Emerging Tools for Early Detection of Alzheimer Disease

Michael Irizarry, MD

Alzheimer disease (AD) is the most common cause of dementia, accounting for 60% to 70% of cases. With worldwide population growth and aging, the prevalence of the disease is increasing dramatically.¹ One of the frustrating aspects of this disease for patients and families—as well as for their health care professionals—is the diagnosis itself. Yet, with a growing number of cognitive-assessment options, we are in a new era of early detection.

The clinical diagnosis of AD is usually made at the mild-to-moderate syndromic dementia stage, outside of academic and/or clinical trial centers. However, a growing body of medical evidence indicates that early detection is key.² Specifically, detecting the disease at the predementia stages (ie, during the preclinical and prodromal phase) is critical for numerous reasons.

First, early detection would facilitate the implementation of preventive strategies in at-risk individuals, for example, through multidomain lifestyle changes.³ In fact, recent, large-scale evidence suggests that around 40% of dementia cases worldwide could be prevented or delayed by addressing modifiable risk factors, such as reducing alcohol consumption, social isolation, physical inactivity, and various cardiovascular risk factors (eg, diabetes) to name a few (FIGURE).^4,5

Second, researchers are working to discover and develop therapies that could have disease-modifying effects (ie, biological treatments that could slow disease progression by focusing on underlying pathophysiological processes). Scientists are increasingly targeting the biological alterations during earlier stages of the disease.

Finally, and most importantly, early detection and diagnosis of AD could help in the overall health and wellbeing of affected individuals, their families, and caregivers, by empowering them to:

FIGURE. The importance of early diagnosis.

Click to enlarge.

• Make important decisions about future treatment and care proactively.
• Anticipate and adapt to the cognitive and behavioral changes associated with the disease.
• Seek out opportunities for participating in clinical trials that evaluate potential, disease-modifying treatments.

This could also help with recruiting a more ethnically and racially diverse population for clinical trials. From a socioeconomic perspective, an early, accurate diagnosis would be more cost-effective for health care systems.²

Despite a strong rationale for early detection and diagnosis, pitfalls in current medical practice exist, and underdiagnosis or misdiagnosis of AD is unfortunately quite common.⁶ International research in diagnostic criteria that reflect the conceptualization of AD as a progressive, clinical-biological disease are largely not yet incorporated into the clinical guidelines and have not been used in clinical practice outside of research and trial settings.

It is widely anticipated that primary care physicians (PCPs) would play a crucial role in the evolving AD patient journey, including early detection and diagnosis. Presently, knowledge of the most up-to-date clinical guidelines is limited, making it challenging for PCPs to access the tools and training that they need to recognize and classify individuals affected by AD accurately. The challenge is even greater with the shift to early detection, because the most currently available clinical instruments have been developed to assess patients between the late-mild and severe-clinical dementia stages and are not sensitive enough to detect the earliest prodromal symptomatic changes.⁷

A new era of cognitive assessment is here. It is important to highlight the fact that reliable biomarkers charting key, AD-related, pathophysiological changes—such as the amyloid-ß pathway, the tau pathway, and neuronal injury/neurodegeneration—have been developed and validated over the past few decades;they are close to being integrated into AD clinical practice and serve as vital tools in early detection and diagnosis. These include both cerebrospinal fluid (CSF)-based and PET imaging–based biomarkers. Integration of biomarker assessment in the diagnostic workup of AD is crucial when disease-modifying treatments become available since an in vivo demonstration of defined AD biological features may be necessary for AD diagnosis and treatment initiation.⁷

Larisa Reyderman, PhD

Blood-based biomarkers are a fascinating area of advancing AD research, representing a critical and sustainable solution to aid in the early detection and diagnosis of the disease. Currently, several blood-based biomarker candidates have shown promising results in predicting and detecting the early pathophysiological changes associated with AD and differentiating it from other types of neurodegenerative diseases. Blood tests are globally accessible and cost-, resource- and time-effective. They can potentially be used as first-tier screening tools in primary care to identify individuals who should be followed up with more definitive diagnostic tests, such as PET imaging or CSF analysis. Eventually, blood tests may replace PET and CSF.⁸

The rise of digital tools (such as those using widely available mobile technologies) to detect and monitor cognitive changes in an at-home setting presents another promising approach to AD identification early on. These include cognitive or neuropsychiatric tests that are newly developed or adapted for mobile platforms, and those that use new types of data for cognitive assessment, such as speech and physical movement. Various digital tools are currently being developed, and several have shown encouraging, preliminary results in detecting early stages of AD. Coupled with older adults’ increasing use of smart technology and the Internet, such devices could serve as efficient, convenient, and cost-effective methods for screening and monitoring cognitive impairment and progression.

Collaboration between technology-driven enterprises with health care industry partners is critical. Work is already underway on cognitive function tests that enable individuals to self-assess brain performance to support healthy lifestyle choices and preventative measures in daily life. The goal is to develop these tests into a clinically validated medical device or application to aid health care professionals in the clinical diagnosis of mild cognitive impairment and dementia.⁹

It is essential to note that these emerging tools are still under development or in the process of validation and standardization. Nevertheless, they offer hope to families and their doctors, and that is promising.

Michael Irizarry, MD, and Larisa Reyderman, PhD, both of Eisai Inc, contributed to this post.

REFERENCES
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