Optimal combinations of CSF biomarkers for predicting cognitive decline and clinical conversion in cognitively unimpaired participants and mild cognitive impairment patients: A multi-cohort study

• Introduction: Our objective was determining the optimal combinations of cerebrospinal fluid (CSF) biomarkers for predicting disease progression in Alzheimer's disease (AD) and other neurodegenerative diseases.Methods: We included 1,983 participants from three different cohorts with longitudinal cognitive and clinical data, and baseline CSF levels of A beta 42, A beta 40, phosphorylated tau at threonine-181 (p-tau), neurofilament light (NfL), neurogranin, alpha-synuclein, soluble triggering receptor expressed on myeloid cells 2 (sTREM2), glial fibrillary acidic protein (GFAP), YKL-40, S100b, and interleukin 6 (IL-6) (Elecsys NeuroToolKit).Results: Change of modified Preclinical Alzheimer's Cognitive Composite (mPACC) in cognitively unimpaired (CU) was best predicted by p-tau/A beta 42 alone (R-2 >= 0.31) or together with NfL (R-2 = 0.25), while p-tau/A beta 42 (R-2 >= 0.19) was sufficient to accurately predict change of the Mini-Mental State Examination (MMSE) in mild cognitive impairment (MCI) patients. P-tau/A beta 42 (AUC >= 0.87) and p-tau/A beta 42 together with NfL (AUC >= 0.75) were the best predictors of conversion to AD and all-cause dementia, respectively.Discussion: P-tau/A beta 42 is sufficient for predicting progression in AD, with very high accuracy. Adding NfL improves the prediction of all-cause dementia conversion and cognitive decline.

Ämnesord

MEDICIN OCH HÄLSOVETENSKAP  -- Medicinska och farmaceutiska grundvetenskaper -- Neurovetenskaper (hsv//swe)

MEDICAL AND HEALTH SCIENCES  -- Basic Medicine -- Neurosciences (hsv//eng)

MEDICIN OCH HÄLSOVETENSKAP  -- Klinisk medicin -- Neurologi (hsv//swe)

MEDICAL AND HEALTH SCIENCES  -- Clinical Medicine -- Neurology (hsv//eng)

Nyckelord

amyloid-beta

BioFINDER

cognitive decline

conversion to dementia

glial activation

inflammation

neurodegeneration

tau ratio

WADRC

WRAP

cerebrospinal-fluid biomarkers

alzheimers-disease

ratio

association

concordance

Neurosciences & Neurology

amyloid-β

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