Diagnostic Value of the CSF α-Synuclein Real-Time Quaking-Induced Conversion Assay at the Prodromal MCI Stage of Dementia With Lewy Bodies. (31st August 2021)

• Record Type: Journal Article
• Authors: Rossi, Marcello; Baiardi, Simone; Teunissen, Charlotte E.; Quadalti, Corinne; van de Beek, Marleen; Mammana, Angela; Stanzani-Maserati, Michelangelo; Van der Flier, Wiesje M.; Sambati, Luisa; Zenesini, Corrado; Caughey, Byron; Capellari, Sabina; Lemstra, Afina W.; Parchi, Piero
• Is Part Of: Neurology. Volume 97:Number 9(2021)
• Publication Date: 2021-08-31
• Subjects: Neurology -- Periodicals; Neurology -- Periodicals; Neurologie -- Périodiques; 616.8
• DOI: 10.1212/WNL.0000000000012438
• Languages: English
• ISSNs: 0028-3878

Abstract

Abstract : Objective: To investigate whether the CSF α-synuclein (α-syn) real-time quaking-induced conversion (RT-QuIC) assay accurately identifies patients with mild cognitive impairment (MCI) due to probable Lewy body (LB) disease. Methods: We applied α-syn RT-QuIC to 289 CSF samples obtained from 2 independent cohorts, including 81 patients with probable MCI-LB (age 70.7 ± 6.6 years, 13.6% female, Mini-Mental State Examination [MMSE] score 26.1 ± 2.4), 120 with probable MCI due to Alzheimer disease (AD) (age 68.6 ± 7.4 years, 45.8% female, MMSE score 25.5 ± 2.8), and 30 with unspecified MCI (age 65.4 ± 9.3 years, 30.0% female, MMSE score 27.0 ± 3.0). Fifty-eight individuals with no cognitive decline or evidence of neurodegenerative disease and 121 individuals lacking brain α-syn deposits at the neuropathologic examination were used as controls. Results: RT-QuIC identified patients with MCI-LB against cognitively unimpaired controls with 95% sensitivity, 97% specificity, and 96% accuracy and showed 98% specificity in neuropathologic controls. The accuracy of the test for MCI-LB was consistent between the 2 cohorts (97.3% vs 93.7%). Thirteen percent of patients with MCI-AD also had a positive test; of note, 44% of them developed 1 core or supportive clinical feature of dementia with Lewy bodies (DLB) at follow-up, suggesting an underlying LB copathology. Conclusions: These findings indicate that CSF α-syn RT-QuIC is a robust biomarker for prodromal DLB. Further studies are needed to fully explore the added value of the assay to the current research criteria for MCI-LB. Classification of Evidence: This study provides Class III evidence that CSF α-syn RT-QuIC accurately identifies patients with MCI-LB.