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Association of CAG Repeat Length in the Huntington Gene With Cognitive Performance in Young Adults
Journal article   Peer reviewed

Association of CAG Repeat Length in the Huntington Gene With Cognitive Performance in Young Adults

Jordan L Schultz, Carsten Saft and Peggy C Nopoulos
Neurology, Vol.96(19), pp.e2407-e2413
03/10/2021
DOI: 10.1212/WNL.0000000000011823
PMCID: PMC10508647
PMID: 33692166

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Abstract

To investigate the relationships between CAG repeat length in the huntingtin gene and cognitive performance in participants above and below the disease threshold for Huntington's Disease (HD), we performed a cross-sectional analysis of the Enroll-HD database. We analyzed data from young, developing adults (≤ 30 years) without a history of depression, apathy, or cognitive deficits. We included participants with and without the gene-expansion (CAG ≥ 36) for HD. All participants had to have a Total Functional Capacity Score of 13, a diagnostic confidence level of zero, a total motor score of <10, and be more than 28.6 years from their predicted motor onset. We performed regression analyses to investigate the non-linear relationship between CAG repeat length and various cognitive measures controlling for age, sex, and education level. There were significant positive relationships between CAG repeat length and the Symbol Digit Modalities, Stroop Color Naming, and Stroop Interference Tests. There were significant negative relationships between CAG repeat length and parts A and B of the Trails Making Test (p<0.05) indicating that longer CAG repeat lengths were associated with better performance. An increasing number of CAG repeats in the huntingtin gene below disease threshold and low pathological CAG ranges was associated with some improvements in cognitive performance. These findings outline the relationship between CAG repeats within the huntingtin gene and cognitive development. This study provides Class IV evidence that CAG repeat length is positively associated with cognitive function across a spectrum of CAG repeat lengths.

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