More than 3800 new publications with “Alzheimer’s Disease” in the title were added to the National Library of Medicine database in the first half of 2024. This constantly accelerating volume of published studies on such an important topic creates the necessity for frequently updated summaries, critical analyses, integration, and consensus reviews of all that data. The National Institute on Aging and The Alzheimer’s Association periodically convene expert working groups of researchers and clinicians to do just that. Their latest analysis was published in June 2024. Their mission–to assess and report the most recent experimental findings defining Alzheimer’s disease (AD).

The Goal:

To establish purely objective diagnostic criteria for AD going forward. Prior to the introduction of biomarker testing, the diagnosis of Alzheimer’s disease was a clinicaI one. It was inferred from the presence of characteristic signs and symptoms, corroborating neurocognitive test results, and conformity with the disease’s classically described clinical course. In the best of hands, such clinical diagnoses were confirmed in 80% to 90% of those infrequent occasions when patients came to autopsy. (Budson & Solomon, 2022) The 2024 analysis incorporates recent dramatic advances in biomarker accuracy and availability to connect that state-of-the-art research with daily clinical care.

The Conclusions:

These two agencies that (through education, outreach, and funding) are at the forefront of Alzheimer’s research:

1. Define Alzheimer’s disease as “a purely biological process” that begins before the onset of any symptoms “with the appearance of the unique brain changes that characterize AD”;
2. Attribute the subsequent “appearance and progression of clinical symptoms” to the continued accumulation of those abnormal brain proteins (amyloid and tau); and
3. Declare that regardless of age, history, family history, or symptoms, any abnormal biomarker (either brain imaging or biofluid testing) that reveals the presence of amyloid and/or tau “is sufficient to establish a diagnosis of AD and to inform clinical decision making throughout the disease continuum.”

It’s Official:

“The detection of AD neuropathologic change by biomarkers is equivalent to diagnosing the disease.”

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“Symptoms are a result of the disease process and are not necessary to diagnose AD.”

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If you fail one of these biomarker tests, no matter how old you are or how you feel,

YOU HAVE ALZHEIMER’S DISEASE!

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Signs and symptoms can follow a biomarker-based diagnosis of preclinical AD by as many as 15-20 years.

The Benefits of Biomarker Testing

1. These indicators allow medical experts to quickly and confidently uncover the presence of this devastating illness, an “essential aspect of good medical practice.”
2. In clinical patient care, a definitive biological diagnosis of AD can predict one’s eligibility for treatments targeting beta-amyloid, the disease’s core pathology.

However,

Even having that terrifying positive blood test in hand is not a ticket to treatment. At the present time, disease-targeted therapies (such as recently-approved Donanemab) are not available to cognitively unimpaired individuals with AD.

BUT HERE’S THE GOOD NEWS:

Largely as a function of the long symptom-free periods after biomarkers become positive:

Nearly 75% Of Those Identified by Biomarkers Alone As Having Preclinical Disease Will Never Develop Clinical AD In Their Lifetime.

References:   

Budson A, Solomon P. Memory loss, Alzheimer’s disease and Dementia. 3. ed. Elsevier, Inc; 2022

Articles cited below are open-access and can be downloaded for free.

Jack CR Jr, et al.. Revised criteria for diagnosing and staging Alzheimer’s disease: Alzheimer’s Association Workgroup. Alzheimers Dement. 2024 Jun 27. doi: 10.1002/alz.13859. https://alz-journals.onlinelibrary.wiley.com/doi/10.1002/alz.13859),

Li Y, et al. Timing of Biomarker Changes in Sporadic Alzheimer’s Disease in Estimated Years from Symptom Onset. Ann Neurol. 2024 May;95(5):951-965. doi: 10.1002/ana.26891. https://onlinelibrary.wiley.com/doi/epdf/10.1002/ana.26891,

National Academies of Sciences, Engineering, and Medicine; Division of Behavioral and Social Sciences and Education; Board on Behavioral, Cognitive, and Sensory Sciences. Implications for Behavioral and Social Research of Preclinical Markers of Alzheimer’s Disease and Related Dementias: Proceedings of a Workshop—in Brief. Forstag EH, editor. Washington (DC): National Academies Press (US); 2021 Aug 24. PMID: 34460185. https://nap.nationalacademies.org/catalog/26295/implications-for-behavioral-and-social-research-of-preclinical-markers-of-alzheimers-disease-and-related-dementias