(HealthNewsDigest.com) – An early diagnosis of Alzheimer’s disease (AD) has become a critical factor in determining if a patient’s symptoms are due to AD or another condition that might be curable or managed with different interventions. Current diagnostic tests only measure proteins that are associated with but not necessarily causative of AD.
Without a definitive diagnosis, stakeholders face a frustrating and expensive uphill battle in the care journey. Physicians struggle to identify patients with AD early in the disease progression, often relying on invasive procedures, such as amyloid PET, MRI and CSF-based biomarker testing. After cognitive tests assess the degree of cognitive impairment and blood work rules out other, potentially treatable dementias, they must then utilize additional diagnostic testing that is fraught with error and cost which often prompt payers to refuse coverage.
What’s more, the treatment landscape is expanding, with nearly 100 disease-modifying agents in clinical development. In addition to being very expensive, many of these drugs are associated with significant side effects, including amyloid-related imaging abnormalities (ARIA)– abnormal differences seen in MRIs of the brain of Alzheimer’s disease patients—which may be very costly to monitor, including routine MRIs for a minimum of eight months. This is bringing more focus on the importance of diagnosing and treating early-stage AD, when it is more difficult to assess the disease utilizing current modalities.
Fortunately, there is good news in the form of a promising breakthrough: the first accurate, minimally invasive test for the definitive diagnosis of AD versus other forms of dementia. This test accurately assesses the loss of synaptic activity in the brain, where memories lie, due to AD.
Current Diagnosis Limitations
AD is a diagnosis of exclusion and relies on a battery of imaging, cognitive and invasive tests that are questionable. A study performed by Duke University suggests the combination of imaging, cognitive and invasive tests still had a misclassification rate of 28.4%, an improvement from 41.3% misclassification rate from neuropsychological testing and other clinical data alone. Emphasis on developing more convenient and less invasive tests to focus on the same markers that are used today may make them more accessible to clinicians, but do not necessarily improve diagnosis rates.
While not a requirement for clinical practice, the National Institutes of Health (NIH) Research framework from 2018 expands the definitions to include neurodegeneration in classifications of AD, with the goal of adding this to traditional amyloid plaque and tau to improve the benefits of drugs in development.
Early Diagnosis Critical for Proper Treatment
Symptoms of AD occur because nerve cells (neurons) and their connections (synapses) in parts of the brain involved in thinking, learning and memory (cognitive function) have been damaged or destroyed. Individuals typically live with AD symptoms for years. Over time, symptoms tend to increase and start interfering with individuals’ ability to perform everyday activities.
At this point, the individual is said to have dementia due to AD. Two abnormal structures called plaques and tangles are the pathologic hallmarks that, together with dementia in the clinic, identify AD at autopsy. Plaques are deposits of a protein fragment called beta-amyloid that build up in the spaces between nerve cells. Tangles are twisted fibers of another protein called tau that build up inside cells. In fact, the NIH gold standard definition of AD is dementia in life and plaque and tau at autopsy.
It’s important to understand that a number of medical issues can bring on memory loss, such as Lyme disease, vitamin deficiencies, thyroid issues, drug interactions and various forms of dementia. 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.
An early, accurate AD diagnosis allows patients to start clinical interventions sooner, saving time, money and the anguish of patients and caregivers not knowing what is happening medically. Early diagnosis also gives patients the chance to make decisions about their care.
Until now, only autopsy findings at death provided a definitive diagnosis of AD in people who lived with dementia. Adding to the challenge, AD often co-develops with other age-related neurological disorders, such as Parkinson’s disease, strokes and different types of dementias.
Understanding the Causes of AD
Most experts agree that the causes of AD are likely due to a combination of age-related changes in the brain, along with genetic, environmental and lifestyle factors. The importance of these factors can increase or decrease the risk of AD and vary from person to person.
As a progressive brain disease, AD is characterized by changes in the brain—including amyloid plaques and neurofibrillary, or tau tangles—that result in loss of neurons and their connections. This impacts a person’s ability to remember and think and, eventually, to live independently.
Many studies have demonstrated that as people age, they may have brains riddled with plaques and tau but have no cognitive impairment whatsoever. While many researchers believe plaques and tangles play a role in blocking communication among nerve cells and disrupting processes that cells require, questions remain about their role in progressive dementia.
A recent study of centenarians found varying levels of plaque and tau at autopsy, with no correlation to a reduction in mental 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. Growing 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.
Accurate AD Test Available Today
For the benefit of patients, caregivers and healthcare providers, having a definitive diagnosis as early as possible is essential for establishing care plans and planning for the future. Tests to assess the primary driver of disease, loss of synapse and neural activity can improve the diagnosis of AD across the spectrum of early to late-onset disease. The new AD test’s assays have demonstrated >95% sensitivity and specificity. It also 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. Because this new AD test assesses synaptic loss, it should be considered a tool to manage appropriate patient access to future approved therapies, in addition to the clinical and economic benefits of improved early, accurate diagnosis.
Key factors to look for in AD test include:
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Accurate diagnosis of AD through a minimally invasive skin punch biopsy
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Composed of three specific assays that highly correlate to synaptic and neural network loss in the brain
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Developed by testing and following patients with dementia over several years prior to death, establishing plaque and tau at autopsy, which is validated against the NIH gold standard
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Demonstrates high specificity and sensitivity >95% in both early and late-stage AD
It’s also important to use a test that has received Breakthrough Designation or full approval by the FDA and has been awarded reimbursement codes and a payment amount set by the Centers for Medicare & Medicaid.
Giving providers, patients and their families a clear answer about AD helps them focus the patient journey, enables pharmaceutical companies to identify appropriate clinical trial participants and allows payers to establish protocols and prior authorizations for prescribing and reimbursing treatment.