that patients who received Aricept at an effective dose of at least 5 mg a day for at least 9 to 12 months had a 21-month longer delay in nursing home placement than patients who received no or limited doses of Aricept. These medications are generally well tolerated and come in a variety of formulations, but the possible benefit from these drugs tend to diminish if they are started “too late” or after the disease has seriously advanced.

A second medication called Memantine, with the trade name of Namenda, blocks the NMDA receptors in the brain and thereby down regulates the centrally acting stimulatory neurotransmitter glutamate. This is thought to stabilize the brain cell membranes, and though does not deter ongoing degeneration, may stabilize the intracerebral neurochemical environment to attenuate some of the clinical manifestations of Alzheimer’s. One of the early studies from 2004 in patients with moderate to severe Alzheimer’s Disease demonstrated that treatment with Namenda was associated with improvement in behaviors such as agitation, irritability and appetite changes. And the addition of Namenda to Aricept had greater benefit than with either agent used alone.

Despite all this hope, and possibly even hype, Alzheimer’s is a horrible disease and we remain limited in what we can do therapeutically. Yet, this realization should not deter us in doing everything we can do to prevent it. Yes, prevent it!

Most recently confirmed in the Honolulu-Asia Aging Study, several large population-based studies, both retrospective and prospective, have demonstrated that targeting and controlling the same risk factors for coronary and cerebral vascular disease directly alters the incidence of Alzheimer’s disease. So strong is this association that in October 2017 the American Heart Association and American Stroke Association Presidential Advisory Committee issued a statement that modifying cardiovascular risk factors in midlife may delay or prevent all causes of cognitive impairment. The linking association may not merely be that healthy living usually translates to healthy aging, but that the oxidative stress that contributes to atherosclerotic injury may similarly lead to the accumulation of neurofibrillary plaques and tangles.

When accompanied with supporting elements like maintenance of social engagement and management of hearing loss, controlling for the seven common vascular disease risk factors may lower the incidence by nearly 30% in people susceptible to vascular-induced and Lewy Body Dementia and up to 7% if not higher in people with the ApoE genetic predisposition for developing Alzheimer’s. The American Heart Association has labeled these risk factors as “Life’s Simple Seven for Optimal Brain Health”.

These seven factors include: 1) nonsmoking/smoking cessation, 2) regular physical activity, 3) healthy diet, 4) keeping BMI lower than 25 kg/m2, 5) blood pressure control lower than 120/80, 6) lowering cholesterol lower than 200 mg/dL, and 7) maintaining fasting glucose less than 100 mg/dL. So when patients express concerns regarding Alzheimer’s and dementia, currently we have some medications to help manage the manifestations of these conditions, there is reasonable hope for future disease modifying therapies, and importantly don’t forget…the Simple Seven.