{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,31]],"date-time":"2026-10-31T01:03:53Z","timestamp":1793408633834,"version":"4.5.0"},"reference-count":50,"publisher":"American Medical Association (AMA)","issue":"11","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JAMA Netw Open"],"abstract":"<jats:sec id=\"ab-zoi221176-4\"><jats:title>Importance<\/jats:title><jats:p>Studies investigating the association of threat-related and deprivation-related adverse childhood experiences (ACEs) with later-life cognitive decline are lacking.<\/jats:p><\/jats:sec><jats:sec id=\"ab-zoi221176-5\"><jats:title>Objectives<\/jats:title><jats:p>To evaluate the independent association of threat-related and deprivation-related ACEs with cognitive decline over time among middle-aged and older Chinese adults and to examine the modifying role of social isolation in such associations.<\/jats:p><\/jats:sec><jats:sec id=\"ab-zoi221176-6\"><jats:title>Design, Setting, and Participants<\/jats:title><jats:p>This prospective cohort study used cognitive data from the China Health and Retirement Longitudinal Study (CHARLS) baseline survey that was administered between June 1, 2011, and March 31, 2012, and the CHARLS follow-up survey administered between July 1 and September 30, 2015. The life history survey with information of ACEs was additionally administered between June 1 and December 31, 2014. Statistical analysis was performed from March 1 to July 31, 2022. The study population consisted of middle-aged and older adults (age range, 45-97 years) with complete data on ACEs and 2 cognitive assessments and without cognitive impairment at baseline.<\/jats:p><\/jats:sec><jats:sec id=\"ab-zoi221176-7\"><jats:title>Exposures<\/jats:title><jats:p>Five threat-related ACEs (ie, physical abuse, household substance abuse, domestic violence, unsafe neighborhood, and bullying) and 5 deprivation-related ACEs (ie, emotional neglect, household mental illness, incarcerated household member, parental separation or divorce, and parental death) before 17 years of age were queried by questionnaires. The cumulative scores of the 2 ACE dimensions were calculated and grouped into 3 categories as 0, 1, and 2 or more in main analyses.<\/jats:p><\/jats:sec><jats:sec id=\"ab-zoi221176-8\"><jats:title>Main Outcomes and Measures<\/jats:title><jats:p>Cognitive function was measured by episodic memory and executive function. Global cognition was further calculated as the total score of these 2 dimensions. The raw scores of each cognitive test were standardized to <jats:italic>z<\/jats:italic> scores using baseline means and SDs. Linear mixed-effects models were constructed to examine the association between 2 dimensions of ACEs and the rate of annual cognitive decline. The modifying role of baseline social isolation in such associations was assessed with 3-way interaction tests.<\/jats:p><\/jats:sec><jats:sec id=\"ab-zoi221176-9\"><jats:title>Results<\/jats:title><jats:p>Of the 6466 participants included in main analyses, 3301 (51.1%) were men and the mean (SD) age was 57.2 (8.3) years. Compared with no exposures, experience of 1 deprivation-related ACE was associated with faster cognitive decline in global cognition (\u03b2\u2009=\u2009\u22120.012 [95% CI, \u22120.022 to \u22120.002] SD\/y) and executive function (\u03b2\u2009=\u2009\u22120.010 [95% CI, \u22120.020 to \u22120.00002] SD\/y), whereas individuals with at least 2 childhood deprivations had faster cognitive declines in all cognitive tests (\u03b2\u2009=\u2009\u22120.035 [95% CI, \u22120.050 to \u22120.019] SD\/y for global cognition; \u03b2\u2009=\u2009\u22120.047 [95% CI, \u22120.068 to \u22120.025] SD\/y for episodic memory; \u03b2\u2009=\u2009\u22120.019 [95% CI, \u22120.034 to \u22120.004] SD\/y for executive function). However, such an association was not observed for threat-related ACEs. In addition, baseline social isolation was a significant modifier in the associations between deprivation-related ACEs and cognitive declines in global cognition (\u03b2\u2009<jats:italic>=<\/jats:italic>\u2009\u22120.033 [95% CI, \u22120.061 to \u22120.005] SD\/y; <jats:italic>P<\/jats:italic> =\u2009.02 for 3-way interaction) and executive function (\u03b2\u2009=\u2009\u22120.032 [95% CI, \u22120.059 to \u22120.005] SD\/y; <jats:italic>P<\/jats:italic> =\u2009.02 for 3-way interaction).<\/jats:p><\/jats:sec><jats:sec id=\"ab-zoi221176-10\"><jats:title>Conclusions and Relevance<\/jats:title><jats:p>Deprivation-related ACEs, but not threat-related ACEs, were associated with faster decline in later-life cognitive function, whereas social isolation could modify such detrimental impact. These findings highlight the potential benefits of promoting social integration in maintaining later-life cognitive function among individuals who have experienced childhood deprivation.<\/jats:p><\/jats:sec>","DOI":"10.1001\/jamanetworkopen.2022.41714","type":"journal-article","created":{"date-parts":[[2022,11,11]],"date-time":"2022-11-11T16:33:28Z","timestamp":1668184408000},"page":"e2241714","source":"Crossref","is-referenced-by-count":198,"title":["Association of Adverse Childhood Experiences and Social Isolation With Later-Life Cognitive Function Among Adults in China"],"prefix":"10.1001","volume":"5","author":[{"given":"Li","family":"Lin","sequence":"first","affiliation":[{"name":"Department of Epidemiology, School of Public Health, Sun Yat-sen University, Guangzhou, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bing","family":"Cao","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, Wu Tsai Neuroscience Institute, Stanford University School of Medicine, Stanford, California"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Weiqing","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Epidemiology, School of Public Health, Sun Yat-sen University, Guangzhou, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jinghua","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Biostatistics, School of Public Health, Sun Yat-sen University, Guangzhou, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuying","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Child Healthcare, Shenzhen Longhua Maternity and Child Healthcare Hospital, Shenzhen, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vivian Yawei","family":"Guo","sequence":"additional","affiliation":[{"name":"Department of Epidemiology, School of Public Health, Sun Yat-sen University, Guangzhou, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"10","published-online":{"date-parts":[[2022,11,11]]},"reference":[{"key":"zoi221176r1","doi-asserted-by":"publisher","DOI":"10.1016\/j.arr.2020.101174","article-title":"A research agenda for ageing in China in the 21st century (2nd edition): focusing on basic and translational research, long-term care, policy and social networks.","volume":"64","author":"Fang","year":"2020","journal-title":"Ageing Res Rev"},{"issue":"1","key":"zoi221176r2","doi-asserted-by":"publisher","first-page":"595","DOI":"10.1186\/s12877-021-02556-5","article-title":"Prevalence of cognitive impairment in Chinese older inpatients and its relationship with 1-year adverse health outcomes: a multi-center cohort study.","volume":"21","author":"Yuan","year":"2021","journal-title":"BMC Geriatr"},{"key":"zoi221176r3","doi-asserted-by":"publisher","first-page":"231","DOI":"10.1016\/j.dadm.2018.12.003","article-title":"What outcomes are important to patients with mild cognitive impairment or Alzheimer\u2019s disease, their caregivers, and health-care professionals? a systematic review.","volume":"11","author":"Tochel","year":"2019","journal-title":"Alzheimers Dement (Amst)"},{"issue":"12","key":"zoi221176r4","doi-asserted-by":"publisher","first-page":"e661","DOI":"10.1016\/S2468-2667(20)30185-7","article-title":"Prevalence, risk factors, and management of dementia and mild cognitive impairment in adults aged 60 years or older in China: a cross-sectional study.","volume":"5","author":"Jia","year":"2020","journal-title":"Lancet Public Health"},{"issue":"3","key":"zoi221176r5","doi-asserted-by":"publisher","first-page":"182","DOI":"10.7326\/0003-4819-153-3-201008030-00258","article-title":"Systematic review: factors associated with risk for and possible prevention of cognitive decline in later life.","volume":"153","author":"Plassman","year":"2010","journal-title":"Ann Intern Med"},{"issue":"2","key":"zoi221176r6","doi-asserted-by":"publisher","DOI":"10.1001\/jamanetworkopen.2019.20740","article-title":"Association between adverse childhood experiences and dementia in older Japanese adults.","volume":"3","author":"Tani","year":"2020","journal-title":"JAMA Netw Open"},{"key":"zoi221176r7","doi-asserted-by":"publisher","first-page":"351","DOI":"10.1016\/j.schres.2017.05.014","article-title":"Defining the impact of childhood adversities on cognitive deficits in psychosis: an exploratory analysis.","volume":"192","author":"Schalinski","year":"2018","journal-title":"Schizophr Res"},{"issue":"10","key":"zoi221176r8","doi-asserted-by":"publisher","DOI":"10.3390\/ijerph17103451","article-title":"Early-life conditions and cognitive function in middle-and old-aged Chinese adults: a longitudinal study.","volume":"17","author":"Yang","year":"2020","journal-title":"Int J Environ Res Public Health"},{"issue":"8","key":"zoi221176r9","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0256297","article-title":"The influence of childhood adversities on mid to late cognitive function: from the perspective of life course.","volume":"16","author":"Ma","year":"2021","journal-title":"PLoS One"},{"issue":"11","key":"zoi221176r10","doi-asserted-by":"publisher","first-page":"580","DOI":"10.1016\/j.tics.2014.09.001","article-title":"Dimensions of early experience and neural development: deprivation and threat.","volume":"18","author":"Sheridan","year":"2014","journal-title":"Trends Cogn Sci"},{"key":"zoi221176r11","doi-asserted-by":"publisher","first-page":"578","DOI":"10.1016\/j.neubiorev.2014.10.012","article-title":"Childhood adversity and neural development: deprivation and threat as distinct dimensions of early experience.","volume":"47","author":"McLaughlin","year":"2014","journal-title":"Neurosci Biobehav Rev"},{"issue":"11","key":"zoi221176r12","doi-asserted-by":"publisher","DOI":"10.1001\/jamapediatrics.2021.2511","article-title":"Associations of early-life threat and deprivation with executive functioning in childhood and adolescence: a systematic review and meta-analysis.","volume":"175","author":"Johnson","year":"2021","journal-title":"JAMA Pediatr"},{"issue":"3","key":"zoi221176r13","doi-asserted-by":"publisher","first-page":"929","DOI":"10.1017\/S0954579416000584","article-title":"Differential associations of threat and deprivation with emotion regulation and cognitive control in adolescence.","volume":"29","author":"Lambert","year":"2017","journal-title":"Dev Psychopathol"},{"key":"zoi221176r14","doi-asserted-by":"publisher","first-page":"80","DOI":"10.3389\/fnbeh.2019.00080","article-title":"Differential associations of deprivation and threat with cognitive control and fear conditioning in early childhood.","volume":"13","author":"Machlin","year":"2019","journal-title":"Front Behav Neurosci"},{"key":"zoi221176r15","doi-asserted-by":"publisher","DOI":"10.1017\/S1355617721001466","article-title":"Effects of early-life adversities on neuropsychiatric and executive functions in HIV-positive adults.","author":"Clark","year":"2022","journal-title":"J Int Neuropsychol Soc"},{"issue":"10","key":"zoi221176r16","doi-asserted-by":"publisher","DOI":"10.1001\/jamanetworkopen.2021.30143","article-title":"Adverse childhood experiences and subsequent chronic diseases among middle-aged or older adults in China and associations with demographic and socioeconomic characteristics.","volume":"4","author":"Lin","year":"2021","journal-title":"JAMA Netw Open"},{"issue":"2","key":"zoi221176r17","doi-asserted-by":"publisher","first-page":"216","DOI":"10.1037\/amp0000773","article-title":"Community-wide resilience mitigates adverse childhood experiences on adult and youth health, school\/work, and problem behaviors.","volume":"76","author":"Longhi","year":"2021","journal-title":"Am Psychol"},{"issue":"15","key":"zoi221176r18","doi-asserted-by":"publisher","first-page":"2628","DOI":"10.1017\/S0033291717001027","article-title":"Buffering effects of safe, supportive, and nurturing relationships among women with childhood histories of maltreatment.","volume":"47","author":"Jaffee","year":"2017","journal-title":"Psychol Med"},{"issue":"2","key":"zoi221176r19","doi-asserted-by":"publisher","first-page":"225","DOI":"10.1016\/j.amepre.2021.01.045","article-title":"Adverse childhood experiences and dementia: interactions with social capital in the Japan Gerontological Evaluation Study Cohort.","volume":"61","author":"Tani","year":"2021","journal-title":"Am J Prev Med"},{"issue":"9","key":"zoi221176r20","doi-asserted-by":"publisher","DOI":"10.1136\/bmjopen-2016-013228","article-title":"Adverse childhood experiences (ACEs) and later-life depression: perceived social support as a potential protective factor.","volume":"7","author":"Cheong","year":"2017","journal-title":"BMJ Open"},{"issue":"14","key":"zoi221176r21","doi-asserted-by":"publisher","first-page":"2414","DOI":"10.1017\/S0033291720001014","article-title":"Social isolation, rather than loneliness, is associated with cognitive decline in older adults: the China Health and Retirement Longitudinal Study.","volume":"51","author":"Yu","year":"2021","journal-title":"Psychol Med"},{"issue":"12","key":"zoi221176r22","doi-asserted-by":"publisher","first-page":"1233","DOI":"10.1016\/j.jagp.2020.08.005","article-title":"Social isolation and loneliness in older adults: review and commentary of a National Academies Report.","volume":"28","author":"Donovan","year":"2020","journal-title":"Am J Geriatr Psychiatry"},{"issue":"1","key":"zoi221176r23","doi-asserted-by":"publisher","first-page":"61","DOI":"10.1093\/ije\/dys203","article-title":"Cohort profile: the China Health and Retirement Longitudinal Study (CHARLS).","volume":"43","author":"Zhao","year":"2014","journal-title":"Int J Epidemiol"},{"issue":"6","key":"zoi221176r24","doi-asserted-by":"publisher","first-page":"492","DOI":"10.1016\/j.jalz.2009.02.007","article-title":"Telephone Interview for Cognitive Status: creating a crosswalk with the Mini-Mental State Examination.","volume":"5","author":"Fong","year":"2009","journal-title":"Alzheimers Dement"},{"issue":"3","key":"zoi221176r25","doi-asserted-by":"publisher","first-page":"525","DOI":"10.1037\/0882-7974.22.3.525","article-title":"Latent variable analyses of age trends of cognition in the Health and Retirement Study, 1992-2004.","volume":"22","author":"McArdle","year":"2007","journal-title":"Psychol Aging"},{"issue":"3","key":"zoi221176r26","doi-asserted-by":"publisher","first-page":"645","DOI":"10.1016\/j.clnu.2021.12.039","article-title":"Association of plasma uric acid levels with cognitive function among non-hyperuricemia adults: a prospective study.","volume":"41","author":"Huang","year":"2022","journal-title":"Clin Nutr"},{"issue":"4","key":"zoi221176r27","doi-asserted-by":"publisher","first-page":"245","DOI":"10.1016\/S0749-3797(98)00017-8","article-title":"Relationship of childhood abuse and household dysfunction to many of the leading causes of death in adults: the Adverse Childhood Experiences (ACE) Study.","volume":"14","author":"Felitti","year":"1998","journal-title":"Am J Prev Med"},{"key":"zoi221176r28","doi-asserted-by":"publisher","first-page":"270","DOI":"10.1016\/j.appdev.2019.03.004","article-title":"A dimensional risk approach to assessing early adversity in a national sample.","volume":"62","author":"Wolf","year":"2019","journal-title":"J Appl Dev Psychol"},{"issue":"6","key":"zoi221176r29","doi-asserted-by":"publisher","first-page":"1342","DOI":"10.1111\/jan.2009.65.issue-6","article-title":"Social isolation in older adults: an evolutionary concept analysis.","volume":"65","author":"Nicholson","year":"2009","journal-title":"J Adv Nurs"},{"key":"zoi221176r30","doi-asserted-by":"publisher","first-page":"71","DOI":"10.1016\/j.jad.2021.01.022","article-title":"Social isolation and depression onset among middle-aged and older adults in China: moderating effects of education and gender differences.","volume":"283","author":"Luo","year":"2021","journal-title":"J Affect Disord"},{"issue":"2","key":"zoi221176r31","doi-asserted-by":"publisher","first-page":"e164","DOI":"10.1212\/WNL.0000000000200583","article-title":"Associations of social isolation and loneliness with later dementia.","volume":"99","author":"Shen","year":"2022","journal-title":"Neurology"},{"issue":"11","key":"zoi221176r32","doi-asserted-by":"publisher","first-page":"1083","DOI":"10.1001\/jama.2022.1816","article-title":"Causal directed acyclic graphs.","volume":"327","author":"Lipsky","year":"2022","journal-title":"JAMA"},{"key":"zoi221176r33","doi-asserted-by":"publisher","first-page":"70","DOI":"10.1186\/1471-2288-8-70","article-title":"Reducing bias through directed acyclic graphs.","volume":"8","author":"Shrier","year":"2008","journal-title":"BMC Med Res Methodol"},{"issue":"4","key":"zoi221176r34","doi-asserted-by":"publisher","first-page":"377","DOI":"10.1002\/sim.v30.4","article-title":"Multiple imputation using chained equations: issues and guidance for practice.","volume":"30","author":"White","year":"2011","journal-title":"Stat Med"},{"issue":"5588","key":"zoi221176r35","doi-asserted-by":"publisher","first-page":"705","DOI":"10.1038\/264705a0","article-title":"Selective stabilisation of developing synapses as a mechanism for the specification of neuronal networks.","volume":"264","author":"Changeux","year":"1976","journal-title":"Nature"},{"issue":"4","key":"zoi221176r36","doi-asserted-by":"publisher","first-page":"1012","DOI":"10.1111\/j.1467-8624.1998.tb06158.x","article-title":"Environmental input and cognitive growth: a study using time-period comparisons.","volume":"69","author":"Huttenlocher","year":"1998","journal-title":"Child Dev"},{"issue":"4","key":"zoi221176r37","doi-asserted-by":"publisher","first-page":"239","DOI":"10.1177\/0963721416655883","article-title":"Beyond cumulative risk: a dimensional approach to childhood adversity.","volume":"25","author":"McLaughlin","year":"2016","journal-title":"Curr Dir Psychol Sci"},{"issue":"8","key":"zoi221176r38","doi-asserted-by":"publisher","first-page":"629","DOI":"10.1016\/j.biopsych.2013.08.016","article-title":"Widespread reductions in cortical thickness following severe early-life deprivation: a neurodevelopmental pathway to attention-deficit\/hyperactivity disorder.","volume":"76","author":"McLaughlin","year":"2014","journal-title":"Biol Psychiatry"},{"issue":"1","key":"zoi221176r39","doi-asserted-by":"publisher","first-page":"641","DOI":"10.1073\/pnas.1911264116","article-title":"Early childhood deprivation is associated with alterations in adult brain structure despite subsequent environmental enrichment.","volume":"117","author":"Mackes","year":"2020","journal-title":"Proc Natl Acad Sci U S A"},{"issue":"6","key":"zoi221176r40","doi-asserted-by":"publisher","first-page":"343","DOI":"10.1016\/S1474-4422(04)00767-7","article-title":"An active and socially integrated lifestyle in late life might protect against dementia.","volume":"3","author":"Fratiglioni","year":"2004","journal-title":"Lancet Neurol"},{"issue":"2","key":"zoi221176r41","doi-asserted-by":"publisher","first-page":"310","DOI":"10.1037\/0033-2909.98.2.310","article-title":"Stress, social support, and the buffering hypothesis.","volume":"98","author":"Cohen","year":"1985","journal-title":"Psychol Bull"},{"issue":"2","key":"zoi221176r42","doi-asserted-by":"publisher","first-page":"205","DOI":"10.1016\/0959-4388(95)80028-X","article-title":"Stress and cognitive function.","volume":"5","author":"McEwen","year":"1995","journal-title":"Curr Opin Neurobiol"},{"issue":"9","key":"zoi221176r43","doi-asserted-by":"publisher","first-page":"1905","DOI":"10.1007\/s00125-021-05496-2","article-title":"Social networks and type 2 diabetes: a narrative review.","volume":"64","author":"Schram","year":"2021","journal-title":"Diabetologia"},{"issue":"2","key":"zoi221176r44","doi-asserted-by":"publisher","first-page":"174","DOI":"10.1017\/S1041610209991189","article-title":"Systematic review of health behavioral risks and cognitive health in older adults.","volume":"22","author":"Lee","year":"2010","journal-title":"Int Psychogeriatr"},{"issue":"7","key":"zoi221176r45","doi-asserted-by":"publisher","first-page":"1080","DOI":"10.1016\/j.neubiorev.2009.11.002","article-title":"Episodic memory across the lifespan: the contributions of associative and strategic components.","volume":"34","author":"Shing","year":"2010","journal-title":"Neurosci Biobehav Rev"},{"key":"zoi221176r46","doi-asserted-by":"publisher","DOI":"10.1016\/j.chieco.2020.101541","article-title":"Late-life cognition: do childhood conditions play any role?","volume":"63","author":"Pan","year":"2020","journal-title":"China Econ Rev"},{"issue":"7","key":"zoi221176r47","doi-asserted-by":"publisher","first-page":"729","DOI":"10.1016\/j.chiabu.2003.08.009","article-title":"Assessing the reliability of retrospective reports of adverse childhood experiences among adult HMO members attending a primary care clinic.","volume":"28","author":"Dube","year":"2004","journal-title":"Child Abuse Negl"},{"issue":"4","key":"zoi221176r48","doi-asserted-by":"publisher","first-page":"1154","DOI":"10.1161\/HYPERTENSIONAHA.120.16149","article-title":"Longitudinal changes of input impedance, pulse wave velocity, and wave reflection in a middle-aged population: the Asklepios Study.","volume":"77","author":"Campos-Arias","year":"2021","journal-title":"Hypertension"},{"key":"zoi221176r49","doi-asserted-by":"publisher","first-page":"5","DOI":"10.1186\/s41512-018-0024-7","article-title":"Repeatedly measured predictors: a comparison of methods for prediction modeling.","volume":"2","author":"Welten","year":"2018","journal-title":"Diagn Progn Res"},{"issue":"1","key":"zoi221176r50","doi-asserted-by":"publisher","first-page":"33","DOI":"10.1016\/j.jaac.2015.10.012","article-title":"Child neglect and maltreatment and childhood-to-adulthood cognition and mental health in a prospective birth cohort.","volume":"55","author":"Geoffroy","year":"2016","journal-title":"J Am Acad Child Adolesc Psychiatry"}],"container-title":["JAMA Network Open"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/jamanetwork.com\/journals\/jamanetworkopen\/articlepdf\/2798318\/lin_2022_oi_221176_1667403063.77306.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,11,11]],"date-time":"2022-11-11T16:33:31Z","timestamp":1668184411000},"score":1,"resource":{"primary":{"URL":"https:\/\/jamanetwork.com\/journals\/jamanetworkopen\/fullarticle\/2798318"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,11,11]]},"references-count":50,"journal-issue":{"issue":"11","published-print":{"date-parts":[[2022,11,1]]}},"URL":"https:\/\/doi.org\/10.1001\/jamanetworkopen.2022.41714","relation":{},"ISSN":["2574-3805"],"issn-type":[{"value":"2574-3805","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,11,11]]}}}