18F-FDG PET can effectively rule out conversion to dementia and the presence of CSF biomarker of neurodegeneration: a real-world data analysis

Abstract

Background: Precisely defining the delay in onset of dementia is a particular challenge for early diagnosis. Brain [¹⁸F] fluoro-2-deoxy-2-D-glucose (¹⁸F-FDG) Positron Emission Tomography (PET) is a particularly interesting tool for the early diagnosis of neurodegenerative diseases, through the measurement of the cerebral glucose metabolic rate. There is currently a lack of longitudinal studies under real-life conditions, with sufficient patients, to accurately evaluate the predictive values of brain ¹⁸F-FDG PET scans. Here, we aimed to estimate the value of brain ¹⁸F-FDG PET for predicting the risk of dementia conversion and the risk of occurrence of a neurodegenerative pathology.

Methods: Longitudinal data for a cohort of patients with no diagnosis of dementia at the time of recruitment referred by a tertiary memory clinic for brain ¹⁸F-FDG PET were matched with (Prince M, Wimo A, Guerchet Maëlenn, Ali G-C, Wu Y-T et al. World Alzheimer Report 2015. The Global Impact of Dementia: An analysis of prevalence, incidence, cost and trends. [Research Report] Alzheimer's Disease International. 2015. 2015.) data from the French National Health Data System (NHDS), (Jack CR, Bennett DA, Blennow K, Carrillo MC, Dunn B, Haeberlein SB, et al. NIA-AA Research Framework: Toward a biological definition of Alzheimer's disease. Alzheimers Dement. 2018;14(4):535-62.) data from the National Alzheimer Bank (NAB), and (Davis M, O`Connell T, Johnson S, Cline S, Merikle E, Martenyi F, et al. Estimating Alzheimer's Disease Progression Rates from Normal Cognition Through Mild Cognitive Impairment and Stages of Dementia. CAR. 2018;15(8):777-88.) lumbar puncture (LP) biomarker data. The criteria for dementia conversion were the designation, within the three years after the brain ¹⁸F-FDG PET scan, of a long-term condition for dementia in the NHDS and a dementia stage of cognitive impairment in the NAB. The criterion for the identification of a neurodegenerative disease in the medical records was the determination of LP biomarker levels.

Results: Among the 403 patients (69.9 ± 11.4 years old, 177 women) from the initial cohort with data matched with the NHDS data, 137 were matched with the NAB data, and 61 were matched with LP biomarker data. Within three years of the scan, a ¹⁸F-FDG PET had negative predictive values of 85% for dementia conversion (according to the NHDS and NAB datasets) and 95% for the presence of LP neurodegeneration biomarkers.

Conclusion: A normal brain ¹⁸F-FDG PET scan can help rule out the risk of dementia conversion and the presence of cerebrospinal fluid (CSF) biomarker of neurodegeneration early with high certainty, allowing modifications to patient management regimens in the short term.

Trial registration: Clinical Trials database (NCT04804722). March 18, 2021. Retrospectively registered.

Keywords: FDG PET; Neurodegenerative disease; Prognosis; Real-world data; national health data system.

Fig. 1

Example of the combined visual (upper panel, axial and coronal slices of brain ¹⁸F-FDG PET images) and semiquantitative (lower panel, with hypometabolisms in green projected on axial MR slices on the left and hypometabolisms in blue on a 3D volume rendered on the right) analysis for a 65-year-old male patient (initially diagnosed with MCI); these results were consistent with Alzheimer’s disease. The final diagnosis in the National Alzheimer’s database was Alzheimer’s disease and conversion to dementia after 31.5 months

Fig. 2

Flowchart for the inclusion of patients in this study. MCI, mild cognitive impairment; LP, lumbar puncture; LTC, long-term condition; NAB, National Alzheimer Bank; NHDS, National Health Data System; SCI, subjective cognitive impairment

Fig. 3

Dementia-free (left panel) and overall (right panel) survival curves and their 95% confidence intervals for patients with PET images demonstrating patterns supporting and not supporting a diagnosis of a neurodegenerative disease (survival according to the National Health Data System, N = 403). The red dotted lines indicate the 3 years threshold of follow-up to respond to the primary and one secondary objectives. Numbers below the respective figures represent the number of patients under follow-up without any dementia (left panel) or alive (right panel) with a PET scan not in favor of a neurodegenerative pattern (first row) and in favor of a neurodegenerative pattern (second row)