Baseline MRI and CSF measurements in cognitively normal individuals as prognostic markers of progression to mild cognitive impairment

Abstract Background Alzheimer’s disease is currently one of our greatest socioeconomic challenges. Understanding the ability biomarkers to predict clinical progression, prior significant cognitive decline, critical when considering secondary prevention strategies. Here we consider association between a range single time‐point baseline in cognitively‐normal group and subsequent risk developing Mild Cognitive Impairment (MCI). Method Data from Disease Neuroimaging Initiative (ADNIGO/2/3) were used. Baseline markers (CSF amyloid 1‐42, CSF ptau, white matter hyperintensities [WMH], microbleeds, whole‐brain volume, hippocampal volume) obtained for 192 (CN) individuals (controls with memory concern; see table). Longitudinal diagnostic data calculate conversion time was also collected. Cox regression models fitted diagnosis MCI. Models each marker separately, fully‐adjusted model (containing all markers); adjustments total intracranial volume (TIV) performed needed. refitted adjusting age. Result There strong evidence that increased WMH lower associated This found both individual models, (see figure). Decreased whole brain amyloid, microbleeds be MCI considered individually but not model. ptau conversion, either or Adjustments age did materially change results. Conclusion Single measurements decreased independently predictive progression Hippocampal may represent different processes; volumes representing greater neurodegeneration as surrogate numerous pathologies, including cerebrovascular disease. While assessed their non‐significant suggests these are strongly conversion.