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.
Sluimer
Jasper D
JD
Alzheimer Centre and Department of Diagnostic Radiology, VU University Medical Center, Amsterdam, The Netherlands. jd.sluimer@vumc.nl
Bouwman
Femke H
FH
Vrenken
Hugo
H
Blankenstein
Marinus A
MA
Barkhof
Frederik
F
van der Flier
Wiesje M
WM
Scheltens
Philip
P
D000368:Aged; D000544:Alzheimer Disease / Q000134:cerebrospinal fluid* / Q000473:pathology*; D016229:Amyloid beta-Peptides / Q000134:cerebrospinal fluid; D000704:Analysis of Variance; D001284:Atrophy / Q000473:pathology; D015415:Biomarkers / Q000134:cerebrospinal fluid; D001921:Brain / Q000473:pathology*; D016009:Chi-Square Distribution; D003072:Cognition Disorders / Q000134:cerebrospinal fluid* / Q000473:pathology*; D005260:Female; D006801:Humans; D008137:Longitudinal Studies; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D009483:Neuropsychological Tests; D010766:Phosphorylation; D016875:tau Proteins / Q000134:cerebrospinal fluid
D016229:Amyloid beta-Peptides; D015415:Biomarkers; D016875:tau Proteins