Daily Archives: March 10, 2017

The Brain Hypometabolism Hypothesis: Part 11 – Summary of Posts To Date

glucose_2

Simply stated the Brain Hypometabolism Hypothesis (BHH) is

‘Brain hypometabolism leads to neuropathology’

This is a very simple but broad statement which is a starting point for elaboration.

What is the value for Brain Glucose Metabolism?

One of the key concepts in understanding brain glucose metabolism is the cerebral metabolic rate of glucose. This was calculated by comparing the glucose content of cerebral arterial and cerebral venous blood. When this difference is calculated it can be combined with the cerebral blood flow values to estimate the rate of glucose metabolism by the brain.

The value given in the article is (see Appendix A for calculations)

6–7 mg/100 g/min

or approximately

31 μmol/100 g/min

 

What is the Link Between Alzheimer’s Disease and Brain Glucose Metabolism?

In their 2016 paper, Cunnane and colleagues outline several supporting lines of evidence as the basis for their paper

(i) Lower glucose uptake in the frontal cortex of older adults

(ii) Regional deficits in brain glucose uptake in younger adults at risk of Alzheimer’s Type Dementia

(iii) Preservation of ketone uptake in the brain

(iv) Further evidence on consequences of ketone based interventions.

Is there Lower Glucose Uptake in the Frontal Cortex of Older Adults?

Cannane and colleagues published a paper on brain metabolism and aging based on a database they had compiled using radioactive tracers for glucose and ketone metabolism in the brain.

fnmol-09-00053-g002

Figure 2 from Cunnane and colleagues, CC BY

Is Insulin Resistance As a Risk Factor?

The Rotterdam study looked at insulin resistance in a large prospective cohort. Researchers found a correlation between insulin resistance and incident Alzheimer’s Type Dementia but only within the first three years.

However we know from Kuhn’s work on ‘The Structure of Scientific Revolutions‘ that central paradigms are successful even if there are lines of evidence that do not support the paradigm (as models are approximations to reality).

A Review of ‘The Structure of Scientific Revolutions’

 

Does atrophy in a brain region account for brain hypometabolism?

Cunnane and colleagues answer this question in two ways.

Firstly there is a specific research methodology that is able to answer this question – correction for atrophy. In their 2011 paper, Cunnane and colleagues review the literature on brain glucose metabolism studies in Alzheimer’s Type Dementia and summarise the results in Table 1 in the paper.

They note that in some studies, there is correction for atrophy and in those studies there is still a preservation of the relationship between Alzheimer’s Type Dementia and brain glucose hypometabolism.

Secondly Cunnane and colleagues also answer this question by referencing risk factors for Alzheimer’s Type Dementia where brain glucose hypometabolism occurs even in the absence of cognitive impairment

  • Pre-senilin-1 mutation,
  • Apolipoprotein E4 carrier status
  • Matrilinear AD
  • Cognitively healthy aging
  • Insulin resistance

There are five lines of evidence for further investigation of the question above. However the relationship cited above looks at cognitive impairment. Cognitive impairment is a proxy marker. The key question is whether there is brain atrophy which is causing the brain hypometabolism.

So the question can be asked for each of the five risk factors identified above.

 

What is the Mechanism for Glucose Uptake in the Brain?

In their 2011 paper, Cunnane and colleagues note that there are three separate isoforms of GLUT1 that facilitate glucose uptake in the brain

(1) One isoform facilitates glucose uptake across the blood-brain barrier

(2) Another isoform facilitates glucose uptake in astrocytes

(3) A third isoform facilitates glucose uptake in neurons

There are however other mechanisms for glucose uptake in the brain.

Appendix A – Calculations for Unit Conversion

A mole is 6 x 10²³ molecules.

The molecular weight for glucose is 180.1559 g per mole.

Therefore 31 μmol of glucose is equivalent to 180.1559 g x 31/1000000

= 0.00558 g

= 5.58 mg

which is in the range described above.

There is also a conversion calculator here.

Index: There are indices for the TAWOP site here and here

Twitter: You can follow ‘The Amazing World of Psychiatry’ Twitter by clicking on this link.

TAWOP Channel: You can follow the TAWOP Channel on YouTube by clicking on this link.

Responses: If you have any comments, you can leave them below or alternatively e-mail justinmarley17@yahoo.co.uk.

Disclaimer: The comments made here represent the opinions of the author and do not represent the profession or any body/organisation. The comments made here are not meant as a source of medical advice and those seeking medical advice are advised to consult with their own doctor. The author is not responsible for the contents of any external sites that are linked to in this blog.

Conflicts of Interest: *For potential conflicts of interest please see the About section

ICD-11 Beta: Bodily Distress Disorder

computer-keyboard-1380475577zzm

Looking through ICD-11 beta version there is a diagnostic category – Bodily Distress Disorder which replaces the somatoform disorders. This is stratified into mild, moderate and severe and excludes hypochondriasis. Interestingly hypochondriasis is now categorised under anxiety and fear related disorders. However this is the Beta and not the final version of ICD-11.

Appendix A – Other Posts in the Series on Health Information Exchanges

A Literature Review of 40 years of SNOMED

Arizona Statewide Health Information Exchange

A History of The Health Information Exchange in Pennsylvania

The Arkansas Health Information Exchange – SHARE

The California Health Information Exchange – Cal Index

Creating a Health Information Exchange in Arizona

Health Information Exchanges

Health Information Exchanges and Chronic Conditions

HIPPA and Health Information Exchanges

ICD-11 and SNOMED CT®

ICD-SNOMED-CT® Harmonisation

Physical Objects in SNOMED CT®

ICD-1 – Well…near enough

ICD-2

ICD-3

ICD-4

ICD-5

ICD-6

ICD-7

ICD-8

ICD-9

ICD-10

ICD-11

ICD-11 Conference 2016

Körner Data and SNOMED: A Snapshot from 1988

Mapping ICD 9 (or 10) to SNOMED CT®

Over 1 Million Relationships: SNOMED CT ®

SNOMED CT® International Browser

SNOMED CT® Utilises the Brodmann Area Classification for Brain Regions

The Insular Cortex and SNOMED CT®

Administrative Statuses in SNOMED CT®

Environment Descriptors in SNOMED CT®

Event Descriptors in SNOMED CT®

Generic Specifiers in SNOMED CT®

Physical Forces in SNOMED CT®

The Classification of Life in SNOMED CT®

Procedure Descriptors in SNOMED CT®

Observable Phenomenon in SNOMED CT®

Medication in SNOMED CT®

Specific Situations in SNOMED CT®

Social Concepts in SNOMED CT®

Special Concepts in SNOMED CT®

Specimens in SNOMED CT®

Staging and Scales in SNOMED CT®

Substances in SNOMED CT®

SNOMED CT® Resources at NHS Digital

SNOMED CT® and Interoperability at the Tokyo Olympics

What’s a Kinkajou got to do with 21st Century Medical Terminology?

Standardisation of Health Information Technology in New Zealand

Statisticians were Responsible for the Development of an International Classification of Diseases

Why Do We Need Electronic Record Systems to Talk to Each Other

Appendix B – Definition of Health Information Exchange

This is the definition of the Health Information Exchange that I use (Hersh et al, 2015)

Health information exchange (HIE), the electronic sharing of clinical information across the boundaries of health care organizations

Index: There are indices for the TAWOP site here and here

Twitter: You can follow ‘The Amazing World of Psychiatry’ Twitter by clicking on this link.

TAWOP Channel: You can follow the TAWOP Channel on YouTube by clicking on this link.

Responses: If you have any comments, you can leave them below or alternatively e-mail justinmarley17@yahoo.co.uk.

Disclaimer: The comments made here represent the opinions of the author and do not represent the profession or any body/organisation. The comments made here are not meant as a source of medical advice and those seeking medical advice are advised to consult with their own doctor. The author is not responsible for the contents of any external sites that are linked to in this blog.

Conflicts of Interest: *For potential conflicts of interest please see the About section