{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,21]],"date-time":"2026-10-21T18:23:16Z","timestamp":1792606996851,"version":"4.5.0"},"reference-count":75,"publisher":"SAGE Publications","issue":"2","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JAD"],"published-print":{"date-parts":[[2023,1,17]]},"abstract":"<jats:p>Background: It is now acknowledged that Alzheimer\u2019s disease (AD) processes are present decades before the onset of clinical symptoms, but it remains unknown whether lifestyle factors can protect against these early AD processes in mid-life. Objective: We asked whether modifiable lifestyle activities impact cognition in middle-aged individuals who are cognitively healthy, but at risk for late life AD. Participants (40\u201359 years) completed cognitive and clinical assessments at baseline (N\u200a=\u200a206) and two years follow-up (N\u200a=\u200a174). Methods: Mid-life activities were measured with the Lifetime of Experiences Questionnaire. We assessed the impact of lifestyle activities, known risk factors for sporadic late-onset AD (Apolipoprotein E \u025b4 allele status, family history of dementia, and the Cardiovascular Risk Factors Aging and Dementia score), and their interactions on cognition. Results: More frequent engagement in physically, socially, and intellectually stimulating activities was associated with better cognition (verbal, spatial, and relational memory), at baseline and follow-up. Critically, more frequent engagement in these activities was associated with stronger cognition (verbal and visuospatial functions, and conjunctive short-term memory binding) in individuals with family history of dementia. Impaired visuospatial function is one of the earliest cognitive deficits in AD and has previously associated with increased AD risk in this cohort. Additionally, conjunctive memory functions have been found impaired in the pre-symptomatic stages of AD. Conclusion: These findings suggest that modifiable lifestyle activities offset cognitive decrements due to AD risk in mid-life and support the targeting of modifiable lifestyle activities for the prevention of AD.<\/jats:p>","DOI":"10.3233\/jad-220267","type":"journal-article","created":{"date-parts":[[2022,12,6]],"date-time":"2022-12-06T13:09:33Z","timestamp":1670332173000},"page":"833-846","source":"Crossref","is-referenced-by-count":14,"title":["Modifiable Lifestyle Activities Affect Cognition in Cognitively Healthy Middle-Aged Individuals at Risk for Late-Life Alzheimer\u2019s Disease"],"prefix":"10.1177","volume":"91","author":[{"given":"Amy","family":"Heneghan","sequence":"first","affiliation":[{"name":"Trinity College Institute of Neuroscience, School of Psychology, Trinity College Dublin, Dublin, Ireland"},{"name":"Global Brain Health Institute, Trinity College Dublin, Dublin, Ireland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Feng","family":"Deng","sequence":"additional","affiliation":[{"name":"Trinity College Institute of Neuroscience, School of Psychology, Trinity College Dublin, Dublin, Ireland"},{"name":"Global Brain Health Institute, Trinity College Dublin, Dublin, Ireland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katie","family":"Wells","sequence":"additional","affiliation":[{"name":"Edinburgh Dementia Prevention, University of Edinburgh, Edinburgh, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karen","family":"Ritchie","sequence":"additional","affiliation":[{"name":"Edinburgh Dementia Prevention, University of Edinburgh, Edinburgh, UK"},{"name":"INSERM and University of Montpellier, Montpellier, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Graciela","family":"Muniz-Terrera","sequence":"additional","affiliation":[{"name":"Edinburgh Dementia Prevention, University of Edinburgh, Edinburgh, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Craig W.","family":"Ritchie","sequence":"additional","affiliation":[{"name":"Edinburgh Dementia Prevention, University of Edinburgh, Edinburgh, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brian","family":"Lawlor","sequence":"additional","affiliation":[{"name":"Trinity College Institute of Neuroscience, School of Psychology, Trinity College Dublin, Dublin, Ireland"},{"name":"Global Brain Health Institute, Trinity College Dublin, Dublin, Ireland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lorina","family":"Naci","sequence":"additional","affiliation":[{"name":"Trinity College Institute of Neuroscience, School of Psychology, Trinity College Dublin, Dublin, Ireland"},{"name":"Global Brain Health Institute, Trinity College Dublin, Dublin, Ireland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"179","reference":[{"key":"10.3233\/JAD-220267_ref1","doi-asserted-by":"crossref","first-page":"207","DOI":"10.1016\/S1474-4422(12)70291-0","article-title":"Tracking pathophysiological processes in Alzheimer\u2019sdisease: An updated hypothetical model of dynamic biomarkers","volume":"12","author":"Jack","year":"2013","journal-title":"Lancet Neurol"},{"key":"10.3233\/JAD-220267_ref2","doi-asserted-by":"crossref","first-page":"122","DOI":"10.1016\/j.trci.2015.06.004","article-title":"Is late-onset Alzheimer\u2019s disease really a disease of midlife?","volume":"1","author":"Ritchie","year":"2015","journal-title":"Alzheimers Dement (N Y)"},{"key":"10.3233\/JAD-220267_ref3","first-page":"348","article-title":"The Scottish Brain Health Service Model: Rationale and scientific basis for a national care pathway of brain healthservices in Scotland","volume":"9","author":"Ritchie","year":"2022","journal-title":"J Prev Alzheimers Dis"},{"key":"10.3233\/JAD-220267_ref4","doi-asserted-by":"crossref","first-page":"413","DOI":"10.1016\/S0140-6736(20)30367-6","article-title":"Dementiaprevention, intervention, and care: 2020 report of the Lancet Commission","volume":"396","author":"Livingston","year":"2020","journal-title":"Lancet"},{"key":"10.3233\/JAD-220267_ref5","doi-asserted-by":"crossref","first-page":"275","DOI":"10.3389\/fnagi.2018.00275","article-title":"Healthy aging and dementia: Two roads diverging in midlife?","volume":"10","author":"Irwin","year":"2018","journal-title":"Front Aging Neurosci"},{"key":"10.3233\/JAD-220267_ref6","doi-asserted-by":"crossref","first-page":"20","DOI":"10.1177\/0165025414533223","article-title":"Midlife as a pivotal period in the life course: Balancing growth and decline at the crossroads of youth and old age","volume":"39","author":"Lachman","year":"2015","journal-title":"Int J Behav Dev"},{"key":"10.3233\/JAD-220267_ref7","doi-asserted-by":"crossref","first-page":"1443","DOI":"10.1001\/jama.2017.3090","article-title":"Association between midlife vascular risk factors and estimated brain amyloid deposition","volume":"317","author":"Gottesman","year":"2017","journal-title":"JAMA"},{"key":"10.3233\/JAD-220267_ref8","doi-asserted-by":"crossref","first-page":"960","DOI":"10.1097\/NEN.0b013e318232a379","article-title":"Stages of the pathologic process in Alzheimer disease: Age categories from 1 to 100 years","volume":"70","author":"Braak","year":"2011","journal-title":"J Neuropathol Exp Neurol"},{"key":"10.3233\/JAD-220267_ref9","doi-asserted-by":"crossref","first-page":"239","DOI":"10.1007\/BF00308809","article-title":"Neuropathological stageing of Alzheimer-related changes","volume":"82","author":"Braak","year":"1991","journal-title":"Acta Neuropathol"},{"key":"10.3233\/JAD-220267_ref10","doi-asserted-by":"crossref","first-page":"eabj2511","DOI":"10.1126\/scitranslmed.abj2511","article-title":"and neuropathologydata support locus coeruleus integrity as indicator of Alzheimer\u2019sdisease pathology and cognitive decline","volume":"13","author":"Jacobs","year":"2021","journal-title":"Sci Transl Med"},{"key":"10.3233\/JAD-220267_ref11","doi-asserted-by":"crossref","first-page":"115","DOI":"10.1002\/alz.12192","article-title":"Hypothesis: Tau pathology is an initiating factor in sporadicAlzheimer\u2019s disease","volume":"17","author":"Arnsten","year":"2021","journal-title":"Alzheimers Dement"},{"key":"10.3233\/JAD-220267_ref12","doi-asserted-by":"crossref","first-page":"25","DOI":"10.3389\/fnins.2018.00025","article-title":"Reconsideration of amyloid hypothesis and tau hypothesis in Alzheimer\u2019s disease","volume":"12","author":"Kametani","year":"2018","journal-title":"Front Neurosci"},{"key":"10.3233\/JAD-220267_ref13","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1007\/978-3-319-12679-1_1","article-title":"Neuroanatomy and pathology of sporadic Alzheimer\u2019s disease","volume":"215","author":"Braak","year":"2015","journal-title":"Adv Anat Embryol Cell Biol"},{"key":"10.3233\/JAD-220267_ref14","doi-asserted-by":"crossref","first-page":"205","DOI":"10.1016\/j.jalz.2018.09.001","article-title":"Multisite study of the relationships between antemortem [11C] PIB-PET Centiloid values and postmortem measures ofAlzheimer\u2019s disease neuropathology","volume":"15","author":"La Joie","year":"2019","journal-title":"Alzheimers Dement"},{"key":"10.3233\/JAD-220267_ref15","doi-asserted-by":"crossref","first-page":"1495","DOI":"10.1212\/01.WNL.0000063311.58879.01","article-title":"Tangle and neuron numbers, but not amyloid load, predict cognitive status in Alzheimer\u2019s disease","volume":"60","author":"Giannakopoulos","year":"2003","journal-title":"Neurology"},{"key":"10.3233\/JAD-220267_ref16","doi-asserted-by":"crossref","first-page":"298","DOI":"10.1007\/s11065-012-9193-2","article-title":"Family history and APOE-4 genetic risk in Alzheimer\u2019s disease","volume":"22","author":"Donix","year":"2012","journal-title":"Neuropsychol Rev"},{"key":"10.3233\/JAD-220267_ref17","doi-asserted-by":"crossref","first-page":"106","DOI":"10.1038\/nrneurol.2012.263","article-title":"Apolipoprotein E and Alzheimer disease: Risk, mechanisms and therapy","volume":"9","author":"Liu","year":"2013","journal-title":"Nat Rev Neurol"},{"key":"10.3233\/JAD-220267_ref18","doi-asserted-by":"crossref","first-page":"1452","DOI":"10.1038\/ng.2802","article-title":"Meta-analysis of 74,046 individuals identifies 11 new susceptibility loci for Alzheimer\u2019sdisease","volume":"45","author":"Lambert","year":"2013","journal-title":"Nat Genet"},{"key":"10.3233\/JAD-220267_ref19","doi-asserted-by":"crossref","first-page":"2325.e2317","DOI":"10.1016\/j.neurobiolaging.2011.01.001","article-title":"Structural brain changes in normal individuals with a maternal history of Alzheimer\u2019s","volume":"32","author":"Berti","year":"2011","journal-title":"Neurobiol Aging"},{"key":"10.3233\/JAD-220267_ref20","doi-asserted-by":"crossref","first-page":"250","DOI":"10.1002\/ajmg.b.32399","article-title":"Influence of family history of dementia in thedevelopment and progression of late-onset Alzheimer\u2019s disease","volume":"171B","author":"Scarabino","year":"2016","journal-title":"Am J Med Genet B Neuropsychiatr Genet"},{"key":"10.3233\/JAD-220267_ref21","doi-asserted-by":"crossref","first-page":"656","DOI":"10.1016\/j.jalz.2013.11.006","article-title":"Development and validation of a brief dementia screening indicator for primary care","volume":"10","author":"Barnes","year":"2014","journal-title":"Alzheimers Dement"},{"key":"10.3233\/JAD-220267_ref22","doi-asserted-by":"crossref","first-page":"234","DOI":"10.1002\/gps.4245","article-title":"Target riskfactors for dementia prevention: A systematic review and Delphi consensus study on the evidence fromobservational studies","volume":"30","author":"Deckers","year":"2015","journal-title":"Int J Geriatr Psychiatry"},{"key":"10.3233\/JAD-220267_ref23","doi-asserted-by":"crossref","first-page":"735","DOI":"10.1016\/S1474-4422(06)70537-3","article-title":"Risk score for the prediction of dementia risk in 20 years among middle aged people: A longitudinal, population-based study","volume":"5","author":"Kivipelto","year":"2006","journal-title":"Lancet Neurol"},{"key":"10.3233\/JAD-220267_ref24","doi-asserted-by":"crossref","first-page":"562","DOI":"10.1016\/j.jalz.2013.05.1772","article-title":"Midlife risk score for the prediction of dementia four decades later","volume":"10","author":"Exalto","year":"2014","journal-title":"Alzheimers Dement"},{"key":"10.3233\/JAD-220267_ref25","doi-asserted-by":"crossref","first-page":"e001893","DOI":"10.1136\/bmjopen-2012-001893","article-title":"The PREVENT study: A prospective cohort study to identify mid-life biomarkers of late-onset Alzheimer\u2019s disease","volume":"2","author":"Ritchie","year":"2012","journal-title":"BMJ Open"},{"key":"10.3233\/JAD-220267_ref26","doi-asserted-by":"crossref","first-page":"36","DOI":"10.1016\/j.neurobiolaging.2020.03.006","article-title":"Volumetric alterations in the hippocampal subfields of subjects at increased risk of dementia","volume":"91","author":"Dounavi","year":"2020","journal-title":"Neurobiol Aging"},{"key":"10.3233\/JAD-220267_ref27","doi-asserted-by":"crossref","first-page":"117749","DOI":"10.1016\/j.neuroimage.2021.117749","article-title":"Proximity to dementia onset and multi-modal neuroimaging changes: The prevent-dementia study","volume":"229","author":"Mak","year":"2021","journal-title":"Neuroimage"},{"key":"10.3233\/JAD-220267_ref28","doi-asserted-by":"crossref","first-page":"861","DOI":"10.1136\/jnnp-2020-322924","article-title":"Regional hyperperfusion in cognitively normal APOE \u025b4 allele carriers in mid-life: Analysis of ASL pilot data from the PREVENT-Dementia cohort","volume":"91","author":"McKiernan","year":"2020","journal-title":"J Neurol Neurosurg Psychiatry"},{"key":"10.3233\/JAD-220267_ref29","doi-asserted-by":"crossref","first-page":"902","DOI":"10.1016\/j.jalz.2018.01.016","article-title":"Effects of APOE-\u025b4 allele load on brainmorphology in a cohort of middle-aged healthy individuals with enriched genetic risk for Alzheimer\u2019s disease","volume":"14","author":"Cacciaglia","year":"2018","journal-title":"Alzheimers Dement"},{"key":"10.3233\/JAD-220267_ref30","doi-asserted-by":"crossref","first-page":"49","DOI":"10.3233\/JAD-2011-0002","article-title":"Presence of ApoE \u025b4 allele associated with thinnerfrontal cortex in middle age","volume":"26 Suppl3","author":"Fennema-Notestine","year":"2011","journal-title":"J Alzheimers Dis"},{"key":"10.3233\/JAD-220267_ref31","doi-asserted-by":"crossref","first-page":"1211","DOI":"10.3233\/JAD-200238","article-title":"Hippocampal subfield volumes in middle-aged adults at risk of dementia","volume":"75","author":"McKeever","year":"2020","journal-title":"J Alzheimers Dis"},{"key":"10.3233\/JAD-220267_ref32","doi-asserted-by":"crossref","first-page":"1962","DOI":"10.1007\/s00415-020-10383-8","article-title":"Higher midlife CAIDE score is associated with increased brain atrophy in a cohort of cognitively healthy middle-aged individuals","volume":"268","author":"Liu","year":"2021","journal-title":"J Neurol"},{"key":"10.3233\/JAD-220267_ref33","doi-asserted-by":"crossref","first-page":"158","DOI":"10.1136\/jnnp-2019-321652","article-title":"Association between midlife dementia risk factors and longitudinal brain atrophy: The PREVENT-Dementia study","volume":"91","author":"O\u2019Brien","year":"2020","journal-title":"J Neurol Neurosurg Psychiatry"},{"key":"10.3233\/JAD-220267_ref34","doi-asserted-by":"crossref","first-page":"1089","DOI":"10.1016\/j.jalz.2017.02.008","article-title":"The midlife cognitive profiles of adults at high risk of late-onset Alzheimer\u2019s disease: The PREVENT study","volume":"13","author":"Ritchie","year":"2017","journal-title":"Alzheimers Dement"},{"key":"10.3233\/JAD-220267_ref36","doi-asserted-by":"crossref","first-page":"832. e815","DOI":"10.1016\/j.neurobiolaging.2011.07.016","article-title":"APOE \u025b4 differentially influences change in memory performance depending on age. The SMART-MR study","volume":"33","author":"Jochemsen","year":"2012","journal-title":"Neurobiol Aging"},{"key":"10.3233\/JAD-220267_ref37","doi-asserted-by":"crossref","first-page":"e46179","DOI":"10.7554\/eLife.46179","article-title":"Family history ofAlzheimer\u2019s disease alters cognition and is modified by medical andgenetic factors","volume":"8","author":"Talboom","year":"2019","journal-title":"Elife"},{"key":"10.3233\/JAD-220267_ref38","doi-asserted-by":"crossref","first-page":"2071","DOI":"10.1212\/WNL.0b013e3181c67833","article-title":"Association of parental dementia with cognitive and brain MRI measures in middle-aged adults","volume":"73","author":"Debette","year":"2009","journal-title":"Neurology"},{"key":"10.3233\/JAD-220267_ref39","doi-asserted-by":"crossref","first-page":"695","DOI":"10.3233\/JAD-170092","article-title":"Associations of CAIDE Dementia Risk Score with MRI, PIB-PET measures, and cognition","volume":"59","author":"Stephen","year":"2017","journal-title":"J Alzheimers Dis"},{"key":"10.3233\/JAD-220267_ref40","doi-asserted-by":"crossref","first-page":"180","DOI":"10.1016\/j.neurobiolaging.2018.06.012","article-title":"Lifestyle activities in mid-life contribute to cognitive reserve in late-life, independent of education, occupation, and late-life activities","volume":"70","author":"Chan","year":"2018","journal-title":"Neurobiol Aging"},{"key":"10.3233\/JAD-220267_ref41","doi-asserted-by":"crossref","first-page":"2673","DOI":"10.1016\/S0140-6736(17)31363-6","article-title":"Dementia prevention, intervention, and care","volume":"390","author":"Livingston","year":"2017","journal-title":"Lancet"},{"key":"10.3233\/JAD-220267_ref42","doi-asserted-by":"crossref","first-page":"e1002251","DOI":"10.1371\/journal.pmed.1002251","article-title":"Association of lifelong exposure to cognitive reserve-enhancing factors with dementia risk: A community-based cohort study","volume":"14","author":"Wang","year":"2017","journal-title":"PLoS Med"},{"key":"10.3233\/JAD-220267_ref43","doi-asserted-by":"crossref","first-page":"68","DOI":"10.1002\/ana.25501","article-title":"Genetic risk of dementia mitigated by cognitive reserve: A cohort study","volume":"86","author":"Dekhtyar","year":"2019","journal-title":"Ann Neurol"},{"key":"10.3233\/JAD-220267_ref44","doi-asserted-by":"crossref","first-page":"501","DOI":"10.1002\/alz.12032","article-title":"Predicting sporadic Alzheimer\u2019s disease progression via inherited Alzheimer\u2019s disease-informed machine-learning","volume":"16","author":"Franzmeier","year":"2020","journal-title":"Alzheimers Dement"},{"key":"10.3233\/JAD-220267_ref45","doi-asserted-by":"crossref","first-page":"1375","DOI":"10.1016\/j.neurobiolaging.2013.11.028","article-title":"A right hemisphere role in cognitive reserve","volume":"35","author":"Robertson","year":"2014","journal-title":"Neurobiol Aging"},{"key":"10.3233\/JAD-220267_ref46","doi-asserted-by":"crossref","first-page":"298","DOI":"10.1016\/j.neurobiolaging.2012.05.019","article-title":"A noradrenergic theory of cognitive reserve: Implications for Alzheimer\u2019s disease","volume":"34","author":"Robertson","year":"2013","journal-title":"Neurobiol Aging"},{"key":"10.3233\/JAD-220267_ref47","doi-asserted-by":"crossref","first-page":"1712","DOI":"10.1038\/s41467-020-15410-w","article-title":"Noradrenergic-dependent functions are associated with age-related locus coeruleus signal intensity differences","volume":"11","author":"Liu","year":"2020","journal-title":"Nat Commun"},{"key":"10.3233\/JAD-220267_ref48","doi-asserted-by":"crossref","first-page":"617","DOI":"10.1002\/ana.20637","article-title":"A life course approach to cognitive reserve: A model for cognitive aging and development?","volume":"58","author":"Richards","year":"2005","journal-title":"Ann Neurol"},{"key":"10.3233\/JAD-220267_ref49","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1093\/geronb\/gbw124","article-title":"Lifecourse activity participation from early, mid, and later adulthood as determinants of cognitive aging: The Lothian Birth Cohort 1921","volume":"72","author":"Gow","year":"2017","journal-title":"J Gerontol B Psychol Sci Soc Sci"},{"key":"10.3233\/JAD-220267_ref50","doi-asserted-by":"crossref","first-page":"1015","DOI":"10.1017\/S003329170600938X","article-title":"Assessment of complex mental activity across the lifespan: Development of the Lifetime of Experiences Questionnaire (LEQ)","volume":"37","author":"Valenzuela","year":"2007","journal-title":"Psychol Med"},{"key":"10.3233\/JAD-220267_ref51","doi-asserted-by":"crossref","first-page":"107","DOI":"10.1186\/s12916-020-01578-x","article-title":"Risk prediction models for dementia: Role of age and cardiometabolic risk factors","volume":"18","author":"Fayosse","year":"2020","journal-title":"BMC Med"},{"key":"10.3233\/JAD-220267_ref52","doi-asserted-by":"crossref","first-page":"328","DOI":"10.1016\/j.dadm.2015.06.005","article-title":"The CAIDE Dementia Risk Score App: The development of an evidence-based mobile application to predict the risk of dementia","volume":"1","author":"Sindi","year":"2015","journal-title":"Alzheimers Dement (Amst)"},{"key":"10.3233\/JAD-220267_ref53","doi-asserted-by":"crossref","first-page":"242","DOI":"10.1159\/000351671","article-title":"Validation of the Addenbrooke\u2019s Cognitive Examination III in frontotemporal dementia and Alzheimer\u2019s disease","volume":"36","author":"Hsieh","year":"2013","journal-title":"Dement Geriatr Cogn Disord"},{"key":"10.3233\/JAD-220267_ref54","first-page":"2","article-title":"COGNITO: Computerized assessment of information processing","volume":"4","author":"Ritchie","year":"2014","journal-title":"J Psychol Psychother"},{"key":"10.3233\/JAD-220267_ref55","doi-asserted-by":"crossref","first-page":"885","DOI":"10.3233\/JAD-180432","article-title":"Allocentric and egocentric spatial processing in middle-aged adults at high risk of late-onset Alzheimer\u2019s disease: The PREVENT Dementia Study","volume":"65","author":"Ritchie","year":"2018","journal-title":"J Alzheimers Dis"},{"key":"10.3233\/JAD-220267_ref56","doi-asserted-by":"crossref","first-page":"2702","DOI":"10.1093\/brain\/awq148","article-title":"Visual short-term memory bindingdeficits in familial Alzheimer\u2019s disease","volume":"133","author":"Parra","year":"2010","journal-title":"Brain"},{"key":"10.3233\/JAD-220267_ref57","doi-asserted-by":"crossref","first-page":"2015","DOI":"10.1016\/j.neuropsychologia.2009.03.004","article-title":"Cognitive reserve","volume":"47","author":"Stern","year":"2009","journal-title":"Neuropsychologia"},{"key":"10.3233\/JAD-220267_ref58","doi-asserted-by":"crossref","first-page":"1006","DOI":"10.1016\/S1474-4422(12)70191-6","article-title":"Cognitive reserve in ageing and Alzheimer\u2019s disease","volume":"11","author":"Stern","year":"2012","journal-title":"Lancet Neurol"},{"key":"10.3233\/JAD-220267_ref59","doi-asserted-by":"crossref","first-page":"124","DOI":"10.1016\/j.neurobiolaging.2019.03.022","article-title":"Brain reserve, cognitive reserve, compensation, and maintenance: Operationalization, validity, and mechanisms of cognitive resilience","volume":"83","author":"Stern","year":"2019","journal-title":"Neurobiol Aging"},{"key":"10.3233\/JAD-220267_ref60","doi-asserted-by":"crossref","first-page":"167","DOI":"10.1002\/gps.4700","article-title":"Lifestyle for Brain Health (LIBRA): A new model for dementia prevention","volume":"33","author":"Schiepers","year":"2018","journal-title":"Int J Geriatr Psychiatry"},{"key":"10.3233\/JAD-220267_ref62","doi-asserted-by":"crossref","first-page":"119","DOI":"10.1016\/S1474-4422(09)70299-6","article-title":"Hypothetical model of dynamic biomarkers of the Alzheimer\u2019s pathological cascade","volume":"9","author":"Jack","year":"2010","journal-title":"Lancet Neurol"},{"key":"10.3233\/JAD-220267_ref63","doi-asserted-by":"crossref","first-page":"1169","DOI":"10.3233\/JAD-191268","article-title":"Profiles of cognitive change in preclinical and prodromal Alzheimer\u2019s disease using change-point analysis","volume":"75","author":"Williams","year":"2020","journal-title":"J Alzheimers Dis"},{"key":"10.3233\/JAD-220267_ref64","doi-asserted-by":"crossref","first-page":"191","DOI":"10.1017\/S1355617711001718","article-title":"Preclinical cognitive trajectories differ for Alzheimer\u2019s disease and vascular dementia","volume":"18","author":"Laukka","year":"2012","journal-title":"J Int Neuropsychol Soc"},{"key":"10.3233\/JAD-220267_ref65","doi-asserted-by":"crossref","first-page":"951","DOI":"10.1016\/j.jalz.2019.03.012","article-title":"Association of TLR4 with Alzheimer\u2019s disease risk and presymptomatic biomarkersof inflammation","volume":"15","author":"Miron","year":"2019","journal-title":"Alzheimers Dement"},{"key":"10.3233\/JAD-220267_ref66","doi-asserted-by":"crossref","first-page":"87","DOI":"10.1001\/archneurol.2009.308","article-title":"Association of C-reactive protein with cognitive impairment","volume":"67","author":"Noble","year":"2010","journal-title":"Arch Neurol"},{"key":"10.3233\/JAD-220267_ref67","doi-asserted-by":"crossref","first-page":"1573","DOI":"10.3233\/JAD-210094","article-title":"Association of stress with risk of dementia and mild cognitive impairment: A systematic review and meta-analysis","volume":"82","author":"Franks","year":"2021","journal-title":"J Alzheimers Dis"},{"key":"10.3233\/JAD-220267_ref68","doi-asserted-by":"crossref","first-page":"340","DOI":"10.1111\/inr.12194","article-title":"Caregiver burden for informal caregivers of patients with dementia: A systematic review","volume":"62","author":"Chiao","year":"2015","journal-title":"Int Nurs Rev"},{"key":"10.3233\/JAD-220267_ref69","doi-asserted-by":"crossref","first-page":"e0132168","DOI":"10.1371\/journal.pone.0132168","article-title":"Measuring the caregiver burden of caring for community-residing people with Alzheimer\u2019s disease","volume":"10","author":"Yu","year":"2015","journal-title":"PLoS One"},{"key":"10.3233\/JAD-220267_ref70","doi-asserted-by":"crossref","first-page":"732","DOI":"10.1097\/PSY.0000000000000518","article-title":"Alzheimer\u2019s disease caregivers\u2019 health and important resources: Next steps in intervention research","volume":"79","author":"Ross","year":"2017","journal-title":"Psychosom Med"},{"key":"10.3233\/JAD-220267_ref71","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1186\/s13024-019-0325-5","article-title":"Neuroimaging biomarkers for Alzheimer\u2019s disease","volume":"14","author":"M\u00e1rquez","year":"2019","journal-title":"Mol Neurodegener"},{"key":"10.3233\/JAD-220267_ref72","doi-asserted-by":"crossref","first-page":"147","DOI":"10.1016\/0301-0082(77)90016-8","article-title":"The locus coeruleus: Neurobiology of a central noradrenergic nucleus","volume":"9","author":"Amaral","year":"1977","journal-title":"Prog Neurobiol"},{"key":"10.3233\/JAD-220267_ref73","doi-asserted-by":"crossref","first-page":"1358","DOI":"10.1177\/0956797618774253","article-title":"How much does education improve intelligence? A meta-analysis","volume":"29","author":"Ritchie","year":"2018","journal-title":"Psychol Sci"},{"key":"10.3233\/JAD-220267_ref74","doi-asserted-by":"crossref","first-page":"e0230077","DOI":"10.1371\/journal.pone.0230077","article-title":"Greater lifestyle engagement is associated with better age-adjusted cognitive abilities","volume":"15","author":"Borgeest","year":"2020","journal-title":"PLoS One"},{"key":"10.3233\/JAD-220267_ref75","doi-asserted-by":"crossref","first-page":"2844","DOI":"10.1177\/0271678X211020863","article-title":"Evidence of cerebral hemodynamic dysregulation in middle-aged APOE \u025b4 carriers: The PREVENT-Dementia study","volume":"41","author":"Dounavi","year":"2021","journal-title":"J Cereb Blood Flow Metab"},{"key":"10.3233\/JAD-220267_ref76","doi-asserted-by":"crossref","first-page":"124","DOI":"10.1016\/j.neurobiolaging.2020.10.029","article-title":"Inherited risk of dementia and the progression of cerebral small vessel disease and inflammatory markers in cognitively healthy midlife adults: The PREVENT-Dementia study","volume":"98","author":"Low","year":"2021","journal-title":"Neurobiol Aging"},{"key":"10.3233\/JAD-220267_ref77","doi-asserted-by":"crossref","first-page":"653","DOI":"10.1038\/s41582-018-0070-3","article-title":"Lifestyle interventions to prevent cognitive impairment, dementia and Alzheimer disease","volume":"14","author":"Kivipelto","year":"2018","journal-title":"Nat Rev Neurol"}],"container-title":["Journal of Alzheimer's Disease"],"original-title":[],"link":[{"URL":"https:\/\/content.iospress.com\/download?id=10.3233\/JAD-220267","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,4,28]],"date-time":"2026-04-28T10:08:06Z","timestamp":1777370886000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.sagepub.com\/doi\/full\/10.3233\/JAD-220267"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,1,17]]},"references-count":75,"journal-issue":{"issue":"2"},"URL":"https:\/\/doi.org\/10.3233\/jad-220267","relation":{"has-preprint":[{"id-type":"doi","id":"10.1101\/2022.03.14.22272340","asserted-by":"object"}]},"ISSN":["1387-2877","1875-8908"],"issn-type":[{"value":"1387-2877","type":"print"},{"value":"1875-8908","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,1,17]]}}}