Skip to main content Accessibility help
×
Home

Cognitive Reserve and Brain Reserve in Prodromal Huntington's Disease

  • Aaron Bonner-Jackson (a1), Jeffrey D. Long (a2), Holly Westervelt (a3) (a4), Geoffrey Tremont (a3) (a4), Elizabeth Aylward (a5), Jane S. Paulsen (a2) and The PREDICT-HD Investigators and Coordinators of the Huntington Study Group...

Abstract

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).

Copyright

Corresponding author

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

References

Hide All
Alexander, G.E., Furey, M.L., Grady, C.L., Pietrini, P., Brady, D.R., Mentis, M.J., Schapiro, M.B. (1997). Association of premorbid intellectual function with cerebral metabolism in Alzheimer's disease: Implications for the cognitive reserve hypothesis. American Journal of Psychiatry, 154(2), 165172.
Arenaza-Urquijo, E.M., Bosch, B., Sala-Llonch, R., Sole-Padulles, C., Junque, C., Fernandez-Espejo, D., Bartres-Faz, D. (2011). Specific anatomic associations between white matter integrity and cognitive reserve in normal and cognitively impaired elders. American Journal Geriatric Psychiatry, 19(1), 3342. doi:10.1097/JGP.0b013e3181e448e1
Aylward, E.H. (2007). Change in MRI striatal volumes as a biomarker in preclinical Huntington's disease. Brain Research Bulletin, 72(2-3), 152158. doi:S0361-9230(06)00324-8 [pii] 10.1016/j.brainresbull.2006.10.028
Aylward, E.H., Li, Q., Stine, O.C., Ranen, N., Sherr, M., Barta, P.E., Ross, C.A. (1997). Longitudinal change in basal ganglia volume in patients with Huntington's disease. Neurology, 48(2), 394399.
Aylward, E.H., Nopoulos, P.C., Ross, C.A., Langbehn, D.R., Pierson, R.K., Mills, J.A., Paulsen, J.S. (2011). Longitudinal change in regional brain volumes in prodromal Huntington disease. Journal of Neurology, Neurosurgery, & Psychiatry, 82(4), 405410. doi:jnnp.2010.208264 [pii] 10.1136/jnnp.2010.208264
Bachoud-Levi, A.C., Maison, P., Bartolomeo, P., Boisse, M.F., Dalla Barba, G., Ergis, A.M., Peschanski, M. (2001). Retest effects and cognitive decline in longitudinal follow-up of patients with early HD. Neurology, 56(8), 10521058.
Bamford, K.A., Caine, E.D., Kido, D.K., Cox, C., Shoulson, I. (1995). A prospective evaluation of cognitive decline in early Huntington's disease: Functional and radiographic correlates. Neurology, 45(10), 18671873.
Bates, D.M. (2011). lme4: Mixed-effects modeling with R. New York: Springer.
Beck, A.T., Steer, R.A., Brown, G.K. (1996). BDI-II, Beck depression inventory: Manual (2nd ed.). Boston: Harcourt Brace.
Beglinger, L.J., Duff, K., Allison, J., Theriault, D., O'Rourke, J.J.F., Leserman, A., Paulsen, J.S. (2010). Cognitive change in patients with Huntington disease on the Repeatable Battery for the Assessment of Neuropsychological Status. Journal of Clinical and Experimental Neuropsychology, 32, 573578.
Benedict, R.H., Morrow, S.A., Weinstock Guttman, B., Cookfair, D., Schretlen, D.J. (2010). Cognitive reserve moderates decline in information processing speed in multiple sclerosis patients. Journal of International Neuropsychology Society, 16(5), 829835. doi:S1355617710000688 [pii] 10.1017/S1355617710000688
Brandt, J., Bylsma, F.W., Aylward, E.H., Rothlind, J., Gow, C.A. (1995). Impaired source memory in Huntington's disease and its relation to basal ganglia atrophy. Journal of Clinical Experimental Neuropsychology, 17(6), 868877. doi:10.1080/01688639508402436
Burnham, K.P., Anderson, D.R. (2002). Model selection and multimodal inference. New York: Springer.
Campodonico, J.R., Codori, A.M., Brandt, J. (1996). Neuropsychological stability over two years in asymptomatic carriers of the Huntington's disease mutation. Journal of Neurology, Neurosurgery, & Psychiatry, 61(6), 621624.
Carlozzi, N.E., Stout, J.C., Mills, J.A., Duff, K., Beglinger, L.J., Aylward, E.H., … the PREDICT-HD Investigators of the Huntington Study Group. (2011). Estimating premorbid IQ in the prodromal phase of a neurodegenerative disease. The Clinical Neuropsychologist, 25, 757777.
Del Ser, T., Gonzalez-Montalvo, J.I., Martinez-Espinosa, S., Delgado-Villapalos, C., Bermejo, F. (1997). Estimation of premorbid intelligence in Spanish people with the Word Accentuation Test and its application to the diagnosis of dementia. Brain and Cognition, 33(3), 343356. doi:S0278-2626(97)90877-0 [pii] 10.1006/brcg.1997.0877
Fratiglioni, L., Wang, H.X. (2007). Brain reserve hypothesis in dementia. Journal of Alzheimers Disease, 12(1), 1122.
Fritsch, T., McClendon, M.J., Smyth, K.A., Ogrocki, P.K. (2002). Effects of educational attainment and occupational status on cognitive and functional decline in persons with Alzheimer-type dementia. International Psychogeriatrics, 14(4), 347363.
Goul, W.R., Brown, M. (1970). Effects of age and intelligence on trail making test performance and validity. Perceptual and Motor Skills, 30, 319326.
Grober, E., Sliwinski, M. (1991). Development and validation of a model for estimating premorbid verbal intelligence in the elderly. Journal of Clinical Experimental Neuropsychology, 13(6), 933949. doi:10.1080/01688639108405109
Hahn-Barma, V., Deweer, B., Durr, A., Dode, C., Feingold, J., Pillon, B., Dubois, B. (1998). Are cognitive changes the first symptoms of Huntington's disease? A study of gene carriers. Journal of Neurology, Neurosurgery, and Psychiatry, 64, 172177.
Ho, A.K., Sahakian, B.J., Brown, R.G., Barker, R.A., Hodges, J.R., Ane, M.N., Bodner, T. (2003). Profile of cognitive progression in early Huntington's disease. Neurology, 61(12), 17021706.
Hobbs, N.Z., Barnes, J., Frost, C., Henley, S.M., Wild, E.J., Macdonald, K., Tabrizi, S.J. (2010). Onset and progression of pathologic atrophy in Huntington disease: A longitudinal MR imaging study. AJNR American Journal of Neuroradiology, 31(6), 10361041. doi:ajnr.A2018 [pii] 10.3174/ajnr.A2018
Jurgens, C.K., van de Wiel, L., van Es, A.C., Grimbergen, Y.M., Witjes-Ane, M.N., van der Grond, J., Roos, R.A. (2008). Basal ganglia volume and clinical correlates in ‘preclinical’ Huntington's disease. Journal of Neurology, 255(11), 17851791. doi:10.1007/s00415-008-0050-4
Lawrence, A.D., Hodges, J.R., Rosser, A.E., Kershaw, A., ffrench-Constant, C., Rubinsztein, D.C., Sahakian, B.J. (1998). Evidence for specific cognitive deficits in preclinical Huntington's disease. Brain, 121, 13291341.
Lemiere, J., Decruyenaere, M., Evers-Kiebooms, G., Vandenbussche, E., Dom, R. (2004). Cognitive changes in patients with Huntington's disease (HD) and asymptomatic carriers of the HD mutation--a longitudinal follow-up study. Journal of Neurology, 251(8), 935942. doi:10.1007/s00415-004-0461-9
Long, J.D. (2011). Longitudinal data analysis for the behavioral sciences using R. Thousand Oaks, CA: Sage Publications Inc.
Lopez-Sendon, J.L., Royuela, A., Trigo, P., Orth, M., Lange, H., Reilmann, R., de Yebenes, J.G. (2011). What is the impact of education on Huntington's disease? Movement Disorders, 26(8), 14891495. doi:10.1002/mds.23385
Magnotta, V.A., Harris, G., Andreasen, N.C., O'Leary, D.S., Yuh, W.T., Heckel, D. (2002). Structural MR image processing using the BRAINS2 toolbox. Computerized Medical Imaging and Graphics, 26(4), 251264. doi:S0895611102000113 [pii]
Mazzocchi-Jones, D., Dobrossy, M., Dunnett, S.B. (2011). Environmental enrichment facilitates long-term potentiation in embryonic striatal grafts. Neurorehabilitation and Neural Repair, 25, 548557.
Montoya, A., Price, B.H., Menear, M., Lepage, M. (2006). Brain imaging and cognitive dysfunctions in Huntington's disease. Journal of Psychiatry and Neuroscience, 31(1), 2129.
Nelson, H.E., Willison, J. (1991). The National Adult Reading Test (NART): Test manual (2nd ed.). Windsor, England: NFER Nelson.
Nithianantharajah, J., Barkus, C., Vijiaratnam, N., Clement, O., Hannan, A.J. (2009). Modeling brain reserve: Experience-dependent neuronal plasticity in healthy and Huntington's disease transgenic mice. American Journal of Geriaticr Psychiatry, 17(3), 196209. doi:10.1097/JGP.0b013e318196a632 00019442-200903000-00004 [pii]
Pang, T.Y., Stam, N.C., Nithianantharajah, J., Howard, M.L., Hannan, A.J. (2006). Differential effects of voluntary physical exercise on behavioral and brain-dervied neurotrophic factor expression deficits in Huntington's disease transgenic mice. Neuroscience, 141, 569584.
Paulsen, J.S., Hayden, M., Stout, J.C., Langbehn, D.R., Aylward, E., Ross, C.A., … Predict-HD Investigators of the Huntington Study Group. (2006). Preparing for preventative clinical trials: The Predict-HD study. Archives of Neurology, 63, 883890.
Paulsen, J.S., Langbehn, D.R., Stout, J.C., Aylward, E., Ross, C.A., Nance, M., Hayden, M. (2008). Detection of Huntington's disease decades before diagnosis: The Predict-HD study. Journal of Neurology, Neurosurgery, & Psychiatry, 79(8), 874880. doi:jnnp.2007.128728 [pii] 10.1136/jnnp.2007.128728
Paulsen, J.S., Zhao, H., Stout, J.C., Brinkman, R.R., Guttman, M., Ross, C.A., The Huntington Study Group. (2001). Clinical markers of early disease in persons near onset of Huntington's disease. Neurology, 57, 658662.
Pierson, R.K., Johnson, H.J., Harris, G., Keefe, H., Paulsen, J., Andreasen, N.C., Magnotta, V.A. (2011). Fully automated analysis using BRAINS: AutoWorkup. Neuroimage, 54, 328336.
Powell, S., Magnotta, V.A., Johnson, H., Jammalamadaka, V.K., Pierson, R., Andreasen, N.C. (2008). Registration and machine learning-based automated segmentation of subcortical and cerebellar brain structures. Neuroimage, 39(1), 238247. doi:S1053-8119(07)00713-6 [pii] 10.1016/j.neuroimage.2007.05.063
Reading, S.A., Yassa, M.A., Bakker, A., Dziorny, A.C., Gourley, L.M., Yallapragada, V., Ross, C.A. (2005). Regional white matter change in pre-symptomatic Huntington's disease: A diffusion tensor imaging study. Psychiatry Research, 140(1), 5562. doi:S0925-4927(05)00106-X [pii] 10.1016/j.pscychresns.2005.05.011
Reitan, R.M. (1958). Validity of the trail making test as an indicator of organic brain damage. Perceptual and Motor Skills, 8, 271276.
Roe, C.M., Xiong, C., Miller, J.P., Morris, J.C. (2007). Education and Alzheimer disease without dementia: Support for the cognitive reserve hypothesis. Neurology, 68(3), 223228. doi:68/3/223 [pii] 10.1212/01.wnl.0000251303.50459.8a
Rupp, J., Blekher, T., Jackson, J., Beristain, X., Marshall, J., Hui, S., Foroud, T. (2010). Progression in prediagnostic Huntington disease. Journal of Neurology, Neurosurgery & Psychiatry, 81(4), 379384. doi:jnnp.2009.176982 [pii] 10.1136/jnnp.2009.176982
Salthouse, T.A. (2011). What cognitive abilities are involved in trail-making performance? Intelligence, 39, 222232.
Schmidt, K., Metzler, P. (1992). Wortschatztest (WST). Weinheim: Beltz Verlag.
Smith, A. (1991). Symbol Digit Modalities Test. Los Angeles: Western Psychological Services.
Smith, M.M., Mills, J.A., Epping, E.A., Westervelt, H.J., Paulsen, J.S., …The PREDICT-HD Investigators and Coordinators of the Huntington Study Group. (2012). Depressive symptom severity is related to poorer cognitive performance in prodromal Huntington disease. Neuropsychology, 26, 664669.
Snowden, J.S., Craufurd, D., Thompson, J., Neary, D. (2002). Psychomotor, executive, and memory function in preclinical Huntington's disease. Journal of Clinical and Experimental Neuropsychology, 24(2), 133145.
Solomon, A.C., Stout, J.C., Weaver, M., Queller, S., Tomusk, A., Whitlock, K.B., Foroud, T. (2008). Ten-year rate of longitudinal change in neurocognitive and motor function in prediagnosis Huntington disease. Movement Disorders, 23(13), 18301836. doi:10.1002/mds.22097
Starkstein, S.E., Brandt, J., Folstein, S., Strauss, M., Berthier, M.L., Pearlson, G.D., Folstein, M. (1988). Neuropsychological and neuroradiological correlates in Huntington's disease. Journal of Neurology, Neurosurgery, & Psychiatry, 51(10), 12591263.
Stern, Y. (2009). Cognitive reserve. Neuropsychologia, 47(10), 20152028. doi:S0028-3932(09)00123-7 [pii] 10.1016/j.neuropsychologia.2009.03.004
Stout, J.C., Jones, R., Labuschagne, I., O'Regan, A.M., Say, M.J., Dumas, E.M., Frost, C. (2012). Evaluation of longitudinal 12 and 24 month cognitive outcomes in premanifest and early Huntington's disease. Journal of Neurology, Neurosurgery, and Psychiatry, 83, 687694.
Stout, J.C., Paulsen, J.S., Queller, S., Solomon, A.C., Whitlock, K.B., Campbell, J.C., Aylward, E.H. (2011). Neurocognitive signs in prodromal Huntington disease. Neuropsychology, 25(1), 114. doi:2010-20839-001 [pii] 10.1037/a0020937
Stout, J.C., Weaver, M., Solomon, A.C., Queller, S., Hui, S., Johnson, S.A., Foroud, T. (2007). Are cognitive changes progressive in prediagnostic HD? Cognitive and Behavioral Neurology, 20(4), 212218. doi:10.1097/WNN.0b013e31815cfef8 00146965-200712000-00002 [pii]
Stroop, J.R. (1935). Studies of interference and serial verbal reactions. Journal of Experimental Psychology, 18, 643662.
Sumowski, J.F., Wylie, G.R., Chiaravalloti, N., DeLuca, J. (2010). Intellectual enrichment lessens the effect of brain atrophy on learning and memory in multiple sclerosis. Neurology, 74(24), 19421945. doi:74/24/1942 [pii] 10.1212/WNL.0b013e3181e396be
Tabrizi, S.J., Scahill, R.I., Durr, A., Roos, R.A., Leavitt, B.R., Jones, R., … TRACK-HD Investigators. (2011). Biological and clinical changes in premanifest and early stage Huntington's disease in the TRACK-HD study: The 12-month longitudinal analysis. Lancet Neurology, 10, 3142.
Teipel, S.J., Meindl, T., Wagner, M., Kohl, T., Burger, K., Reiser, M.F., Hampel, H. (2009). White matter microstructure in relation to education in aging and Alzheimer's disease. Journal of Alzheimers Disease, 17(3), 571583. doi:J4213346J64N534X [pii] 10.3233/JAD-2009-1077
Zhang, Y., Long, J.D., Mills, J.A., Warner, J.H., Lu, W., Paulsen, J.S. (2011). Indexing disease progression at study entry with individuals at-risk for Huntington disease. American Journal of Medical Genetetics Part B: Neuropsychiatric Genetics, 156B(7), 751763. doi:10.1002/ajmg.b.31232

Keywords

Related content

Powered by UNSILO

Cognitive Reserve and Brain Reserve in Prodromal Huntington's Disease

  • Aaron Bonner-Jackson (a1), Jeffrey D. Long (a2), Holly Westervelt (a3) (a4), Geoffrey Tremont (a3) (a4), Elizabeth Aylward (a5), Jane S. Paulsen (a2) and The PREDICT-HD Investigators and Coordinators of the Huntington Study Group...

Metrics

Altmetric attention score

Full text views

Total number of HTML views: 0
Total number of PDF views: 0 *
Loading metrics...

Abstract views

Total abstract views: 0 *
Loading metrics...

* Views captured on Cambridge Core between <date>. This data will be updated every 24 hours.

Usage data cannot currently be displayed.