[Skip to Content]
Access to paid content on this site is currently suspended due to excessive activity being detected from your IP address 35.172.195.82. Please contact the publisher to request reinstatement.
[Skip to Content Landing]

Association of Retinal Nerve Fiber Layer Thinning With Current and Future Cognitive DeclineA Study Using Optical Coherence Tomography

Educational Objective
To determine whether changes in the retinal nerve fiber layer (RNFL) are associated with current or future cognitive function.
1 Credit CME
Key Points

Question  Are changes in the retinal nerve fiber layer (RNFL) associated with current or future cognitive function in a large community cohort of healthy participants?

Findings  In this community-based cohort study of more than 500 000 UK residents aged 40 to 69 years who received optical coherence tomography measurements of RNFL thickness and cognitive testing, there was a significant association between RNFL thickness and cognitive function at baseline. Furthermore, those with a thinner RNFL were twice as likely to experience cognitive decline over 3 years.

Meaning  A thinner RNFL is associated with worse current cognitive function and may have a role in screening those at risk of future cognitive decline.

Abstract

Importance  Identifing potential screening tests for future cognitive decline is a priority for developing treatments for and the prevention of dementia.

Objective  To examine the potential of retinal nerve fiber layer (RNFL) thickness measurement in identifying those at greater risk of cognitive decline in a large community cohort of healthy people.

Design, Setting, and Participants  UK Biobank is a prospective, multicenter, community-based study of UK residents aged 40 to 69 years at enrollment who underwent baseline retinal optical coherence tomography imaging, a physical examination, and a questionnaire. The pilot study phase was conducted from March 2006 to June 2006, and the main cohort underwent examination for baseline measures from April 2007 to October 2010. Four basic cognitive tests were performed at baseline, which were then repeated in a subset of participants approximately 3 years later. We analyzed eyes with high-quality optical coherence tomography images, excluding those with eye disease or vision loss, a history of ocular or neurological disease, or diabetes. We explored associations between RNFL thickness and cognitive function using multivariable logistic regression modeling to control for demographic as well as physiologic and ocular variation.

Main Outcomes and Measures  Odds ratios (ORs) for cognitive performance in the lowest fifth percentile in at least 2 of 4 cognitive tests at baseline, or worsening results on at least 1 cognitive test at follow-up. These analyses were adjusted for age, sex, race/ethnicity, height, refraction, intraocular pressure, education, and socioeconomic status.

Results  A total of 32 038 people were included at baseline testing, for whom the mean age was 56.0 years and of whom 17 172 (53.6%) were women. A thinner RNFL was associated with worse cognitive performance on baseline assessment. A multivariable regression controlling for potential confounders showed that those in the thinnest quintile of RNFL were 11% more likely to fail at least 1 cognitive test (95% CI, 2.0%-2.1%; P = .01). Follow-up cognitive tests were performed for 1251 participants (3.9%). Participants with an RNFL thickness in the 2 thinnest quintiles were almost twice as likely to have at least 1 test score be worse at follow-up cognitive testing (quintile 1: OR, 1.92; 95% CI, 1.29-2.85; P < .001; quintile 2: OR, 2.08; 95% CI, 1.40-3.08; P < .001).

Conclusions and Relevance  A thinner RNFL is associated with worse cognitive function in individuals without a neurodegenerative disease as well as greater likelihood of future cognitive decline. This preclinical observation has implications for future research, prevention, and treatment of dementia.

Sign in to take quiz and track your certificates

Buy This Activity

JN Learning™ is the home for CME and MOC from the JAMA Network. Search by specialty or US state and earn AMA PRA Category 1 CME Credit™ from articles, audio, Clinical Challenges and more. Learn more about CME/MOC

Article Information

Accepted for Publication: April 27, 2018.

Corresponding Author: Paul J. Foster, PhD, UCL Institute of Ophthalmology, 11-43 Bath St, London EC1V 9EL, England (p.foster@ucl.ac.uk).

Published Online: June 25, 2018. doi:10.1001/jamaneurol.2018.1578

Author Contributions: Dr Ko had full access to all the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis. Drs Patel and Foster contributed equally to the authorship of this article.

Concept and design: Ko, Gallacher, Khaw, Reisman, Foster, Patel.

Acquisition, analysis, or interpretation of data: Ko, Muthy, Gallacher, Sudlow, Rees, Yang, Keane, Petzold, Reisman, Strouthidis, Foster, Patel.

Drafting of the manuscript: Ko, Muthy, Gallacher, Rees, Yang, Foster, Patel.

Critical revision of the manuscript for important intellectual content: Ko, Muthy, Gallacher, Sudlow, Rees, Keane, Petzold, Khaw, Reisman, Strouthidis, Foster, Patel.

Statistical analysis: Ko, Gallacher, Rees, Reisman, Foster.

Obtained funding: Ko, Sudlow, Khaw, Foster, Patel.

Administrative, technical, or material support: Ko, Muthy, Sudlow, Rees, Keane, Khaw, Reisman, Foster.

Supervision: Petzold, Reisman, Strouthidis, Foster, Patel.

Conflict of Interest Disclosures: Dr Ko receives grant support from University College of London (UCL). Ms Muthy receives personal fees from UCL. Prof Sudlow is chief scientist at UK Biobank. Prof Rees receives grant support from Wellcome Trust and personal fees from Google DeepMind. Dr Yang and Mr Reisman are employed by Topcon Medical Systems Inc. Dr Keane receives personal fees from Allergan, Topcon, Heidelberg Engineering, Haag-Streit, Novartis, Bayer, Optos, and DeepMind as well as grant support from a Clinician Scientist award (CS-2014-14-023) from the National Institute for Health Research (NIHR). Dr Petzold receives personal fees and grant support from Novartis and is a member of the steering committee of the Optical Coherence Tomography Trial in Multiple Sclerosis (OCTiMS), which is sponsored by Novartis and for which he has not received honoraria Prof Foster receives personal fees from Allergan, Carl Zeiss, Google/DeepMind, and Santen; grant support from Alcon, and support from the Richard Desmond Charitable Trust, via Fight for Sight, London. Dr Patel receives grant support from Topcon Medical Systems Inc. Prof Khaw is supported in part by the Helen Hamlyn Trust. No other disclosures are reported.

Funding/Support: This analysis was supported by the Eranda Foundation via the International Glaucoma Association in the design and conduct of the study. The UCL Overseas Research Scholarship and Graduate Research Scholarship programs provided scholarship support for Dr Ko. Ms Muthy, Drs Strouthidis and Patel and Profs Khaw and Foster received salary support from the NIHR Biomedical Research Centres at Moorfields Eye Hospital NHS Foundation Trust. Dr Foster received support from the Richard Desmond Charitable Trust via Fight for Sight, London. UK Biobank Eye and Vision Consortium is supported by grants from Moorfields Eye Charity, the NIHR Biomedical Research Centre at Moorfields Eye Hospital NHS Foundation Trust, and the UCL Institute of Ophthalmology and the Alcon Research Institute.

Role of the Funder/Sponsor: No funders had a direct role in the collection, management, analysis, or interpretation of the data; preparation, review, or approval of the manuscript; nor in the decision to submit the manuscript for publication.

UK Biobank Eye & Vision Consortium: The UK Biobank Eye & Vision Consortium members are Tariq Aslam, PhD, Manchester University, Sarah A. Barman, PhD, Kingston University, Jenny H. Barrett, PhD, University of Leeds, Paul Bishop, PhD, Manchester University, Peter Blows, BSc, NIHR Biomedical Research Centre, Catey Bunce, DSc, King’s College London, Roxana O. Carare, PhD, University of Southampton, Usha Chakravarthy, FRCOphth, Queens University Belfast, Michelle Chan, FRCOphth, NIHR Biomedical Research Centre, Sharon Y.L. Chua, PhD, NIHR Biomedical Research Centre, David P. Crabb, PhD, UCL, Philippa M. Cumberland, MSc, UCL Great Ormond Street Institute of Child Health, Alexander Day, PhD, NIHR Biomedical Research Centre, Parul Desai, PhD, NIHR Biomedical Research Centre, Bal Dhillon, FRCOphth, University of Edinburgh, Andrew D. Dick, FRCOphth, University of Bristol, Cathy Egan, FRCOphth, NIHR Biomedical Research Centre, Sarah Ennis, PhD, University of Southampton, Paul Foster, PhD, NIHR Biomedical Research Centre, Marcus Fruttiger, PhD, NIHR Biomedical Research Centre, John E.J. Gallacher, PhD, University of Oxford, David F. GARWAY-HEATH FRCOphth- NIHR Biomedical Research Centre, Jane Gibson, PhD, University of Southampton, Dan Gore, FRCOphth, NIHR Biomedical Research Centre, Jeremy A. Guggenheim, PhD, Cardiff University, Chris J. Hammond, FRCOphth, King's College London, Alison Hardcastle, PhD, NIHR Biomedical Research Centre, Simon P. Harding, MD, University of Liverpool, Ruth E. Hogg, PhD, Queens University Belfast, Pirro Hysi, PhD, King's College London, Pearse A. Keane, MD, NIHR Biomedical Research Centre, Sir Peng T. Khaw, PhD, NIHR Biomedical Research Centre, Anthony P. Khawaja, DPhil, NIHR Biomedical Research Centre, Gerassimos Lascaratos, PhD, NIHR Biomedical Research Centre, Andrew J. Lotery, MD, University of Southampton, Tom Macgillivray, PhD, University of Edinburgh, Sarah Mackie, PhD, University of Leeds, Keith Martin, FRCOphth, University of Cambridge, Michelle McGaughey, Queen’s University Belfast, Bernadette McGuinness, PhD, Queen’s University Belfast, Gareth J. McKay, PhD, Queen's University Belfast, Martin McKibbin, FRCOphth, Leeds Teaching HospitalsNHS Trust, Danny Mitry, PhD, NIHR Biomedical Research Centre, Tony Moore, FRCOphth, NIHR Biomedical Research Centre, James E. Morgan, DPhil, Cardiff University, Zaynah A. Muthy, BSc, NIHR Biomedical Research Centre, Eoin O’Sullivan, MD, King's College Hospital NHS Foundation Trust, Chris G. Owen, PhD, University of London, Praveen Patel, FRCOphth, NIHR Biomedical Research Centre, Euan Paterson, BSc, Queens University Belfast, Tunde Peto, PhD, Queen's University Belfast, Axel Petzold, PhD, UCL, Jugnoo S. Rahi, PhD, UCL Great Ormond Street Institute of Child Health, Alicja R. Rudnikca, PhD, University of London, Jay Self, PhD, University of Southampton, Sobha Sivaprasad, FRCOphth, NIHR Biomedical Research Centre, David Steel, FRCOphth, Newcastle University, Irene Stratton, MSc, Gloucestershire HospitalsNHS Foundation Trust, Nicholas Strouthidis, PhD, NIHR Biomedical Research Centre, Cathie Sudlow, DPhil, University of Edinburgh, Dhanes Thomas, FRCOphth, NIHR Biomedical Research Centre, Emanuele Trucco, PhD, University of Dundee, Adnan Tufail, FRCOphth, NIHR Biomedical Research Centre, Veronique Vitart, PhD, University of Edinburgh, Stephen A. Vernon, DM, Nottingham University HospitalsNHS Trust, Ananth C. Viswanathan, FRCOphth, NIHR Biomedical Research Centre, Cathy Williams, PhD, University of Bristol, Katie Williams, PhD, King's College London, Jayne V. Woodside, MRCOphth, PhD, Queen's University Belfast, Max M. Yates, PhD, University of East Anglia, Jennifer Yip, PhD, University of Cambridge, and Yalin Zheng, PhD, University of Liverpool.

Disclaimer: The views expressed in this publication are those of the author(s) and not necessarily those of the National Health Service, the NIHR, or the Department of Health.

Additional Contributions: We thank the UK Department of Health for providing financial support through an award from the NIHR to Moorfields Eye Hospital NHS Foundation Trust and the UCL Institute of Ophthalmology for a Biomedical Research Centre for Ophthalmology. We also thank Kay-Tee Khaw, PhD, University of Cambridge, for providing analytic advice. No individuals were compensated for their contributions.

References
1.
GBD 2015 Neurological Disorders Collaborator Group.  Global, regional, and national burden of neurological disorders during 1990-2015: a systematic analysis for the Global Burden of Disease Study 2015.  Lancet Neurol. 2017;16(11):877-897. doi:10.1016/S1474-4422(17)30299-5PubMedGoogle ScholarCrossref
2.
Saint Martin  M, Sforza  E, Barthélémy  JC,  et al; PROOF group study.  Long-lasting active lifestyle and successful cognitive aging in a healthy elderly population: the PROOF cohort.  Rev Neurol (Paris). 2017;173(10):637-644. doi:10.1016/j.neurol.2017.05.009PubMedGoogle ScholarCrossref
3.
Mormino  EC, Betensky  RA, Hedden  T,  et al.  Synergistic effect of β-amyloid and neurodegeneration on cognitive decline in clinically normal individuals.  JAMA Neurol. 2014;71(11):1379-1385. doi:10.1001/jamaneurol.2014.2031PubMedGoogle ScholarCrossref
4.
Wirth  M, Villeneuve  S, Haase  CM,  et al.  Associations between Alzheimer disease biomarkers, neurodegeneration, and cognition in cognitively normal older people.  JAMA Neurol. 2013;70(12):1512-1519.PubMedGoogle Scholar
5.
Bateman  RJ, Xiong  C, Benzinger  TL,  et al; Dominantly Inherited Alzheimer Network.  Clinical and biomarker changes in dominantly inherited Alzheimer’s disease.  N Engl J Med. 2012;367(9):795-804. doi:10.1056/NEJMoa1202753PubMedGoogle ScholarCrossref
6.
Hebert  LE, Weuve  J, Scherr  PA, Evans  DA.  Alzheimer disease in the United States (2010-2050) estimated using the 2010 census.  Neurology. 2013;80(19):1778-1783. doi:10.1212/WNL.0b013e31828726f5PubMedGoogle ScholarCrossref
7.
Hebert  LE, Scherr  PA, Bienias  JL, Bennett  DA, Evans  DA.  Alzheimer disease in the US population: prevalence estimates using the 2000 census.  Arch Neurol. 2003;60(8):1119-1122. doi:10.1001/archneur.60.8.1119PubMedGoogle ScholarCrossref
8.
Brookmeyer  R, Johnson  E, Ziegler-Graham  K, Arrighi  HM.  Forecasting the global burden of Alzheimer’s disease.  Alzheimers Dement. 2007;3(3):186-191. doi:10.1016/j.jalz.2007.04.381PubMedGoogle ScholarCrossref
9.
Huang  D, Swanson  EA, Lin  CP,  et al.  Optical coherence tomography.  Science. 1991;254(5035):1178-1181. doi:10.1126/science.1957169PubMedGoogle ScholarCrossref
10.
Yang  Q, Reisman  CA, Wang  Z,  et al.  Automated layer segmentation of macular OCT images using dual-scale gradient information.  Opt Express. 2010;18(20):21293-21307. doi:10.1364/OE.18.021293PubMedGoogle ScholarCrossref
11.
Paquet  C, Boissonnot  M, Roger  F, Dighiero  P, Gil  R, Hugon  J.  Abnormal retinal thickness in patients with mild cognitive impairment and Alzheimer’s disease.  Neurosci Lett. 2007;420(2):97-99. doi:10.1016/j.neulet.2007.02.090PubMedGoogle ScholarCrossref
12.
Weil  RS, Schrag  AE, Warren  JD, Crutch  SJ, Lees  AJ, Morris  HR.  Visual dysfunction in Parkinson’s disease.  Brain. 2016;139(11):2827-2843. doi:10.1093/brain/aww175PubMedGoogle ScholarCrossref
13.
Moreno-Ramos  T, Benito-León  J, Villarejo  A, Bermejo-Pareja  F.  Retinal nerve fiber layer thinning in dementia associated with Parkinson’s disease, dementia with Lewy bodies, and Alzheimer’s disease.  J Alzheimers Dis. 2013;34(3):659-664.PubMedGoogle ScholarCrossref
14.
Cheung  CY, Ong  YT, Hilal  S,  et al.  Retinal ganglion cell analysis using high-definition optical coherence tomography in patients with mild cognitive impairment and Alzheimer’s disease.  J Alzheimers Dis. 2015;45(1):45-56.PubMedGoogle ScholarCrossref
15.
Garcia-Martin  ES, Rojas  B, Ramirez  AI,  et al.  Macular thickness as a potential biomarker of mild Alzheimer’s disease.  Ophthalmology. 2014;121(5):1149-1151.e3. doi:10.1016/j.ophtha.2013.12.023PubMedGoogle ScholarCrossref
16.
Coppola  G, Di Renzo  A, Ziccardi  L,  et al.  Optical coherence tomography in Alzheimer’s Disease: a meta-analysis.  PLoS One. 2015;10(8):e0134750. doi:10.1371/journal.pone.0134750PubMedGoogle ScholarCrossref
17.
van Koolwijk  LME, Despriet  DDG, Van Duijn  CM,  et al.  Association of cognitive functioning with retinal nerve fiber layer thickness.  Invest Ophthalmol Vis Sci. 2009;50(10):4576-4580. doi:10.1167/iovs.08-3181PubMedGoogle ScholarCrossref
18.
Khawaja  AP, Chan  MPY, Yip  JLY,  et al.  Retinal nerve Fiber layer measures and cognitive function in the EPIC-Norfolk cohort study.  Invest Ophthalmol Vis Sci. 2016;57(4):1921-1926. doi:10.1167/iovs.16-19067PubMedGoogle ScholarCrossref
19.
Shi  Z, Wu  Y, Wang  M,  et al.  Greater attenuation of retinal nerve fiber layer thickness in Alzheimer’s disease patients.  J Alzheimers Dis. 2014;40(2):277-283.PubMedGoogle ScholarCrossref
20.
Ko  F, Foster  PJ, Strouthidis  NG,  et al; UK Biobank Eye & Vision Consortium.  Associations with retinal pigment epithelium thickness measures in a large cohort: results from the UK Biobank.  Ophthalmology. 2017;124(1):105-117. doi:10.1016/j.ophtha.2016.07.033PubMedGoogle ScholarCrossref
21.
Patel  PJ, Foster  PJ, Grossi  CM,  et al; UK Biobank Eyes and Vision Consortium.  Spectral-domain optical coherence tomography imaging in 67 321 adults: associations with macular thickness in the UK Biobank study.  Ophthalmology. 2016;123(4):829-840. doi:10.1016/j.ophtha.2015.11.009PubMedGoogle ScholarCrossref
22.
Cruz-Herranz  A, Balk  LJ, Oberwahrenbrock  T,  et al; IMSVISUAL consortium.  The APOSTEL recommendations for reporting quantitative optical coherence tomography studies.  Neurology. 2016;86(24):2303-2309. doi:10.1212/WNL.0000000000002774PubMedGoogle ScholarCrossref
23.
Tewarie  P, Balk  L, Costello  F,  et al.  The OSCAR-IB consensus criteria for retinal OCT quality assessment.  PLoS One. 2012;7(4):e34823. doi:10.1371/journal.pone.0034823PubMedGoogle ScholarCrossref
24.
Hinton  DR, Sadun  AA, Blanks  JC, Miller  CA.  Optic-nerve degeneration in Alzheimer’s disease.  N Engl J Med. 1986;315(8):485-487. doi:10.1056/NEJM198608213150804PubMedGoogle ScholarCrossref
25.
Kesler  A, Vakhapova  V, Korczyn  AD, Naftaliev  E, Neudorfer  M.  Retinal thickness in patients with mild cognitive impairment and Alzheimer’s disease.  Clin Neurol Neurosurg. 2011;113(7):523-526. doi:10.1016/j.clineuro.2011.02.014PubMedGoogle ScholarCrossref
26.
Whitson  HE, Farsiu  S, Stinnett  S,  et al.  Retinal imaging biomarkers for early diagnosis of Alzheimer’s disease.  Invest Ophthalmol Vis Sci. 2015;56(7):389. http://iovs.arvojournals.org/article.aspx?articleid=2333793&resultClick=1Google Scholar
27.
Gao  L, Liu  Y, Li  X, Bai  Q, Liu  P.  Abnormal retinal nerve fiber layer thickness and macula lutea in patients with mild cognitive impairment and Alzheimer’s disease.  Arch Gerontol Geriatr. 2015;60(1):162-167. doi:10.1016/j.archger.2014.10.011PubMedGoogle ScholarCrossref
28.
Inzelberg  R, Ramirez  JA, Nisipeanu  P, Ophir  A.  Retinal nerve fiber layer thinning in Parkinson disease.  Vision Res. 2004;44(24):2793-2797. doi:10.1016/j.visres.2004.06.009PubMedGoogle ScholarCrossref
29.
Jonas  JB, Wang  YX, Wei  WB, Zhu  LP, Shao  L, Xu  L.  Cognitive function and subfoveal choroidal thickness: the Beijing Eye Study.  Ophthalmology. 2016;123(1):220-222. doi:10.1016/j.ophtha.2015.06.020PubMedGoogle ScholarCrossref
30.
Tilvis  RS, Kähönen-Väre  MH, Jolkkonen  J, Valvanne  J, Pitkala  KH, Strandberg  TE.  Predictors of cognitive decline and mortality of aged people over a 10-year period.  J Gerontol A Biol Sci Med Sci. 2004;59(3):268-274. doi:10.1093/gerona/59.3.M268PubMedGoogle ScholarCrossref
31.
Marquis  S, Moore  MM, Howieson  DB,  et al.  Independent predictors of cognitive decline in healthy elderly persons.  Arch Neurol. 2002;59(4):601-606. doi:10.1001/archneur.59.4.601PubMedGoogle ScholarCrossref
32.
Liew  G, Wong  TY, Mitchell  P, Cheung  N, Wang  JJ.  Retinopathy predicts coronary heart disease mortality.  Heart. 2009;95(5):391-394. doi:10.1136/hrt.2008.146670PubMedGoogle ScholarCrossref
33.
Curcio  CA, Drucker  DN.  Retinal ganglion cells in Alzheimer’s disease and aging.  Ann Neurol. 1993;33(3):248-257. doi:10.1002/ana.410330305PubMedGoogle ScholarCrossref
34.
Davies  DC, McCoubrie  P, McDonald  B, Jobst  KA.  Myelinated axon number in the optic nerve is unaffected by Alzheimer’s disease.  Br J Ophthalmol. 1995;79(6):596-600. doi:10.1136/bjo.79.6.596PubMedGoogle ScholarCrossref
35.
Parisi  V, Restuccia  R, Fattapposta  F, Mina  C, Bucci  MG, Pierelli  F.  Morphological and functional retinal impairment in Alzheimer’s disease patients.  Clin Neurophysiol. 2001;112(10):1860-1867. doi:10.1016/S1388-2457(01)00620-4PubMedGoogle ScholarCrossref
36.
Kergoat  H, Kergoat  MJ, Justino  L, Chertkow  H, Robillard  A, Bergman  H.  An evaluation of the retinal nerve fiber layer thickness by scanning laser polarimetry in individuals with dementia of the Alzheimer type.  Acta Ophthalmol Scand. 2001;79(2):187-191. doi:10.1034/j.1600-0420.2001.079002187.xPubMedGoogle ScholarCrossref
37.
Kergoat  H, Kergoat  MJ, Justino  L, Robillard  A, Bergman  H, Chertkow  H.  Normal optic nerve head topography in the early stages of dementia of the Alzheimer type.  Dement Geriatr Cogn Disord. 2001;12(6):359-363. doi:10.1159/000051281PubMedGoogle ScholarCrossref
38.
Ward  ME, Chen  R, Huang  HY,  et al.  Individuals with progranulin haploinsufficiency exhibit features of neuronal ceroid lipofuscinosis.  Sci Transl Med. 2017;9(385):eaah5642. doi:10.1126/scitranslmed.aah5642PubMedGoogle ScholarCrossref
39.
Hood  DC, Raza  AS.  On improving the use of OCT imaging for detecting glaucomatous damage.  Br J Ophthalmol. 2014;98(suppl 2):ii1-ii9. doi:10.1136/bjophthalmol-2014-305156PubMedGoogle ScholarCrossref
If you are not a JN Learning subscriber, you can either:
Subscribe to JN Learning for one year
Buy this activity
jn-learning_Modal_LoginSubscribe_Purchase
If you are not a JN Learning subscriber, you can either:
Subscribe to JN Learning for one year
Buy this activity
jn-learning_Modal_LoginSubscribe_Purchase
With a personal account, you can:
  • Access free activities and track your credits
  • Personalize content alerts
  • Customize your interests
  • Fully personalize your learning experience
Education Center Collection Sign In Modal Right

Name Your Search

Save Search
With a personal account, you can:
  • Track your credits
  • Personalize content alerts
  • Customize your interests
  • Fully personalize your learning experience
jn-learning_Modal_SaveSearch_NoAccess_Purchase

Lookup An Activity

or

My Saved Searches

You currently have no searches saved.

With a personal account, you can:
  • Access free activities and track your credits
  • Personalize content alerts
  • Customize your interests
  • Fully personalize your learning experience
Education Center Collection Sign In Modal Right
Topics
State Requirements