Alzheimer's disease (AD), the most common form of dementia, poses a significant challenge to both patients and healthcare professionals. This progressive brain disorder is characterized by the abnormal accumulation of proteins, particularly amyloid deposits and tau tangles, that disrupt the communication and functionality of brain cells. These disturbances lead to memory loss and difficulties in daily tasks. While the exact cause of AD remains elusive, various risk factors, including genetics, lifestyle choices and environmental elements have been identified.
As of 2023, the prevalence of AD is striking, with an estimated 6.7 million Americans aged 65 and older living with the disease. This condition disproportionately affects older individuals, particularly those over 75, and women are more commonly affected. Moreover, research has unveiled disparities among different ethnic groups, with older Latinos and African Americans having higher risks. Regrettably, Alzheimer's has become the seventh leading cause of death in the United States.
Unraveling Risk Factors
Understanding the risk factors for AD is crucial. Age is the most prominent factor, with the likelihood of developing the disease doubling every five years after the age of 65. A family history of AD also plays a role, and certain gene mutations, although rare, can almost guarantee the disease. Research suggests that lifestyle choices significantly impact risk, with factors such as high blood pressure, physical inactivity, obesity, diabetes, depression, smoking, hearing loss and binge drinking contributing to Alzheimer's risk.
While there is no cure for Alzheimer's, various medications may improve or slow the progression of symptoms. Cholinesterase inhibitors, which prevent the breakdown of the neurotransmitter acetylcholine, can help with memory, judgment, language and thinking. Glutamate regulators focus on improving memory, attention, and reasoning.
Novel Approaches to Treatment
Recent years have witnessed new developments in Alzheimer's treatment. Medications like Aduhelm and Leqembi, with potential disease-modifying activity have been approved by the FDA for early AD, work by targeting aggregated forms of amyloid beta in the brain in the hopes of reducing its buildup. Amyloid beta is a protein that occurs naturally in healthy brains but forms clumps or tangles between the brain cells of people with AD, causing brain-cell death that leads to symptoms including memory loss. However, the efficacy of these treatments has sparked controversy. They have been FDA-approved based on their ability to reduce amyloid plaques in the brain, but there is no direct correlation with AD progression and amyloid plaques. Clinical trial success was measured not by cognitive improvement but by slowing in the rate of cognitive and functional decline. Safety issues with both Aduhelm and Leqembi are a concern with warnings for Amyloid Related Imaging Abnormalities (ARIA).
Rexulti, initially approved for schizophrenia and major depressive disorder, has gained supplemental FDA approval for the treatment of agitation associated with dementia due to Alzheimer's disease. It rebalances dopamine and serotonin in the brain, effectively improving thinking, mood and behavior.
Towards a Brighter Future
With potential treatments on the horizon, Alzheimer's disease management is slowly evolving. A third amyloid-targeting monoclonal antibody, donanemab, might gain approval in 2023. While these medications represent progress, they come at a high cost. Aduhelm and Leqembi, although offering unknown long-term clinical and safety benefits, are expensive. With the number of Alzheimer's patients projected to rise, there is a growing demand for more cost-effective and clinically proven disease modifying treatment options to combat this devastating disease.
Alzheimer's disease presents a multifaceted challenge, from understanding its causes and risk factors to navigating the complexities of its treatment. These recent developments in new treatment options may help to pave the path to effectively managing Alzheimer's and improving the lives of those affected remains a complex and evolving journey.
For more in-depth insights into the world of Alzheimer's disease, click here to read this issue’s clinical bulletin.