Predictive value of phospho-tau/total-tau ratio in amyloid-negative Mild Cognitive Impairment. (14th September 2022)

• Record Type: Journal Article
• Authors: Tondelli, Manuela; Salemme, Simone; Vinceti, Giulia; Bedin, Roberta; Trenti, Tommaso; Molinari, Maria Angela; Chiari, Annalisa; Zamboni, Giovanna
• Is Part Of: Neuroscience letters. Volume 787(2022)
• Publication Date: 2022-09-14
• Subjects: MCI (mild cognitive impairment) -- Dementia -- Neuroimaging, biomarkers; Neurology -- Periodicals; Neurology -- Periodicals; Research -- Periodicals; Neurologie -- Périodiques; Neuroanatomie -- Périodiques; Neuropharmacologie -- Périodiques; Neurophysiologie -- Périodiques; Neurology; Periodicals; Electronic journals; 617.48
• DOI: 10.1016/j.neulet.2022.136811
• Languages: English
• ISSNs: 0304-3940

Abstract

Highlights: Prognostication in MCI patients with normal amyloid biomarkers is challenging. Patients with normal CSF amyloid-β1-42 but low p/ t -tau ratio had higher risk of subsequent conversion to dementia . Patients with low p/ t -tau ratio had brain atrophy involving the limbic system including medial temporal lobe, posterior cingulate and subgenual cortex. We speculate that amyloid negative MCI who developed dementia may have had underlying TDP-43 pathology. Abstract: Background: In patients with Mild Cognitive Impairment and normal biomarkers of amyloid-β deposition, prognostication remains challenging. Methods: We aimed at identifying clinical features, patterns of brain atrophy, and risk of subsequent conversion to dementia in a clinical cohort of consecutive patients with Mild Cognitive Impairment and normal CSF amyloid-β1-42 presenting to our Cognitive Neurology Clinic who were followed prospectively over an average of 25 months. We stratified them as Converters/Non-Converters to dementia based on clinical follow-up and compared baseline clinical features, CSF biomarkers, and pattern of atrophy on MRI data between groups. Results: Among 111 eligible patients (mean age 65, 61 years; 56, 8% were male), 41 patients developed a clinical diagnosis of dementia. Subjects with low baseline p/t-tau had twofold risk of future conversion compared to high p/t-tau ratio subjects (HR = 2.0, p = 0.026). When stratifying converters according to CSF p/t-tau ratio cut off value (0, 17), those with values lower than the cut-off had significantly more MRI atrophy at baseline relative to Non-Converters in limbic structures. Conclusion: In Mild Cognitive Impairment patients with negative CSF amyloid biomarker, CSF p/t-tau ratio may be useful to identify those at greater risk of subsequent conversion, possibly because of TDP43-related underlying pathology.