Reduced global brain metabolism but maintained vascular function in amnestic mild cognitive impairment

Abstract

Amnestic mild cognitive impairment represents an early stage of Alzheimer's disease, and characterization of physiological alterations in mild cognitive impairment is an important step toward accurate diagnosis and intervention of this condition. To investigate the extent of neurodegeneration in patients with mild cognitive impairment, whole-brain cerebral metabolic rate of oxygen in absolute units of µmol O/min/100 g was quantified in 44 amnestic mild cognitive impairment and 28 elderly controls using a novel, non-invasive magnetic resonance imaging method. We found a 12.9% reduction ( p = 0.004) in cerebral metabolic rate of oxygen in mild cognitive impairment, which was primarily attributed to a reduction in the oxygen extraction fraction, by 10% ( p = 0.016). Global cerebral blood flow was not found to be different between groups. Another aspect of vascular function, cerebrovascular reactivity, was measured by CO-inhalation magnetic resonance imaging and was found to be equivalent between groups. Therefore, there seems to be a global, diffuse diminishment in neural function in mild cognitive impairment, while their vascular function did not show a significant reduction.

Magnetic resonance imaging for assessment of cerebrovascular reactivity and its relationship to cognition: a systematic review

“…Research was conducted in four countries (USA n = 4, Canada n = 2, Switzerland n = 1, France n = 3). Participants in 7 of the studies had an average age of mid-to-late 60’s to early 70’s [ 10 , 13 , 30 – 32 , 35 , 37 ], one study investigated adults aged 30–50 years (patients mean age 39 ± 5.91 years, controls mean age 41 ± 6.38 years) [ 36 ], one study recruited adults with moyamoya disease aged over 18 years (range 29–73, mean age 40.4 years) [ 34 ], while the remaining study involved a cohort of older (mean age 63 ± 5 years) and younger adults (mean age 24 ± 3 years) [ 33 ].…”

Validation of T2‐based oxygen extraction fraction measurement with 15O positron emission tomography

“…Cerebral oxygen extraction fraction (OEF) is a potential biomarker in a variety of diseases, such as Alzheimer's disease, 1,2 cerebrovascular diseases, [3][4][5][6][7][8] multiple sclerosis, 9 and sickle cell anemia. 3,[10][11][12] The current gold-standard for image-based OEF quantification inside the human brain is positron emission tomography (PET) with three different 15 O-labeled radiotracers, 13 including 15 O-labeled carbon monoxide (C 15 O) to estimate cerebral blood volume (CBV), 15 O-labeled water (H 2 15 O) to measure cerebral blood flow (CBF), and 15 O-labeled oxygen ( 15 O 2 ) to measure oxygen utilization.…”

“…[17][18][19][22][23][24][25][26][27][28] Many of these MRI-based methods have found clinical utility in various diseases. [1][2][3]6,9,29,30 However, few studies have validated MRI-based OEF estimations with gold standard 15 O-PET, 31 which would be important to ensure the accuracy of these methods and facilitate their broader clinical applications. T 2 -relaxation-under-spin-tagging (TRUST) is a widely used MRI technique to measure whole-brain OEF based on the relationship between blood T 2 and oxygenation.…”

Volume‐localized measurement of oxygen extraction fraction in the brain using MRI

“…The sensitivity of TRUST to changes in OEF has been demonstrated using hypercapnia, hyperoxia, hypoxia, and caffeine challenges . The robustness and applicability of the method has been demonstrated further in a number of single and multi‐site studies and in a variety of cerebrovascular conditions . Overall, the TRUST method has been highly influential, however, a key limitation of the method is its lack of spatial specificity.…”

“…[12][13][14][15] The robustness and applicability of the method has been demonstrated further in a number of single and multi-site studies and in a variety of cerebrovascular conditions. [16][17][18] Overall, the TRUST method has been highly influential, however, a key limitation of the method is its lack of spatial specificity.…”