Whole-brain atrophy rate and CSF biomarker levels in MCI and AD: a longitudinal study.

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-amyloid(1-42) (A beta(1-42)), tau and tau phosphorylated at threonine-181 (P-tau(181)), and whole-brain atrophy rate were measured.

RESULTS: Across groups, baseline A beta(1-42) and tau were modestly associated with whole-brain atrophy rate. Adjusted for age, sex and diagnosis, we found no association between A beta(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 A beta(1-42,) tau or P-tau(181) provide complementary information in patients with MCI and AD.