This study tested the hypothesis that frequent participation in cognitively-stimulating activities, specifically those related to playing games and puzzles, is beneficial to brain health and cognition among middle-aged adults at increased risk for Alzheimer’s disease (AD). Three hundred twenty-nine cognitively normal, middle-aged adults (age range, 43.2–73.8 years) enrolled in the Wisconsin Registry for Alzheimer’s Prevention (WRAP) participated in this study. They reported their current engagement in cognitive activities using a modified version of the Cognitive Activity Scale (CAS), underwent a structural MRI scan, and completed a comprehensive cognitive battery. FreeSurfer was used to derive gray matter (GM) volumes from AD-related regions of interest (ROIs), and composite measures of episodic memory and executive function were obtained from the cognitive tests. Covariate-adjusted least squares analyses were used to examine the association between the Games item on the CAS (CAS-Games) and both GM volumes and cognitive composites. Higher scores on CAS-Games were associated with greater GM volumes in several ROIs including the hippocampus, posterior cingulate, anterior cingulate, and middle frontal gyrus. Similarly, CAS-Games scores were positively associated with scores on the Immediate Memory, Verbal Learning & Memory, and Speed & Flexibility domains. These findings were not modified by known risk factors for AD. In addition, the Total score on the CAS was not as sensitive as CAS-Games to the examined brain and cognitive measures. For some individuals, participation in cognitive activities pertinent to game playing may help prevent AD by preserving brain structures and cognitive functions vulnerable to AD pathophysiology.
This is a preview of subscription content, log in to check access.
Buy single article
Instant access to the full article PDF.
Tax calculation will be finalised during checkout.
Subscribe to journal
Immediate online access to all issues from 2019. Subscription will auto renew annually.
Tax calculation will be finalised during checkout.
Alexander, G. E., Bergfield, K. L., Chen, K., Reiman, E. M., Hanson, K. D., Lin, L., et al. (2012). Gray matter network associated with risk for Alzheimer’s disease in young to middle-aged adults. Neurobiol Aging, 33(12), 2723–2732. doi:10.1016/j.neurobiolaging.2012.01.014.
Alzheimer’s Association. (2013). 2013 Alzheimer’s disease facts and figures. Alzheimers Dement, 9(2), 208–245. doi:10.1016/j.jalz.2013.02.003.
ASA-Metlife Foundation. (2006). Attitudes and awareness of brain health poll. San Francisco: American Society on Aging.
Blacker, D., Lee, H., Muzikansky, A., Martin, E. C., Tanzi, R., McArdle, J. J., et al. (2007). Neuropsychological measures in normal individuals that predict subsequent cognitive decline. Arch Neurol, 64(6), 862–871. doi:10.1001/archneur.64.6.862.
Carlson, M. C., Parisi, J. M., Xia, J., Xue, Q. L., Rebok, G. W., Bandeen-Roche, K., et al. (2012). Lifestyle activities and memory: variety may be the spice of life. The women’s health and aging study II. J Int Neuropsychol Soc, 18(2), 286–294. doi:10.1017/S135561771100169X.
CDC and the Alzheimer’s Association. (2007). The healthy brain initiative: a national public health road map to maintaining cognitive health. Chicago: Alzheimer’s Association.
Chen, P., Ratcliff, G., Belle, S. H., Cauley, J. A., DeKosky, S. T., & Ganguli, M. (2001). Patterns of cognitive decline in presymptomatic Alzheimer disease: a prospective community study. Arch Gen Psychiatry, 58(9), 853–858.
Chetelat, G., & Baron, J. C. (2003). Early diagnosis of Alzheimer's disease: contribution of structural neuroimaging. Neuroimage, 18(2), 525–541.
Chiang, G. C., Insel, P. S., Tosun, D., Schuff, N., Truran-Sacrey, D., Raptentsetsang, S., et al. (2011). Identifying cognitively healthy elderly individuals with subsequent memory decline by using automated MR temporoparietal volumes. Radiology, 259(3), 844–851. doi:10.1148/radiol.11101637.
Cohen, J., Cohen, P., West, S. G., & Aiken, L. S. (2003). Applied multiple regression/correlation analysis fot the behavioral sciences (3rd ed.). New Jersey: Lawrence Erlbaum Associates.
Cracchiolo, J. R., Mori, T., Nazian, S. J., Tan, J., Potter, H., & Arendash, G. W. (2007). Enhanced cognitive activity–over and above social or physical activity–is required to protect Alzheimer’s mice against cognitive impairment, reduce Abeta deposition, and increase synaptic immunoreactivity. Neurobiol Learn Mem, 88(3), 277–294. doi:10.1016/j.nlm.2007.07.007.
Crowe, M., Andel, R., Pedersen, N. L., Johansson, B., & Gatz, M. (2003). Does participation in leisure activities lead to reduced risk of Alzheimer’s disease? a prospective study of swedish twins. J Gerontol B Psychol Sci Soc Sci, 58(5), 249–255.
Dale, A. M., Fischl, B., & Sereno, M. I. (1999). Cortical surface-based analysis. I. segmentation and surface reconstruction. Neuroimage, 9(2), 179–194. doi:10.1006/nimg.1998.0395.
Dickerson, B. C., Stoub, T. R., Shah, R. C., Sperling, R. A., Killiany, R. J., Albert, M. S., et al. (2011). Alzheimer-signature MRI biomarker predicts AD dementia in cognitively normal adults. Neurology, 76(16), 1395–1402. doi:10.1212/WNL.0b013e3182166e96.
Fischl, B., Sereno, M. I., & Dale, A. M. (1999). Cortical surface-based analysis. II: Inflation, flattening, and a surface-based coordinate system. Neuroimage, 9(2), 195–207. doi:10.1006/nimg.1998.0396.
Hall, C. B., Lipton, R. B., Sliwinski, M., Katz, M. J., Derby, C. A., & Verghese, J. (2009). Cognitive activities delay onset of memory decline in persons who develop dementia. Neurology, 73(5), 356–361. doi:10.1212/WNL.0b013e3181b04ae3.
Jonaitis, E., La Rue, A., Mueller, K. D., Koscik, R. L., Hermann, B., & Sager, M. A. (2013). Cognitive activities and cognitive performance in middle-aged adults at risk for Alzheimer’s disease. Psychol Aging, 28(4), 1004–1014. doi:10.1037/a0034838.
Koscik, R. L., La Rue, A., Jonaitis, E., Okonkwo, O. C., Johnson, S. C., Bendlin, B. B., et al. (2014). Emergence of mild cognitive impairment in late-middle-aged adults in the Wisconsin Registry for Alzheimer’s Prevention. Dementia and Geriatric Cognitive Disorders, in press.
Landau, S. M., Marks, S. M., Mormino, E. C., Rabinovici, G. D., Oh, H., O’Neil, J. P., et al. (2012). Association of lifetime cognitive engagement and low beta-amyloid deposition. Arch Neurol, 69(5), 623–629. doi:10.1001/archneurol.2011.2748.
Leung, G. T., Fung, A. W., Tam, C. W., Lui, V. W., Chiu, H. F., Chan, W. M., et al. (2010). Examining the association between participation in late-life leisure activities and cognitive function in community-dwelling elderly Chinese in Hong Kong. Int Psychogeriatr, 22(1), 2–13. doi:10.1017/S1041610209991025.
Mora, F. (2013). Successful brain aging: plasticity, environmental enrichment, and lifestyle. Dialogues Clin Neurosci, 15(1), 45–52.
Okonkwo, O. C., Xu, G., Dowling, N. M., Bendlin, B. B., Larue, A., Hermann, B. P., et al. (2012). Family history of Alzheimer disease predicts hippocampal atrophy in healthy middle-aged adults. Neurology, 78(22), 1769–1776. doi:10.1212/WNL.0b013e3182583047.
Pillai, J. A., Hall, C. B., Dickson, D. W., Buschke, H., Lipton, R. B., & Verghese, J. (2011). Association of crossword puzzle participation with memory decline in persons who develop dementia. J Int Neuropsychol Soc, 17(6), 1006–1013. doi:10.1017/S1355617711001111.
Reinvang, I., Grambaite, R., & Espeseth, T. (2012). Executive dysfunction in MCI: subtype or early symptom. Int J Alzheimers Dis, 2012, 936272. doi:10.1155/2012/936272.
Reitan, R. M. (1958). Validity of the trail making test as an indicator of organic brain damage. Percept Mot Skills, 8, 271–276.
Sager, M. A., Hermann, B., & La Rue, A. (2005). Middle-aged children of persons with Alzheimer’s disease: APOE genotypes and cognitive function in the Wisconsin Registry for Alzheimer’s prevention. J Geriatr Psychiatry Neurol, 18(4), 245–249. doi:10.1177/0891988705281882.
Schmidt, M. (1996). Rey auditory verbal learning test: a handbook. Torrance: Western Psychological Services.
Sperling, R. A., Jack, C. R., Jr., & Aisen, P. S. (2011). Testing the right target and right drug at the right stage. Sci Transl Med, 3(111), 111 cm133. doi: 10.1126/scitranslmed.3002609
Stern, Y. (2012). Cognitive reserve in ageing and Alzheimer’s disease. Lancet Neurol, 11(11), 1006–1012. doi:10.1016/S1474-4422(12)70191-6.
Storandt, M., & Hill, R. D. (1989). Very mild senile dementia of the Alzheimer type. II. psychometric test performance. Arch Neurol, 46(4), 383–386.
Tabachnick, B. G., & Fidell, L. S. (2007). Using multivariate statistics (5th ed.). New York: Harper Collins.
Trenerry, M., Crosson, B., DeBoe, J., & Leber, L. (1989). Stroop neuropsychological screening test. Odessa: Psychological Assessment Resources, Inc.
Valenzuela, M. J., Sachdev, P., Wen, W., Chen, X., & Brodaty, H. (2008). Lifespan mental activity predicts diminished rate of hippocampal atrophy. PLoS One, 3(7), e2598. doi:10.1371/journal.pone.0002598.
Vemuri, P., Lesnick, T. G., Przybelski, S. A., Knopman, D. S., Roberts, R. O., Lowe, V. J., et al. (2012). Effect of lifestyle activities on Alzheimer disease biomarkers and cognition. Ann Neurol, 72(5), 730–738. doi:10.1002/ana.23665.
Verghese, J., Cuiling, W., Katz, M. J., Sanders, A., & Lipton, R. B. (2009). Leisure activities and risk of vascular cognitive impairment in older adults. J Geriatr Psychiatry Neurol, 22(2), 110–118. doi:10.1177/0891988709332938.
Wechsler, D. (1997). WAIS-III: Wechsler adult intelligence scale - (3rd ed.). San Antonio: The Psychological Corporation.
Wilson, R. S., Mendes De Leon, C. F., Barnes, L. L., Schneider, J. A., Bienias, J. L., Evans, D. A., et al. (2002). Participation in cognitively stimulating activities and risk of incident Alzheimer disease. JAMA, 287(6), 742–748.
Wilson, R. S., Barnes, L. L., Aggarwal, N. T., Boyle, P. A., Hebert, L. E., Mendes de Leon, C. F., et al. (2010). Cognitive activity and the cognitive morbidity of Alzheimer disease. Neurology, 75(11), 990–996. doi:10.1212/WNL.0b013e3181f25b5e.
We thank Caitlin A. Cleary, BSc, Sandra Harding, MS, Jennifer Bond, BA, and the WRAP psychometrists for assistance with study data collection. In addition, we gratefully acknowledge the support of researchers and staff at the Waisman Center, University of Wisconsin–Madison, where the brain scans took place. Finally, we thank participants in the Wisconsin Registry for Alzheimer’s Prevention for their continued dedication.
This work was supported by National Institute on Aging grants K23 AG045957 (OCO), R01 AG027161 (MAS), R01 AG021155 (SCJ), P50 AG033514 (SA), and P50 AG033514-S1 (OCO); by a Veterans Administration Merit Review Grant I01CX000165 (SCJ); and by a Clinical and Translational Science Award (UL1RR025011) to the University of Wisconsin, Madison. Portions of this research were supported by the Wisconsin Alumni Research Foundation, the Helen Bader Foundation, Northwestern Mutual Foundation, Extendicare Foundation, and from the Veterans Administration including facilities and resources at the Geriatric Research Education and Clinical Center of the William S. Middleton Memorial Veterans Hospital, Madison, WI.
Conflict of interest
The authors indicate no potential conflicts of interest.
About this article
Cite this article
Schultz, S.A., Larson, J., Oh, J. et al. Participation in cognitively-stimulating activities is associated with brain structure and cognitive function in preclinical Alzheimer’s disease. Brain Imaging and Behavior 9, 729–736 (2015). https://doi.org/10.1007/s11682-014-9329-5
- Preclinical Alzheimer’s disease
- Cognitive activity
- Brain imaging
- AD prevention