ObjectiveTo determine whether MRI-based cerebrovascular reactivity (CVR) can predict cognitive performance independent of Alzheimer’s pathological markers, we studied the relationship between cognition, CVR, and CSF-derived Aâ42 and Tau in a group of elderly individuals with mixed Alzheimer’s and vascular cognitive impairment and dementia.MethodsA cross-sectional study of 72 participants, aged 69±8 years, consisting of individuals with normal cognition (n=28) and cognitive impairment (n=44) (including 36 mild cognitive impairment, MCI, and 8 mild dementia). CVR was measured with hypercapnia-MRI. Whole-brain CVR (% BOLD per mmHg of EtCO2) was used to estimate vasodilatory capacity. Montreal Cognitive Assessment (MoCA), cognitive domains scores, and a global composite cognitive score were obtained. AD biomarkers included CSF assays of Aâ42 and Tau.ResultsWhole-brain CVR was lower in the impaired (mean±SE, 0.132±0.006%/mmHg) compared to the normal (0.151±0.007%/mmHg) group (β= -0.02 %/mmHg; 95% CI, -0.038 to -0.001). After adjusting for CSF Aβ42 and tau, higher whole-brain CVR was associated with better performance on the MoCA (β=29.64, 95% CI, 9.94 to 49.34) and with a global composite cognitive score (β=4.32, 95% CI, 0.05 to 8.58). When comparing the CVR marker with Fazekas score based on white-matter-hyperintensities and Vascular-Risk-Score in a single regression model predicting the MoCA, only CVR revealed a significant effect (β=28.09, 95% CI, 6.14 to 50.04), while the other two measures were not significant.ConclusionsCVR was significantly associated with cognitive performance independent of AD pathology. Whole-brain CVR may be a useful biomarker for evaluating cognitive impairment related to vascular disease in older individuals.Classification of Evidence:This study provides Class II evidence that CVR was significantly associated with cognitive performance independent of AD pathology.

Background: Alzheimer's disease and vascular cognitive impairment (VCI), as well as their concurrence, represent the most common types of cognitive dysfunction. Treatment strategies for these two conditions are quite different; however, there exists a considerable overlap in their clinical manifestations, and most biomarkers reveal similar abnormalities between these two conditions. Purpose: To evaluate the potential of cerebral oxygen extraction fraction (OEF) as a biomarker for differential diagnosis of Alzheimer's disease and VCI. We hypothesized that in Alzheimer's disease OEF will be reduced (decreased oxygen consumption due to decreased neural activity), while in vascular diseases OEF will be elevated (increased oxygen extraction due to abnormally decreased blood flow). Study Type: Prospective cross-sectional. Population: Sixty-five subjects aged 52-89 years, including 33 mild cognitive impairment (MCI), 7 dementia, and 25 cognitively normal subjects. Field Strength/Sequence: 3T T 2-relaxation-under-spin-tagging (TRUST) and fluid-attenuated inversion recovery imaging (FLAIR). Assessment: OEF, consensus diagnoses of cognitive impairment, vascular risk factors (such as hypertension, hypercholesterolemia, diabetes, smoking, and obesity), cognitive assessments, and cerebrospinal fluid concentration of amyloid and tau were assessed. Statistical Tests: Multiple linear regression analyses of OEF with diagnostic category (normal, MCI, or dementia), vascular risks, cognitive performance, amyloid and tau pathology. Results: When evaluating the entire group, OEF was found to be lower with more severe cognitive impairment (β = −2.70 AE 1.15, T = −2.34, P = 0.02), but was higher with greater vascular risk factors (β = 1.36 AE 0.55, T = 2.48, P = 0.02). Further investigation of the subgroup of participants with low vascular risks (N = 44) revealed that lower OEF was associated with worse cognitive performance (β = 0.04 AE 0.01, T = 3.27, P = 0.002) and greater amyloid burden (β = 92.12 AE 41.23, T = 2.23, P = 0.03). Among cognitively impaired individuals (N = 40), higher OEF was associated with greater vascular risk factors (β = 2.19 AE 0.71, T = 3.08, P = 0.004). Data Conclusion: These findings suggest that OEF is differentially affected by Alzheimer's disease and VCI pathology and may be useful in etiology-based diagnosis of cognitive impairment. Level of Evidence: 1 Technical Efficacy: Stage 3

This work suggests that harmonized TRUST MRI can yield highly compatible Y measurements across different vendors. Magn Reson Med 80:1125-1131, 2018. © 2018 International Society for Magnetic Resonance in Medicine.

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