{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,3]],"date-time":"2026-09-03T11:50:10Z","timestamp":1788436210687,"version":"build-2803163510"},"reference-count":78,"publisher":"SAGE Publications","issue":"2","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JAD"],"published-print":{"date-parts":[[2022,9,13]]},"abstract":"<jats:p>Background: The co-occurrence of apathy and executive dysfunction, a correlate of vascular cognitive impairment (VCI), is highly prevalent, yet facilitating factors are largely unknown. Objective: This study investigates the relationship between lipid peroxidation, apathy, and executive dysfunction in patients at risk for VCI. Methods: In participants with coronary artery disease, who are at a high risk of VCI, apathy (Apathy Evaluation Scale), and executive function (composite z-score based on age and education population norms from trails making test B, animal naming, and phonemic fluency tests) were assessed. Serum concentrations of an early (lipid hydroperoxide (LPH)) and late (8-isoprostane (8-ISO)) lipid peroxidation marker, were measured and the 8-ISO\/LPH ratio was calculated. Results: Participants (n\u200a=\u200a206, age\u00b1SD\u200a=\u200a63.0\u00b17.5, 80% men, total years of education\u200a=\u200a15.9\u00b13.4, AES score\u200a=\u200a28.3\u00b18.8, executive function\u200a=\u200a0\u00b11) demonstrated significantly different 8-ISO\/LPH ratios between groups (F(3, 202)\u200a=\u200a10.915, p\u200a&lt;\u200a0.001) with increasing levels in the following order: no apathy or executive dysfunction, only executive dysfunction (executive function composite score\u2264\u20131), only apathy (AES\u226528), and both apathy and executive dysfunction. A model adjusting for demographics showed that lipid peroxidation was associated with both apathy (B(SE)\u200a=\u200a4.63 (0.954), t\u200a=\u200a4.852, p\u200a&lt;\u200a0.001) and executive function (B(SE)\u200a=\u200a\u20130.19 (0.079), t\u200a=\u200a\u20132.377, p\u200a=\u200a0.018). However, when controlling for both demographics and vascular risk factors, lipid peroxidation was associated with only apathy (B(SE)\u200a=\u200a3.11 (0.987), t\u200a=\u200a3.149, p\u200a=\u200a0.002). Conclusion: The results highlight a potentially important involvement of lipid peroxidation in the co-occurrence of apathy and executive dysfunction in those at risk for VCI.<\/jats:p>","DOI":"10.3233\/jad-220274","type":"journal-article","created":{"date-parts":[[2022,8,2]],"date-time":"2022-08-02T11:38:45Z","timestamp":1659440325000},"page":"733-743","source":"Crossref","is-referenced-by-count":4,"title":["Lipid Peroxidation as a Marker of Apathy and Executive Dysfunction in Patients at Risk for Vascular Cognitive Impairment"],"prefix":"10.1177","volume":"89","author":[{"given":"Kritleen K.","family":"Bawa","sequence":"first","affiliation":[{"name":"Neuropsychopharmacology Research Group, Sunnybrook Research Institute, Toronto, ON, Canada"},{"name":"Hurvitz Brain Sciences Program, Sunnybrook Research Institute, Toronto, ON, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joycelyn","family":"Ba","sequence":"additional","affiliation":[{"name":"Neuropsychopharmacology Research Group, Sunnybrook Research Institute, Toronto, ON, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alex","family":"Kiss","sequence":"additional","affiliation":[{"name":"ICES, Sunnybrook Research Institute, Toronto, ON, Canada"},{"name":"Institute of Health Policy, Management and Evaluation, University of Toronto, Toronto, ON, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"RuoDing","family":"Wang","sequence":"additional","affiliation":[{"name":"Neuropsychopharmacology Research Group, Sunnybrook Research Institute, Toronto, ON, Canada"},{"name":"Hurvitz Brain Sciences Program, Sunnybrook Research Institute, Toronto, ON, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vivian","family":"Feng","sequence":"additional","affiliation":[{"name":"Neuropsychopharmacology Research Group, Sunnybrook Research Institute, Toronto, ON, Canada"},{"name":"Hurvitz Brain Sciences Program, Sunnybrook Research Institute, Toronto, ON, Canada"},{"name":"Department of Pharmacology & Toxicology, University of Toronto, Toronto, ON, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Walter","family":"Swardfager","sequence":"additional","affiliation":[{"name":"Hurvitz Brain Sciences Program, Sunnybrook Research Institute, Toronto, ON, Canada"},{"name":"Department of Pharmacology & Toxicology, University of Toronto, Toronto, ON, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ana","family":"Andreazza","sequence":"additional","affiliation":[{"name":"Department of Pharmacology & Toxicology, University of Toronto, Toronto, ON, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Damien","family":"Gallagher","sequence":"additional","affiliation":[{"name":"Department of Psychiatry, Faculty of Medicine, University of Toronto, Toronto, ON, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giovanni","family":"Marotta","sequence":"additional","affiliation":[{"name":"Division of Geriatric Medicine, Sunnybrook Health Sciences Centre, Toronto, ON, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nathan","family":"Herrmann","sequence":"additional","affiliation":[{"name":"Neuropsychopharmacology Research Group, Sunnybrook Research Institute, Toronto, ON, Canada"},{"name":"Hurvitz Brain Sciences Program, Sunnybrook Research Institute, Toronto, ON, Canada"},{"name":"Department of Psychiatry, Faculty of Medicine, University of Toronto, Toronto, ON, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Krista L.","family":"Lanct\u00f4t","sequence":"additional","affiliation":[{"name":"Neuropsychopharmacology Research Group, Sunnybrook Research Institute, Toronto, ON, Canada"},{"name":"Hurvitz Brain Sciences Program, Sunnybrook Research Institute, Toronto, ON, Canada"},{"name":"Department of Pharmacology & Toxicology, University of Toronto, Toronto, ON, Canada"},{"name":"Department of Psychiatry, Faculty of Medicine, University of Toronto, Toronto, ON, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"179","reference":[{"key":"10.3233\/JAD-220274_ref1","doi-asserted-by":"crossref","first-page":"573","DOI":"10.1161\/CIRCRESAHA.116.308426","article-title":"Vascular cognitive impairment","volume":"120","author":"Dichgans","year":"2017","journal-title":"Circ Res"},{"key":"10.3233\/JAD-220274_ref2","doi-asserted-by":"crossref","first-page":"447","DOI":"10.1212\/WNL.54.2.447","article-title":"Prevalence and outcomes of vascular cognitive impairment. Vascular Cognitive Impairment Investigators of the Canadian Study of Health and Aging","volume":"54","author":"Rockwood","year":"2000","journal-title":"Neurology"},{"key":"10.3233\/JAD-220274_ref3","doi-asserted-by":"crossref","first-page":"280","DOI":"10.1016\/j.jalz.2017.09.007","article-title":"Progress toward standardized diagnosis of vascular cognitive impairment: Guidelines from the Vascular Impairment of Cognition Classification Consensus Study","volume":"14","author":"Skrobot","year":"2018","journal-title":"Alzheimers Dement"},{"key":"10.3233\/JAD-220274_ref4","doi-asserted-by":"crossref","first-page":"2672","DOI":"10.1161\/STR.0b013e3182299496","article-title":"Vascular contributions to cognitive impairment and dementia","volume":"42","author":"Gorelick","year":"2011","journal-title":"Stroke"},{"key":"10.3233\/JAD-220274_ref5","doi-asserted-by":"crossref","first-page":"18","DOI":"10.1097\/WAD.0000000000000043","article-title":"Vascular disease and risk factors are associated with cognitive decline in the Alzheimer disease spectrum","volume":"29","author":"Lorius","year":"2015","journal-title":"Alzheimer Dis Assoc Disord"},{"key":"10.3233\/JAD-220274_ref6","doi-asserted-by":"crossref","first-page":"R110","DOI":"10.1016\/j.cub.2007.12.014","article-title":"Executive function","volume":"18","author":"Gilbert","year":"2008","journal-title":"Curr Biol"},{"key":"10.3233\/JAD-220274_ref7","doi-asserted-by":"crossref","first-page":"142","DOI":"10.1016\/j.jns.2009.09.017","article-title":"Executive dysfunction in vascular cognitive impairment in the consortium to investigate vascular impairment of cognition study","volume":"288","author":"Moorhouse","year":"2010","journal-title":"J Neurol Sci"},{"key":"10.3233\/JAD-220274_ref8","doi-asserted-by":"crossref","first-page":"754","DOI":"10.1016\/j.jagp.2014.09.008","article-title":"White matter microstructural integrity is associated with executive function and processing speed in older adults with coronary artery disease","volume":"23","author":"Santiago","year":"2015","journal-title":"Am J Geriatr Psychiatry"},{"key":"10.3233\/JAD-220274_ref9","doi-asserted-by":"crossref","first-page":"669","DOI":"10.1017\/S1041610215001751","article-title":"The mediating role of cardiovascular risk factors in the relationship between symptoms of apathy and incident cardiovascular disease in community-dwelling older individuals","volume":"28","author":"Eurelings","year":"2016","journal-title":"Int Psychogeriatr"},{"key":"10.3233\/JAD-220274_ref10","doi-asserted-by":"crossref","first-page":"636","DOI":"10.1001\/archgenpsychiatry.2011.1858","article-title":"Association of vascular factors with apathy in community-dwelling elderly individuals","volume":"69","author":"Ligthart","year":"2012","journal-title":"Arch Gen Psychiatry"},{"key":"10.3233\/JAD-220274_ref11","doi-asserted-by":"crossref","first-page":"266","DOI":"10.1002\/gps.1872","article-title":"Vascular disease and apathy in old age. The Leiden 85-plus Study","volume":"23","author":"van der Mast","year":"2008","journal-title":"Int J Geriatr Psychiatry"},{"key":"10.3233\/JAD-220274_ref12","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1002\/gps.5217","article-title":"Empirical support for the vascular apathy hypothesis: A structured review","volume":"35","author":"Wouts","year":"2020","journal-title":"Int J Geriatr Psychiatry"},{"key":"10.3233\/JAD-220274_ref13","doi-asserted-by":"crossref","first-page":"1892","DOI":"10.1002\/alz.12358","article-title":"Diagnostic criteria for apathy in neurocognitive disorders","volume":"17","author":"Miller","year":"2021","journal-title":"Alzheimers Dement"},{"key":"10.3233\/JAD-220274_ref14","doi-asserted-by":"crossref","first-page":"124","DOI":"10.3389\/fnagi.2017.00124","article-title":"Apathy and executive function in healthy elderly-resting state fMRI study","volume":"9","author":"Kawagoe","year":"2017","journal-title":"Front Aging Neurosci"},{"key":"10.3233\/JAD-220274_ref15","doi-asserted-by":"crossref","first-page":"12","DOI":"10.1016\/j.neuropsychologia.2018.01.039","article-title":"Neuropsychological correlates of cognitive, emotional-affective and auto-activation apathy in Alzheimer\u2019s disease","volume":"118","author":"Perri","year":"2018","journal-title":"Neuropsychologia"},{"key":"10.3233\/JAD-220274_ref16","doi-asserted-by":"crossref","first-page":"431","DOI":"10.1002\/gps.1694","article-title":"Depression and apathy affect functioning in community active subjects with questionable dementia and mild Alzheimer\u2019s disease","volume":"22","author":"Lam","year":"2007","journal-title":"Int J Geriatr Psychiatry"},{"key":"10.3233\/JAD-220274_ref17","doi-asserted-by":"crossref","first-page":"341","DOI":"10.1002\/gps.2125","article-title":"Persistent apathy in Alzheimer\u2019s disease as an independent factor of rapid functional decline: The REAL longitudinal cohort study","volume":"24","author":"Lechowski","year":"2009","journal-title":"Int J Geriatr Psychiatry"},{"key":"10.3233\/JAD-220274_ref18","doi-asserted-by":"crossref","first-page":"416","DOI":"10.1186\/s12883-020-01978-9","article-title":"Correlations of apathy with clinical symptoms of Alzheimer\u2019s disease and olfactory dysfunctions: A cross-sectional study","volume":"20","author":"Yu","year":"2020","journal-title":"BMC Neurol"},{"key":"10.3233\/JAD-220274_ref19","doi-asserted-by":"crossref","first-page":"873","DOI":"10.1016\/j.jagp.2019.02.003","article-title":"The roles of apathy and depression in predicting Alzheimer disease: A longitudinal analysis in older adults with mild cognitive impairment","volume":"27","author":"Ruthirakuhan","year":"2019","journal-title":"Am J Geriatr Psychiatry"},{"key":"10.3233\/JAD-220274_ref20","doi-asserted-by":"crossref","first-page":"885","DOI":"10.3233\/JAD-161248","article-title":"Lipid peroxidation markers in coronary artery disease patients with possible vascular mild cognitive impairment","volume":"58","author":"Suridjan","year":"2017","journal-title":"J Alzheimers Dis"},{"key":"10.3233\/JAD-220274_ref21","doi-asserted-by":"crossref","first-page":"59","DOI":"10.3233\/JAD-2011-110284","article-title":"Peripheral oxidative stress biomarkers in mild cognitive impairment and alzheimer\u2019s disease","volume":"26","author":"Torres","year":"2011","journal-title":"J Alzheimers Dis"},{"key":"10.3233\/JAD-220274_ref22","first-page":"e88","article-title":"Oxidative stress: Predictive marker for coronary artery disease","volume":"18","author":"Vichova","year":"2013","journal-title":"Exp Clin Cardiol"},{"key":"10.3233\/JAD-220274_ref23","doi-asserted-by":"crossref","first-page":"140","DOI":"10.2174\/1570159X11666131120230309","article-title":"Oxidative stress and psychological disorders","volume":"12","author":"Salim","year":"2014","journal-title":"Curr Neuropharmacol"},{"key":"10.3233\/JAD-220274_ref24","doi-asserted-by":"crossref","first-page":"188","DOI":"10.1016\/S1369-5274(99)80033-2","article-title":"Oxidative stress","volume":"2","author":"Storz","year":"1999","journal-title":"Curr Opin Microbiol"},{"key":"10.3233\/JAD-220274_ref25","doi-asserted-by":"crossref","first-page":"327","DOI":"10.2165\/00007256-200636040-00004","article-title":"Oxidative stress: Relationship with exercise and training","volume":"36","author":"Finaud","year":"2006","journal-title":"Sports Med"},{"key":"10.3233\/JAD-220274_ref26","doi-asserted-by":"crossref","first-page":"1605","DOI":"10.1056\/NEJMoa030535","article-title":"Glutathione peroxidase 1 activity and cardiovascular events in patients with coronary artery disease","volume":"349","author":"Blankenberg","year":"2003","journal-title":"N Engl J Med"},{"key":"10.3233\/JAD-220274_ref27","doi-asserted-by":"crossref","first-page":"308","DOI":"10.1111\/j.1365-2796.2004.01373.x","article-title":"Oxidative stress and its association with coronary artery disease and different atherogenic risk factors","volume":"256","author":"Vassalle","year":"2004","journal-title":"J Intern Med"},{"key":"10.3233\/JAD-220274_ref28","doi-asserted-by":"crossref","first-page":"65","DOI":"10.1016\/j.jchromb.2005.04.023","article-title":"Oxidative stress in brain aging, neurodegenerative and vascular diseases: An overview","volume":"827","author":"Mariani","year":"2005","journal-title":"J Chromatogr B Analyt Technol Biomed Life Sci"},{"key":"10.3233\/JAD-220274_ref29","doi-asserted-by":"crossref","first-page":"129","DOI":"10.1159\/000319452","article-title":"Oxidative imbalance in different neurodegenerative diseases with memory impairment","volume":"8","author":"Gironi","year":"2011","journal-title":"Neurodegener Dis"},{"key":"10.3233\/JAD-220274_ref30","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1186\/s12974-017-1026-z","article-title":"Oxidative stress predicts cognitive decline with aging in healthy adults: An observational study","volume":"15","author":"Hajjar","year":"2018","journal-title":"J Neuroinflammation"},{"key":"10.3233\/JAD-220274_ref31","doi-asserted-by":"crossref","first-page":"262","DOI":"10.1080\/13854049608406689","article-title":"Neuropsychological tests\u2019 norms above age 55: COWAT, BNT, MAE token, WRAT-R reading, AMNART, STROOP, TMT, and JLO","volume":"10","author":"Ivnik","year":"1996","journal-title":"Clin Neuropsychol"},{"key":"10.3233\/JAD-220274_ref32","first-page":"167","article-title":"Normative data stratified by age and education for two measures of verbal fluency: FAS and Animal Naming","volume":"14","author":"Tombaugh","year":"1999","journal-title":"Arch Clin Neuropsychology"},{"key":"10.3233\/JAD-220274_ref33","doi-asserted-by":"crossref","first-page":"1147","DOI":"10.1042\/BST0351147","article-title":"Biochemistry of oxidative stress","volume":"35","author":"Halliwell","year":"2007","journal-title":"Biochem Soc Trans"},{"key":"10.3233\/JAD-220274_ref34","doi-asserted-by":"crossref","first-page":"270","DOI":"10.1016\/j.jad.2018.02.071","article-title":"Determining the optimal clinical cutoff on the CES-D for depression in a community corrections sample","volume":"234","author":"Henry","year":"2018","journal-title":"J Affect Disord"},{"key":"10.3233\/JAD-220274_ref35","doi-asserted-by":"crossref","first-page":"e0155431","DOI":"10.1371\/journal.pone.0155431","article-title":"Screening for depression in the general population with the Center for Epidemiologic Studies Depression (CES-D): A systematic review with meta-analysis","volume":"11","author":"Vilagut","year":"2016","journal-title":"PLoS One"},{"key":"10.3233\/JAD-220274_ref36","first-page":"12","article-title":"Selective neuronal vulnerability to oxidative stress in the brain","volume":"2","author":"Wang","year":"2010","journal-title":"Front Aging Neurosci"},{"key":"10.3233\/JAD-220274_ref37","doi-asserted-by":"crossref","first-page":"692","DOI":"10.1002\/1873-3468.12964","article-title":"Role of mitochondrial ROS in the brain, Fromhysiology to neurodegeneration","volume":"592","author":"Angelova","year":"2018","journal-title":"FEBS Lett"},{"key":"10.3233\/JAD-220274_ref38","doi-asserted-by":"crossref","first-page":"155","DOI":"10.1097\/NEN.0b013e3181cb5af4","article-title":"Oxidative stress in the progression of Alzheimer disease in the frontal cortex","volume":"69","author":"Ansari","year":"2010","journal-title":"J Neuropathol Exp Neurol"},{"key":"10.3233\/JAD-220274_ref39","doi-asserted-by":"crossref","first-page":"4711","DOI":"10.2174\/1381612825666190115121018","article-title":"Oxidative stress and accelerated aging in neurodegenerative and neuropsychiatric disorder","volume":"24","author":"Wadhwa","year":"2018","journal-title":"Curr Pharm Des"},{"key":"10.3233\/JAD-220274_ref40","doi-asserted-by":"crossref","first-page":"1347","DOI":"10.1111\/ene.13985","article-title":"Oxidative stress, inflammation and risk of neurodegeneration in a population sample","volume":"26","author":"Cherbuin","year":"2019","journal-title":"Eur J Neurol"},{"key":"10.3233\/JAD-220274_ref41","doi-asserted-by":"crossref","first-page":"159","DOI":"10.3233\/JAD-2004-6207","article-title":"Oxidative stress in mild cognitive impairment and Alzheimer disease: A continuum","volume":"6","author":"Mecocci","year":"2004","journal-title":"J Alzheimers Dis"},{"key":"10.3233\/JAD-220274_ref42","doi-asserted-by":"crossref","first-page":"245","DOI":"10.3233\/JAD-2009-1041","article-title":"Oxidative stress in vascular dementia and Alzheimer\u2019s disease: A common pathology","volume":"17","author":"Bennett","year":"2008","journal-title":"J Alzheimers Dis"},{"key":"10.3233\/JAD-220274_ref43","doi-asserted-by":"crossref","first-page":"161","DOI":"10.1111\/j.1447-0594.2009.00571.x","article-title":"Lipids\u2019 peroxidation markers in Alzheimer\u2019s disease and vascular dementia","volume":"10","author":"Gustaw-Rothenberg","year":"2010","journal-title":"Geriatr Gerontol Int"},{"key":"10.3233\/JAD-220274_ref44","doi-asserted-by":"crossref","first-page":"181","DOI":"10.1016\/j.clinbiochem.2006.09.007","article-title":"Correlation of oxidative stress parameters and inflammatory markers in coronary artery disease patients","volume":"40","author":"Kotur-Stevuljevic","year":"2007","journal-title":"Clin Biochem"},{"key":"10.3233\/JAD-220274_ref45","doi-asserted-by":"crossref","first-page":"81","DOI":"10.1016\/j.freeradbiomed.2016.06.005","article-title":"Functional role of mitochondrial reactive oxygen species in physiology","volume":"100","author":"Angelova","year":"2016","journal-title":"Free Radic Biol Med"},{"key":"10.3233\/JAD-220274_ref46","doi-asserted-by":"crossref","first-page":"770","DOI":"10.1002\/med.21712","article-title":"Mitochondria and lipid peroxidation in the mechanism of neurodegeneration: Finding ways for prevention","volume":"41","author":"Angelova","year":"2021","journal-title":"Med Res Rev"},{"key":"10.3233\/JAD-220274_ref47","doi-asserted-by":"crossref","first-page":"822","DOI":"10.1016\/j.bbadis.2011.12.009","article-title":"Oxidative stress and cerebral endothelial cells: Regulation of the blood\u2013brain-barrier and antioxidant based interventions","volume":"1822","author":"Freeman","year":"2012","journal-title":"Biochim Biophys Acta"},{"key":"10.3233\/JAD-220274_ref48","doi-asserted-by":"crossref","first-page":"620","DOI":"10.1016\/S0891-5849(02)00807-9","article-title":"Lipid peroxidation in aging brain and Alzheimer\u2019s disease","volume":"33","author":"Montine","year":"2002","journal-title":"Free Radic Biol Med"},{"key":"10.3233\/JAD-220274_ref49","doi-asserted-by":"crossref","first-page":"54","DOI":"10.1016\/j.neuropsychologia.2017.07.003","article-title":"The anatomy of apathy: A neurocognitive framework for amotivated behaviour","volume":"118","author":"Le Heron","year":"2018","journal-title":"Neuropsychologia"},{"key":"10.3233\/JAD-220274_ref50","doi-asserted-by":"crossref","first-page":"119","DOI":"10.1016\/j.jagp.2021.06.016","article-title":"Apathy as a treatment target in Alzheimer\u2019s disease: Implications for clinical trials","volume":"30","author":"Mortby","year":"2021","journal-title":"Am J Geriatr Psychiatry"},{"key":"10.3233\/JAD-220274_ref51","doi-asserted-by":"crossref","first-page":"141","DOI":"10.31887\/DCNS.2007.9.2\/rbonelli","article-title":"Frontal-subcortical circuitry and behavior","volume":"9","author":"Bonelli","year":"2007","journal-title":"Dialogues Clin Neurosci"},{"key":"10.3233\/JAD-220274_ref52","doi-asserted-by":"crossref","first-page":"180","DOI":"10.1016\/j.neubiorev.2014.02.005","article-title":"Prefrontal cortex and executive functions in healthy adults: A meta-analysis of structural neuroimaging studies","volume":"42","author":"Yuan","year":"2014","journal-title":"Neurosci Biobehav Rev"},{"key":"10.3233\/JAD-220274_ref53","doi-asserted-by":"crossref","first-page":"1601","DOI":"10.1007\/s11064-012-0755-8","article-title":"Elevated oxidative stress and decreased antioxidant function in the human hippocampus and frontal cortex with increasing age: Implications for neurodegeneration in Alzheimer\u2019s disease","volume":"37","author":"Venkateshappa","year":"2012","journal-title":"Neurochem Res"},{"key":"10.3233\/JAD-220274_ref54","doi-asserted-by":"crossref","first-page":"77","DOI":"10.1126\/science.3299701","article-title":"Localization of amyloid beta protein messenger RNA in brains from patients with Alzheimer\u2019s disease","volume":"237","author":"Bahmanyar","year":"1987","journal-title":"Science"},{"key":"10.3233\/JAD-220274_ref55","doi-asserted-by":"crossref","first-page":"457","DOI":"10.1002\/ana.410270502","article-title":"Synapse loss in frontal cortex biopsies in Alzheimer\u2019s disease: Correlation with cognitive severity","volume":"27","author":"DeKosky","year":"1990","journal-title":"Ann Neurol"},{"key":"10.3233\/JAD-220274_ref56","doi-asserted-by":"crossref","first-page":"1385","DOI":"10.1212\/01.WNL.0000141848.45315.A6","article-title":"Protein markers for Alzheimer disease in the frontal cortex and cerebellum","volume":"63","author":"Verdile","year":"2004","journal-title":"Neurology"},{"key":"10.3233\/JAD-220274_ref57","doi-asserted-by":"crossref","first-page":"625","DOI":"10.1016\/j.bbadis.2011.10.003","article-title":"Elevation of glutathione as a therapeutic strategy in Alzheimer disease","volume":"1822","author":"Pocernich","year":"2012","journal-title":"Biochim Biophys Acta"},{"key":"10.3233\/JAD-220274_ref58","first-page":"201","article-title":"Evaluation of the neuroprotective potential of n-acetylcysteine for prevention and treatment of cognitive aging and dementia","volume":"4","author":"Hara","year":"2017","journal-title":"J Prev Alzheimers Dis"},{"key":"10.3233\/JAD-220274_ref59","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1586\/14737175.2015.955853","article-title":"Strategy to reduce free radical species in Alzheimer\u2019s disease: An update of selected antioxidants","volume":"15","author":"Di Domenico","year":"2015","journal-title":"Expert Rev Neurother"},{"key":"10.3233\/JAD-220274_ref60","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.pneurobio.2016.07.005","article-title":"Oxidative stress: A major pathogenesis and potential therapeutic target of antioxidative agents in Parkinson\u2019s disease and Alzheimer\u2019s disease","volume":"147","author":"Jiang","year":"2016","journal-title":"Prog Neurobiol"},{"key":"10.3233\/JAD-220274_ref61","doi-asserted-by":"crossref","first-page":"373","DOI":"10.1017\/S1355617702813182","article-title":"Apathy and executive function in Alzheimer\u2019s disease","volume":"8","author":"McPherson","year":"2002","journal-title":"J Int Neuropsychol Soc"},{"key":"10.3233\/JAD-220274_ref62","doi-asserted-by":"crossref","first-page":"175","DOI":"10.3233\/JAD-2010-1352","article-title":"Neuropsychiatric predictors of progression from amnestic-mild cognitive impairment to Alzheimer\u2019s disease: The role of depression and apathy","volume":"20","author":"Palmer","year":"2010","journal-title":"J Alzheimers Dis"},{"key":"10.3233\/JAD-220274_ref63","doi-asserted-by":"crossref","first-page":"204","DOI":"10.1159\/000338239","article-title":"Symptoms of apathy are associated with progression from mild cognitive impairment to Alzheimer\u2019s disease in non-depressed subjects","volume":"33","author":"Richard","year":"2012","journal-title":"Dement Geriatr Cogn Disord"},{"key":"10.3233\/JAD-220274_ref64","doi-asserted-by":"crossref","first-page":"1012","DOI":"10.1001\/jamapsychiatry.2018.1877","article-title":"Association of apathy with risk of incident dementia: A systematic review and meta-analysis","volume":"75","author":"van Dalen","year":"2018","journal-title":"JAMA Psychiatry"},{"key":"10.3233\/JAD-220274_ref65","doi-asserted-by":"crossref","first-page":"390","DOI":"10.1159\/000210045","article-title":"Differential impact of apathy and depression in the development of dementia in mild cognitive impairment patients","volume":"27","author":"Vicini Chilovi","year":"2009","journal-title":"Dement Geriatr Cogn Disord"},{"key":"10.3233\/JAD-220274_ref66","doi-asserted-by":"crossref","first-page":"470","DOI":"10.1002\/gps.4161","article-title":"Apathy as a feature of prodromal Alzheimer\u2019s disease: An FDG-PET ADNI study","volume":"30","author":"Delrieu","year":"2015","journal-title":"Int J Geriatr Psychiatry"},{"key":"10.3233\/JAD-220274_ref67","doi-asserted-by":"crossref","first-page":"683","DOI":"10.1016\/j.jagp.2016.12.017","article-title":"Regional 18F-fluorodeoxyglucose hypometabolism is associated with higher apathy scores over time in early Alzheimer disease","volume":"25","author":"Gatchel","year":"2017","journal-title":"Am J Geriatr Psychiatry"},{"key":"10.3233\/JAD-220274_ref68","doi-asserted-by":"crossref","first-page":"1168","DOI":"10.1016\/j.jagp.2013.03.006","article-title":"Regional cortical thinning predicts worsening apathy and hallucinations across the Alzheimer disease spectrum","volume":"22","author":"Donovan","year":"2014","journal-title":"Am J Geriatr Psychiatry"},{"key":"10.3233\/JAD-220274_ref69","doi-asserted-by":"crossref","first-page":"e22","DOI":"10.1176\/appi.neuropsych.13060141","article-title":"Apathy is associated with lower inferior temporal cortical thickness in mild cognitive impairment and normal elderly individuals","volume":"27","author":"Guercio","year":"2015","journal-title":"J Neuropsychiatry Clin Neurosci"},{"key":"10.3233\/JAD-220274_ref70","doi-asserted-by":"crossref","first-page":"1905","DOI":"10.3390\/ijms20081905","article-title":"Low-grade inflammation is associated with apathy indirectly via deep white matter lesions in community-dwelling older adults: The Sefuri Study","volume":"20","author":"Yao","year":"2019","journal-title":"Int J Mol Sci"},{"key":"10.3233\/JAD-220274_ref71","doi-asserted-by":"crossref","first-page":"363","DOI":"10.3233\/JAD-122359","article-title":"Biomarkers of vascular risk, systemic inflammation, and microvascular pathology and neuropsychiatric symptoms in Alzheimer\u2019s disease","volume":"35","author":"Hall","year":"2013","journal-title":"J Alzheimers Dis"},{"key":"10.3233\/JAD-220274_ref72","doi-asserted-by":"crossref","first-page":"218","DOI":"10.1161\/01.ATV.0000193626.22269.45","article-title":"Low-density lipoprotein cholesterol determines oxidative stress and endothelial dysfunction in saphenous veins from patients with coronary artery disease","volume":"26","author":"Al-Benna","year":"2006","journal-title":"Arterioscler Thromb Vasc Biol"},{"key":"10.3233\/JAD-220274_ref73","doi-asserted-by":"crossref","first-page":"73","DOI":"10.2174\/187221309787158371","article-title":"Chronic inflammation and oxidative stress as a major cause of age-related diseases and cancer","volume":"3","author":"Khansari","year":"2009","journal-title":"Recent Pat Inflamm Allergy Drug Discov"},{"key":"10.3233\/JAD-220274_ref74","doi-asserted-by":"crossref","first-page":"657","DOI":"10.1002\/gps.5062","article-title":"The impact of apathy on cognitive performance in the elderly","volume":"34","author":"Montoya-Murillo","year":"2019","journal-title":"Int J Geriatr Psychiatry"},{"key":"10.3233\/JAD-220274_ref75","doi-asserted-by":"crossref","first-page":"819","DOI":"10.1017\/S1041610209991402","article-title":"Apathy and cognitive and functional decline in community-dwelling older adults: Results from the Baltimore ECA longitudinal study","volume":"22","author":"Clarke","year":"2010","journal-title":"Int Psychogeriatr"},{"key":"10.3233\/JAD-220274_ref76","doi-asserted-by":"crossref","first-page":"447","DOI":"10.1017\/S0033291798008046","article-title":"Apathy and depressed mood in acquired brain damage: Relationship to lesion localization and psychophysiological reactivity","volume":"29","author":"Andersson","year":"1999","journal-title":"Psychol Med"},{"key":"10.3233\/JAD-220274_ref77","doi-asserted-by":"crossref","first-page":"87","DOI":"10.1080\/026990598122908","article-title":"Prevalence of apathy following head injury","volume":"12","author":"Kant","year":"1998","journal-title":"Brain Inj"},{"key":"10.3233\/JAD-220274_ref78","doi-asserted-by":"crossref","first-page":"421","DOI":"10.3233\/JAD-150146","article-title":"The Apathy Evaluation Scale: A comparison of subject, informant, and clinician report in cognitively normal elderly and mild cognitive impairment","volume":"47","author":"Guercio","year":"2015","journal-title":"J Alzheimers Dis"}],"container-title":["Journal of Alzheimer's Disease"],"original-title":[],"link":[{"URL":"https:\/\/content.iospress.com\/download?id=10.3233\/JAD-220274","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,4,28]],"date-time":"2026-04-28T10:06:47Z","timestamp":1777370807000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.sagepub.com\/doi\/full\/10.3233\/JAD-220274"}},"subtitle":[],"editor":[{"given":"Julius","family":"Popp","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2022,9,13]]},"references-count":78,"journal-issue":{"issue":"2"},"URL":"https:\/\/doi.org\/10.3233\/jad-220274","relation":{},"ISSN":["1387-2877","1875-8908"],"issn-type":[{"value":"1387-2877","type":"print"},{"value":"1875-8908","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,9,13]]}}}