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Med."],"published-print":{"date-parts":[[2022,12]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec id=\"S0033291721001070_sec_a1\"><jats:title>Background<\/jats:title><jats:p>Cognitive impairment is common in late-life depression, which may increase Alzheimer disease (AD) risk. Therefore, we aimed to investigate whether late-life major depressive disorder (MDD) has worse cognition and increases the characteristic AD neuropathology. Furthermore, we carried out a comparison between treatment-resistant depression (TRD) and non-TRD. We hypothesized that patients with late-life depression and TRD may have increased <jats:italic>\u03b2<\/jats:italic>-amyloid (A<jats:italic>\u03b2<\/jats:italic>) deposits in brain regions responsible for global cognition.<\/jats:p><\/jats:sec><jats:sec id=\"S0033291721001070_sec_a2\" sec-type=\"methods\"><jats:title>Methods<\/jats:title><jats:p>We recruited 81 subjects, including 54 MDD patients (27 TRD and 27 non-TRD) and 27 matched healthy controls (HCs). Neurocognitive tasks were examined, including Mini-Mental State Examination and Montreal Cognitive Assessment to detect global cognitive functions. PET with Pittsburgh compound-B and fluorodeoxyglucose were used to capture brain A<jats:italic>\u03b2<\/jats:italic> pathology and glucose use, respectively, in some patients.<\/jats:p><\/jats:sec><jats:sec id=\"S0033291721001070_sec_a3\" sec-type=\"results\"><jats:title>Results<\/jats:title><jats:p>MDD patients performed worse in Montreal Cognitive Assessment (<jats:italic>p<\/jats:italic> = 0.003) and had more A<jats:italic>\u03b2<\/jats:italic> deposits than HCs across the brain (family-wise error-corrected <jats:italic>p<\/jats:italic> &lt; 0.001), with the most significant finding in the left middle frontal gyrus. Significant negative correlations between global cognition and prefrontal A<jats:italic>\u03b2<\/jats:italic> deposits existed in MDD patients, whereas positive correlations were noted in HCs. TRD patients had significantly more deposits in the left-sided brain regions (corrected <jats:italic>p<\/jats:italic> &lt; 0.001). The findings were not explained by APOE genotypes. No between-group fluorodeoxyglucose difference was detected.<\/jats:p><\/jats:sec><jats:sec id=\"S0033291721001070_sec_a4\" sec-type=\"conclusions\"><jats:title>Conclusions<\/jats:title><jats:p>Late-life depression, particularly TRD, had increased brain A<jats:italic>\u03b2<\/jats:italic> deposits and showed vulnerability to A<jats:italic>\u03b2<\/jats:italic> deposits. A detrimental role of A<jats:italic>\u03b2<\/jats:italic> deposits in global cognition in patients with late-onset or non-late-onset MDD supported the theory that late-life MDD could be a risk factor for AD.<\/jats:p><\/jats:sec>","DOI":"10.1017\/s0033291721001070","type":"journal-article","created":{"date-parts":[[2021,10,26]],"date-time":"2021-10-26T06:56:13Z","timestamp":1635231373000},"page":"4116-4126","update-policy":"https:\/\/doi.org\/10.1017\/policypage","source":"Crossref","is-referenced-by-count":6,"title":["Global cognitive dysfunction and <i>\u03b2<\/i>-amyloid neuropathology in late-life and treatment-resistant major depression"],"prefix":"10.1017","volume":"52","author":[{"given":"Cheng-Ta","family":"Li","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jong-Ling","family":"Fuh","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bang-Hung","family":"Yang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chen-Ji","family":"Hong","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chi-Wei","family":"Chang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Pei-Chi","family":"Tu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jia-Shyun","family":"Jeng","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mu-Hong","family":"Chen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shih-Jen","family":"Tsai","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ya-Mei","family":"Bai","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tung-Ping","family":"Su","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hsuan","family":"Lee","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wen-Sheng","family":"Huang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"56","published-online":{"date-parts":[[2021,10,26]]},"reference":[{"key":"S0033291721001070_ref52","doi-asserted-by":"publisher","DOI":"10.1002\/gps.4409"},{"key":"S0033291721001070_ref28","doi-asserted-by":"publisher","DOI":"10.1002\/hbm.23085"},{"key":"S0033291721001070_ref43","doi-asserted-by":"publisher","DOI":"10.1017\/S1092852913000072"},{"key":"S0033291721001070_ref18","doi-asserted-by":"publisher","DOI":"10.1016\/S1053-8119(03)00072-7"},{"key":"S0033291721001070_ref1","doi-asserted-by":"publisher","DOI":"10.3389\/fnagi.2014.00266"},{"key":"S0033291721001070_ref12","doi-asserted-by":"publisher","DOI":"10.1177\/0891988710363715"},{"key":"S0033291721001070_ref7","doi-asserted-by":"publisher","DOI":"10.1001\/archpsyc.61.6.587"},{"key":"S0033291721001070_ref46","doi-asserted-by":"publisher","DOI":"10.4161\/cc.8.11.8503"},{"key":"S0033291721001070_ref48","doi-asserted-by":"publisher","DOI":"10.1016\/j.semcdb.2011.03.011"},{"key":"S0033291721001070_ref10","doi-asserted-by":"publisher","DOI":"10.4088\/JCP.v68n0419"},{"key":"S0033291721001070_ref22","doi-asserted-by":"publisher","DOI":"10.1006\/nimg.2002.1255"},{"key":"S0033291721001070_ref27","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awu109"},{"key":"S0033291721001070_ref34","doi-asserted-by":"publisher","DOI":"10.3389\/fnagi.2016.00250"},{"key":"S0033291721001070_ref21","doi-asserted-by":"publisher","DOI":"10.1111\/j.2044-8260.1967.tb00530.x"},{"key":"S0033291721001070_ref20","doi-asserted-by":"publisher","DOI":"10.3233\/ADR-190143"},{"key":"S0033291721001070_ref38","doi-asserted-by":"publisher","DOI":"10.1016\/S2215-0366(16)00097-3"},{"key":"S0033291721001070_ref40","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuropsychologia.2004.10.004"},{"key":"S0033291721001070_ref41","doi-asserted-by":"publisher","DOI":"10.1111\/j.1532-5415.2005.53221.x"},{"key":"S0033291721001070_ref8","doi-asserted-by":"publisher","DOI":"10.1038\/nrneurol.2011.60"},{"key":"S0033291721001070_ref50","doi-asserted-by":"publisher","DOI":"10.1007\/s00259-016-3591-2"},{"key":"S0033291721001070_ref32","doi-asserted-by":"publisher","DOI":"10.1192\/bjp.bp.113.140434"},{"key":"S0033291721001070_ref24","doi-asserted-by":"publisher","DOI":"10.1017\/S0033291707001134"},{"key":"S0033291721001070_ref9","doi-asserted-by":"publisher","DOI":"10.1016\/j.jad.2020.05.150"},{"key":"S0033291721001070_ref23","unstructured":"Heaton, R. 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