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

Abstract 

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 (Aβ_1–42), tau and tau phosphorylated at threonine-181 (P-tau₁₈₁), and whole-brain atrophy rate were measured.

Results

Across groups, baseline Aβ_1–42 and tau were modestly associated with whole-brain atrophy rate. Adjusted for age, sex and diagnosis, we found no association between Aβ_1–42 or tau, and whole-brain atrophy rate. By contrast, high CSF levels of P-tau₁₈₁ 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 Aβ_1–42, tau or P-tau₁₈₁ provide complementary information in patients with MCI and AD.

Keywords: Alzheimer's disease, Mild cognitive impairment, CSF, Longitudinal, Beta-amyloid, tau, P-tau, MRI, Whole-brain atrophy rate, MMSE