CSF Biomarkers and Amyloid PET Equally Accurate in Identifying Early-Stage Alzheimer’s Disease

VBCN - April 2016 Volume 3, No 1

Cerebrospinal fluid (CSF) biomarkers and cerebral beta-amyloid and amyloid positron emission tomography (PET) measures are equally accurate in the identification of early Alzheimer’s disease.

The first head-to-head comparison of regional amyloid PET imaging and different CSF beta-amyloid biomarker assays revealed no differences between the 2 modalities, and no advantage in combining the 2 techniques for identifying mild cognitive impairment (MCI) in early stages of Alzheimer’s disease (Palmqvist S, et al. Neurology. 2015;85:1240-1249).

“The similar results we found for CSF biomarkers and amyloid PET suggest that other factors than their diagnostic accuracy may be considered when deciding which biomarker to use,” noted Sebastian Palmqvist, MD, PhD, Clinical Memory Research Unit, Lund University, Sweden, and colleagues. These factors include cost, procedure availability, and physician and patient preferences.

Dr Palmqvist and colleagues included 122 healthy elderly individuals and 34 patients with MCI who progressed to Alzheimer’s disease (MCI-AD) within 3 years from the prospective, longitudinal BioFINDER study. Beta-amyloid deposition in 9 bilateral brain regions was visualized using [18F]-flutemetamol PET. The INNOTEST and EUROIMMUN assays were used to analyze the CSF for various biomarkers, including t-tau, Aβ40, Aβ42, and p-tau.

Overall, 8 variables were derived from the CSF analysis.

CSF biomarkers had diagnostic accuracy ranging from an area under the curve (AUC) of 0.82 (Aβ42EI) to 0.94 (Aβ42/p-tau).

The AUCs of the amyloid PET measures ranged from 0.75 to 0.92. The AUCs of the best PET of the posterior cingulate/precuneus region (AUC, 0.93) and anterior cingulate (AUC, 0.92), and a composite of the anterior cingulate and posterior cingulate/precuneus (AUC, 0.92) “were equally good,” the investigators noted.

The best CSF biomarkers had AUCs similar to the best PET measures.

Accuracies for CSF and PET biomarkers were also not significantly different when assessed in an independent cohort of 64 patients with MCI-AD and 146 cognitively healthy elderly individuals.

According to the investigators, CSF analysis has an advantage over PET in that it may easily incorporate other biomarkers (eg, leukocytes, albumin ratio, neurofilament, alpha-synuclein) to improve the differential diagnosis of early Alzheimer’s disease, requires less-advanced instruments than PET, and may be more available in clinical practice than PET.

“Amyloid PET, on the other hand, is less invasive and has a higher reliability in longitudinal examinations and between centers,” the researchers noted. “With appropriate standardized procedures, CSF analysis and amyloid PET perform equally well and either method can be used in the clinical workup of AD for increased diagnostic accuracy.”

Ronald C. Petersen, MD, PhD, Director, Alzheimer’s Disease Research Center, Mayo Clinic, Rochester, MN, told Value-Based Care in Neurology that the use of these biomarkers in the workup of patients with suspected Alzheimer’s disease is still an active area of research, “but this information is filtering into clinical practice.”

Currently, CSF values are used in the clinic, and 3 PET tracers for amyloid have been approved by the FDA, Dr Petersen noted. “However, no third-­party payers cover the PET scans at present, pending data to validate utility,” he said.

These techniques can be useful in the differential diagnosis of young patients, in those with MCI, or in patients with dementia in whom the cause is not apparent, Dr Petersen added.

He added that the Centers for Medicare & Medicaid Services and the Alzheimer’s Association are conducting a study called IDEAS to determine the practical utility of amyloid PET imaging in influencing patient outcomes.

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