Background Amyotrophic lateral sclerosis (ALS) is often associated with cognitive and/or behavioural impairment. Cognitive reserve (CR) may play a protective role in offsetting cognitive impairment. This study examined the relationship between CR and longitudinal change in cognition in an Irish ALS cohort.
Methods Longitudinal neuropsychological assessment was carried out on 189 patients over 16 months using the Edinburgh cognitive and behavioural ALS screen (ECAS) and an additional battery of neuropsychological tests. CR was measured by combining education, occupation and physical activity data. Joint longitudinal and time-to-event models were fitted to investigate the associations between CR, performance at baseline and decline over time while controlling for non-random drop-out.
Results CR was a significant predictor of baseline neuropsychological performance, with high CR patients performing better than those with medium or low CR. Better cognitive performance in high CR individuals was maintained longitudinally for ECAS, social cognition, executive functioning and confrontational naming. Patients displayed little cognitive decline over the course of the study, despite controlling for non-random drop-out.
Conclusions These findings suggest that CR plays a role in the presentation of cognitive impairment at diagnosis but is not protective against cognitive decline. However, further research is needed to examine the interaction between CR and other objective correlates of cognitive impairment in ALS.
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Contributors EC, OH and NP designed and conceptualised the study. EC, JR, MP-G, TB, ME, PB, MH and AV played a major role in the acquisition of data. EC and JR analysed and interpreted the data. EC drafted the manuscript for intellectual content. EC, JR, MP-G, TB, ME, RM, SD, PB, MH, OH and NP revised the manuscript for intellectual content.
Funding This research has received funding from Science Foundation Ireland (SFI), grant 16/ERCD/3854, grant number 205532, the European Community's Seventh Framework Programme (FP7/2007-2013) under the Health Cooperation programme and the project EUROMOTOR (no 259867), and the Charities Research Motor Neurone (no grant number) and Irish Motor Neurone Disease Association (no grant number). Peter Bede is supported by the Health Research Board (HRB EIA-2017-019), the EU Joint Programme–Neurodegenerative Disease Research (JPND-2017-1), the Andrew Lydon scholarship (No grant number), and the Iris O'Brien Foundation (no grant number). JR is supported by the European Union Marie Skłodowska-Curie Action (no 846794).
Competing interests NP serves as Associate Editor of the International Journal of Neuroscience and has received speaker honoraria from Novartis. OH has received speaking honoraria from Janssen Cilag, Biogen Idec, Sanofi Aventis, Novartis and MerckSerono. She has been a member of advisory panels for Biogen Idec, Allergen, Ono Pharmaceuticals, Novartis, Cytokinetics and Sanofi Aventis. She serves as editor-in-chief of the journal Amyotrophic Lateral Sclerosis and Frontotemporal Dementia.
Patient consent for publication Not required.
Ethics approval Ethical approval was granted by Beaumont Hospital ethics committee (ID: REC Ref- 06/79 and REC Ref- 13/102).
Provenance and peer review Not commissioned; externally peer reviewed.
Data availability statement Anonymised data are available on reasonable request.
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