PET scans reveal metabolic changes in the brain during delirium

Article: 2-18F-fluoro-2-deoxyglucose positron emission tomography in delirium

Journal of Cerebral Blood Flow & Metabolism 2017, Vol. 37(11) 3556-3567
Doi: 10.1177/0271678X17701764. Published online Mar 28 2017
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5669345/

Authors:

Lucy R Haggstrom,1 Julia A Nelson,2 Eva A Wegner,2 and Gideon A Caplan 1,2

Affiliations:

1 Faculty of Medicine, University of New South Wales, Sydney, Australia
2 Prince of Wales Hospital, Randwick, NSW, Australia

Funders:

The research received funding from the Julia Lowy Foundation and Harry Triguboff Foundation.

Aim:

Chemical reactions in the brain (metabolism) are thought to be altered in delirium. These changes to brain metabolism could help explain the symptoms of delirium which include confusion, lack of attention and reduced consciousness.
Sadly, it can be difficult to prevent and treat delirium as there is limited knowledge of the core biology.
This study aims to investigate the possible brain metabolic changes that occur in delirium and how this may relate to clinical features. In particular, examining the posterior cingulate cortex (PCC) theorised to play an important role in delirium.

Terminology:

Fluorodeoxyglucose F18 (FDG): A radiopharmaceutical tracer used in PET neuroimaging
Positron emission tomography (PET) scan: An imaging test that uses radiopharmaceuticals, a camera and computer to assess the metabolic activity of tissues and organs
Delirium: A common medical condition which affects brain functioning and may lead to confusion, inattention and reduced consciousness
Cerebral metabolism: The chemical reactions that happen in the brain to make energy
Functional neuroimaging: Technology used to assess brain function and how regions of the brain may link to brain function
Posterior cingulate cortex: In the medial part of the inferior parietal lobe of the brain and seen as the hub for the resting state network/default-mode network

Method:

FDG PET scanning was used to examine brain metabolism in 13 participants during delirium and after delirium. Each scan was separated by at least four weeks. A range of clinical tests were carried out within a day of the PET scan to establish delirium, severity and auditory attention.
Participants included 8 females and 4 males with a median age of 82 and a history of dementia. The most common cause of delirium in participants was infection.
Participants fasted for six hours before their PET scans and were administered an intravenous FDG tracer. The tracer gets taken up by brain tissue with high chemical activity (metabolism). Areas of the brain with higher metabolism would show brighter colours on the PET scan image.
PET scans during and after delirium were compared with visual analysis and semi-quantitative analysis. Visual analysis involved sectioning of the brain and scoring low metabolism based on “brightness” of the imaging. NeuroQ was used for semi-quantitative analysis to determine how much FDG was absorbed by areas in the brain and this was linked to metabolism. The more FDG absorbed, the greater the metabolism was in that tissue area.
This data was statistically analysed.

Results:

Visual analysis of PET scans revealed that brain metabolism was lower during delirium and then increased after delirium. NeuroQ semi-quantitative analysis showed that metabolism was higher after delirium in the bilateral PCC region and brain as a whole. Higher metabolism in the PCC was linked to improved attention and a shorter span of delirium in participants.

Conclusion:

During delirium, metabolism is reduced in the brain. These changes in the PCC can be linked to poor attention which is a symptom of delirium. After delirium, metabolism seems to increase again but did not return to normal levels in participants.

Relevance:

Delirium is a common syndrome with age being a major risk factor. Currently, there is little understanding of delirium which creates barriers for prevention and meaningful treatment. The syndrome is also a significant economic cost for Australia and reached almost AU$9 billion dollars in 2016 – 2017 (1)
Understanding the biological drivers behind delirium and other mental disorders is vital for healing and prevention strategies. In turn, this knowledge will help minimise the burden on health and related costs.

HRA Comment:

Animals such as rodents and primates are often used to study brain disorders. Without really knowing the underlying biological pathways in delirium, it is unsuitable to try and replicate the syndrome in an animal study. In addition to this, the clinical presentation of delirium is cognitive (eg. lack of attention, confusion) and may be difficult to observe and diagnose accurately in non-human models. Direct investigation in humans will provide more relevant results which will help form the basis of prevention strategies or treatment in the future.

References

1 https://bmjopen.bmj.com/content/9/9/e027514.full

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