Monthly Archives: April 2009

Book Review: Phantoms in the Brain

The featured book is ‘Phantoms in the Brain’ by Sandra Blakeslee and V.S. Ramachandran. As Blakeslee and Ramachandran are both authors, I wasn’t sure what the contributions were by each although in the Acknowledgements section, Ramachandran thanks Blakeslee, a science writer for helping to make the book more accessible suggesting the role that each has played. Ramachandran has a lot of experience in the field of neuroscience research which is relevant to this book. Ramachandran shows  versatility in writing a fascinating account of a number of psychiatric illnesses and aspects of psychological functioning (e.g. visual perception) from an inquisitive neurobiological perspective. Along the way he weaves disparate themes and illustrative cases into the narrative. Ramachandran’s explanations of cases of Capgras, Charles Bonnet and  Couvades syndrome are thought provoking and offer a paradigmatic shift that can be applied to other areas. For instance, with Capgras syndrome, Ramachandran proposes that there a disconnection between the amygdala and temporal cortex leads people to lose the the feeling of familiarity they experience when they see people close to them. Particularly interesting is Ramachandran’s use of mirrors to investigate a number of phenomenon. The book is named after the ‘Phantom Limb’ with which he also uses mirrors in order to ‘trick’ the brain into remapping areas involved in perception. His approach to the phantom limbs has been widely reported and has even permeated popular culture. As there is some similarity to Oliver Sack’s interests it is fitting that Sacks writes a foreward to Ramachandran’s book. Ramachandran has a very distinctive style which also reflects his inquistive approach, a belief in using ‘low-tech’ experiments and seeking a cause for the unusual . In each chapter he takes us on a journey filled with insights. For instance in ‘The Unbearable Likeness of Being’ he writes

This idea teaches us an important principle about brain function, namely, that all our perceptions – indeed, maybe all aspects of our minds – are governed by comparisons and not by absolute values

‘Phantoms in the Brain’ is a fascinating ‘tour de force’ of neurobiology which focuses on a number of psychiatric conditions and offers powerful insights into how some of these may arise.

References

Sandra Blakeslee and V.S.Ramachandran. Phantoms in the Brain. Harper Perennial. 2005.

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.

Review: Cognitive Decline in CADASIL

The featured article is ‘Insidious Cognitive Decline in CADASIL’ by Amberla and colleagues and freely available (at the time of writing) here. The authors introduce CADASIL as a small-vessel disease involving mutations at the Notch3 gene with resulting accumulation of granular osmiophilic material (GOM) in the vascular smooth muscle cells. There is also a recognisable pattern of cognitive decline although the authors point out that there is little research characterising the nature of this decline before going onto summarise the literature there is in this area.

The authors choose a cross-sectional design involving 34 people with confirmed identical mutations in the NOTCH3 gene.  They divide up these people into those with and without dementia. For the latter group, they are compared with non-carriers of the mutation. The authors state that the non-carriers are from the same kindred. There are well established drawbacks to using a cross-sectional design for answering these kinds of questions – such designs do not establish causality but instead produce associations. In practical terms however, they can still provide useful information particularly for informing further studies. Other points include the relatively small sample size, the large number of potential confounders and the relevance of the gene mutations in terms of phenotype for those involved in the study.

DSM-III criteria were used for diagnosis and then a neuropsychological battery was undertaken which include a range of tests including those examining executive functioning and various types memory in some detail. The authors used ANOVA to compare the characteristics of the groups but the distribution of neuropsychological values in the  comparison groups is unclear and consequently it is also unclear if a mixed-effects, random effects or fixed effects model is being used.

The poststroke group is just under 10 years older on average than the prestroke group while the dementia group is roughly 15 years older on average than the prestroke group.  The dementia group has roughly half the number of years of formal education of the control group although the sample sizes are small e.g. the dementia group has 8 members.

The authors use a discriminant analysis to distinguish between the controls, pre-stroke and post-stroke groups. They find that the groups can be effectively discriminated using three tests – the Rey-Osterreith memory test (executive function mainly), digit span backwards (working memory mainly) and digit symbol (mental speed). They illustrate this with a scatter plot showing a small number of cases being misclassified but the majority of cases falling into one of three clusters corresponding to the three study groups (excluding the dementia group).

The pre-stroke group are described as having difficulties with strategy and task completion which meant they could be discriminated from the control group. The post-stroke group are described as having ‘mental slowing’ relative to the pre-stroke group. They also identify the relative preservation of verbal episodic memory but were surprised that the finger-tapping test was not effective in discrimination in view of previous research in this area.

Despite the limitations mentioned above this is a useful study which suggests a possible phenotypic expression of the NOTCH3 gene mutations identified in this study. Furthermore a sequential path of cognitive decline is suggested which would need to be explored using a longitudinal study.

STT4

Steps To Treatment (STT)

STT = Steps To Treatment. An estimate of the number of steps between the results and translation into practice i.e. treatment. This is an opinion.

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.

Review: Metabolic Syndrome and Risk for Vascular Dementia

The featured paper is ‘Metabolic Syndrome and Risk for Incident Alzheimer’s Disease or Vascular Dementia. The Three-City Study’ by Raffaitin and colleagues and freely available here.

As the title suggests, the aim of this study was to investigate the relationship between the metabolic syndrome and two types of dementia. Participants were obtained from an epidemiological study – ‘Three City Study’. Those in institutions are excluded from the study (although the characteristics of the institutions is not characterised). This means that the sample population may have been slightly ‘healthier’ than the general population. A number of further exclusions were then made on the basis of people already having dementia or insufficient information being available for baseline metabolic syndrome identification. Again the characteristics of this excluded sample are not given in this section and so it is difficult to work out the impact this might have had on the sample population other than to speculate that those excluded may already have had a vascular dementia which could have deteriorated over the course of the study (and therefore added potentially useful information about the relation of the risk factors to the evolving pathology) or may have had another type of dementia which then developed into a mixed picture again providing potentially useful information. Given the nature of the study question and the scale of the study this is probably necessary anyway. We dont have the characteristics of the subjects who dropped out of the study for various reasons and whilst this might represent a random sample of the population there may equally be a defining feature of this sample which interacts with the main study variables e.g. were they too unwell to participate?

While the MMSE was used and the number of measures is unclear, DSM-IV criteria are used with a consensus on diagnosis being obtained by a group of neurologists with the usual work-up for dementia and then further subclassification according to established criteria. Metabolic syndrome was diagnosed using established criteria and the investigations used are detailed. There is a description of confounding variables that are also identified including APOE4 status and sociodemographic data. The authors then identify the t-test and Pearson’s test for the different data types. However we are not given the justification for using these tests – for instance is the continuous data normally distributed – it most probably is but it would be interesting to see the justification. Proportional hazards models were then used to identify the relationships between variables. Similarly in the method section there is no justification for supposing that the proportional hazards assumption holds with the study sample.

In the results section it is stated that 651 people did not have follow-up. This is considered as a homogenous group although as above we see that there are various subpopulations within the sample. However we are informed there was no significant difference between those who were not followed-up and the sample population. 208 cases of incident dementia developed at follow-up, a relatively small number compared to the overall sample size. There was no significant relationship between metabolic syndrome and dementia although perhaps a larger sample size was needed to identify a relationship. An analysis (presumably secondary) between the components of the metabolic syndrome and dementia revealed high triglyceride levels as being significantly associated although this must be assessed in terms of the absent primary outcome. There wasn’t a significant relationship between metabolic syndrome and Alzheimer’s Disease. However a positive association was found between Vascular Dementia and Metabolic syndrome after adjusting for APOE4 status. High triglyceride levels were also significantly associated with VaD. Diabetes was also significantly associated with VaD and all-cause dementia.

The authors concluded that the metabolic syndrome didn’t have significant value in stratifying risk. In effect they are suggesting that the individual components of the metabolic syndrome are more useful. They have highlighted the relationship between the triglycerides and VaD and all-cause dementia as worth pursuing. However, they have identified a significant relationship between the metabolic syndrome and vascular dementia so it could be argued that there is some utility in this concept for the purposes of identifying risk.

While it would be useful to have further information about those excluded from the study in order to translate these findings to other populations, this is a large study with rigorous methods for identifying caseness and with some useful results which can be explored further.

Steps to Treatment = 3

Steps To Treatment (STT)

STT = Steps To Treatment. An estimate of the number of steps between the results and translation into practice i.e. treatment. This is an opinion.

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.

News Round-Up: April 2009 4th Edition

Research In Dementia

A longitudinal study with post-mortem showed an association between Alzheimer’s Disease and evidence of vascular remodelling – alphavbeta3 immunoreactivity. This was also correlated with ABeta located in the hippocampus (Desai et al, 2009)(STT5). An association between amnestic mild cognitive impairment and cholinergic basal forebrain volume was found in this MRI study (Muth et al, 2009)(STT4). A recent study  showed evidence of a neuroprotective role of Methylene blue in a model of optic neuropathy further supporting evidence from last year again as a neuroprotective agent in neurodegenerative processes (Rojas et al, 2009)(STT4). The authors of a Cochrane review concluded that Rivastigmine was effective in the treatment of mild to moderate Alzheimer’s Disease after reviewing the results of 9 trials with a combined total of 4775 participants (Birks et al, 2009)(STT3).

News In Brief

Playing Baroque music at work improved the productivity and mood of radiologists in this study.  An intriguing finding is that proton pump inhibitors such as omeprazole have been shown to reduce the inflammatory response of microglia and the authors speculate as to whether this might impact on conditions such as Alzheimer’s disease which would need further investigation. Humanin peptide which has a role in cell death has also been found to strongly influence glucose metabolism offering a potential link between glucose metabolism and neurodegenerative processes. A prospective study showed evidence of an increased association with Alzheimer’s Disease in ‘heavy’ users of NSAID’s which have previously been suggested to have a protective effect. Stigma and perceptions about memory were found to influence memory performance in older adults in this study. Improved research methodology has been recommended for studies looking at delivery of psychological therapies in older adults. Two compounds have been identified which modify the action of insulin-degrading enzyme on A-Beta offering another potential therapeutic approach in Alzheimer’s Disease.

A Portuguese study has found that the two leading cause of alcohol related mortality are liver disease and car accidents. Research has further supported the association of the MPDZ and alcohol dependency. An M1 Acetycholine agonist has been recently discovered. Over 3000 genes that are differentially expressed within a 24-hour period have been identified. An increase in the number of neonates born with withdrawal syndrome has been reported in this Australian study – a 40 fold increase from 1980. A Finnish group has been characterising a subgroup of children with delayed speech and walking and it will be interesting to follow further research in this area. A Canadian study provides evidence of an association between perinatal factors and the comorbidity of ADHD and Tourette syndrome. A number of studies have been presented at a meeting recently identifying a link between sleep disorders and risk of type II diabetes and obesity – and this is covered in more detail here. Similar research found that a 2.5 fold increased prevalence of diabetes II was associated with sleeping less than 7 or more than 8 hours a night which may be relevant to previous epidemiological data on sleep duration.

References

Birks J et al. Rivastigmine for Alzheimer’s Disease. Cochrane Database Syst Rev. 2009. Apr 15. 2.

Desai B et al. Evidence of angiogenic vessels in Alzheimer’s Disease. J Neural Transm. 2009. April. Epub.

Muth K et al. Mild Cognitive Impairment in the elderly is associated with volume loss of the cholinergic basal forebrain region. Biol Psychiatry. 2009. April. Epub.

Rojas J et al. Methylene blue provides behavioral and metabolic neuroprotection against optic neuropathy. Neurotox Res. 2009. Apr. 15(3). 260-73.

Steps To Treatment (STT)

STT = Steps To Treatment. An estimate of the number of steps between the results and translation into practice i.e. treatment. This is an opinion.

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.

Podcast Review: April 2009 4th Edition – A Look at Vascular Dementia

I thought i’d try something slightly different today.

Audio podcasts are a useful way of keeping up to date or learning about a subject. However a potentially richer source of material is that of video, obviously because there are also visual cues. Interviews become that much more interesting when you see the person talking as well as hearing them. The internet is filled with video material and one of the most popular sites for videos is YouTube. As you might expect from a site now owned by Google, the videos are searchable, making use of the tag indexing and allowing the viewer to use boolean operators to identify relevant clips. The main difficulty is that it is difficult to guarantee the quality of the material, and the quality assessment has to be done on the fly. Quality assessment is always needed anyway. For instance, articles in respected peer reviewed journals may have shortcomings and the findings overturned a few years later.

So I wanted to see what video material there was on vascular dementia. So first of all I visited the YouTube site and simply typed in ‘Vascular Dementia’ in the search box. This produced ‘about 31′ results. One of the first results was from MedPageToday and is an interview about a trial that took place looking at the use of Donepezil in vascular dementia. The interview is with a Dr Gorelick who describes the main results of the trial with no significant benefit although there was an improvement in one of the subscales. The interview was brief but focuses on the most relevant aspects of the study and seems to be aimed at an audience with a medical background.

Moving further down the search results, there was this clip which is from the University of California Television Channel and features a 29-minute video presented by Dr Dee Silver, neurologist who talks about the treatment of a number of neurodegenerative conditions. The presentation is very good, with Silver explaining the different types of dementia. However although it appears in the search for vascular dementia, this isn’t really the main focus for the program. This program seems to be an introduction to the subject of dementia.

This video looks at ‘recovering cognition after stroke’ and is the 4th in a series. This is another useful feature of YouTube, because by looking on the right hand side of the browser window a list of related videos is given which includes the first in the series. So by simply clicking on this we are taken to the first in the series. Although both videos appear to represent an introduction to the field, the fourth in the series while brief does contain some interesting suggestions from the presenter including obtaining SALT input in cases of vascular dementia.

Further down the search results there is also a clip of an elderly lady with dementia playing cards in a nursing home but most of the other videos here are both short in duration and cover dementia more generally.

Perhaps the search should be refined…

As expected, by combining ‘Vascular Dementia’ with ‘treatment’ a smaller number of results were elicited and all seemed to have been covered in the original search. While there are a large number of videos on YouTube, the ‘specialist’ videos are relatively few in number. Maybe I was missing something in my search. Unfortunately there doesn’t appear to be an advanced search feature, so I needed to modify the search terms. I broadened out the search by using the term dementia which resulted in ‘about 131′ videos. Scanning through the video titles and descriptions didn’t take too long. The focus seemed to be on Alzheimer’s Disease and Lewy Body Dementia.

Switching to CADASIL a more obscure cause of vascular dementia identified this video which gives a very good overview of this rare condition. A search for stroke produced many thousands of videos but this was because the term was used in other phrases e.g. in swimming.

In conclusion, on the basis of the above, a basic search of YouTube for medical information on vascular dementia wasn’t an efficient way of obtaining more advanced knowledge in this area. For introductory material however there were was more material for dementia in general and for certain subtypes such as Alzheimer’s Diseaes and Lewy Body Dementia.

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.

Blog Review: The Tangled Neuron

The featured blog is ‘The Tangled Neuron‘. This is a blog about a ‘layperson’ who’s father developed dementia and sadly passed away. It was a little difficult to know who the author is as there is no ‘about’ section other than that on the home page. This sits beneath a photograph of a lady comforting an elderly man which I am confident in saying is the author as  she later appears in a photograph in the blog. The blog begins in November 2005 and we hear the harrowing tale of how her father has already passed away and the family are looking into the possibility of an autopsy. This is a very sensitive time and a narrative quickly develops when the author receives the results of the autopsy and queries the absence of comments on plaques and tangles in the report. Her father’s case is due to be presented at the case conference and she is invited to attend. In the interim, the neurologist requests some information on the grandmother’s medical history which prompts the author to obtain some further details and to include a photograph of her grandmother. We learn that the father had cerebral amyloid angiopathy and although there is a false start with the possibility of haemochromatosis this is later excluded.The author is conversant with the medical literature and selects a number of articles from medical journals, appraising them and putting them into the context of her father’s illness. The author also contacts and interviews a number of the authors of these papers and in the process takes on the role of an investigative journalist who is both extremely comfortable with and competent at understanding recent medical advances in the field of dementia.  Along the way, the author does an excellent job of summarising many of the main areas in Alzheimer’s Research from the role of insulin and diabetes through to putative role of infectious agents and cholesterol in the pathogenesis of Alzheimer’s Disease. There are helpful posts about the difficulties caregivers face such as this one on the illness burden in caregivers. The author also registers with a study for children of people with Alzheimer’s Disease and gives us an account of this process. There are various other topics which are all extremely relevant to dementia. Here for instance the author looks at a theory that amyloid may have a protective role while in this article she considers the role of cognitive rehabilitation.  The ‘Tangled Neuron’ is an excellent blog resource for Alzheimer’s Disease and other forms of dementia while also showing us the way in which this affects people’s lives through the authors own at times poignant experiences.

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.

Book Review: The Executive Brain

The featured book is ‘The Executive Brain. Frontal Lobes and the Civilized Mind’ by Elkhonon Goldberg. There is a foreward by Oliver Sacks which is particularly relevant as Goldberg was a former student of the illustrious Luria who Sacks has written about frequently. Goldberg’s book is about the Frontal lobes and he writes from the perspective of one who has conducted research in this area for many decades. The book contains a number of interesting discussions of various psychiatric conditions and their possible relation to the functioning of the frontal lobes. This is best summarised in the forward by Sacks in which he states that

..the inertia of parkinsonism, the impulsiveness of Tourette’s syndrome, the distractibility of ADHD, the perseveration of OCD, the lack of empathy or ‘theory of mind’ in autism or chronic schizophrenia, can all be understood, in large part, Goldberg feels, as due to the resonances, the secondary disturbances, in the function of the frontal lobes‘.

Goldberg introduces us to his gradiential principle in which he suggests that cortical function is graduated from one area to another. In other words if we move from area A in the cortex to area C via area B, then area B will have a function intermediate between A and C. Goldberg also takes us on an interesting journey through the properties of the frontal cortex including the asymmetry between the right and left frontal lobes, the implied functions of the orbitofrontal cortex, prefrontal cortex as well as interhemispheric differences. Particularly useful are Goldberg’s descriptions of classic neuropsychologic techniques for investigating the function of different brain regions including double dissociation and the use of the tachistoscope. He also introduces us to his theory that the right hemisphere is responsible for processing novel information and that the left hemisphere for managing previously stored knowledge. I was particularly intrigued by Goldberg’s description of his encounter with a Gibbon in Thailand and the ‘executive’ behaviour that so impressed him. He argues that the Gibbon’s frontal cortex accounts for 11.5% of their cortex and even though they are one of the ‘lesser apes’ my experience is that their human-like behaviour is uncanny (see here for an example). However this might also be attributable to areas other than the frontal cortex alone. Some of Goldberg’s discussion crosses over into areas covered in Crow’s model of schizophrenia which focuses on the role of brain asymmetry although neither Crow nor Goldberg’s model explain geographical differences in the epidemiology of schizophrenia. Similarly recent findings in the ‘great apes’ reveal ‘new’ behaviours which challenge another of the hypotheses. As with similar works covering other brain regions (e.g. Damasio’s ‘Descartes Error’ see here), there is still a need to produce a model which seamlessly traverses different levels of representation. Within each level of representation Goldberg helps the reader to navigate the theoretical complexities.

This is an interesting book, which would particularly appeal to the reader with a mental health/neuroscience background.

References

Elkhonon Goldberg. The Executive Brain. Frontal Lobes and the Civilized Mind. Oxford University Press. 2001.

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.