International group revises diagnostic guidance for Alzheimer’s
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Key takeaways:
- The guidance outlines core biomarkers for Alzheimer’s, including cerebrospinal fluid, evidence of tau protein and amyloid-beta.
- It also includes three new terms for stages of disease progression.
The International Working Group has updated diagnostic guidelines for Alzheimer’s disease to include individuals with normal cognition who test positive for core biomarkers indicative of disease pathology.
“These recommendations are the collaborative effort of 46 international experts who emphasize that diagnosing Alzheimer’s disease should primarily rely on clinical evaluation supported by biomarkers,” Bruno Dubois, MD, MSc, of the Institute of Memory and Alzheimer’s disease in the department of neurology at Salpetriere Hospital in Paris, said in a release related to the guidelines, which were published in JAMA Neurology.
The recommendations, which revise the organization’s 2021 guidelines, were presented at the 2024 Clinical Trials on Alzheimer’s Disease (CTAD) conference in Madrid. They permit that biological evidence may not be the sole manner in which AD can be defined, with core biomarkers being cerebrospinal fluid (CSF), amyloid-beta and tau, as well as plasma phosphorylated tau 217 (pTau-217) found via positron emission tomography.
The revisions were also intended to separate patients into two groups: individuals who display typical AD-related symptoms along with evidence of disease-specific biomarkers who are diagnosed with AD vs. those who have evidence of disease-specific biomarkers but no symptoms which predict eventual disease progression, Dubois added.
The guidelines additionally encourage clinicians to embrace three specific terms relating to disease pathology and progression.
Those deemed asymptomatic but at risk for AD:
- are cognitively normal but are at elevated risk for becoming cognitively impaired due to unknown risk from a biomarker profile;
- are at increased risk for progression to cognitive impairment compared to those without biomarker presence; and
- should not be defined as having the condition.
Individuals found to have presymptomatic AD:
- are cognitively normal individuals who show a pattern of biomarkers consistent with a very high risk for progression to cognitive impairment;
- possess dominant genetic variations associated with a 100% risk for development to clinical AD such as APP, PSEN1 and PSEN2; and
- demonstrate biomarker changes, coupled with genetic risk factors, associated with elevated risk for clinical AD development such as those confirmed by PET.
Those with AD:
- are cognitively impaired individuals with specific clinical phenotypes including aphasia, cortical atrophy along with behavioral or executive dysfunction;
- test positive for AD-related pathology through analysis of plasma biomarkers, CSF or PET; and
- show signs of the above in the prodromal and dementia stages of disease.
“Further developing brain health services for the prevention of dementia could lead to better evaluation of risk, communication of risk and risk reduction strategies targeting modifiable risk factors,” Giovanni B. Frisoni, MD, professor in the department of psychiatry at Geneva University Hospital in Switzerland, said in the release.
Reference:
International Working Group publishes revised diagnostic criteria for Alzheimer’s disease. https://www.eurekalert.org/news-releases/1063432. Published Nov. 1, 2024. Accessed Nov. 1, 2024.
Perspective
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Rajesh R. Tampi, MD, MS, DFAPA, DFAAGP
These updated IWG criteria continue to advocate for AD to be described as a clinical, biological entity with the diagnosis of AD only being made in the presence of an established clinical phenotype plus additional data being available in the form of pathophysiological biomarkers of AD pathology.
These include CSF biomarkers, amyloid or tau PET, or plasma biomarkers such as p-tau 217, once they are approved for use in clinical practice. This is a welcome improvement from the recently revised Alzheimer’s Association (AA) criteria for AD, which proposes that AD be defined on biological evidence, with a diagnosis of AD being made with one positive core AD biomarker (CSF, amyloid beta/tau ratios and plasma p-tau 217), that is validated against amyloid PET, even among cognitively normal individuals.
In my opinion, the AA criteria are restrictive and may have the unintended consequence of further stigmatizing a diagnosis of AD.
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