Elsevier

Neurobiology of Aging

Volume 27, Issue 3, March 2006, Pages 394-401
Neurobiology of Aging

Longitudinal CSF and MRI biomarkers improve the diagnosis of mild cognitive impairment

https://doi.org/10.1016/j.neurobiolaging.2005.07.003Get rights and content

Abstract

The diagnosis of Alzheimer's disease (AD) in patients with mild cognitive impairment (MCI) is limited because it is based on non-specific behavioral and neuroimaging findings. The lesions of Alzheimer's disease: amyloid beta (Aβ) deposits, tau pathology and cellular oxidative damage, affect the hippocampus in the earlier stages causing memory impairment. In a 2-year longitudinal study of MCI patients and normal controls, we examined the hypothesis that cerebrospinal fluid (CSF) markers for these pathological features improve the diagnostic accuracy over memory and magnetic resonance imaging (MRI)-hippocampal volume evaluations. Relative to control, MCI patients showed decreased memory and hippocampal volumes and elevated CSF levels of hyperphosphorylated tau and isoprostane. These two CSF measures consistently improved the diagnostic accuracy over the memory measures and the isoprostane measure incremented the accuracy of the hippocampal volume achieving overall diagnostic accuracies of about 90%. Among MCI patients, over 2 years, longitudinal hippocampal volume losses were closely associated with increasing hyperphosphorylated tau and decreasing amyloid beta-42 levels. These results demonstrate that CSF biomarkers for AD contribute to the characterization of MCI.

Section snippets

Subjects

All subjects gave their informed consent to this NYU-IRB approved study. Individuals with medical conditions or history of significant conditions that may affect brain structure or function (e.g. stroke, insulin dependent diabetes, head trauma, other neurodegenerative disease, or depression) were excluded. Nine normal elderly volunteers and seven MCI patients recruited from a larger on-going longitudinal MRI study were included. MCI was defined by a global deterioration scale (GDS) [31] score

Results

For all the following results, removing the one MCI case that declined to AD did not affect the baseline, follow-up, prediction accuracy, or longitudinal results. As such all results are presented with this patient included.

Discussion

This is the first longitudinal study of normal and MCI subjects to examine CSF biomarkers, memory and hippocampal volume. We studied exemplars from five principal classes of AD markers: delayed recall, hippocampal atrophy, cellular oxidative damage, hyperphosphorylated tau and amyloid beta. The results of this study show that most of the AD markers demonstrated good to excellent cross-sectional accuracy in distinguishing MCI patients from controls and excellent reproducibility overtime.

Acknowledgements

We thank Ms. Schantel Williams, Ms. Catherine Cianci and Ms. Ronit Notkin for their excellent study coordination and neuropsychological testing and Ms. Terry Heyman for her superb care of the patients during the LP and MRI procedures. Drs. Antonio Convit (New York, USA), Philip Scheltens (Amsterdam, The Netherlands), Kaj Blennow Anders Wallin and Magnus Sjogren (Goteborg, Sweden) provided numerous discussions that improved the quality of this paper. This study was supported by: NIH-NIA AG12101,

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