The Future of Alzheimer Disease Care Depends on Early Diagnosis

Alzheimer disease (AD) is one of the greatest public health challenges of our time. More than 55 million people around the world live with dementia—the majority with AD—and that number is projected to nearly triple to 152 million by 2050. Despite having been at the forefront of discussions within the scientific, clinical, and patient communities for many years, many questions still remain about AD. With so much work to be done, it can be difficult to prioritize. In a recent Twitter poll, sponsored by Genentech and conducted by Practical Neurology, we asked neurologists what they believe is the most urgent challenge in AD today. The response was resoundingly clear: we must diagnose people living with AD earlier.

An Exciting Evolution

We are in the midst of an exciting evolution in our understanding of AD. We know that in many people, the disease process starts long before—perhaps 10 or 20 years–symptoms become noticeable. We have also learned more about amyloid pathology, which has allowed investigation of a more targeted approach to reducing forms of amyloid thought to be pathogenic at the right time in the appropriate patient population. There is still much work to be done, and the road to improving diagnosis and treatment has been far from smooth. We continue to persevere, however, with the hope that we will be able to make a meaningful impact for people living with AD and those who care for them.

Over the past 2 decades, drug discovery research has been active—yet volatile—with many investigational potentially disease-modifying therapies (DMTs) in the pipeline aimed at slowing pathogenic processes early, even before symptom onset. Attempts to treat AD as early as possible have raised the stakes for clinicians to identify pathology consistent with AD sooner–at a time when patients have mild cognitive impairment, prodromal AD, or even sooner. Identifying AD earlier is expected to give more people the opportunity to access these new approaches.

Beyond eligibility for potential DMTs, early diagnosis holds incalculable value, allowing people with AD time to make decisions and be clear on what they want and how they want to live their lives. They may prioritize participating in major life events, such as attending family events or taking a trip overseas. Early diagnosis may also enable individuals with AD to organize their financial and legal affairs prior to a stage of AD when questions of capacity to make decisions arise, potentially allowing greater independence for a longer period of time.

Theoretically, with AD, the earlier we intervene in the disease process, the more we could do to potentially slow the progression of neuronal damage and cognitive decline. Looking even longer term, in an ideal future, AD will hopefully shift from being a fatal to a chronic disease, manageable with DMTs.

Moving the Field Forward

The AD field has evolved greatly in the way we define the disease. In the past, AD diagnosis was based on a constellation of clinical symptoms and, in fact, could only be definitively diagnosed at autopsy. Today, the definition of AD still incorporates those important clinical presentations but relies more heavily on the analysis of biomarkers and underlying pathology. In parallel with the development of potential DMTs, a biomarker-centric framework has emerged with pioneering work in neuro-imaging and the analysis of cerebrospinal fluid-based and, more recently, blood-based biomarkers.

Genentech, a member of the Roche Group, is among the drug developers at the forefront of incorporating these new biomarkers into AD research. We are exploring multiple approaches and molecules that may address key pathways of AD, including amyloid β (Aβ) and tau, as we pursue our goal of developing a DMT that could positively impact people living with AD. For example, the Roche Group developed a laboratory assay of multiple biomarkers—both standard and novel—that is now used in our clinical development programs, as well as by other companies and research organizations. The Elecsys NeuroToolKit includes Aβ_1-42, Aβ_1-40, α-synuclein, glial fibrillary acidic protein (GFAP), interleukin-6 (IL-6), neurogranin, neurofilament light chain (NfL), phosphorylated tau (181P), S100B, sTREM2, total tau, and YKL-40.

Our hope is that such efforts will help propel the entire field forward and enhance our collective understanding of AD pathophysiology, including the effects of various mechanisms of action for investigational DMTs and downstream effects of intervention at different points in the pathophysiologic cascade.

With the continued development of biomarkers and DMTs, we are on the cusp of being able to identify AD earlier and select appropriate treatments for patients, which would be a significant advance. In the future, selection of DMTs may increasingly be individualized, targeting the pathophysiologic process most driving progression in each patient’s current disease stage.

Tackling Barriers to Change

Although there has been great progress in AD, challenges remain in adopting a more targeted and timely approach to diagnosis. A concern is that many health care providers still define AD clinically at symptom onset or later, which could result in a delayed diagnosis compared with a more rapid and earlier biomarker-based approach. Additionally, AD is associated with significant stigma—with many considering it a diagnosis worse than cancer. This stigma can prevent people from seeking care when symptoms are present and ultimately, delay diagnosis until it may be too late for interventions to have a beneficial effect. The widely held idea that memory loss is a normal part of aging and the perception that little can be done if a person is inevitably diagnosed with AD also continue to hinder progress.

AD is more common among traditionally underserved populations of Black and Hispanic people, as well as in women. Lack of access to health care resources for underserved populations and those living in rural areas is also a significant problem. For those in rural areas or with limited resources, reliable transportation or the means to travel long distances to a hospital or specialist can be particularly difficult. If people with AD cannot be seen in a timely manner by a qualified health care professional and receive appropriate workup and accurate diagnosis, they will not receive optimal, or even adequate, treatment.

To continue moving the field forward, we will need effective education across the health care system and in the general population, as well as the removal of systemic hurdles.

A Time of Great Transition

We are at an inflection point in the diagnosis of AD, but, as we know so well, progress takes time. I hope 5 years from now that the accuracy of diagnosis in the broader medical community will be improved—even if incrementally—and that we will see an increase in the availability of confirmatory diagnostic testing and the use of validated biomarkers to monitor responses to new DMTs. The biggest change will likely be the more widespread availability of AD screening, such as blood-based assays, that can be applied in a primary care setting.

Preserving cognition, function, and quality of life, and transforming AD from a relentlessly progressive, terminal disease to a chronic, manageable condition is the paramount hope as we look to the future. With the broad availability of biomarker-based testing, an AD diagnosis will be made proactively and with greater precision. My hope is that people with AD will also require less care in the immediate years after diagnosis, preserving who they are, and remaining functional in society for longer, with a broadly beneficial societal impact.

Progress has been slow–and at times frustrating–in AD, but I believe we are moving steadily in the right direction, and I am confident the rigorous science and bold choices being made now will make a new future for those with AD possible.