Topic 3.11. Cognitive function in Friedreich ataxia
This chapter of the Clinical Management Guidelines for Friedreich Ataxia and the recommendations and best practice statements contained herein were endorsed by the authors and the Friedreich Ataxia Guidelines Panel in 2022.
Topic Contents
3.11.1 The effects of Friedreich ataxia on cognitive function
3.11.2 Functional consequences of disturbance of cognitive function
Disclaimer / Intended Use / Funding
Disclaimer
The Clinical Management Guidelines for Friedreich ataxia (‘Guidelines’) are protected by copyright owned by the authors who contributed to their development or said authors’ assignees.
These Guidelines are systematically developed evidence statements incorporating data from a comprehensive literature review of the most recent studies available (up to the Guidelines submission date) and reviewed according to the Grading of Recommendations, Assessment Development and Evaluations (GRADE) framework © The Grade Working Group.
Guidelines users must seek out the most recent information that might supersede the diagnostic and treatment recommendations contained within these Guidelines and consider local variations in clinical settings, funding and resources that may impact on the implementation of the recommendations set out in these Guidelines.
The authors of these Guidelines disclaim all liability for the accuracy or completeness of the Guidelines, and disclaim all warranties, express or implied to their incorrect use.
Intended Use
These Guidelines are made available as general information only and do not constitute medical advice. These Guidelines are intended to assist qualified healthcare professionals make informed treatment decisions about the care of individuals with Friedreich ataxia. They are not intended as a sole source of guidance in managing issues related to Friedreich ataxia. Rather, they are designed to assist clinicians by providing an evidence-based framework for decision-making.
These Guidelines are not intended to replace clinical judgment and other approaches to diagnosing and managing problems associated with Friedreich ataxia which may be appropriate in specific circumstances. Ultimately, healthcare professionals must make their own treatment decisions on a case-by-case basis, after consultation with their patients, using their clinical judgment, knowledge and expertise.
Guidelines users must not edit or modify the Guidelines in any way – including removing any branding, acknowledgement, authorship or copyright notice.
Funding
The authors of this document gratefully acknowledge the support of the Friedreich Ataxia Research Alliance (FARA). The views and opinions expressed in the Guidelines are solely those of the authors and do not necessarily reflect the official policy or position of FARA.
3.11 Cognitive function in Friedreich ataxia
Gilles Naeije, Louise Corben and Jörg B. Schulz
This chapter describes the effects of Friedreich ataxia on cognitive function, the functional consequences of these effects, and recommendations for managing disturbance of cognitive function. In making recommendations, the authors were tasked with answering the question:
For individuals with Friedreich ataxia, what management strategies could be implemented for disturbance of cognitive function?
3.11.1 The effects of Friedreich ataxia on cognitive function
Cognition in Friedreich Ataxia (FRDA) is not as well studied as motor, sensory and gait disorders, and individuals with FRDA and their caregivers have low awareness of potential cognitive impairment (1). Past decades have unveiled a prominent role of the cerebellum and its efferent tracts, emerging from the cerebellum dentate nuclei (DN), in perception, higher cortical functions and affect modulation (2, 3). In regards to pathology, FRDA is hallmarked by progressive cerebellar DN atrophy (4). Thus, DN pathology in FRDA could have an impact on various domains of cognition through cerebello-cortical loops dysfunction.
Seminal investigations showed lower, but within normal limits, cognitive performance in individuals with FRDA compared to controls (5-7) and contemporary studies have reported normal mini-mental state examination (MMSE) scores (8-13) and slightly abnormal MOntreal Cognitive Assessment (MOCA) scores (14, 15). Yet, studies based on thorough neuropsychological evaluation found that individuals with FRDA displayed significant differences in almost all spheres of cognition, when specifically evaluated, compared to control participants.
Language fluencies are the most studied and individuals with FRDA show lower phonemic (12, 14-18) and semantic (7-9, 11, 15, 18, 19) fluencies, as well as lower action verbal fluencies (8, 9, 11) than controls. Attentional and executive function, measured by the Stroop Interference Test (8, 13, 20-23) or the trail making test (13, 15, 20, 23, 24) are also less efficient, and digit span assessment highlights poorer digit span forward (7, 11, 15, 16, 25-27) and backward (7, 11, 16, 25-27) recall. Similarly, memory assessments in individuals with FRDA show poorer performance in the California verbal learning test (11, 18, 27), the 10/36 spatial recall test (11, 18, 27) and in logical memory evaluations (11, 18) compared to controls. Visuospatial abilities, assessed in fewer studies, are also altered (6, 11, 12, 18, 19, 28).
Emotion recognition and social cognitive abilities are poorly characterized, but individuals with FRDA display less skill in facial expression, emotion recognition (11, 15, 18, 21) and in identifying social faux-pas (27). Thus, individuals with FRDA do not perform as well as controls in most cognition domains: language, attentional and executive functions, memory, visuospatial, emotion recognition and social cognitive abilities (1). This widespread involvement suggests that the cerebellum is the common factor. The combination of relatively mild but global higher neocortical dysfunction is characteristic of the cerebellum cognitive affective syndrome, a thought dysmetria that hampers language, emotions, memory, attention, visuospatial and executive functions (29, 30).
3.11.2 Functional consequences of disturbance of cognitive function
In addressing the sensitive issue of cognitive function in people with FRDA it should be noted that the deficits described do not generally preclude a person with FRDA from participating in education at school and college/university, gaining meaningful and even cognitively demanding employment, partnering and raising a family (31). Cognitive disorders in FRDA are considered to be relatively subtle and do not cause obvious functional impairment, which explains why it is often overlooked (32). However, even if missed by classic screening tools, cognitive and affective impairments may affect the ability of individuals with FRDA to study, work and develop their full potential, both intellectually and socially. Thus, cognitive impairments should be considered when difficulties arise in any of those areas.
There is limited evidence on the potential progression of cognitive impairments in individuals with FRDA and dedicated studies are needed (1). Yet, there seems to be a correlation between structural alterations of the dentate nuclei, dentato-rubral tracts and posterior cerebellar lobes and cognitive performance (33, 34). Language fluency as well as attention and processing speed worsen over time (7, 8), and there is a relationship between the magnitude of cognitive impairment and ataxia severity (35). This suggests that cognitive impairment relates to cerebellar pathology in FRDA and that cognitive disorders may appear as the disease progresses, with a severity that is correlated with the extent of cerebellar ataxic symptoms.
Education
QUESTION: Should education regarding possible cognitive impairment versus no education regarding possible cognitive impairment be used for all individuals with Friedreich ataxia?
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[/sg_popup]STRENGTH OF RECOMMENDATION: ↑
[sg_popup id=”658″ event=”click”][/sg_popup]LEVEL OF EVIDENCE: ⨁◯◯◯
RECOMMENDATION: We suggest development and implementation of an educational program for affected individuals and their families and carers to improve information about the potential for, and management of, cognitive dysfunction in individuals with Friedreich ataxia.
JUSTIFICATION: There is increasing evidence of cognitive dysfunction in individuals with Friedreich ataxia that has the potential to affect academic, vocational and interpersonal pursuits. There is a need to identify and address this potential, particularly as individuals with Friedreich ataxia may be unaware of the possibility of cognitive dysfunction.
SUBGROUP CONSIDERATION: This recommendation is for individuals with Friedreich ataxia and their parents, carers, partners and family.
Evidence to Recommendation Table PDFNeuromodulation
QUESTION: Should active neuromodulation (tDCS, TMS) versus sham neuromodulation be used for all individuals with Friedreich ataxia?
[sg_popup id=”587″ event=”click”][/sg_popup]STRENGTH OF RECOMMENDATION: ↓↓
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RECOMMENDATION: We recommend that clinicians should not use active neuromodulation (tDCS, TMS) as part of clinical practice to improve cognitive function in individuals with Friedreich ataxia.
JUSTIFICATION: There are no data available to support positive effects of active neuromodulation to improve cognitive function in individuals with Friedreich ataxia.
SUBGROUP CONSIDERATION: This recommendation is for individuals with Friedreich ataxia with concerns about cognitive function.
Evidence to Recommendation Table PDFLay summary of clinical recommendations for disturbance of cognitive function in Friedreich ataxia
Cognition is a term that relates to thinking processes such as remembering, judging, decision making and problem solving. These processes are involved in how we comprehend, understand and interact with the world around us. There is increasing evidence that cognition may be affected in Friedreich ataxia, with possible important consequences. However, individuals with Friedreich ataxia and their carers may not be aware that cognitive problems can arise with Friedreich ataxia.
Why these recommendations?
We suggest that educational programs for individuals with Friedreich ataxia and their families may help to improve understanding of the potential cognitive problems related to Friedreich ataxia and what can be done to address these problems. However, there is currently no research evidence to support this recommendation. There is a need, therefore, to do research to find out if educational programs on cognition would help individuals with Friedreich ataxia or their carers to identify, understand and manage any cognitive difficulties that may happen.
Education programs might be helpful to individuals with cognitive difficulties that affect their ability to study, work or have successful personal relationships.
In addition, there is some evidence in similar conditions to Friedreich ataxia that stimulation to the brain may be of benefit in improving cognition. However, this has not been shown in people with Friedreich ataxia, so we do not recommend brain stimulation at present.
What does this mean for you as a person living with Friedreich ataxia or caring for someone living with Friedreich ataxia?
It might be important for you to speak with your healthcare professional about Friedreich ataxia and potential associated cognitive problems. This is particularly important if you, or the person you care for, are having problems managing work, study or personal relationships which may be related to changes in cognition.
Who are these recommendations specifically for?
These recommendations are for all individuals with Friedreich ataxia and their carers, partners and family.
Louise Corben, PhD
Principal Research Fellow, Murdoch Children’s Research Institute, Melbourne, Victoria, Australia
Email: louise.corben@mcri.edu.au
Gilles Naeije, MD, PhD
Assistant Professor, Neurology Department, CUB-Hôpital Erasme, Brussels, Belgium
Email: gilles.naeije@erasme.ulb.ac.be
Jörg B. Schulz, MD
Chair of Neurology, Department of Neurology, RWTH Aachen University, Aachen, NRW, Germany
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These Guidelines are systematically developed evidence statements incorporating data from a comprehensive literature review of the most recent studies available (up to the Guidelines submission date) and reviewed according to the Grading of Recommendations, Assessment Development and Evaluations (GRADE) framework © The Grade Working Group.
This chapter of the Clinical Management Guidelines for Friedreich Ataxia and the recommendations and best practice statements contained herein were endorsed by the authors and the Friedreich Ataxia Guidelines Panel in 2022.
It is our expectation that going forward individual topics can be updated in real-time in response to new evidence versus a re-evaluation and update of all topics simultaneously.