IC-P2-145: Whole-brain atrophy rate and CSF biomarker levels in MCI and AD: A longitudinal study

Abstract

To assess associations between baseline and longitudinal cerebrospinal fluid (CSF) biomarker levels and whole-brain atrophy rate in mild cognitive impairment (MCI) and Alzheimer's disease (AD), and the ability of these markers to predict disease progression. We included 101 patients (47 AD, 30 MCI, 24 controls) who underwent lumbar puncture at baseline and repeat MRI (interval 1.7±0.7y). A subgroup of 49 patients (20 AD, 18 MCI, 11 controls) underwent a second lumbar puncture. CSF levels of beta-amyloid1–42 (Aβ1–42), tau and tau phosphorylated at threonine-181 (P-tau181) were measured. Whole-brain atrophy rate was measured from serial MRI and clinical progression was determined using the MMSE. Across diagnostic groups, baseline Aβ1–42 (r=0.30, p<0.01), and tau (r=-0.25, p=0.01) were associated with whole-brain atrophy rate, while P-tau181 was not (r=-0.13, p=0.18). After adjustment for age, sex and diagnosis, we found no association between Aβ1–42 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 (β[SE] 0.77 [0.36], p=0.04) but not in controls or MCI patients. Finally, whole-brain atrophy rate was associated with change in MMSE (r=0.40, p<0.05), while change in CSF levels of Aβ1–42, (r=0.18, p=0.22), tau (r=-0.03, p=0.83), and P-tau181(r=-0.01, p=0.97) was not. Whole-brain atrophy rate and CSF levels of Aβ1–42, tau or P-tau181 provide independent information in patients with MCI and AD, with CSF markers reflecting a disease state, while whole-brain atrophy rate measured from serial MRI, reflects the rate of disease progression.