Alzheimer’s Disease: Accurate Diagnosis Ensures Appropriate Prescribing and Treatment for Alzheimer’s
The introduction of new drugs to treat Alzheimer’s disease (AD), coupled with growing public awareness of dementia and its potential precursor—mild cognitive impairment (MCI)—challenges geriatricians to address this question that is top-of-mind for a growing number of families: “How do I know if my loved one has dementia or AD?”
Geriatricians understand age is the biggest risk factor for developing dementia. The Alzheimer’s Society estimates that in the United States there are more than six million people living with AD. By 2050, this number is projected to rise to almost 13 million.1
Physician practices serving older patients also recognize the importance of getting an accurate dementia diagnosis, especially with the pressure to prescribe expensive new therapies and ensure they are safely administered to the right patients. This is particularly significant since the current diagnostic pathway to accurately diagnose AD is woefully inadequate. Taking it a step further and implementing an objective, definitive diagnostic would immensely help clinicians manage this burgeoning disease state.
People who visit a geriatrician with vague symptoms often do not meet the criteria to be referred for tests, resulting in long delays to a definitive diagnosis and appropriate treatment. In fact, the Alzheimer’s Association reports that in the community setting, 50% to 70% of symptomatic patients are incorrectly diagnosed with AD and that number is reduced to 25% to 30% even in specialized memory clinics. The association faults the inconsistency of routine cognitive screening and the lack of easily accessible, accurate, and time- and cost-effective diagnostic tools.2
This diagnostic dilemma is even worse in early stages of the disease, affecting patients without dementia who have either subjective cognitive decline (SCD) or MCI.3 Unfortunately, cognitive tests now available for primary care settings are inadequate to differentiate SCD and MCI.4 In fact, very few patients with MCI are eligible for treatment with FDA-approved Leqembi, which is associated with serious safety issues. In the absence of cognitive criteria being met, the pool of potential patients would double in size. The Mayo Clinic Study of Aging applied the entry criteria for the drug to its database of 237 MCI and concluded the following5:
• applying the entry criteria: 8%, or 19 of 237, would qualify for treatment with Leqembi;
Causes of Dementia: Reversible Health Conditions
• difficulty with one or more types of mental function, like learning, memory, language, and judgment;
• problems that differ from the person’s usual abilities;
• problems that make it difficult for them to manage everyday life responsibilities like work or family; and
• problems that aren’t caused by another mental disorder, such as depression.
Geriatricians are tasked to determine who is the right candidate for the drug and what other options are available to manage MCI and AD dementia for those who are not candidates. Performing cognitive testing can improve the identification of patients at risk and reduce the burden on patients, providers, and the health care system.
In geriatric medical practices nationwide, physicians are following CMS current requirements to perform cognitive testing as part of the annual wellness visits for Medicare recipients. Cognitive assessments and care plans are covered under CPT code 99483 and reimbursed when provided in an office setting.7 The annual wellness visit specifically requires “detection of any cognitive impairment,” defined as “assessment of an individual’s cognitive function by direct observation, with due consideration of information obtained by way of patient report, concerns raised by family members, friends, caretakers, or others.”8
Importance of Early Intervention
The CDC has identified factors such as hypertension, diabetes, depression, hearing loss, obesity, cigarette smoking, and a lack of physical activities as modifiable risk factors for AD and related dementias.10 Geriatric physicians are uniquely positioned to point out meaningful opportunities for people to make lifestyle changes that slow disease progression. As an example, hearing aids are documented to reduce the rate of cognitive decline in older adults at high risk of dementia by almost 50% over a three-year period. Treating hearing loss may be a simple way to lower the risk of dementia in vulnerable populations.11
A recent population-based study suggested that excluding genetic risk factors that are not preventable, about 40% of dementia cases in the present population could be attributable to preventable comorbid diseases, which are also associated with increased mortality.12 Even modest lifestyle changes can be impactful, with data recently presented at the Clinical Trials in Alzheimer’s Disease conference suggesting that mild physical activity could stabilize cognition over a 12-month period in people with MCI.13
For example, various studies have shown that between 20% to 40% of middle-aged and older individuals are amyloid positive without apparent signs of dementia.16 In individuals 80 years of age or older, 60% presented at autopsy with AD neuropathology but no cognitive impairment during life.17
Cerebrospinal Fluid Biomarkers
Doctors perform a lumbar puncture, also called a spinal tap, to get CSF.20 The most widely used CSF biomarkers for AD measure beta-amyloid 42 (the major component of amyloid plaques in the brain), tau, and phospho-tau (major components of tau tangles in the brain, which are another hallmark of AD).
As noted previously, patients with normal cognition may have levels of amyloid plaque consistent with AD based on a PET scan. Given that MCI and dementia can be caused by a variety of risk factors, some of which are modifiable, assessing amyloid positivity before ruling out other causes may lead to excessive diagnostic workups and potential exposure to inappropriate treatments.
DISCERN has received reimbursement PLA (CPT) codes (206U and 207U) and can be reimbursed by Medicare. The test is based on a 3 mm skin punch biopsy that’s minimally invasive and can easily be administered in the geriatric physician office setting, with the skin sample then processed in an approved laboratory. This test is the only autopsy-validated test (at 98%) to identify AD and meets the National Institutes of Health Gold Standard for confirming diagnostic accuracy, with patients followed for as long as eight years prior to death. The test comprises three assays that assess the factors directly related to the formation of synaptic connections in the brain impacting loss of memory and cognition in people living with AD. The assays are also related to the formation of amyloid plaques and tau in neurofibrillary tangles, hallmarks of AD at autopsy.
For older patients with MCI and in the absence of drug treatment, geriatric specialists are helping people to better manage the condition and avoid disease progression by recommending lifestyle changes that include the following25:
• following a daily routine;
Looking ahead, both physicians and older patients remain hopeful that more people will receive an accurate diagnosis and appropriate treatment.
— Frank Amato is CEO and president of SYNAPS Dx, an Alzheimer’s disease diagnostic company. After more than two decades in the pharmaceutical and biotech industry, he became president, CEO, and director of electroCore, a NASDAQ-traded bioelectronic medicine company focused on treating neurological conditions. Prior to electroCore, Amato was vice president of the Specialty Commercial Operations at Merck.
2. Hansson O, Edelmayer RM, Boxer AL, et al. The Alzheimer's Association appropriate use recommendations for blood biomarkers in Alzheimer's disease. Alzheimers Dement. 2022;18(12):2669-2686.
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7. Cognitive assessment & care plan services. Centers for Medicare & Medicaid Services website. https://www.cms.gov/cognitive. Published February 1, 2023. Accessed August 17, 2023.
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