Cognition in thalassaemia: the next milestone

Abstract

Since thalassaemia was first described by Cooley and Lee (1925), the field of haematology has made great progress in the recognition, treatment and supportive care of the disease. The ability to diagnose thalassaemia at the molecular level and to predict the phenotype has been developed. It is generally possible to determine if a patient will be transfusion-dependent or -independent, in order to offer accurate prenatal genetic counselling. With significant improvements in supportive care and novel therapies on the horizon, in addition to increased understanding of the pathogenesis of the ineffective erythropoiesis which characterizes the disease, it is possible to look back and feel satisfaction with our accomplishments on behalf of our patients (Rund, 2016).

It is therefore troubling to read the study of Tartaglione et al (2019a) which reports that adult patients with thalassaemia have cognitive impairment, with disappointing employment and educational achievements. This study assessed 53 adult transfusion-dependent thalassaemia patients and 21 non-transfusion dependent patients from 4 hospitals in southern Italy. These authors compared these patients with an age-matched normal control group of 45 individuals who were recruited mainly from individuals accompanying the patients, in order to minimize bias. These patients and controls were studied using a number of modalities including a basic neurological examination, neuroimaging (magnetic resonance imaging), psychological assessment (a standard psychiatric rating scale), and a standard intelligence quotient (IQ) test. In addition, the authors assessed employment and education achievements of the patients and controls. The authors also extensively reviewed the conflicting literature that has been published on the subject, to identifiy the potential reasons for the lack of clarity of the existing literature, including the lack of normal controls in many studies.

The results presented by Tartaglione et al (2019a) leave little room for denial. The differences that were found between the patients and the controls were not extremely large but were significant. Non-transfusion dependent patients had less impairment in some measurements and achievements than did transfusion-dependent patients. Upon reading the work published in this issue of the BJH, haematologists treating adult thalassaemia patients are left with much to ponder.

The message is clear. Longer survival and better supportive care are not enough for our patients, not in the 21st century. Haematologists need to face the fact that successful treatment of thalassaemia is not only measured by life expectancy, or even by better-tolerated supportive care (such as oral chelation), but also by the ability of our patients to achieve the societal norms of today's world. We should strive for our patients to have an optimal quality of life, which includes education and employment at the level of healthy individuals, according to each patient's abilities and aspirations. Furthermore, both transfused and non-transfused patients suffer psychologically. The cause and effect relationship between psychological issues and poor employment and educational achievements has yet to be unravelled. The current study is particularly discomforting since these same authors recently published a related article demonstrating that in 75 transfusion-dependent thalassaemia patients, there was no evidence of silent cerebral ischaemia or cerebral iron overload (Tartaglione et al, 2019b). Therefore, the solution does not lie within the realm of improving the medical treatment of our patients, such as even better chelation, transfusion or antithrombotic therapy.

The authors call for further studies in other Mediterranean countries to verify their findings. They note that some of their specific findings differ from those reported in other parts of the world and they suggest that the cognitive profile of thalassaemia patients is affected by environmental or treatment-related local factors. They are cautious in recognizing that this study, while in-depth, involves only 75 Italian patients, whose psychological, social and intellectual abilities and expectations may not be the same as those of patients in other parts of the world.

The authors do allude to potential approaches to remedy these problems, such as integrating psychological and neurocognitive assessments into the routine follow-up of these patients. They suggest the establishment of interdisciplinary teams to evaluate the causative problems and plan appropriate intervention. Indeed, part of the quandary may be the tendency of the treating physicians to deny the existence of the problem, partly due to the desire to avoid worsening the stigma of the disease for our patients. The solution may be to introduce the assessments that were performed by Tartaglione et al (2019a) routinely, for all adult patients who agree to undergo testing, so as to identify the contributory problems. Identification of the specific problems may be challenging as they may vary among individual patients and families. Even more difficult may be the practical issues of how to implement educational, employment and psychological support and assistance for those who desire it, at an early stage.

All physicians treating transfusion-dependent thalassemia would be advised to consider the issues raised here. Three years ago, this author reviewed the milestones of achievement for the diagnosis and treatment of thalassaemia, including mention of the complex issues related to cognition (Rund, 2016). Hopefully, with further research into this area, addressing cognitive issues will be the next milestone in attaining not only longer, but truly better, lives for our patients.