Chapter 7 Whole - brain atrophy rate and CSF biomarker levels in MCI and AD : a longitudinal study Neurobiology of Aging 2010

Objectives: To assess associations between cerebrospinal fluid (CSF) biomarker levels and MRI-based whole-brain atrophy rate in mild cognitive impairment (MCI) and Alzheimer’s disease (AD). Methods: We included 99 patients (47 AD, 29 MCI, 23 controls) who underwent lumbar puncture at baseline and repeat MRI. A subgroup of 48 patients underwent a second lumbar puncture. CSF levels of beta-amyloid1-42 (Aß 1-42 ), tau and tau phosphorylated at threonine-181 (P-tau 181 ), and wholebrain atrophy rate were measured. Results: Across groups, baseline Aß 1-42 and tau were modestly associated with whole-brain atrophy rate. Adjusted for age, sex and diagnosis, we found no association between Aß 1-42 or tau, and whole-brain atrophy rate. By contrast, high CSF levels of P-tau 181 showed a mild association with a lower whole-brain atrophy rate in AD but not in controls or MCI patients. Finally, whole-brain atrophy rate was associated with change in MMSE, but change in CSF biomarker levels was not. Conclusions: Whole-brain atrophy rate and CSF levels of Aß 1-42 , tau or P-tau 181 provide complementary information in patients with MCI and AD.