Diagnostic Impact of Cerebrospinal Fluid Biomarkers in Atypical Dementias in Canada

Abstract

Background: In Canada, standard dementia workup consists of clinical, neurological, and cognitive evaluation, as well as structural brain imaging. For atypical dementia presentations, additional FDG-PET brain imaging is recommended. Cerebrospinal fluid (CSF) biomarkers have recently been proposed as the gold standard for in vivo detection of Alzheimer’s disease (AD) pathophysiology (NIA-AA research framework, 2018). As clinical implementation of CSF assessment is still limited in Canada, the present study assessed its impact on diagnostic accuracy in atypical neurodegenerative disorders in the clinical practice. Methods: This retrospective clinical chart review included patients with cognitive complaints who underwent lumbar puncture (LP) in addition to the standard diagnostic workup. CSF analysis determined the presence of biological AD based on reduced amyloid-β42-to-total-tau index (ATI) and increased phosphorylated-tau (p-tau) levels. CSF-based diagnoses were compared to standard workup and FDG-PET-based diagnoses. Results: A total of 28 patients with atypical dementia presentations were included in the present study after evaluation for cognitive complaints at a specialized dementia clinic between November 2017 and July 2019. CSF analysis changed or better specified the initial clinical diagnosis in 43.0% of cases (alternative diagnosis revealed in 25% and excluded in 18%). In patients with additional FDG-PET imaging (n = 23), FDG-PET and CSF-based diagnosis did not correspond in 35% of patients, even though FDG-PET appeared to increase diagnostic accuracy compared to the initial clinical diagnosis. Conclusion: CSF biomarkers improved diagnostic accuracy in atypical cognitively-impaired patients beyond standard workup and FDG-PET imaging. These results support CSF analysis implementation for atypical dementias in Canada, in addition to the standard diagnostic workup.

Association between neuropsychological assessment and amyloid status in a clinical setting.

“…The small number of patients who underwent LP may also have contributed to a spuriously high number of indeterminate CSF studies (30%), which represented all the indeterminate biomarker cases. However, this may also have been due to selection bias as described above, as the rate of indeterminate cases is similar to other studies performing Athena ADMark testing in patients with atypical dementia presentations (Oboudiyat et al, 2017; van den Brink et al, 2021). Future studies including Aβ 42 /Aβ 40 ratio may improve diagnostic accuracy of CSF biomarker studies, which would reduce the number of indeterminate cases and improve interpretability of results (Hansson et al, 2019).…”