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.