Journal of the International Neuropsychological Society

Research Articles

Cognitive Reserve and Brain Reserve in Prodromal Huntington's Disease

Aaron Bonner-Jacksona1, Jeffrey D. Longa2, Holly Westervelta3a4, Geoffrey Tremonta3a4, Elizabeth Aylwarda5, Jane S. Paulsena2 c1 and The PREDICT-HD Investigators and Coordinators of the Huntington Study Group

a1 Cleveland Clinic, Cleveland, Ohio

a2 University of Iowa, Iowa City, Iowa

a3 Rhode Island Hospital, Providence, Rhode Island

a4 Alpert Medical School of Brown University, Providence, Rhode Island

a5 Seattle Children's Research Institute, Seattle, Washington


Huntington disease (HD) is associated with decline in cognition and progressive morphological changes in brain structures. Cognitive reserve may represent a mechanism by which disease-related decline may be delayed or slowed. The current study examined the relationship between cognitive reserve and longitudinal change in cognitive functioning and brain volumes among prodromal (gene expansion-positive) HD individuals. Participants were genetically confirmed individuals with prodromal HD enrolled in the PREDICT-HD study. Cognitive reserve was computed as the composite of performance on a lexical task estimating premorbid intellectual level, occupational status, and years of education. Linear mixed effects regression (LMER) was used to examine longitudinal changes on four cognitive measures and three brain volumes over approximately 6 years. Higher cognitive reserve was significantly associated with a slower rate of change on one cognitive measure (Trail Making Test, Part B) and slower rate of volume loss in two brain structures (caudate, putamen) for those estimated to be closest to motor disease onset. This relationship was not observed among those estimated to be further from motor disease onset. Our findings demonstrate a relationship between cognitive reserve and both a measure of executive functioning and integrity of certain brain structures in prodromal HD individuals. (JINS, 2013, 19, 1–12).

(Received October 10 2012)

(Revised April 04 2013)

(Accepted April 04 2013)

(Online publication May 23 2013)


  • Huntington disease;
  • Prodromal;
  • Cognitive reserve;
  • Cognition;
  • Caudate;
  • Putamen


c1 Correspondence and reprint requests to: Jane S. Paulsen, 500 Newton Road, 1-305 MEB, Iowa City, IA 52242. E-mail: