{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,7]],"date-time":"2026-04-07T05:53:32Z","timestamp":1775541212154,"version":"3.50.1"},"reference-count":24,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2023,3,23]],"date-time":"2023-03-23T00:00:00Z","timestamp":1679529600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"NIA\/NIH","award":["U24 AG072122"],"award-info":[{"award-number":["U24 AG072122"]}]},{"name":"NIA\/NIH","award":["1R03AG070579-01"],"award-info":[{"award-number":["1R03AG070579-01"]}]},{"name":"NIA\/NIH","award":["1R03AG072110-01A1"],"award-info":[{"award-number":["1R03AG072110-01A1"]}]},{"name":"National Institute of Health","award":["U24 AG072122"],"award-info":[{"award-number":["U24 AG072122"]}]},{"name":"National Institute of Health","award":["1R03AG070579-01"],"award-info":[{"award-number":["1R03AG070579-01"]}]},{"name":"National Institute of Health","award":["1R03AG072110-01A1"],"award-info":[{"award-number":["1R03AG072110-01A1"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JCM"],"abstract":"<jats:p>Alzheimer\u2019s disease (AD) is characterized by cognitive impairment in the presence of cerebral amyloid plaques and neurofibrillary tangles. Less is known about the characteristics and predictors of resilience to cognitive impairment in the presence of neuropathological evidence of AD, the focus of this study. Of 3170 adults age \u226565 years in the National Alzheimer\u2019s Coordinating Center (NACC) brain autopsy cohort, 1373 had evidence of CERAD level moderate to frequent neuritic plaque density and Braak stage V\u2013VI neurofibrillary tangles. Resilience was defined by CDR-SOB and CDR-Global scores of 0\u20132.5 and 0\u20130.5, respectively, and non-resilience, CDR-SOB and CDR-Global scores &gt;2.5 and &gt;0.5, respectively. Multivariable logistic regression models were used to examine the independent associations of patient characteristics with resilience. There were 62 participants (4.8%) with resilience. Those with resilience were older (mean age, 88.3 vs. 82.4 years), more likely to be women (61.3% vs. 47.3%) and had a lower prevalence of the APOE-e4 carrier (41.9% vs. 56.2%). They also had a higher prevalence of hypertension, heart failure, atrial fibrillation, diuretic use, beta-blocker use, and APOE-e2 carrier status. Greater age at death, diuretic use, and APOE-e2 were the only characteristics independently associated with higher odds of the AD resilience phenotype (adjusted OR, 1.09; 95% CI, 1.05\u20131.13; p &lt; 0.01; 2.00 (1.04\u20133.87), p = 0.04, 2.71 (1.31\u20135.64), p &lt; 0.01, respectively). The phenotype of resilience to cognitive impairment is uncommon in older adults who have neuropathological evidence of AD.<\/jats:p>","DOI":"10.3390\/jcm12072463","type":"journal-article","created":{"date-parts":[[2023,3,24]],"date-time":"2023-03-24T02:34:54Z","timestamp":1679625294000},"page":"2463","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Characteristics and Predictors of Alzheimer\u2019s Disease Resilience Phenotype"],"prefix":"10.3390","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7482-1782","authenticated-orcid":false,"given":"Mo-Kyung","family":"Sin","sequence":"first","affiliation":[{"name":"College of Nursing, Seattle University, Seattle, WA 98122-1090, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7189-3991","authenticated-orcid":false,"given":"Yan","family":"Cheng","sequence":"additional","affiliation":[{"name":"The School of Medicine & Health Sciences, George Washington University, Washington, DC 20037, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jeffrey M.","family":"Roseman","sequence":"additional","affiliation":[{"name":"School of Public Health, University of Alabama at Birmingham, Birmingham, AL 35233, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Caitlin","family":"Latimer","sequence":"additional","affiliation":[{"name":"Laboratory Medicine & Pathology, University of Washington, Seattle, WA 98104, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6832-6424","authenticated-orcid":false,"given":"Ali","family":"Ahmed","sequence":"additional","affiliation":[{"name":"The School of Medicine & Health Sciences, George Washington University, Washington, DC 20037, USA"},{"name":"VA Medical Center, Washington, DC 20242, USA"},{"name":"Georgetown University, Washington, DC 20057, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Edward","family":"Zamrini","sequence":"additional","affiliation":[{"name":"The School of Medicine & Health Sciences, George Washington University, Washington, DC 20037, USA"},{"name":"VA Medical Center, Washington, DC 20242, USA"},{"name":"Irvine Clinical Research, Irvine, CA 92614, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2023,3,23]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"91","DOI":"10.1186\/s40478-019-0743-1","article-title":"Resistance and resilience to Alzheimer\u2019s disease pathology are associated with reduced cortical pTau and absence of limbic-predominant age-related TDP-43 encephalopathy in a community-based cohort","volume":"7","author":"Latimer","year":"2019","journal-title":"Acta Neuropathol. Commun."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"100","DOI":"10.1097\/NEN.0000000000000153","article-title":"Cerebral Cortical A\u03b242 and PHF-\u03c4 in 325 Consecutive Brain Autopsies Stratified by Diagnosis, Location, and APOE","volume":"74","author":"Postupna","year":"2015","journal-title":"J. Neuropathol. Exp. Neurol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"145","DOI":"10.3233\/JAD-121069","article-title":"Using Alzgene-like Approaches to Investigate Susceptibility Genes for Vascular Cognitive Impairment","volume":"34","author":"Dwyer","year":"2013","journal-title":"J. Alzheimer\u2019s Dis."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"611","DOI":"10.3233\/JAD-143102","article-title":"Genetics of Vascular Dementia: Systematic Review and Meta-Analysis","volume":"46","author":"Sun","year":"2015","journal-title":"J. Alzheimer\u2019s Dis."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"760","DOI":"10.1016\/j.nicl.2017.03.016","article-title":"Family history and APOE4 risk for Alzheimer\u2019s disease impact the neural correlates of episodic memory by early midlife","volume":"14","author":"Rajah","year":"2017","journal-title":"NeuroImage Clin."},{"key":"ref_6","first-page":"a006189","article-title":"Neuropathological Alterations in Alzheimer Disease","volume":"1","author":"Frosch","year":"2011","journal-title":"Cold Spring Harb. Perspect. Med."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"2510","DOI":"10.1093\/brain\/awt171","article-title":"Dissecting phenotypic traits linked to human resilience to Alzheimer\u2019s pathology","volume":"136","author":"Stein","year":"2013","journal-title":"Brain"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1071","DOI":"10.3233\/JAD-180942","article-title":"Cognitive Resilience to Alzheimer\u2019s Disease Pathology in the Human Brain","volume":"68","author":"Bowles","year":"2019","journal-title":"J. Alzheimer\u2019s Dis."},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"SOLVD Investigators, Yusuf, S., Pitt, B., Davis, C.E., Hood, W.B., and Cohn, J.N. (1992). Effect of Enalapril on Mortality and the Development of Heart Failure in Asymptomatic Patients with Reduced Left Ventricular Ejection Fractions. N. Engl. J. Med., 327, 685\u2013691.","DOI":"10.1056\/NEJM199209033271003"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"479","DOI":"10.1212\/WNL.41.4.479","article-title":"The Consortium to Establish a Registry for Alzheimer\u2019s Disease (CERAD): Part II. Standardization of the neuropathologic assessment of Alzheimer\u2019s disease","volume":"41","author":"Mirra","year":"1991","journal-title":"Neurology"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"389","DOI":"10.1007\/s00401-006-0127-z","article-title":"Staging of Alzheimer disease-associated neurofibrillary pathology using paraffin sections and immunocytochemistry","volume":"112","author":"Braak","year":"2006","journal-title":"Acta Neuropathol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1091","DOI":"10.1001\/archneur.65.8.1091","article-title":"Staging dementia using clinical dementia rating scale sum of boxes scores: A Texas Alzheimer\u2019s research consortium study","volume":"65","author":"Lupo","year":"2008","journal-title":"Arch. Neurol."},{"key":"ref_13","unstructured":"(2023, February 03). Traj. Group-Based Modeling of Longitudinal Data. Available online: https:\/\/www.andrew.cmu.edu\/user\/bjones\/."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"4747","DOI":"10.1038\/s41467-020-18198-x","article-title":"Association of APOEe2 genotype with Alzheimer\u2019s and non-Alzheimer\u2019s neurodegenerative pathologies","volume":"11","author":"Goldberg","year":"2020","journal-title":"Nat. Commun."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"853","DOI":"10.3233\/JAD-201205","article-title":"APOE E2\/E2 Is Associated with Slower Rate of Cognitive Decline with Age","volume":"83","author":"Sweigart","year":"2021","journal-title":"J. Alzheimer\u2019s Dis."},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Govindpani, K., McNamara, L.G., Smith, N.R., Vinnakota, C., Waldvogel, H.J., Faull, R.L.M., and Kwakowsky, A. (2019). Vascular Dysfunction in Alzheimer\u2019s Disease: A Prelude to the Pathological Process or a Consequence of It?. J. Clin. Med., 8.","DOI":"10.3390\/jcm8050651"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"418","DOI":"10.1001\/archneur.1996.00550050048022","article-title":"Apolipoprotein E Genotype Determines Survival in the Oldest Old (85 Years or Older) Who Have Good Cognition","volume":"53","author":"Corder","year":"1996","journal-title":"Arch. Neurol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"e62199","DOI":"10.7554\/eLife.62199","article-title":"APOE2 is associated with longevity independent of Alzheimer\u2019s disease","volume":"9","author":"Shinohara","year":"2020","journal-title":"Elife"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"896","DOI":"10.1212\/WNL.0b013e3182a35228","article-title":"Antihypertensive drugs decrease risk of Alzheimer disease: Ginkgo Evaluation of Memory Study","volume":"81","author":"Yasar","year":"2013","journal-title":"Neurology"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"686","DOI":"10.1001\/archneur.63.5.noc60013","article-title":"Antihypertensive medication use and incident Alzheimer disease: The cache county study","volume":"63","author":"Khachaturian","year":"2006","journal-title":"Arch. Neurol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"3286","DOI":"10.1093\/brain\/awx243","article-title":"Tau pathology and neurodegeneration contribute to cognitive impairment in Alzheimer\u2019s disease","volume":"140","author":"Bejanin","year":"2017","journal-title":"Brain"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"16808","DOI":"10.1038\/s41598-020-73911-6","article-title":"Disease progression modeling of Alzheimer\u2019s disease according to education level","volume":"10","author":"Kim","year":"2020","journal-title":"Sci. Rep."},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"Chang, C.-Y., Lan, S.-J., Chu, C.-L., and Ho, C.-S. (2021). The Relationship between Clinic Visit Accompanied by Family and Dementia Severity in Taiwan. Int. J. Environ. Res. Public Health, 18.","DOI":"10.3390\/ijerph18041792"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"333","DOI":"10.3233\/JAD-220808","article-title":"High Soluble Amyloid-\u03b242 Predicts Normal Cognition in Amyloid-Positive Individuals with Alzheimer\u2019s Disease-Causing Mutations","volume":"90","author":"Sturchio","year":"2022","journal-title":"J. Alzheimer\u2019s Dis."}],"container-title":["Journal of Clinical Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2077-0383\/12\/7\/2463\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T19:01:43Z","timestamp":1760122903000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2077-0383\/12\/7\/2463"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,3,23]]},"references-count":24,"journal-issue":{"issue":"7","published-online":{"date-parts":[[2023,4]]}},"alternative-id":["jcm12072463"],"URL":"https:\/\/doi.org\/10.3390\/jcm12072463","relation":{},"ISSN":["2077-0383"],"issn-type":[{"value":"2077-0383","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,3,23]]}}}