Contributor: The Importance of Early Diagnosis of Alzheimer Disease

Greg Cooper, MD, PhD

Alzheimer disease currently affects nearly 7 million people in the United States alone, including approximately 1 out of every 9 people over 65 years. With the continued aging of the population, this number is expected to increase markedly, with some describing it is an “oncoming tsunami” that we may be ill-prepared for.

Current projections place the number of people with Alzheimer disease in the US alone at nearly 14 million by 2060. However, with the recent introduction and full FDA approval of multiple anti-amyloid agents,^1-3 early recognition of this condition (when these medications are most effective) is increasingly important.

Early Symptoms of Alzheimer Disease

The earliest symptom of Alzheimer disease is most often impairment in recent memory or increasing forgetfulness. It can be thought of as an impairment of learning, leading to an inability to recall recent events or recent conversations, and to misplace or lose objects. As a result, patients with Alzheimer disease frequently repeat themselves, asking the same questions or telling the same stories over and over. Other commonly observed symptoms may include increased difficulty recalling words, disorientation and impaired ability to plan, organize, and manage items, such as household finances and medications.

While the earliest recognition of Alzheimer disease often takes the form of mild cognitive impairment, the pathological changes of Alzheimer disease within the brain are thought to begin as long as 20 years earlier. Current thinking, according to the amyloid cascade hypothesis, posits that β-amyloid—a fragment cleaved by enzymes called secretases from the larger amyloid precursor protein—begins to form oligomers and subsequently plaques within the brain. This is followed by the formation of neurofibrillary tangles with elevated levels of phosphorylated tau (p-tau), dysfunction of synapses and, ultimately, the cognitive impairment typical of Alzheimer disease.

In fact, due to the recognition that amyloid deposition has nearly peaked and significant cell or neuronal loss has already taken place by the time symptoms are recognized, there is growing interest in recognizing and intervening as early as possible, in an attempt to preserve cognitive function longer. Clinical trials currently are underway testing anti-amyloid treatments in patients with evidence of Alzheimer pathology in the absence of clinical symptoms. If successful, this might be an example of secondary prevention. At the same time, lifestyle strategies increasingly are being studied for potential primary, secondary, and even tertiary prevention. It is likely that some combination of treatments will be necessary in the future.

New Class of Medications

While these prevention strategies might be on the horizon, we now have the opportunity to treat some patients with Alzheimer disease with anti-amyloid agents, a new class of medication that is the first to show a disease course-modifying effect. In clinical trials, clinical progression was slowed by approximately 30%.^4,5 Unfortunately, these medications are only proven to be effective when started very early in the clinical course of Alzheimer disease, in the stages of mild cognitive impairment or mild dementia. Access to timely evaluation is a significant barrier, particular in many parts of the country where relatively few specialists in the field of dementia (eg, neurologists and geriatricians) exist. This can be further exacerbated, for those potentially eligible for new disease-modifying treatments, by the need for additional diagnostic testing, including MRI with sequences sensitive for microhemorrhages (gradient echo or susceptibility weighted imaging) and biomarker testing.

Overcoming Barriers to Early Diagnosis

However, with careful and coordinated planning, many practices and health care organizations can effectively tackle these issues. First, effective collaboration with primary care can expedite the evaluation of appropriate patients. With relatively little disruption of the normal primary care clinical flow, office staff or a navigator could potentially flag at-risk individuals. A family member or caregiver could be asked to fill out a short survey, such as the Eight-item Informant Interview to Differentiate Aging and Dementia, or AD8, screening, and medical assistants could be trained to do brief cognitive testing, such as the Mini Mental State Examination, upon rooming.

If potential cognitive impairment is detected, an expedited referral could be made to a specialist. Some specialist programs have created separate clinic visits within schedules that are reserved specifically for patients potentially eligible and interested in antiamyloid therapies, creating a more expedited approach for these patients. We have found the addition of well-trained and supported advanced practice providers has been invaluable, both to increase overall access within our own memory center and to facilitate the timely evaluation of patients for antiamyloid therapies.

Once in the specialty clinic, close collaboration with radiology has streamlined our ability to obtain timely and high-quality neuroimaging and cerebrospinal fluid studies for Alzheimer’s disease biomarkers. It is likely the eventual availability of high-quality blood-based biomarkers will further facilitate evaluation in the future. As we have grown our own antiamyloid program, the addition of a nurse navigator also has been invaluable, serving as a primary point of contact for patients and their families, as well as with the various component groups involved in the care of these patients, including pharmacy, infusion center, lab, radiology and reimbursement/finance departments. In addition, maintaining a regular cadence of meetings with various stakeholders, identifying any problems and continually improving the system has led to improving efficiency, which in turn allows for gradually expanding capacity.

With careful planning, thoughtful partnerships and frequent open communications among primary care, specialists and other stakeholders, we can improve our recognition of patients with memory impairment and facilitate timely evaluation, accurate diagnoses, and access to appropriate care and treatment. In this way, we can begin to realize the promise of disease-modifying therapies already available and pave the way for further innovations in the future.

Greg Cooper, MD, PhD, is chief of adult neurology and director of the Memory Center at Norton Neuroscience Institute. He briefly directed the dementia clinic at the University of Iowa before joining the Sanders-Brown Center on Aging at the University of Kentucky, and later formed and directed the Baptist Health Memory Care Program until joining Norton in 2021. Cooper has also been active in research serving as principal investigator on a number of clinical trials and has a strong interest in education and caregiver support.

References

1. FDA grants accelerated approval for Alzheimer’s drug. FDA. News release. June 7, 2021. Accessed October 28, 2024. https://www.fda.gov/news-events/press-announcements/fda-grants-accelerated-approval-alzheimers-drug

2. Joszt L. FDA grants full approval for Alzheimer drug lecanemab. AJMC®. July 6, 2023. Accessed October 28, 2024. https://www.ajmc.com/view/fda-grants-full-approval-for-alzheimer-drug-lecanemab

3. Jeremias S. FDA approves donanemab for early Alzheimer disease. AJMC. July 2, 2024. Accessed October 28, 2024. https://www.ajmc.com/view/fda-approves-donanemab-for-early-alzheimer-disease

4. van Dyck CH, Swanson CJ, Aisen P, et al. Lecanemab in early Alzheimer's disease. N Engl J Med. 2023;388(1):9-21. doi:10.1056/NEJMoa2212948

5. Sims JR, Zimmer JA, Evans CD, et al; TRAILBLAZER-ALZ 2 investigators. Donanemab in early symptomatic Alzheimer disease: the TRAILBLAZER-ALZ 2 randomized clinical trial. JAMA. 2023;330(6):512–527. doi:10.1001/jama.2023.13239