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

OBJECTIVE

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.