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Although genetic factors surrounding the production and clearance of amyloid-\u03b2 and phosphorylated tau proteins are known to be responsible for a subset of early-onset AD cases, they do not explain the pathogenesis of the far more prevalent sporadic late-onset variant of the disease. It is thus likely that lifestyle and environmental factors contribute to neurodegenerative processes implicated in the pathogenesis of AD. Herein, we review evidence that (1) excess sucrose consumption induces AD-associated liver pathologies and brain insulin resistance, (2) chronic stress overdrives activity of locus coeruleus neurons, leading to loss of function (a common event in neurodegeneration), (3) high-sugar diets and stress promote the loss of neuroprotective sex hormones in men and women, and (4) Western dietary trends set the stage for a lithium-deficient state. We propose that these factors may intersect as part of a \u201cperfect storm\u201d to contribute to the widespread prevalence of neurodegeneration and AD. In addition, we put forth the argument that exercise and supplementation with trace lithium can counteract many of the deleterious consequences associated with excessive caloric intake and perpetual stress. We conclude that lifestyle and environmental factors likely contribute to AD pathogenesis and that simple lifestyle and dietary changes can help counteract their effects.<\/jats:p>","DOI":"10.1159\/000503451","type":"journal-article","created":{"date-parts":[[2019,10,14]],"date-time":"2019-10-14T21:00:33Z","timestamp":1571086833000},"page":"60-77","source":"Crossref","is-referenced-by-count":27,"title":["Poor Diet, Stress, and Inactivity Converge to Form a \u201cPerfect Storm\u201d That Drives Alzheimer\u2019s Disease Pathogenesis"],"prefix":"10.1159","volume":"19","author":[{"given":"Anthony\u00a0G.","family":"Pacholko","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Caitlin\u00a0A.","family":"Wotton","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lane\u00a0K.","family":"Bekar","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"127","published-online":{"date-parts":[[2019,10,10]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jalz.2016.03.001"},{"key":"ref2","doi-asserted-by":"publisher","DOI":"10.1016\/j.brainresrev.2004.02.002"},{"key":"ref3","doi-asserted-by":"publisher","DOI":"10.1001\/archneur.60.3.337"},{"key":"ref4","doi-asserted-by":"publisher","DOI":"10.1155\/1999\/256382"},{"key":"ref5","doi-asserted-by":"publisher","DOI":"10.1126\/science.482927"},{"key":"ref6","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2007.08.013"},{"key":"ref7","doi-asserted-by":"publisher","DOI":"10.1016\/j.expneurol.2004.08.023"},{"key":"ref8","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M203256200"},{"key":"ref9","doi-asserted-by":"publisher","DOI":"10.1038\/nature05193"},{"key":"ref10","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.72.9.3726"},{"key":"ref11","doi-asserted-by":"publisher","DOI":"10.1038\/jcbfm.2012.115"},{"key":"ref12","doi-asserted-by":"publisher","DOI":"10.2307\/j.ctvjsf433"},{"key":"ref13","doi-asserted-by":"publisher","DOI":"10.1093\/ajcn.81.2.341"},{"key":"ref14","doi-asserted-by":"publisher","DOI":"10.1093\/ajcn\/72.4.929"},{"key":"ref15","doi-asserted-by":"publisher","DOI":"10.1542\/peds.2007-2834"},{"key":"ref16","doi-asserted-by":"publisher","DOI":"10.1111\/j.2047-6310.2013.00156.x"},{"key":"ref17","doi-asserted-by":"publisher","DOI":"10.1111\/obr.12785"},{"key":"ref18","doi-asserted-by":"publisher","DOI":"10.1001\/jama.282.16.1530"},{"key":"ref19","doi-asserted-by":"publisher","DOI":"10.1007\/s40273-014-0243-x"},{"key":"ref20","doi-asserted-by":"publisher","DOI":"10.2105\/AJPH.2005.083782"},{"key":"ref21","doi-asserted-by":"publisher","DOI":"10.1038\/nn2055"},{"key":"ref22","doi-asserted-by":"publisher","DOI":"10.1016\/j.nlm.2008.05.005"},{"key":"ref23","doi-asserted-by":"publisher","DOI":"10.1038\/srep45693"},{"key":"ref24","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.97.20.11056"},{"key":"ref25","doi-asserted-by":"publisher","DOI":"10.1016\/S0006-8993(98)00115-2"},{"key":"ref26","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbi.2009.07.008"},{"key":"ref27","doi-asserted-by":"publisher","DOI":"10.3109\/10253890903080379"},{"key":"ref28","doi-asserted-by":"publisher","DOI":"10.1038\/srep09442"},{"key":"ref29","doi-asserted-by":"publisher","DOI":"10.1172\/JCI116424"},{"key":"ref30","doi-asserted-by":"publisher","DOI":"10.2337\/diab.45.1.86"},{"key":"ref31","doi-asserted-by":"publisher","DOI":"10.1186\/s12944-015-0087-1"},{"key":"ref32","doi-asserted-by":"publisher","DOI":"10.1194\/jlr.M006866"},{"key":"ref33","doi-asserted-by":"publisher","DOI":"10.1016\/j.metabol.2011.01.008"},{"key":"ref34","doi-asserted-by":"publisher","DOI":"10.1152\/ajpendo.00478.2015"},{"key":"ref35","doi-asserted-by":"publisher","DOI":"10.1038\/nrendo.2011.72"},{"key":"ref36","doi-asserted-by":"publisher","DOI":"10.1016\/j.plipres.2005.11.002"},{"key":"ref37","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmet.2014.08.002"},{"key":"ref38","doi-asserted-by":"publisher","DOI":"10.3233\/JAD-2012-111727"},{"key":"ref39","doi-asserted-by":"publisher","DOI":"10.1007\/s00125-009-1546-x"},{"key":"ref40","doi-asserted-by":"publisher","DOI":"10.1111\/j.1478-3231.2007.01475.x"},{"key":"ref41","doi-asserted-by":"publisher","DOI":"10.3233\/JAD-2010-091726"},{"key":"ref42","doi-asserted-by":"publisher","DOI":"10.1042\/bst0320144"},{"key":"ref43","doi-asserted-by":"publisher","DOI":"10.1007\/s11064-007-9297-x"},{"key":"ref44","doi-asserted-by":"publisher","DOI":"10.1201\/b17849-12"},{"key":"ref45","doi-asserted-by":"publisher","DOI":"10.1111\/j.2047-6310.2013.00156.x"},{"key":"ref46","doi-asserted-by":"publisher","DOI":"10.1542\/peds.2007-2834"},{"key":"ref47","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M703561200"},{"key":"ref48","doi-asserted-by":"publisher","DOI":"10.2337\/db11-1186"},{"key":"ref49","doi-asserted-by":"publisher","DOI":"10.3233\/JAD-130005"},{"key":"ref50","doi-asserted-by":"publisher","DOI":"10.1007\/s11011-018-0263-x"},{"key":"ref51","doi-asserted-by":"publisher","DOI":"10.1177\/193229680800200619"},{"key":"ref52","doi-asserted-by":"publisher","DOI":"10.1172\/JCI59903"},{"key":"ref53","doi-asserted-by":"publisher","DOI":"10.3233\/JAD-2012-129025"},{"key":"ref54","doi-asserted-by":"publisher","DOI":"10.1096\/fj.14-253211"},{"key":"ref55","doi-asserted-by":"publisher","DOI":"10.1111\/j.1471-4159.2007.05194.x"},{"key":"ref56","doi-asserted-by":"publisher","DOI":"10.1016\/j.pharmthera.2014.11.016"},{"key":"ref57","d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