The Cognitive Change session of the International Symposium on ALS/MND in Brussels, Belgium did not fail to impress. Chaired by two of the foremost researchers in the field (Prof Sharon Abrahams and Prof Orla Hardiman), it attracted quite the audience. Their chairing did not disappoint, with a great mixture of well-aimed questions, excellent introductions and, for lack of a better phrase, good banter.
The session opened with a rousing honorary speaker in Prof Snowden (UK), exploring ALS, Frontotemporal dementia (FTD) and ALS-FTD. The talk was comprehensive and all encompassing of the research in the continuum of ALS-FTD. It opened a clear background of the clinical presentation/features, neurology, pathological and genetics of FTD and its variants. Nothing was overlooked in this talk with even some interesting, yet very rare, examples of psychosis in FTD. It was followed by an outline of the heterogeneity of FTD in all of these domains, with specific focus on pathological subtype changes. After covering this background and informing the audience well, Prof Snowden proceeded to discuss where ALS-FTD fits in relation to FTD syndromes. She highlighted specific TDP-43 pathological subtypes associated only with ALS-FTD with an additional focus on genetic overlap through C9ORF72 as an aspect of ALS-FTD. She also pointed out that in FTD more behaviour change is observed than in ALS-FTD, whereas grammar and sentence completion problems seem featuresque of ALS-FTD. The talk finished with a level-headed answer to whether there is a continuum of ALS-FTD, in that while people exist who are at risk of developing both ALS and FTD, not all do. Those ‘at risk’ patients may be etiologically distinct from other forms of FTD. This was food for thought for the captive audience.
Dr Spataro (Italy) presented research in relation to Medical decision capacity and its importance in ALS. Medical decision capacity is defined by understanding, appreciation, reasoning through and expressing a choice for treatment options. They explored (through established measures) physical disability, behavioural impairment and cognitive impairments along with how these might weight upon medical decision making as the illness progresses. The most important finding seemed to be that some aspects of medical decision capacity (specifically, understanding, reasoning and expressing a choice) are affected by behavioural change that occurs in ALS. This puts great focus on behavioural impairments found in ALS and ALS-FTD, as it might impede treatment due to the effects it has on these aspects of decision-making. It also begs the question of how to help individuals better understand, make decisions, and, finally, express what they want.
Dr Woolley (USA) had to leave early due to an industrial dispute in relation to transport in Brussels, but Dr Mioshi (UK) kindly delivered Dr Woolley’s talk with great candour and clarity. The research, through the COSMOS study group, tracked the cognition and behaviour of patients with ALS over a 12-month period. They employed an epidemiological, perspective and interdisciplinary approach, looking at variety of variable interactions. This longitudinal study did not find much cognitive deterioration when using a screening tool, but observed numerous behavioural changes, in the realms of disinhibition and negative behaviours (apathy). More concrete examples of this were reduced frustration tolerance, lack of flexibility, reduced emotional responsiveness and lack of insight. Their lack of cognitive deterioration over the 12 months could be attributed to education, as it has been shown to be a confound of cognitive screening. The behavioural changes might mediate the carer and patient relationship, making it more difficult for effective disease management to take place. They also posed the need for better assessment methods of behavioural changes.
Leading further down the behavioural research route, the next talk that followed was by yours truly, based at the University of Edinburgh (UK), which focused on the multidimensionality of apathy in ALS. As I would want to avoid “tooting my own horn” I will try to be quite brief and directed in its description. With our research, we explored profiles of apathy in ALS through a novel way of assessing multidimensional apathy via the Dimensional Apathy Scale (DAS). This was both a patient and carer rated instrument wherein we found no difference between the two in our sample. We did observe a specific profile of apathy in ALS, which we hope to explore further. The DAS was also found to be valid and reliable against an existing apathy measure, with an expected dissociation with depression. The DAS also measured apathy independent of physical disability. From my observations on the podium, it seemed to be very well received, with some stimulating questions following it. But it is hard to put oneself in the shoes of the audience in such moments.
Next to follow was Dr Govaarts (Netherlands) who spoke about non-invasive ventilation (NIV) and frontotemporal syndrome/symptoms and ALS. Through statistical modelling, their study found that ALS patients with evidence of Frontotemporal syndrome were associated with a reduction in survival time, even when controlling for age of onset, bulbar disease, delay to diagnosis and the presence of C9ORF72. Further stratification of the sample showed survival time was found to be shorter in ALS when there was a presence of behavioural and/or cognitive changes. This prompted them to ask a further question, if ALS patients with Frontotemporal syndrome are less likely to use NIV? They found only a few patients that had ALS with Frontotemporal syndrome took on NIV. Further analysis showed that this NIV duration was shorter in ALS patients with Frontotemporal syndrome, which was still true and persisted when controlling for the abovementioned confounders. Frontotemporal syndrome was found to have a negative prognostic value in relation to NIV in ALS.
Finally, in one of the larges scale studies of depression (more than 900 participants), Dr Thakore (USA) presented on various risk factors for, associations with and impact of depression in ALS. The study utilized the recruitment through tablet devices placed around the waiting rooms of the Clinic; a nice, non-invasive method of running a study. The analysis of the data was quite complex but the results yielded a variety of different, revealing results. Female patients were shown to be at greater risk of depression; as well as older patients and those of lower body weight, amongst others. Additionally, the findings showed that depressed ALS patients had a worse quality of life and higher mortality rate, even while controlling for disease severity. This study definitely informed caregivers and healthcare providers of some specific risk factors of the likelihood of depression in ALS. What the audience seemed to take away with them from the talk was that depression is more prevalent and rather more complex as a symptom in ALS.
All in all the Cognitive Changes session was of high quality and informative both from behavioural, cognitive and applicability perspectives. I was happy to be a part of it and to be reporting on it.