This paper documents efforts to use MRI and CSF biomarkers to detect clinically the earliest changes in the brain due to AD. Since changes in brain size (atrophy or the decreasing size of brain areas) detected by MRI are not specific for AD, the use of CSF biomarkers in combination with brain imaging is utilized to improve the diagnostic specificity.  In this ongoing study, the results show that CSF ptau-231 levels are highly correlated with atrophy in the brain as observed by MRI.  This  combination of methods leads to an early and more specific diagnosis of AD and also validates the ptau-231 as a biomarker that is indicative of changes in the brain. This study involved longitudinal analysis of 45 aged cognitively normal individuals at risk for developing AD.  During the study, 13 of the individuals showed cognitive decline and progressed to MCI.

The study reported here is a 2-year longitudinal study of MCI patients and normal controls examining MRI in conjunction with CSF biomarkers. The study consisted of 9 normal elderly volunteers and seven MCI patients.   Patients were given MRI scans and CSF taps for biomarkers at the beginning of the study and during follow-up. ptau-231 levels were elevated in the MCI group relative to the normal group, and it what demonstrated that there was a relationship between hippocampal volume loss and elevated CSF ptau-231 indicating that ptau-231 in the CSF is a measure of loss of neurons involved in AD.   It was also demonstrated that when using a common memory examination test called the “delayed paragraph recall task” to track memory deficit in combination with ptau-231 the overall diagnostic accuracy of using the “delayed recall” test alone (63%) was increased to 88% with the addition of ptau-231.

This is a review article that summarizes the use of MRI, FDG-PET, and CSF markers in the diagnosis of AD and in identifying subjects with mild cognitive impairment.  The conclusion of the paper is that the combined use of conventional imaging (MRI or FDG-PET) with CSF biomarkers, such as ptau-231, contributes to the early and specific diagnosis of AD.

Levels of the p-tau231 biomarker in CSF were shown do correlate with the reduction of hippocampal volumes as measured by MRI.  These findings demonstrate that levels of ptau-231 may be used to predict progression of brain atrophy in patients with Alzheimer’s disease and further validates the use of ptau 231 as a biochemical marker of pathologic changes that
occur in AD.  This study involved MRI and CSF analysis on 22 patients with AD.

The results of this study suggest that the combination of FDG-PET and CSF measures may be sensitive for detection of a preclinical AD state in individuals at risk for future cognitive impairment.