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May/June 2022
Minimally Invasive Testing for Alzheimer’s Disease Testing Guides Clinical Intervention and Reduces Economic Burden In 1906, German physician Dr. Alois Alzheimer first described a disease of profound memory loss and microscopic brain changes—now known as Alzheimer’s disease (AD). Today, researchers are striving to determine as many aspects of AD and other dementias as possible to find new treatments to prevent, halt, or reverse disease progression. As American demographics shift and baby boomers age into diseases such as AD and dementia, the push to find more accurate diagnostics has grown more intense. Furthermore, the new AD drug that recently advanced through the FDA’s accelerated approval process has raised concerns about its appropriateness for patients because it shows activity with surrogate endpoints but without clinical benefit. The challenge is that AD often codevelops with other age-related neurological disorders, such as other types of dementias, including Parkinson’s disease and strokes. Although AD is the most common type of dementia, there are many other kinds, including Lewy body dementia, Huntington’s disease, and Creutzfeldt-Jakob disease. The most promising diagnostic breakthrough to date is the first accurate, minimally invasive test for the definitive diagnosis of AD vs other forms of dementia. This newly available test is designed to accurately assess the decrease in synaptic activity within the brain due to AD, which eventually leads to loss in memory, language, reasoning, and social behavior. This AD test is well positioned to address several of the limitations of current tests, which primarily focus on assessing the presence of plaque and tau. Closer Look at AD AD accounts for 60% to 80% of dementia cases and is not a normal aspect of aging. Scientists believe AD prevents parts of a neuron or brain cell from running properly. As damage spreads, neurons lose their ability to function and eventually die, causing irreversible and devastating changes in the brain. The majority of people with AD are 65 and older, with cognitive deficits that worsen over a relatively short period of time. Memory loss is mild in the early stages of AD, but gradually individuals lose the ability to respond to their environment. Typically, AD patients live four to eight years after diagnosis but can live as long as 20 years, depending on other factors. Causes This progressive brain disease is characterized by changes in the brain—including the accumulation of amyloid plaques and neurofibrillary, or tau tangles—that result in loss of neurons and their connections. These changes to the brain detract from a person’s ability to remember and think and, eventually, to live independently. Plaques and Tangles While autopsy studies demonstrate that most people develop plaques and tangles as they age, individuals with AD typically develop far more of them in areas of memory before spreading to other regions. While most experts believe plaques and tangles play a critical role in blocking communication among nerve cells and disrupting processes that cells require, there are other factors that affect the ability of neurons to communicate effectively. This destruction and death of nerve cells causes memory failure, personality changes, problems carrying out daily activities, and other symptoms of AD. A recent study of centenarians found varying levels of plaque and tau at autopsy, with no correlation with a reduction in cognitive functioning during life. This reinforces that while tau and plaque may be present in brain tissue, they may not be the primary cause of AD. Mounting evidence suggests that memory failure, personality changes, problems carrying out daily activities, and other symptoms of AD are caused by loss of activity of synapses and neurons. Scientists now believe that age-related changes in the brain may harm neurons and affect other types of brain cells to contribute to AD. These changes include atrophy of certain parts of the brain, inflammation, vascular damage, production of unstable molecules called free radicals, and breakdown of energy production within cells. But age is only one risk factor, and many people live into their 90s and beyond without ever developing dementia. Genetics Misdiagnosis vs Benefits of Early Diagnosis One study designed to evaluate potential economic benefits of early rule-out of AD compared annual medical resource use and costs for Medicare beneficiaries potentially misdiagnosed with AD prior to their diagnosis of vascular dementia or Parkinson’s disease vs those of similar patients never diagnosed with AD. The researchers determined that patients with prior AD diagnosis used substantially more medical services every year until their vascular dementia/Parkinson’s disease diagnosis, resulting in incremental annual medical costs of approximately $9,500 to $14,000. After their corrected diagnosis, however, medical costs converged with those of patients never diagnosed with AD. This relationship between timing of correct diagnosis and subsequent reversal in excess costs strongly suggests the role of misdiagnosis of AD, and not AD comorbidity. It also highlights the potential benefits of earlier, accurate diagnosis. An early AD diagnosis allows patients to start clinical interventions sooner, saving time, money, and the despair of caregivers and patients not knowing what is happening medically. Early diagnosis also gives patients the chance to have a say in their own care. It’s important to note that the new drug approved by the FDA is subject to an approval modification that specifies that it only has suggested potential to benefit patients who are early AD patients or are in the very early stages of dementia, called mild cognitive impairment, that has not yet progressed to AD. One in three patients with memory issues does not have AD and can often get treatment that’s more appropriate for a non-AD patient. For AD patients, it’s well understood that no drug, including the one recently approved by the FDA, can treat the underlying disease. Clinicians face a number of challenges, including being unable to make the diagnosis in the first several years of the disease on their own. Secondly, they are unable to validate any biomarker that might assist in making the diagnosis with any degree of certainty. Third, the only valid proof of AD vs other neurodegenerative dementia relies on autopsy validation. AD is often misdiagnosed because, until the arrival of the new AD test, no reliable diagnostic existed that could be utilized in the first four to five years of the dementia diagnosis. Urgent Need for Early, Definitive AD Diagnosis • 72% are age 75 or older. • 11.3% of people age 65 and older have AD. • Almost two-thirds of Americans with AD are women. • Older Black Americans are about twice as likely to have AD or other dementias as older white Americans. • Older Hispanics are about 11/2 times as likely as older white individuals to have AD or other dementias. By 2050, the number of people age 65 and older with AD is projected to reach 12.7 million. It’s also alarming that deaths from AD increased 89% from 2000 to 2014, while deaths from heart disease—the No. 1 cause of death in the United States—decreased 14%. Furthermore, in 2020, AD and other dementias cost the nation $305 billion, including $206 billion in Medicare and Medicaid payments. It’s important for stakeholders to understand that, while the progression and increased severity of symptoms support diagnosis, until the introduction of the new AD test, as noted previously, only autopsy findings provided a definitive diagnosis of AD. An early diagnosis of AD can help determine whether the symptoms a patient experiences are truly due to AD or some other conditions that can be curable or managed with different interventions. Unfortunately, when it comes to diagnostic tests, considerable confusion has prevailed in the marketplace, mainly because they measure proteins that, while associated with AD, are not the only cause of the disease. Diagnosing patients with AD or mild cognitive impairment begins with obtaining information about the medical history of the patient and the patient’s family, as well as mental status tests and physical and neurological exams. After cognitive tests assess the degree of cognitive impairment and blood work rules out other potentially treatable causes of dementia, physicians may utilize additional diagnostic testing modalities to try to identify patients with AD, including amyloid positron emission tomography (PET), MRI, and cerebrospinal fluid–based biomarker testing. But payers perceive these as being fraught with error, costly, and largely invasive. The new AD test overcomes these limitations, putting the patient on the right care path sooner. Addressing Payer Concerns Payers anticipate the cost of a diagnostic test to be relatively minor in comparison to disease-modifying drug therapy. The new AD test has to be performed only once, representing a fraction of total cost and a cost-effective way to ensure appropriate use. Payers are concerned about AD for their Medicare Advantage populations—a significant population that is projected to increase. In terms of cost, sustainability is a key. Therefore, the faster an AD diagnosis can be made, the better. Payers perceive current diagnostic tools to be costly, potentially invasive, and without validity. Few published coverage policies exist for diagnosis of AD. What’s more, emerging biomarkers either are not subject to formal polices or are not covered. This means that accurate and early diagnosis of AD, along with disease-modifying treatments, are critical to meet payer needs. Of the 10 private payers, most do not cover or lack specific polices on the use of amyloid PET scans, MRIs, or cerebrospinal fluid marker–based testing for AD, although paying submitted claims in the absence of an explicit positive coverage policy may apply in these cases. PET scans, for example, can cost thousands of dollars but may not lead to an appropriate diagnosis. Evidence supporting emerging biomarkers serve as the key catalyst to shifting the currently limited payer coverage environment for AD diagnostics. Value of Accurate AD Test DISCERN, the recently launched AD test, has three assays, each of which have demonstrated >95% sensitivity and specificity, giving patients and families the answers they need, enabling providers to make a conclusive diagnosis, and allowing payers to establish protocols and prior authorizations for prescribing and reimbursing treatment. It may also help pharmaceutical companies identify appropriate clinical trial participants. The AD test to assess synaptic loss can be utilized as a tool to manage appropriate patient access to future approved therapies, in addition to the clinical and economic benefits of improved early, accurate diagnosis. The test identifies the AD-specific degeneration biomarker for a definitive diagnosis, differentiates AD from other non-AD dementias, and identifies those with AD in addition to other degenerative pathologies. This is positive news for every stakeholder, especially for patients and their families who are seeking answers and a path forward. — Frank Amato is CEO and president of SYNAPS Dx. |
