Alzheimer’s Energy Metabolism Biomarker Revealed with 7T MRI

Ultra-high field 7T MRI is shedding light on a new potential early indicator of the decline toward Alzheimer’s disease – the level of energy metabolism in the living brain.

Although research efforts have been significant, any effective treatments for Alzheimer’s remain hidden. Identifying markers – such as the accumulation of beta-amyloid and tau protein in the brain – is proving helpful, but researchers from the Center for BrainHealth® at The University of Texas at Dallas wanted to go further.

In a study published recently in Frontiers in Neuroscience, a team led by Namrata Das, Ph.D., a program specialist and research neuroscientist, outlined how they are using phosphorus magnetic resonance spectroscopy with 7T MRI to illustrate the brain’s energy consumption and reserves. This is the first study, the team said, that shows it is possible to measure brain energy metabolism in living subjects.

“Much of what we know about cognitive decline at the molecular level comes from post-mortem brain examinations or animal models,” Das said. “What we set out to do was monitor in real time the biological mechanisms that cause this decline in humans to better understand the multiple factors involved.”

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For their study, the team enrolled 41 participants – 15 who were cognitively normal, 15 with mild cognitive impairment, and 11 with early Alzheimer’s. The patients completed assessments for executive function, memory, attention, visuospatial skills, and language, and the team also completed 7T scans that measured the ratios between adenosine triphosphate (ATP) and phosphocreatine (PCr) – also called the energy reserve index – as well as inorganic intracellular phosphate.

The hypothesis, Das said, is that dysfunction in the mitochondria – the energy powerhouse of the cell – occurs early in Alzheimer’s and that ATP and PCr are not synthesized properly. Existing 3T MRI technology is not powerful enough to visualize these molecular levels accurately, but 7T MRI can.

According to their analysis, the team said, the 7T MRI scans of a participant’s temporal lobes point to a correlation between the energy reserve index and the patient’s cognition level.

“The energy reserve was lower in patients with mild cognitive impairment and lower still in those with Alzheimer’s,” Das said. “We believe this is the first paper to confirm that energy reserve decreases with [mild cognitive impairment], years before Alzheimer’s sets in.”

Specifically, the team saw lower energy reserve (p=0.009) and lower energy consumption (p=0.05) in the mild cognitive impairment group compared to those participants who were cognitively normal. In addition, in cognitively normal patients, the team identified a significant positive correlation between magnesium levels and cognitive performance of memory (p=0.013), executive function (p=0.023), and attention (p=0.0003). However, the same correlation did not exist with patients who had mild cognitive impairment or Alzheimer’s.

The study’s results point to new opportunities for discovery in understanding and treating Alzheimer’s, said senior author Sandra Bond Chapman, Ph.D., chief director of the Center for BrainHealth®.

“This research provides a promising new way to elucidate the brain’s health – or early disturbance of its health – due to changes in metabolism. The new approach is the utilization of [7T MRI], a non-invasive safe technology,” she said. “It has exciting implications for early detection of Alzheimer’s disease and the potential to measure disease response to treatments.”

As a next step, Das said, the team plans to combine the energy-level biomarker with PET scans to measure beta-amyloid and tau protein.

“We hope to determine if the abnormal brain energy metabolism has a relationship with the accumulation of beta-amyloid and tau,” she said. “Researchers have hypothesized for years that such metabolism short falls might precede such accumulations, but only now, with 7T, do we have the modality to find out.”

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