There is an open-access review article on the controversies of Frontotemporal Dementia (FTD) by Cristian Leyton and FTD expert Professor John Hodges titled ‘Frontotemporal dementias: Recent advances and current controversies’ and which is freely available here. This review article makes an interesting comparison with an article on the genetics of Frontotemporal Lobar Degeneration (FTLD) reviewed here. The latter article has a neurobiological slant whereas this article has a psychological perspective. What is also interesting is that there are some subtly different perspectives on taxonomy. In the article, the authors outline different subtypes of FTD broadly dividing it into behaviour variant FTD (bvFTD) and language variants (notably nonfluent progressive aphasia and semantic dementia). The authors also mention how FTD overlaps with other conditions such as Motor Neuron Disease and Corticobasal Degeneration as well as some of the more obscure presentations including one which has subsequently been classified as Alzheimer’s Disease. For me the taxonomic discussion is the most interesting part.
‘However, based on the predominant initial symptoms, FTD can be readily separated into two groups: the behavioral variant (bv-FTD), which is characterized by loss of insight, personality changes, and disturbances in social cognition and the language variant, also referred as primary progressive aphasia (PPA)‘
and further that
‘The latter can be further divided into a well-defined clinical-pathological entity, Semantic Dementia (SD) and Progressive Nonfluent Aphasia‘
In the article by Aswathy and colleagues titled ‘The Genetics of Frontotemporal Lobar Degeneration’ (available here) they write that
‘FTLD has three clinical subtypes–Frontotemporal dementia (FTD), Progressive Nonfluent Aphasia (PNFA), and Semantic Dementia (SD)‘
Thus taxonomically the latter group would consider Progressive Nonfluent Aphasia to be a subtype of FTLD distinct from the other subtype Frontotemporal Dementia whilst the other group would consider Progressive Nonfluent Aphasia to be a subtype of the language variant of FTD.
Why Do These Taxonomic Differences Occur?
In Leyton and Hodges article there is a focus on psychological aspects of the presentation although due consideration is given to the genetics. What is interesting is that there is no mention of FTLD. The reader in comparing both articles will no doubt notice the strong emphasis on cellular biology in Aswathy and colleagues’ article. At the risk of drawing too simplistic an interpretation, in my opinion some of these subtle differences arise from a neurological versus psychological perspective on the same disease processes. This is reflected in difference in the use of language. In Hodges and Leyton’s article there is an emphasis on the signs and symptoms – a more experiential aspect. In their article we are able to see a richness in the description of the illness which hints at the difficulties that result from too dogmatic a use of terminology. We are able to see that a great deal of flexibility is needed in understanding the chameleon-like diseases that cluster under this umbrella often overlapping with each other. In Aswathy and colleagues article we are able to see the arguments for biological determinism. In this model FTLD manifests in clearly defined pathways each branching off with the expectation that one day clear genetic correlates will be found and perhaps biologically tailored treatments will follow closely.
The Middle Ground
What’s left in the middle is the messy netherworld that lies between ‘mind’ and ‘brain’. In reality this is the complex area in which many people fear to tread. In order to move from the abnormal phosphorylation of microtubules to the ’emotional blunting’ there is a long journey which must take place in the minds of those building the models of the disease process. In one fell swoop the successful modeller must understand the cellular biology, the experiences of the person with the disease, the consistency of those experiences between subjects, what these experiences represent in terms of underlying neuronal activity, where this activity is represented and how the regions of activity are connected to other areas. It might sound simple enough in a sentence but one has only to look at one aspect of this to see how complex this whole enterprise is. The simple question for instance of where the activity is represented is contingent on being able to measure activity in the brain. In order to do this the experimenter must be confident that the activity they are measuring is relating to the phenomenon in question.
The closer you look at this, the more difficult it is. One simple tool of investigation is functional MRI and yet a critical examination of this approach throws up a large number of difficulties that make clear interpretation less plausible. One example is that of whether different ‘conscious activities’ require significant differences in blood flow to the brain regions. If different activities in the same brain region utilise similar amounts of oxygen (as a proxy measure of energy consumption) then this won’t be detected by techniques such as MRI. Without going into too much detail each of the other points referred to such as how regions of activity are connected to each other raises its own difficulties. Such is the complexity that modellers are unable to meaningfully navigate this netherworld of the brain and mind. Instead this complexity ‘collapses’ around the edges and we are left with the relative simplicity of clearly defined cellular processes measured in vivo or else performance on standardised tests using a ‘black box’ approach. Move too far away from these idealised conditions however and the complexity becomes too much and the necessary links cannot be easily made.
In order to navigate the netherworld intuition is used as well as empirical data but the ‘exact science’ is to be found at the edges. I am hopeful that the necessary language will one day be found to describe this netherworld. There is a language that describes both the mind and brain but at the moment we use two distinct languages. When a suitable method for describing both mind and brain is found it will provide us with a much richer description of illnesses and facilitate the development of therapeutic interventions.
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