Test sequence of CSF and MRI biomarkers for prediction of AD in subjects with MCI

Abstract

Our aim was to identify the best diagnostic test sequence for predicting Alzheimer's disease (AD)-type dementia in subjects with mild cognitive impairment (MCI) using cerebrospinal fluid (CSF) and magnetic resonance imaging (MRI) biomarkers. We selected 153 subjects with mild cognitive impairment from a multicenter memory clinic-based cohort. We tested the CSF beta amyloid (Aβ)1-42/tau ratio using enzyme-linked immunosorbent assay (ELISA) and hippocampal volumes (HCVs) using the atlas-based learning embeddings for atlas propagation (LEAP) method. Outcome measure was progression to AD-type dementia in 2 years. At follow-up, 48 (31%) subjects converted to AD-type dementia. In multivariable analyses, CSF Aβ1-42/tau and HCV predicted AD-type dementia regardless of apolipoprotein E (APOE) genotype and cognitive scores. Test sequence analyses showed that CSF Aβ1-42/tau increased predictive accuracy in subjects with normal HCV (p < 0.001) and abnormal HCV (p = 0.025). HCV increased predictive accuracy only in subjects with normal CSF Aβ1-42/tau (p = 0.014). Slope analyses for annual cognitive decline yielded similar results. For selection of subjects for a prodromal AD trial, the best balance between sample size and number of subjects needed to screen was obtained with CSF markers. These results provide further support for the use of CSF and magnetic resonance imaging biomarkers to identify prodromal AD.

Alterations in Rapid Eye Movement Sleep Parameters Predict for Subsequent Progression from Mild Cognitive Impairment to Alzheimer’s Disease

“…Evidence has been accumulated to elucidate the predictors of progression to AD in subjects with MCI, which includes investigations of biomarkers obtained in cerebrospinal fluid (CSF), magnetic resonance imaging (MRI), SPECT, and PET. Previous MRI studies have demonstrated that MCI subjects with a smaller volume of the hippocampus [3,4,6] or medial (and inferior) temporal lobe [2,3,5] are at a high risk of progressing to AD. Decreases in regional cerebral blood flow at the precuneus, posterior cingulate [7], or medial temporal lobes [7,8] have been reported to be associated with AD conversion.…”

“…Previous studies demonstrated that a higher risk of AD progression may be involved with an altered function in specific regions such as the posterior cingulate, which are characteristic of AD. Subjects with MCI who developed AD had already exhibited significantly decreased volumes [2][3][4][5][6], decreased levels of regional cerebral blood flow [7,8] and glucose metabolism [5,[9][10][11][12] at the posterior cingulate compared to those who remained in a non-dementia state, when they did not meet criteria for dementia.…”

AlzheimerÂ’s and ParkinsonÂ’s Diseases Face Common Challenges in Therapeutic Development: Role of the Precompetitive Consortium, Coalition Against Major Diseases

“…Analysis of three different datasets produced encouraging results [13][14][15], suggesting that the variability of cutpoints among different studies is low; however, it has been difficult to obtain data from published analyses that could be reanalyzed to confirm this finding.…”

Disclosure of Alzheimer’s Disease Biomarker Status in Subjects with Mild Cognitive Impairment

“…Moreover, diagnostic and prognostic accuracy vary with the position of biomarkers in the amyloid cascade [9]. Amyloid markers have a higher sensitivity for the diagnosis of AD in subjects with MCI than injury markers [4,9,10]. By contrast, injury markers have a better prognostic value than amyloid markers and can predict time to onset of dementia [9].…”