Monthly Archives: February 2017

The Brain Hypometabolism Hypothesis (BHH): Part 1

glucose_2

There are various hypotheses to explain the aetiology of Alzheimer’s Disease which is a  common cause of Dementia. One key hypothesis focuses on brain metabolism. For the sake of convenience I have labelled this hypothesis the ‘Brain Hypometabolism Hypothesis’ (BHH).

The BHH hypothesis stated simply is that:

Brain hypometabolism leads to neuropathology.

This statement references many pathophysiological pathways and lines of evidence from different research teams in studies spanning several decades.

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.

Social Concepts in SNOMED CT®

computer-keyboard-1380475577zzm

In this series of posts I am assessing SNOMED CT® using the international browser.

There is a section which describes social concepts such as class and family structure. There are other concepts including groups and lifestyle.

As an example, whilst there are many group types there is also an opportunity to use the ‘parent’ concept as a descriptor if necessary (i.e. group).

In mental health, where psychosocial constructs play an important role in assessment and treatment, I could see that there may be free text supplementation of key constructs. Qualitative research may be an effective way of investigating and better understanding this.

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

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®

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.

Can Alzheimer’s Disease Result From Altered Brain Metabolism?

glucose_2

In this series of posts, I’m looking at the various hypotheses about Alzheimer’s Disease which is one of the most common causes of Dementia.

We looked at Small and Duff’s Dual Pathway hypothesis which implicated APOE4. In turn we also looked at some of the papers on APOE4 and brain glucose metabolism. At this point we reach a really interesting question – Can Alzheimer’s Disease result from altered brain metabolism?

In one sense, this is a very open ended question. In another sense, it is a very pertinent question. For a while there has been talk of an alteration of glucose metabolism in the brain in Alzheimer’s Disease.

If we ask this question, it leads to other questions. Does excessive utilisation of energy in the brain over the lifespan predispose to Alzheimer’s Disease? Does underutilisation of energy in the brain over the lifespan predispose to Alzheimer’s Disease? I am not attempting to answer these questions in this post – that’s a pretty big topic.

What I am trying to do is take a step back and see how the discussion is framed. For instance there are other lines of research that look at cognition in aging in relation to calorie intake. It is interesting to see how these lines of research might connect.

One paper I came across is this one by Cunnane and colleagues which is quite interesting.

 

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.

Specific Situations in SNOMED CT®

computer-keyboard-1380475577zzm

In this series of posts I am assessing SNOMED CT® using the international browser.

There is a section in SNOMED CT which refers to specific situations. The situations represent a heterogenous group which includes family history, previous services that have been offered as well as past medical conditions. I could see that a search strategy or text analysis algorithm may be useful in facilitating the use of this section of the terminology.

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

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®

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.

APOE4 and Brain Glucose Metabolism

glucose_2

Given that APOE4 is related to Alzheimer’s Disease, I undertook a search for papers in medline using the search term “apoe4 glucose metabolism brain” which returned 100 papers from 1995-2017. Amongst these papers is the one described below.

Nielsen and colleagues have published an MRI study investigating brain metabolism in APOE4 carriers. The researchers compared APOE3 with APOE4. They used MRI to investigate grey matter volume and PET to investigate cerebral metabolism. They undertook a primary analysis of brain volume/cerebral metabolism correlates with APOE4/APOE3 ratios and also an exploratory analysis. They also corrected for multiple comparisons.

Amongst the key findings

(1) APOE4/APOE3 ratio was  negatively correlated with right hippocampus glucose metabolism

(2) APOE4/APOE3 ratio was negatively correlated with poster cingulate volume after correction

There were a few points about this.

(1) Firstly it is slightly odd that the right hippocampus should be negatively correlated and not the bilateral hippocampi. Could this finding be an artefact or is there an asymmetry in the pathology? These are certainly interesting questions.

(2) Secondly why were the hippocampi unaffected in terms of volumes? Perhaps longitudinal rather than cross-sectional data would help to investigate this.

(3) Thirdly I couldn’t find a reference to the size of the effect. The ratio of APOE4/APOE3 must be a simple number without units. However the correlation with both volume and metabolism must have both a size and a number of units and I couldn’t see this. The relationship was stated in terms of the statistical significance.

There were a number of other interesting findings from the paper but i’m just referencing the ones that I found immediately relevant in terms of the Dual Pathway hypothesis.

The question about asymmetry is I think one of the keys to interpreting these results.

Citations

Nielsen HM, Chen K, Lee W, et al. Peripheral apoE isoform levels in cognitively normal APOE ε3/ε4 individuals are associated with regional gray matter volume and cerebral glucose metabolism. Alzheimer’s Research & Therapy. 2017;9:5. doi:10.1186/s13195-016-0231-9.

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.

Medication in SNOMED CT®

iStock_000003993552Small

In this series of posts I am assessing SNOMED CT® using the international browser. Pharmaceutical agents are represented in one section of the terminology. Each size (dose) of tablet of a specific medication is assigned a SNOMED CT® code. As far as I could see, using the browser, the medications were specified with their generic names. As this is a brief appraisal of the system, I would look to learn a little more about any synchronisation that might occur with revisions of the EMC/BNF. There is a brief introduction to an American perspective on the subject of SNOMED CT® and medication in this Pharmacy Times article.

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

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®

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.

Mitochondrial Complex IV Deficiency

DNA code analysis

In previous posts we looked at a review by Dose J, Huebbe P, Nebel A and Rimbach G titled  ‘APOE4 genotype and stress response – a mini review’. Dose and colleagues noted evidence that APOE4 binds to mitochondrial complexes III and IV.

 I looked at ‘mitochondrial complex IV deficiency’ in medline. However a search using the term ‘cytochrome c oxidase (COX) deficiency’ produced more results.

There was one paper by Abdulhag and colleagues, reporting on a mitochondrial complex IV deficiency. There were a number of salient features of the case
(1) This affected the brain, skeletal muscle and heart
(2) This manifested during the neurodevelopmental period
(3) There was Occipital and subcortical involvement

(4) Hydrocephalus

The authors report on other findings described elsewhere with different mutations with variation in phenotype. This aspect of the report suggests that the exact nature of the mutation may be critical in understanding the phenotype and may limit the generalisations that can be drawn.

With that caveat, in Alzheimer’s Disease according to Small and Duff’s Dual Pathway Hypothesis, APOE4 will impact on Tau and Amyloid production. The pathway would be considered brain specific. In this case there is cardiac and skeletal muscle involvement. The pathology is also subcortical and Occipital. Again (as in the case of Mitochondrial Complex III deficiency) the correlates would not be typical of those reported with Alzheimer’s Disease and Alzheimer’s Type Dementia.

The complicating factors are that the two pathologies are being described at different points in the lifespan and are distinct in their localisation.

Citations

Abdulhag UN, Soiferman D, Schueler-Furman O, et al. Mitochondrial complex IV deficiency, caused by mutated COX6B1, is associated with encephalomyopathy, hydrocephalus and cardiomyopathy. European Journal of Human Genetics. 2015;23(2):159-164. doi:10.1038/ejhg.2014.85.

Dose J, Huebbe P, Nebel A, Rimbach G. APOE genotype and stress response – a mini review. Lipids in Health and Disease. 2016;15:121. doi:10.1186/s12944-016-0288-2.

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.