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New Alzheimer's Association Guidelines Emphasize Biological Criteria for Diagnosing, Staging Disease

NEW YORK – A work group organized by the Alzheimer's Association has published updated criteria for diagnosing and staging Alzheimer's disease.

The new guidelines, published this week in Alzheimer's & Dementia: The Journal of the Alzheimer's Association, move away from reliance on clinical symptoms to diagnose and stage Alzheimer's and instead use biological criteria.

According to the authors, the change in guidelines reflect three recent developments in the field: the approval of anti-amyloid drugs, which, they noted, "target core disease pathology"; the development of blood-based biomarkers, which make the tools required for biology-based diagnoses more widely accessible; and research demonstrating that imaging, cerebrospinal fluid-based biomarkers, and blood-based biomarkers can, in some cases, be used interchangeably.

"Defining diseases biologically, rather than based on syndromic presentation, has long been standard in many areas of medicine — including cancer, heart disease, and diabetes — and is becoming a unifying concept common to all neurodegenerative diseases," Clifford Jack, head of the Mayo Clinic's Aging and Dementia Imaging Research Laboratory and lead author of the guidelines, said in a statement. “An unchanging principle is that effective treatment will always rely on the ability to diagnose and stage the biology driving the disease process.”

Publication of the revised guidelines follows the release last year of draft guidelines that proposed the use of blood-based biomarkers for diagnosing Alzheimer's disease.

The new guidelines establish a set of core biomarkers, including amyloid PET imaging and CSF or plasma-based amyloid-β(Aβ)42; CSF or plasma phosphorylated tau (p-tau) 217, 181, and 231; and tau PET and CSF or plasma microtubule-binding region (MTBR)-tau 243 as well as other phosphorylated and non-phosphorylated tau forms.

The authors also provided intended uses for these biomarkers, establishing amyloid PET, plasma p-tau 217, plasma p-tau 217 ratio, and CSF p-tau 181/Aβ42, total-tau/Aβ42, and Aβ42/40 as tools for diagnosis, staging, and determining the prognosis of Alzheimer's as well as assessing the effect of treatment. Tau PET and CSF or plasma MTBR-tau 243 and other phosphorylated and non-phosphorylated tau forms may also be useful for staging, prognosis, and assessing the effect of treatment.

Consistent with previous guidelines, the authors recommended that only biomarkers that perform with 90 percent accuracy as benchmarked against either autopsy samples or amyloid PET or CSF measurements be used for diagnosing the disease.

The guidelines also establish a set of noncore biomarkers, including neurofilament light chain (NfL), glial fibrillary acidic protein (GFAP), and imaging tests, that may be useful for detecting biological processes involved in Alzheimer's but are not specific to the condition, as well as non-Alzheimer's co-pathologies.

While the new guidelines focus on the use of biologic criteria to diagnose and stage Alzheimer's patients, they are not meant to replace traditional clinical evaluation, the authors noted, adding that clinical judgment will be necessary when the results of core biomarkers do not match a patient's clinical symptoms and that clinical judgment is also required to determine if biomarker results are affected by confounding conditions such as impaired kidney function or use of certain medications.

The new guidelines also propose a scheme for integrating biological- and clinical-based staging of Alzheimer's patients, which, the authors wrote, "are regarded as quasi-independent variables." While these two types of disease staging are done independently, the scheme proposed in the new guidelines provides a guide for combining information from both.

The authors cautioned that clinical use of the biomarkers detailed in the guidelines is intended for the evaluation of symptomatic patients only. While Alzheimer's "can be diagnosed in asymptomatic individuals … we do not believe this should be done for clinical purposes at this time," they added.