CoChat
Sign Up
Cited by 88Dementia and Cognitive Impairment ResearchAlzheimer's disease research and treatmentsCognitive Abilities and Testing

Association of Early-Life Cognitive Enrichment With Alzheimer Disease Pathological Changes and Cognitive Decline

Open access
Oveisgharan, Shahram, Wilson, Robert S., Yu, Lei, Schneider, Julie A., Bennett, David A.·2020·JAMA Neurology
DOI 10.1001/jamaneurol.2020.1941PMC PMC7325069
Open this paper in CoChat — free accountOpen PDF

Abstract

Importance: Indicators of early-life cognitive enrichment (ELCE) have been associated with slower cognitive decline and decreased dementia in late life. However, the mechanisms underlying this association have not been elucidated. Objective: To examine the association of ELCE with late-life Alzheimer disease (AD) and other common dementia-related pathological changes. Design, Setting, and Participants: This clinical-pathological community-based cohort study, the Rush Memory and Aging Project, followed up participants before death for a mean (SD) of 7.0 (3.8) years with annual cognitive and clinical assessments. From January 1, 1997, through June 30, 2019, 2044 participants enrolled, of whom 1018 died. Postmortem data were leveraged from 813 participants. Data were analyzed from April 12, 2019, to February 20, 2020. Exposures: Four indicators of ELCE (early-life socioeconomic status, availability of cognitive resources at 12 years of age, frequency of participation in cognitively stimulating activities, and early-life foreign language instruction) were obtained by self-report at the study baseline, from which a composite measure of ELCE was derived. Main Outcomes and Measures: A continuous global AD pathology score derived from counts of diffuse plaques, neuritic plaques, and neurofibrillary tangles. Results: The 813 participants included in the analysis had a mean (SD) age of 90.1 (6.3) years at the time of death, and 562 (69%) were women. In a linear regression model controlled for age at death, sex, and educational level, a higher level of ELCE was associated with a lower global AD pathology score (estimate, -0.057; standard error, 0.022; P = .01). However, ELCE was not associated with any other dementia-related pathological changes. In addition, a higher level of ELCE was associated with less cognitive decline (mean [SD], -0.13 [0.19] units per year; range, -1.74 to 0.85). An indirect effect through AD pathological changes constituted 20% of the association between ELCE and the rate of late-life cognitive decline, and 80% was a direct association. Conclusions and Relevance: These findings suggest that ELCE was associated with better late-life cognitive health, in part through an association with fewer AD pathological changes.

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Integrity signals

Registry

Crossref · 10.1001/jamaneurol.2020.1941

Cites

4 of 4 references verified0 citation errors · 0 not checkable

Statistics

Claims the paper makes

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

  • The beneficial association between early reading for pleasure and cognitive development may partly be due to cognitive enrichment.

    “This may partly be due to cognitive enrichment (Mather, 2020; Milgram, Siwak-Tapp, Araujo, & Head, 2006; Oveisgharan, Wilson, Yu, Schneider, & Bennett, 2020)”

    From Early-Initiated Childhood Reading for Pleasure: Associations with Better Cognitive Performance, Mental Well-being and Brain Structure in Young Adolescence (2024) · cites this paper as Oveisgharan, Wilson, Yu, Schneider, & Bennett, 2020

    The Assessment of ELCE section includes reading books at age 12 among cognitively stimulating activities, and the Discussion says early-life cognitive enrichment is hypothesized to support early-life cognitive development. The paper does not specifically examine reading for pleasure or test whether enrichment explains its association with cognitive development; its measured outcomes concern late-life cognition and Alzheimer disease pathology. (LLM, conf=0.83)

    Experimental — accuracy not yet measured

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

The self-check needs the paper’s full text.

Cites

Flagged first, then by citations

Research works printed but not linked: 37

  1. Bezerra AB, Coutinho ES, Barca ML, Engedal K, Engelhardt E, Laks J. School attainment in childhood is an independent risk factor of dementia in late life: results from a Brazilian sample. Int Psychogeriatr. 2012;24(1):55-61. doi:10.1017/ S1041610211001554 · DOI
  2. Kaplan GA, Turrell G, Lynch JW, Everson SA, Helkala EL, Salonen JT. Childhood socioeconomic position and cognitive function in adulthood. Int J Epidemiol. 2001;30(2):256-263. doi:10.1093/ ije/30.2.256 · DOI
  3. Snowdon DA, Kemper SJ, Mortimer JA, Greiner LH, Wekstein DR, Markesbery WR. Linguistic ability in early life and cognitive function and Alzheimer's disease in late life: findings from the Nun Study. JAMA. 1996;275(7):528-532. doi:10.1001/jama.1996. 03530310034029 · DOI · Paper page
  4. Field TS, Doubal FN, Johnson W, et al. Early life characteristics and late life burden of cerebral small vessel disease in the Lothian Birth Cohort 1936. Aging (Albany NY). 2016;8(9):2039-2061. doi:10. 18632/aging.101043 · DOI
  5. Ko K, Byun MS, Yi D, Lee JH, Kim CH, Lee DY. Early-life cognitive activity is related to reduced neurodegeneration in Alzheimer signature regions in late life. Front Aging Neurosci. 2018;10:70. doi:10. 3389/fnagi.2018.00070 · DOI
  6. Barnes LL, Wilson RS, de Leon CF, Bennett DA. The relation of lifetime cognitive activity and lifetime access to resources to late-life cognitive function in older African Americans. Neuropsychol Dev Cogn B Aging Neuropsychol Cogn. 2006;13 (3-4):516-528. doi:10.1080/138255890969519 · DOI
  7. Wilson RS, Boyle PA, Yang J, James BD, Bennett DA. Early life instruction in foreign language and music and incidence of mild cognitive impairment. Neuropsychology. 2015;29(2):292-302. doi:10.1037/ neu0000129 · DOI
  8. Wilson RS, Boyle PA, Yu L, Barnes LL, Schneider JA, Bennett DA. Life-span cognitive activity, neuropathologic burden, and cognitive aging. Neurology. 2013;81(4):314-321. doi:10.1212/WNL. 0b013e31829c5e8a · DOI
  9. Wilson RS, Scherr PA, Hoganson G, Bienias JL, Evans DA, Bennett DA. Early life socioeconomic status and late life risk of Alzheimer's disease. Neuroepidemiology. 2005;25(1):8-14. doi:10.1159/ 000085307 · DOI
  10. Bennett DA, Buchman AS, Boyle PA, Barnes LL, Wilson RS, Schneider JA. Religious Orders Study and Rush Memory and Aging Project. J Alzheimers Dis. 2018;64(s1):S161-S189. doi:10.3233/JAD-179939 · DOI · Paper page
  11. Uniform Law Commission. National Conference of Commissioners on Uniform State Laws. Uniform Anatomical Gift Act (2006). Published 2017. Accessed May 21, 2020. https://www.uniformlaws. org/HigherLogic/System/ DownloadDocumentFile.ashx?DocumentFileKey= 0e0c3a55-52cf-2082-704f-6185187a21fc& forceDialog=0
  12. Coste J, Bouée S, Ecosse E, Leplège A, Pouchot J. Methodological issues in determining the dimensionality of composite health measures using principal component analysis: case illustration and suggestions for practice. Qual Life Res. 2005;14(3): 641-654. doi:10.1007/s11136-004-1260-6 · DOI
  13. De Jager PL, Ma Y, McCabe C, et al. A multi-omic atlas of the human frontal cortex for aging and Alzheimer's disease research. Sci Data. 2018;5(1):180142. doi:10.1038/sdata.2018.142 · DOI · Paper page
  14. Bennett DA, Schneider JA, Wilson RS, Bienias JL, Arnold SE. Neurofibrillary tangles mediate the association of amyloid load with clinical Alzheimer disease and level of cognitive function. Arch Neurol. 2004;61(3):378-384. doi:10.1001/archneur.61.3.378 · DOI · Paper page
  15. Wilson RS, Beckett LA, Barnes LL, et al. Individual differences in rates of change in cognitive abilities of older persons. Psychol Aging. 2002;17 (2):179-193. doi:10.1037/0882-7974.17.2.179 · DOI · Paper page
  16. Wilson RS, Bienias JL, Berry-Kravis E, Evans DA, Bennett DA. The apolipoprotein E ε 2 allele and decline in episodic memory. J Neurol Neurosurg Psychiatry. 2002;73(6):672-677. doi:10.1136/jnnp.73.6.672 · DOI · Paper page
  17. Barnes LL, Leurgans S, Aggarwal NT, et al. Mixed pathology is more likely in black than white decedents with Alzheimer dementia. Neurology. 2015;85(6):528-534. doi:10.1212/WNL. 0000000000001834 · DOI · Paper page
  18. Wilson RS, Scherr PA, Schneider JA, Tang Y, Bennett DA. Relation of cognitive activity to risk of developing Alzheimer disease. Neurology. 2007;69 (20):1911-1920. doi:10.1212/01.wnl.0000271087. 67782.cb · DOI · Paper page
  19. Oveisgharan S, Buchman AS, Yu L, et al. APOE ε2ε4 genotype, incident AD and MCI, cognitive decline, and AD pathology in older adults. Neurology. 2018;90(24):e2127-e2134. doi:10.1212/WNL. 0000000000005677 · DOI · Paper page
  20. Richards M, James S-N, Sizer A, et al. Identifying the lifetime cognitive and socioeconomic antecedents of cognitive state: seven decades of follow-up in a British birth cohort study. BMJ Open. 2019;9(4):e024404. doi:10.1136/ bmjopen-2018-024404 · DOI
  21. Dekhtyar S, Wang HX, Fratiglioni L, Herlitz A. Childhood school performance, education and occupational complexity: a life-course study of dementia in the Kungsholmen Project. Int J Epidemiol. 2016;45(4):1207-1215. doi:10.1093/ije/dyw008 · DOI
  22. Russ TC, Hannah J, Batty GD, Booth CC, Deary IJ, Starr JM. Childhood cognitive ability and incident dementia: the 1932 Scottish Mental Survey cohort into their 10th decade. Epidemiology. 2017;28(3): 361-364. doi:10.1097/EDE.0000000000000626 · DOI
  23. Osler M, Christensen GT, Garde E, Mortensen EL, Christensen K. Cognitive ability in young adulthood and risk of dementia in a cohort of Danish men, brothers, and twins. Alzheimers Dement. 2017;13(12):1355-1363. doi:10.1016/j.jalz.2017.04.003 · DOI
  24. Morrissey TW, Hutchison L, Winsler A. Family income, school attendance, and academic achievement in elementary school. Dev Psychol. 2014;50(3):741-753. doi:10.1037/a0033848 · DOI
  25. Xu H, Yang R, Qi X, et al. Association of lifespan cognitive reserve indicator with dementia risk in the presence of brain pathologies. JAMA Neurol. 2019; (July). doi:10.1001/jamaneurol.2019.2455 · DOI
  26. Everson-Rose SA, Mendes de Leon CF, Bienias JL, Wilson RS, Evans DA. Early life conditions and cognitive functioning in later life. Am J Epidemiol. 2003;158(11):1083-1089. doi:10.1093/aje/kwg263 · DOI
  27. Staff RT, Hogan MJ, Whalley LJ. The influence of childhood intelligence, social class, education and social mobility on memory and memory decline in late life. Age Ageing. 2018;47(6):847-852. doi: 10.1093/ageing/afy111 · DOI
  28. Gow AJ, Johnson W, Mishra G, Richards M, Kuh D, Deary IJ; HALCyon Study Team. Is age kinder to the initially more able? yes, and no. Intelligence. 2012;40(1):49-59. doi:10.1016/j.intell.2011.10.007 · DOI
  29. Arenaza-Urquijo EM, Bejanin A, Gonneaud J, et al. Association between educational attainment and amyloid deposition across the spectrum from normal cognition to dementia: neuroimaging evidence for protection and compensation. Neurobiol Aging. 2017;59:72-79. doi:10.1016/j. neurobiolaging.2017.06.016 · DOI
  30. Lu K, Nicholas JM, Collins JD, et al. Cognition at age 70: life course predictors and associations with brain pathologies. Neurology. 2019;93(23):e2144- e2156. doi:10.1212/WNL.0000000000008534 · DOI
  31. Bouchard TJ Jr, McGue M. Familial studies of intelligence: a review. Science. 1981;212(4498): 1055-1059. doi:10.1126/science.7195071 · DOI · Paper page
  32. Hu Y-S, Long N, Pigino G, Brady ST, Lazarov O. Molecular mechanisms of environmental enrichment: impairments in Akt/GSK3β, neurotrophin-3 and CREB signaling. PLoS One. 2013;8(5):e64460. doi:10.1371/journal.pone. 0064460 · DOI
  33. Braak H, Del Tredici K. The preclinical phase of the pathological process underlying sporadic Alzheimer's disease. Brain. 2015;138(pt 10):2814- 2833. doi:10.1093/brain/awv236 · DOI · Paper page
  34. Lampit A, Hallock H, Valenzuela M. Computerized cognitive training in cognitively healthy older adults: a systematic review and meta-analysis of effect modifiers. PLoS Med. 2014;11 (11):e1001756. doi:10.1371/journal.pmed.1001756 · DOI
  35. Jaschke AC, Honing H, Scherder EJA. Longitudinal analysis of music education on executive functions in primary school children. Front Neurosci. 2018;12:103. doi:10.3389/fnins. 2018.00103 · DOI
  36. Daley M. Head start: program and legislative update. J Pediatr Nurs. 1999;14(3):186-188. doi:10. 1016/S0882-5963(99)80007-4 · DOI
  37. Phillips D, Gormley W, Anderson S. The effects of Tulsa's CAP Head Start program on middle-school academic outcomes and progress. Dev Psychol. 2016;52(8):1247-1261. doi:10.1037/ dev0000151 · DOI

Cited by

Sorted by citations

Authors
Oveisgharan, S., Wilson, R. S., Yu, L., Schneider, J. A., & Bennett, D. A.
Affiliations
Rush University Medical Center (US)
Corresponding author
Oveisgharan, Shahram
ORCID
Venue
JAMA Neurology
Publisher
American Medical Association (AMA)
Published
2020-10-01
Volume
77
Issue
10
Pages
1217
ISSN
2168-6149 (ISSN-L)
DOI
10.1001/jamaneurol.2020.1941
PMC
PMC7325069
OpenAlex
W3038092219
Cited by
88
References
4
Citations by year
2026: 8 · 2025: 16 · 2024: 6 · 2023: 19 · 2022: 27 · 2021: 10 · 2020: 2
FWCI
10.33
Type
journal article
Language
en
Open access
Locations
  • JAMA Neurology (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
Funders
National Institute on Aging (R01AG017917)
Topics
  • Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
  • Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
  • Social Sciences › Psychology › Experimental and Cognitive Psychology › Cognitive Abilities and Testing
Keywords
Alzheimer disease pathology, cognitive decline, neuritic plaques, neurofibrillary tangles, childhood socioeconomic status, cognitively stimulating activities, dementia risk factors, Rush Memory and Aging Project, postmortem neuropathology, educational attainment
MeSH terms
Aged, Aged, 80 and over, Alzheimer Disease, Child, Child Development, Cognition, Female, Follow-Up Studies, Humans, Male, Cohort Studies, Disease Progression, Cognitive Dysfunction

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review