Journal article
Intellectual enrichment and genetic modifiers of cognition and brain volume in Huntington's disease
Brain communications, Vol.4(6), fcac279
2022
DOI: 10.1093/braincomms/fcac279
PMCID: PMC9732861
PMID: 36519153
Abstract
Papoutsi et al. showed that cognitive function in Huntington's disease is affected by an interplay between genetic and environmental factors. 3a allele carriers had slower cognitive decline and cortical atrophy. In addition, high intellectual enrichment predicted slower cognitive decline and counteracted the detrimental effect of the Met66 allele in brain-derived neurotrophic factor.
An important step towards the development of treatments for cognitive impairment in ageing and neurodegenerative diseases is to identify genetic and environmental modifiers of cognitive function and understand the mechanism by which they exert an effect. In Huntington's disease, the most common autosomal dominant dementia, a small number of studies have identified intellectual enrichment, i.e. a cognitively stimulating lifestyle and genetic polymorphisms as potential modifiers of cognitive function. The aim of our study was to further investigate the relationship and interaction between genetic factors and intellectual enrichment on cognitive function and brain atrophy in Huntington's disease. For this purpose, we analysed data from Track-HD, a multi-centre longitudinal study in Huntington's disease gene carriers and focused on the role of intellectual enrichment (estimated at baseline) and the genes FAN1, MSH3, BDNF, COMT and MAPT in predicting cognitive decline and brain atrophy. We found that carrying the 3a allele in the MSH3 gene had a positive effect on global cognitive function and brain atrophy in multiple cortical regions, such that 3a allele carriers had a slower rate of cognitive decline and atrophy compared with non-carriers, in agreement with its role in somatic instability. No other genetic predictor had a significant effect on cognitive function and the effect of MSH3 was independent of intellectual enrichment. Intellectual enrichment also had a positive effect on cognitive function; participants with higher intellectual enrichment, i.e. those who were better educated, had higher verbal intelligence and performed an occupation that was intellectually engaging, had better cognitive function overall, in agreement with previous studies in Huntington's disease and other dementias. We also found that intellectual enrichment interacted with the BDNF gene, such that the positive effect of intellectual enrichment was greater in Met66 allele carriers than non-carriers. A similar relationship was also identified for changes in whole brain and caudate volume; the positive effect of intellectual enrichment was greater for Met66 allele carriers, rather than for non-carriers. In summary, our study provides additional evidence for the beneficial role of intellectual enrichment and carrying the 3a allele in MSH3 in cognitive function in Huntington's disease and their effect on brain structure.
Details
- Title: Subtitle
- Intellectual enrichment and genetic modifiers of cognition and brain volume in Huntington's disease
- Creators
- Marina Papoutsi - University College LondonMichael Flower - University College LondonDavina J Hensman Moss - University College LondonPeter Holmans - Cardiff UniversityCarlos Estevez-Fraga - UCL, Queen Sq Inst Neurol, UCL Huntingtons Dis Ctr, London, EnglandEileanoir B. Johnson - University College LondonRachael Scahill - University College LondonGeraint Rees - Wellcome Centre for Human NeuroimagingDouglas Langbehn - University of IowaSarah J. Tabrizi - University College LondonTrack-HD InvestigatorsEric D Axelson (Contributor) - Psychiatry
- Resource Type
- Journal article
- Publication Details
- Brain communications, Vol.4(6), fcac279
- Publisher
- Oxford Univ Press
- DOI
- 10.1093/braincomms/fcac279
- PMID
- 36519153
- PMCID
- PMC9732861
- ISSN
- 2632-1297
- eISSN
- 2632-1297
- Number of pages
- 13
- Grant note
- UK Medical Research Council; UK Research & Innovation (UKRI); Medical Research Council UK (MRC) CHDI Foundation Alzheimer's Society and Alzheimer's Research UK Huntington's Disease Society of America (HDSA) Human Biology fellowship UK Dementia Research Institute (DRI) - DRI Ltd
- Language
- English
- Date published
- 2022
- Academic Unit
- Psychiatry; Iowa Neuroscience Institute
- Record Identifier
- 9984622053602771
Metrics
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