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Whole-brain atrophy rate and CSF biomarker levels in MCI and AD: a longitudinal study
Jasper D Sluimer1, Femke H Bouwman, Hugo Vrenken
1Alzheimer Centre and Department of Diagnostic Radiology, VU University Medical Center, Amsterdam, The Netherlands. jd.sluimer@vumc.nl
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.
Insights
Cerebrospinal fluid (CSF) biomarkers like beta-amyloid and tau show modest associations with brain atrophy in Alzheimer's disease (AD) and mild cognitive impairment (MCI). Phosphorylated tau (P-tau) levels correlate with slower atrophy in AD patients.
Area of Science:
- Neurology
- Neuroimaging
- Biomarker Research
Background:
- Alzheimer's disease (AD) and mild cognitive impairment (MCI) are characterized by neurodegeneration.
- Measuring whole-brain atrophy rate via MRI and cerebrospinal fluid (CSF) biomarkers are key diagnostic tools.
Purpose of the Study:
- To investigate the relationship between CSF biomarker levels and the rate of whole-brain atrophy.
- To explore these associations in patients with MCI and AD compared to controls.
Main Methods:
- Included 99 participants (47 AD, 29 MCI, 23 controls) with baseline CSF samples and MRI scans.
- Measured CSF levels of beta-amyloid(1-42) (A beta(1-42)), tau, and phosphorylated tau (P-tau(181)).
- Quantified whole-brain atrophy rate using serial MRI scans.
Main Results:
- Baseline A beta(1-42) and tau showed modest associations with atrophy rate across all groups.
- After adjusting for covariates, no significant association was found between A beta(1-42) or tau and atrophy rate.
- Elevated CSF P-tau(181) levels were mildly associated with a reduced whole-brain atrophy rate in AD patients.
- Whole-brain atrophy rate correlated with changes in Mini-Mental State Examination (MMSE) scores, but not with changes in CSF biomarker levels.
Conclusions:
- Whole-brain atrophy rate and CSF biomarker levels (A beta(1-42), tau, P-tau(181)) offer complementary information for diagnosing and monitoring MCI and AD.
- P-tau(181) may serve as a specific indicator of neurodegenerative processes impacting atrophy rates in AD.
