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J Int Neuropsychol Soc. 2013 Aug;19(7):739-50. doi: 10.1017/S1355617713000507. Epub 2013 May 23.

Cognitive reserve and brain reserve in prodromal Huntington's disease.

Collaborators (231)

Wassink T, Cross S, Kimble M, Ryan P, Epping EA, Chiu E, Yastrubetskaya O, Preston J, Goh A, Antonopoulos S, Loi S, Chua P, Komiti A, Raymond L, Decolongon J, Ross CA, Varvaris M, Mallonee WM, Suter G, Samii A, Macaraeg A, Jones R, Wood-Siverio C, Factor SA, Testa C, Barker RA, Mason S, McCusker E, Griffith J, Loy C, Gunn D, Orth M, Sübmuth S, Barth K, Trautmann S, Quaid K, Wesson M, Wojcieszek J, Guttman M, Sheinberg A, Karmalkar I, Perlman S, Clemente B, Geschwind MD, Kang G, Satris G, Warner T, Burrows M, Rosser A, Price K, Hunt S, Marshall F, Chesire A, Wodarski M, Hickey C, Panegyres P, Lee J, Andrew S, Perlmutter J, Barton S, Schmidt A, Miedzybrodzka Z, Rae D, D'Alessandro M, Craufurd D, Bek J, Howard E, Mazzoni P, Marder K, Wasserman P, Kumar R, Erickson D, Wheelock V, Tempkin T, Kjer L, Martin W, King P, Wieler M, Sran S, Suchowersky O, Ahmed A, Rao S, Reece C, Bura A, Mourany L, Schulz J, Paulsen J, Epping EA, Johnson H, Smith M, Long JD, Aylward E, Montross K, Bockholt J, Blanchard S, Evans K, Matson W, Peterson A, Mills JA, Vonsattell JP, Moskowitz C, Vik S, Harrington D, Castillo G, Morison J, Reed J, Diaz M, Dobbins I, Hershey T, Foster E, Moore D, Westervelt H, Davis J, Tremont G, Smith M, Moser DJ, Gehl C, Matheson K, Siedlecki K, Van Walsem M, Elias G, Gover M, Bernier R, Carlozzi N, Duff K, Georgiou-Karistianis N, Papp K, Williams J, Ro E, Clark LA, Downing N, Harreld M, Vik S, Ready R, Vaccarino A, Farias S, Carlozzi N, Gehl C, MacDonald M, Gusella J, Myers R, Wassink T, Epping EA, Mills J, Miedzybrodzka Z, Ross C, Jones K, Marietta J, Harris G, Kim EY, Johnson H, Ennis G, Wassink T, Ashburner J, Potkin S, Toga A, Aylward E, Axelson E, Ross CA, Miller M, Reading S, Beg MF, Magnotta VA, Helmer K, Lim K, Lowe M, Mori S, Song A, Turner J, Rao S, Beall E, Koenig K, Phillips M, Reece C, Zimbelman J, Jones K, Epping EA, Downing N, Fiedorowicz J, Robinson R, Smith M, Beglinger L, Mills J, Harreld M, Vik S, Williams J, Liu D, Moser D, Rowe K, Anderson K, Craufurd D, Groves M, Vaccarino A, Evans K, Rickards H, van Duijn E, Long JD, Kim JI, Mills JA, Zhang Y, Liu D, Lu W, Stout C, Lourens S, Nance M, Kimble M, Ryan P, Thompson S, Erwin C, Epping EA, Williams J, Mills J, Vik S, Nance M, Hughes L, Bockholt J, Smith J, Zschiegner R, Wyse R, Wade O, Evans J, Weston D, Werling-Witkoske C, Ennis G, Vik S, Anderson K, Lichty B, Davis L, Blanchard S, Montross K, Danzer P.

Author information

Cleveland Clinic, Cleveland, OH, USA.


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.

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