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Task-enhanced arterial spin labeled perfusion MRI predicts longitudinal neurodegeneration in mild cognitive impairment.

ABSTRACT: Mild cognitive impairment (MCI) is considered a prodromal stage of Alzheimer's disease (AD), but is also recognized to be a heterogeneous condition. Biomarkers that predict AD progression in MCI are of clinical significance because they can be used to better identify appropriate candidates for therapeutic intervention studies. It has been hypothesized that comparing to structural measurements, functional ones may be more sensitive to early disease abnormalities and the sensitivity could be further enhanced when combined with cognitive task, a "brain stress test." In this study, we investigated the value of regional cerebral blood flow (CBF), measured by arterial spin labeled perfusion MRI (ASL MRI) during a memory-encoding task, in predicting the estimated rate of hippocampal atrophy, an established marker of AD progression. Thirty-one amnestic MCI patients (20 male and 11 female; age: 70.9?±?6.5 years, range from 56 to 83?years; mini mental status examination: 27.8?±?1.8) and 42 normal control subjects (13 male and 29 female; age: 70.6?±?8.8 years, range from 55 to 88?years; mini mental status examination: 29.1?±?1.2) were included in this study. We compared the predictive value of CBF during task to CBF during rest and structural volumetry. Both region-of-interest and voxelwise analyses showed that baseline CBF measurements during task (strongest effect in fusiform gyrus, region-of-interest analysis statistics: r?=?0.56, p?=?.003), but not resting ASL MRI or structural volumetry, were correlated with the estimated rate of hippocampal atrophy in amnestic MCI patients. Further, stepwise linear regression demonstrated that resting ASL MRI and volumetry did not provide complementary information in prediction. These results support the notion that physiologic measures during a cognitive challenge may increase the ability to detect subtle functional changes that predict progression. As such, ASL MRI could have important utility in stratifying candidates for AD treatment trials.

SUBMITTER: Xie L

PROVIDER: S-EPMC6309706 | biostudies-literature | 2019 Jan

REPOSITORIES: biostudies-literature

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Task-enhanced arterial spin labeled perfusion MRI predicts longitudinal neurodegeneration in mild cognitive impairment.

Xie Long L Das Sandhitsu R SR Pilania Arun A Daffner Molly M Stockbower Grace E GE Dolui Sudipto S Yushkevich Paul A PA Detre John A JA Wolk David A DA

Hippocampus 20181106 1

Mild cognitive impairment (MCI) is considered a prodromal stage of Alzheimer's disease (AD), but is also recognized to be a heterogeneous condition. Biomarkers that predict AD progression in MCI are of clinical significance because they can be used to better identify appropriate candidates for therapeutic intervention studies. It has been hypothesized that comparing to structural measurements, functional ones may be more sensitive to early disease abnormalities and the sensitivity could be furth ...[more]

PMID: 30207006

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Project description:BACKGROUND:With the disappointing outcomes of clinical trials on patients with Alzheimer's disease or mild cognitive impairment (MCI), there is increasing attention to understanding cognitive decline in normal elderly individuals, with the goal of identifying subjects who are most susceptible to imminent cognitive impairment. PURPOSE/HYPOTHESIS:To evaluate the potential of cerebral blood flow (CBF) as a biomarker by investigating the relationship between CBF at baseline and cognition at follow-up. STUDY TYPE:Prospective longitudinal study with a 4-year time interval. POPULATION:309 healthy subjects aged 20-89 years old. FIELD STRENGTH/SEQUENCE:3T pseudo-continuous-arterial-spin-labeling MRI. ASSESSMENT:CBF at baseline and cognitive assessment at both baseline and follow-up. STATISTICAL TESTS:Linear regression analyses with age, systolic blood pressure, physical activity, and baseline cognition as covariates. RESULTS:Linear regression analyses revealed that whole-brain CBF at baseline was predictive of general fluid cognition at follow-up. This effect was observed in the older group (age ?54 years, ??=?0.221, P?=?0.004), but not in younger or entire sample (??=?0.018, P?=?0.867 and ??=?0.089, P?=?0.098, respectively). Among major brain lobes, frontal CBF had the highest sensitivity in predicting future cognition, with a significant effect observed for fluid cognition (??=?0.244 P?=?0.001), episodic memory (??=?0.294, P?=?0.001), and reasoning (??=?0.186, P?=?0.027). These associations remained significant after accounting for baseline cognition. Voxelwise analysis revealed that medial frontal cortex and anterior cingulate cortex, part of the default mode network (DMN), are among the most important regions in predicting fluid cognition. DATA CONCLUSION:In a healthy aging cohort, CBF can predict general cognitive ability as well as specific domains of cognitive function. LEVEL OF EVIDENCE:1 Technical Efficacy: Stage 3 J. MAGN. RESON. IMAGING 2018;48:449-458.

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Task-enhanced arterial spin labeled perfusion MRI predicts longitudinal neurodegeneration in mild cognitive impairment.

Publications

Task-enhanced arterial spin labeled perfusion MRI predicts longitudinal neurodegeneration in mild cognitive impairment.

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