{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,11]],"date-time":"2026-03-11T20:10:43Z","timestamp":1773259843659,"version":"3.50.1"},"reference-count":40,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2020,3,24]],"date-time":"2020-03-24T00:00:00Z","timestamp":1585008000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2020,3,24]],"date-time":"2020-03-24T00:00:00Z","timestamp":1585008000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100004319","name":"Pfizer","doi-asserted-by":"publisher","award":["None"],"award-info":[{"award-number":["None"]}],"id":[{"id":"10.13039\/100004319","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Alz Res Therapy"],"published-print":{"date-parts":[[2020,12]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec>\n                <jats:title>Background<\/jats:title>\n                <jats:p>Abnormal beta-amyloid (A\u03b2) is associated with deleterious changes in central cholinergic tone in the very early stages of Alzheimer\u2019s disease (AD), which may be unmasked by a cholinergic antagonist (J Prev Alzheimers Dis 1:1\u20134, 2017). Previously, we established the scopolamine challenge test (SCT) as a \u201ccognitive stress test\u201d screening measure to identify individuals at risk for AD (Alzheimer\u2019s &amp; Dementia 10(2):262\u20137, 2014) (Neurobiol. Aging 36(10):2709-15, 2015). Here we aim to demonstrate the potential of the SCT as an indicator of cognitive change and neocortical amyloid aggregation after a 27-month follow-up interval.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Methods<\/jats:title>\n                <jats:p>Older adults (<jats:italic>N<\/jats:italic>\u2009=\u200963, aged 55\u201375\u2009years) with self-reported memory difficulties and first-degree family history of AD completed the SCT and PET amyloid imaging at baseline and were then seen for cognitive testing at 9, 18, and 27\u00a0months post-baseline. Repeat PET amyloid imaging was completed at the time of the 27-month exam.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Results<\/jats:title>\n                <jats:p>Significant differences in both cognitive performance and in A\u03b2 neocortical burden were observed between participants who either failed vs. passed the SCT at baseline, after a 27-month follow-up period.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Conclusions<\/jats:title>\n                <jats:p>Cognitive response to the SCT (Alzheimer\u2019s &amp; Dementia 10(2):262\u20137, 2014) at baseline is related to cognitive change and PET amyloid imaging results, over the course of 27\u2009months, in preclinical AD. The SCT may be a clinically useful screening tool to identify individuals who are more likely to both have positive evidence of amyloidosis on PET imaging and to show measurable cognitive decline over several years.<\/jats:p>\n              <\/jats:sec>","DOI":"10.1186\/s13195-020-00599-1","type":"journal-article","created":{"date-parts":[[2020,3,24]],"date-time":"2020-03-24T22:02:57Z","timestamp":1585087377000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["Disruption of cholinergic neurotransmission, within a cognitive challenge paradigm, is indicative of A\u03b2-related cognitive impairment in preclinical Alzheimer\u2019s disease after a 27-month delay interval"],"prefix":"10.1186","volume":"12","author":[{"given":"Jessica","family":"Alber","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Paul","family":"Maruff","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Cl\u00e1udia Y.","family":"Santos","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Brian R.","family":"Ott","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Stephen P.","family":"Salloway","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Don C.","family":"Yoo","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Richard B.","family":"Noto","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Louisa I.","family":"Thompson","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Danielle","family":"Goldfarb","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Edmund","family":"Arthur","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alex","family":"Song","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Peter J.","family":"Snyder","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2020,3,24]]},"reference":[{"issue":"2","key":"599_CR1","doi-asserted-by":"publisher","first-page":"262","DOI":"10.1016\/j.jalz.2014.01.009","volume":"10","author":"PJ Snyder","year":"2014","unstructured":"Snyder PJ, Lim YY, Schindler R, Ott BR, Salloway S, Daiello L, et al. Microdosing of scopolamine as a \u201ccognitive stress test\u201d: rationale and test of a very low dose in an at-risk cohort of older adults. Alzheimers Dement. 2014;10(2):262\u20137.","journal-title":"Alzheimers Dement"},{"issue":"1","key":"599_CR2","doi-asserted-by":"publisher","first-page":"3","DOI":"10.2217\/bmm.09.91","volume":"4","author":"EM Reiman","year":"2010","unstructured":"Reiman EM, Langbaum JB, Tariot PN. Alzheimer\u2019s prevention initiative: a proposal to evaluate presymptomatic treatments as quickly as possible. Biomark Med. 2010;4(1):3\u201314.","journal-title":"Biomark Med"},{"key":"599_CR3","first-page":"143","volume":"6","author":"A de Wilde","year":"2017","unstructured":"de Wilde A, van Maurik IS, Kunneman M, Bouwman F, Zwan M, Willemse EA, et al. Alzheimer's biomarkers in daily practice (ABIDE) project: rationale and design. Alzheimer\u2019s Dementia. 2017;6:143\u201351.","journal-title":"Alzheimer\u2019s Dementia"},{"key":"599_CR4","first-page":"111","volume":"8","author":"S Engelborghs","year":"2017","unstructured":"Engelborghs S, Niemantsverdriet E, Struyfs H, Blennow K, Brouns R, Comabella M, et al. Consensus guidelines for lumbar puncture in patients with neurological diseases. Alzheimer\u2019s Dementia. 2017;8:111\u201326.","journal-title":"Alzheimer\u2019s Dementia"},{"key":"599_CR5","first-page":"201","volume":"6","author":"Y Mo","year":"2017","unstructured":"Mo Y, Stromswold J, Wilson K, Holder D, Sur C, Laterza O, et al. A multinational study distinguishing Alzheimer's and healthy patients using cerebrospinal fluid tau\/A\u03b242 cutoff with concordance to amyloid positron emission tomography imaging. Alzheimer\u2019s Dementia. 2017;6:201\u20139.","journal-title":"Alzheimer\u2019s Dementia"},{"issue":"3","key":"599_CR6","first-page":"358","volume":"1","author":"MM Witte","year":"2015","unstructured":"Witte MM, Foster NL, Fleisher AS, Williams MM, Quaid K, Wasserman M, et al. Clinical use of amyloid-positron emission tomography neuroimaging: practical and bioethical considerations. Alzheimer\u2019s Dementia. 2015;1(3):358\u201367.","journal-title":"Alzheimer\u2019s Dementia"},{"key":"599_CR7","first-page":"15","volume":"5","author":"LG Apostolova","year":"2016","unstructured":"Apostolova LG, Haider JM, Goukasian N, Rabinovici GD, Ch\u00e9telat G, Ringman JM, et al. Critical review of the appropriate use criteria for amyloid imaging: effect on diagnosis and patient care. Alzheimer\u2019s Dementia. 2016;5:15\u201322.","journal-title":"Alzheimer\u2019s Dementia"},{"key":"599_CR8","first-page":"188","volume":"6","author":"E Grober","year":"2017","unstructured":"Grober E, Wakefield D, Ehrlich AR, Mabie P, Lipton RB. Identifying memory impairment and early dementia in primary care. Alzheimer\u2019s Dementia. 2017;6:188\u201395.","journal-title":"Alzheimer\u2019s Dementia"},{"key":"599_CR9","first-page":"1","volume":"1","author":"H Hampel","year":"2017","unstructured":"Hampel H, Mesulam MM, Cuello AC, Khachaturian AS, Vergallo A, Farlow MR, et al. Revisiting the cholinergic hypothesis in Alzheimer\u2019s disease: emerging evidence from translational and clinical research. J Prevention Alzheimer\u2019s Dis. 2017;1:1\u20134.","journal-title":"J Prevention Alzheimer\u2019s Dis"},{"issue":"2","key":"599_CR10","doi-asserted-by":"publisher","first-page":"126","DOI":"10.1016\/j.jalz.2005.09.004","volume":"1","author":"PJ Snyder","year":"2005","unstructured":"Snyder PJ, Bednar MM, Cromer JR, Maruff P. Reversal of scopolamine-induced deficits with a single dose of donepezil, an acetylcholinesterase inhibitor. Alzheimers Dement. 2005;1(2):126\u201335.","journal-title":"Alzheimers Dement"},{"issue":"10","key":"599_CR11","doi-asserted-by":"publisher","first-page":"2709","DOI":"10.1016\/j.neurobiolaging.2015.07.009","volume":"36","author":"YY Lim","year":"2015","unstructured":"Lim YY, Maruff P, Schindler R, Ott BR, Salloway S, Yoo DC, et al. Disruption of cholinergic neurotransmission exacerbates A\u03b2-related cognitive impairment in preclinical Alzheimer's disease. Neurobiol Aging. 2015;36(10):2709\u201315.","journal-title":"Neurobiol Aging"},{"key":"599_CR12","first-page":"19","volume":"2","author":"YY Lim","year":"2016","unstructured":"Lim YY, Snyder PJ, Pietrzak RH, Ukiqi A, Villemagne VL, Ames D. Sensitivity of composite scores to amyloid burden in preclinical Alzheimer\u2019s disease: introducing the Z-scores of attention, verbal fluency, and episodic memory for nondemented older adults composite score. Alzheimer\u2019s Dementia. 2016;2:19\u201326.","journal-title":"Alzheimer\u2019s Dementia"},{"issue":"1","key":"599_CR13","doi-asserted-by":"publisher","first-page":"30","DOI":"10.1186\/2050-7283-1-30","volume":"1","author":"P Maruff","year":"2013","unstructured":"Maruff P, Lim YY, Darby D, Ellis KA, Pietrzak RH, Snyder PJ, et al. Clinical utility of the cogstate brief battery in identifying cognitive impairment in mild cognitive impairment and Alzheimer\u2019s disease. BMC Psychol. 2013;1(1):30.","journal-title":"BMC Psychol"},{"key":"599_CR14","doi-asserted-by":"publisher","unstructured":"Sheikh JI, Yesavage JA. Geriatric depression scale (GDS): recent evidence and development of a shorter version. Clinical Gerontologist: J Aging Mental Health. 1986;5(1-2):165\u201373. https:\/\/doi.org\/10.1300\/J018v05n01_09.","DOI":"10.1300\/J018v05n01_09"},{"issue":"3","key":"599_CR15","doi-asserted-by":"publisher","first-page":"335","DOI":"10.1016\/0005-7967(94)00075-U","volume":"33","author":"PF Lovibond","year":"1995","unstructured":"Lovibond PF, Lovibond SH. The structure of negative emotional states: comparison of the Depression Anxiety Stress Scales (DASS) with the Beck depression and anxiety inventories. Behav Res Ther. 1995;33(3):335\u201343.","journal-title":"Behav Res Ther"},{"issue":"2","key":"599_CR16","doi-asserted-by":"publisher","first-page":"165","DOI":"10.1017\/S1041610292000991","volume":"4","author":"TH Crook","year":"1992","unstructured":"Crook TH, Feher EP, Larrabee GJ. Assessment of memory complaint in age-associated memory impairment: the MAC-Q. Int Psychogeriatr. 1992;4(2):165\u201376.","journal-title":"Int Psychogeriatr"},{"issue":"5","key":"599_CR17","doi-asserted-by":"publisher","first-page":"425","DOI":"10.1002\/hup.942","volume":"23","author":"A Fredrickson","year":"2008","unstructured":"Fredrickson A, Snyder PJ, Cromer J, Thomas E, Lewis M, Maruff P. The use of effect sizes to characterize the nature of cognitive change in psychopharmacological studies: an example with scopolamine. Hum Psychopharmacol Clin Exp. 2008;23(5):425\u201336.","journal-title":"Hum Psychopharmacol Clin Exp"},{"issue":"5","key":"599_CR18","doi-asserted-by":"publisher","first-page":"643","DOI":"10.1007\/s00401-013-1185-7","volume":"126","author":"CR Jack","year":"2013","unstructured":"Jack CR, Barrio JR, Kepe V. Cerebral amyloid PET imaging in Alzheimer\u2019s disease. Acta Neuropathol. 2013;126(5):643\u201357.","journal-title":"Acta Neuropathol"},{"issue":"3","key":"599_CR19","doi-asserted-by":"publisher","first-page":"275","DOI":"10.1001\/jama.2010.2008","volume":"305","author":"CM Clark","year":"2011","unstructured":"Clark CM, Schneider JA, Bedell BJ, Beach TG, Bilker WB, Mintun MA, et al. Use of florbetapir-PET for imaging \u03b2-amyloid pathology. JAMA. 2011;305(3):275\u201383.","journal-title":"JAMA."},{"issue":"20","key":"599_CR20","doi-asserted-by":"publisher","first-page":"2031","DOI":"10.1212\/WNL.0000000000004643","volume":"89","author":"MJ Grothe","year":"2017","unstructured":"Grothe MJ, Barthel H, Sepulcre J, Dyrba M, Sabri O, Teipel SJ. Alzheimer\u2019s disease neuroimaging initiative. In vivo staging of regional amyloid deposition. Neurology. 2017;89(20):2031\u20138.","journal-title":"Neurology."},{"issue":"8","key":"599_CR21","doi-asserted-by":"publisher","first-page":"1275","DOI":"10.1016\/j.neurobiolaging.2010.04.007","volume":"31","author":"CC Rowe","year":"2010","unstructured":"Rowe CC, Ellis KA, Rimajova M, Bourgeat P, Pike KE, Jones G. Amyloid imaging results from the Australian Imaging, Biomarkers and Lifestyle (AIBL) study of aging. Neurobiol Aging. 2010;31(8):1275\u201383.","journal-title":"Neurobiol Aging"},{"issue":"3","key":"599_CR22","doi-asserted-by":"publisher","first-page":"201","DOI":"10.1212\/WNL.0b013e3181cb3e25","volume":"74","author":"RC Petersen","year":"2010","unstructured":"Petersen RC, Aisen PS, Beckett LA, Donohue MC, Gamst AC, Harvey DJ, et al. Alzheimer's disease neuroimaging initiative (ADNI): clinical characterization. Neurology. 2010;74(3):201\u20139.","journal-title":"Neurology."},{"key":"599_CR23","doi-asserted-by":"publisher","first-page":"287","DOI":"10.1016\/0166-2236(81)90090-4","volume":"4","author":"S Corkin","year":"1981","unstructured":"Corkin S. Acetylcholine, aging and Alzheimer\u2019s disease: implications for treatment. Trends Neurosci. 1981;4:287\u201390.","journal-title":"Trends Neurosci"},{"issue":"2","key":"599_CR24","doi-asserted-by":"publisher","first-page":"296","DOI":"10.1007\/s00259-002-1028-6","volume":"30","author":"D Brown","year":"2003","unstructured":"Brown D, Chisholm JA, Owens J, Pimlott S, Patterson J, Wyper D. Acetylcholine muscarinic receptors and response to anti-cholinesterase therapy in patients with Alzheimer's disease. Eur J Nucl Med Mol Imaging. 2003;30(2):296\u2013300.","journal-title":"Eur J Nucl Med Mol Imaging"},{"issue":"3","key":"599_CR25","doi-asserted-by":"publisher","first-page":"272","DOI":"10.1016\/j.jagp.2012.11.016","volume":"21","author":"PB Rosenberg","year":"2013","unstructured":"Rosenberg PB, Wong DF, Edell SL, Ross JS, Joshi AD, Bra\u0161i\u0107 JR, et al. Cognition and amyloid load in Alzheimer disease imaged with florbetapir F 18 (AV-45) positron emission tomography. Am J Geriatr Psychiatry. 2013;21(3):272\u20138.","journal-title":"Am J Geriatr Psychiatry"},{"issue":"1","key":"599_CR26","doi-asserted-by":"publisher","first-page":"43","DOI":"10.1186\/2191-219X-3-43","volume":"3","author":"L Saint-Aubert","year":"2013","unstructured":"Saint-Aubert L, Barbeau EJ, P\u00e9ran P, Nemmi F, Vervueren C, Mirabel H, et al. Cortical florbetapir-PET amyloid load in prodromal Alzheimer\u2019s disease patients. EJNMMI Res. 2013;3(1):43.","journal-title":"EJNMMI Res"},{"key":"599_CR27","first-page":"156","volume":"8","author":"KD Harrington","year":"2017","unstructured":"Harrington KD, Lim YY, Ames D, Hassenstab J, Laws SM, Martins RN, et al. Amyloid \u03b2\u2013associated cognitive decline in the absence of clinical disease progression and systemic illness. Alzheimer\u2019s Dementia. 2017;8:156\u201364.","journal-title":"Alzheimer\u2019s Dementia"},{"key":"599_CR28","first-page":"1","volume":"50","author":"KY Liang","year":"1986","unstructured":"Liang KY, Zeger SL. Longitudinal data analysis using generalized linear models. Econometrika. 1986;50:1\u201325.","journal-title":"Econometrika"},{"key":"599_CR29","doi-asserted-by":"publisher","first-page":"1","DOI":"10.2307\/1912526","volume":"50","author":"H White","year":"1982","unstructured":"White H. Maximum likelihood estimation of misspecified models. Econometrica. 1982;50:1\u201325.","journal-title":"Econometrica"},{"issue":"7","key":"599_CR30","doi-asserted-by":"publisher","first-page":"830","DOI":"10.1001\/jamaneurol.2017.0892","volume":"74","author":"ME Farrell","year":"2017","unstructured":"Farrell ME, Kennedy KM, Rodrigue KM, Wig G, Bischof GN, Rieck JR, et al. Association of longitudinal cognitive decline with amyloid burden in middle-aged and older adults: evidence for a dose-response relationship. JAMA Neurol. 2017;74(7):830\u20138.","journal-title":"JAMA Neurol"},{"key":"599_CR31","doi-asserted-by":"publisher","first-page":"169","DOI":"10.1016\/j.neuropsychologia.2015.04.034","volume":"73","author":"KV Papp","year":"2015","unstructured":"Papp KV, Amariglio RE, Mormino EC, Hedden T, Dekhytar M, Johnson KA. Free and cued memory in relation to biomarker-defined abnormalities in clinically normal older adults and those at risk for Alzheimer\u2019s disease. Neuropsychologia. 2015;73:169\u201375.","journal-title":"Neuropsychologia."},{"issue":"9","key":"599_CR32","doi-asserted-by":"publisher","first-page":"1004","DOI":"10.1016\/j.jalz.2017.01.018","volume":"13","author":"EC Mormino","year":"2017","unstructured":"Mormino EC, Papp KV, Rentz DM, Donohue MC, Amariglio R, Quiroz YT, et al. Early and late change on the preclinical Alzheimer's cognitive composite in clinically normal older individuals with elevated amyloid \u03b2. Alzheimers Dement. 2017;13(9):1004\u201312.","journal-title":"Alzheimers Dement"},{"issue":"3","key":"599_CR33","doi-asserted-by":"publisher","first-page":"1231","DOI":"10.1016\/j.neurobiolaging.2014.12.015","volume":"36","author":"RH Pietrzak","year":"2015","unstructured":"Pietrzak RH, Lim YY, Ames D, Harrington K, Restrepo C, Martins RN, et al. Trajectories of memory decline in preclinical Alzheimer's disease: results from the Australian Imaging, Biomarkers and Lifestyle Flagship Study of Ageing. Neurobiol Aging. 2015;36(3):1231\u20138.","journal-title":"Neurobiol Aging"},{"issue":"6","key":"599_CR34","doi-asserted-by":"publisher","first-page":"940","DOI":"10.1037\/neu0000208","volume":"29","author":"J Hassenstab","year":"2015","unstructured":"Hassenstab J, Ruvolo D, Jasielec M, Xiong C, Grant E, Morris JC. Absence of practice effects in preclinical Alzheimer\u2019s disease. Neuropsychology. 2015;29(6):940.","journal-title":"Neuropsychology."},{"key":"599_CR35","doi-asserted-by":"publisher","first-page":"25","DOI":"10.1016\/j.neurobiolaging.2017.04.004","volume":"56","author":"SE Schindler","year":"2017","unstructured":"Schindler SE, Jasielec MS, Weng H, Hassenstab JJ, Grober E, McCue LM, et al. Neuropsychological measures that detect early impairment and decline in preclinical Alzheimer disease. Neurobiol Aging. 2017;56:25\u201332.","journal-title":"Neurobiol Aging"},{"key":"599_CR36","doi-asserted-by":"publisher","first-page":"146","DOI":"10.1007\/s004010050595","volume":"93","author":"TG Beach","year":"1997","unstructured":"Beach TG, Honer WG, Hughes LH. Cholinergic fibre loss associated with diffuse plaques in the non-demented elderly: the preclinical stage of Alzheimer\u2019s disease? Acta Neuropathol. 1997;93:146\u201353.","journal-title":"Acta Neuropathol"},{"key":"599_CR37","doi-asserted-by":"publisher","first-page":"308","DOI":"10.1093\/jnen\/59.4.308","volume":"59","author":"TG Beach","year":"2000","unstructured":"Beach TG, Kuo YM, Spiegel K, Emmerling MR, Sue LI, Kokjohn K, et al. The cholinergic deficit coincides with Abeta deposition at the earliest histopathologic stages of Alzheimer disease. J Neuropathol Exp Neurol. 2000;59:308\u201313.","journal-title":"J Neuropathol Exp Neurol"},{"key":"599_CR38","doi-asserted-by":"publisher","first-page":"1685","DOI":"10.1093\/cercor\/bhp232","volume":"20","author":"M Grothe","year":"2010","unstructured":"Grothe M, Zaborszky L, Atienza M, Gil-Neciga E, Rodriguez-Romero R, Teipel SJ, et al. Reduction of basal forebrain cholinergic system parallels cognitive impairment in patients at high risk of developing Alzheimer\u2019s disease. Cereb Cortex. 2010;20:1685\u201395.","journal-title":"Cereb Cortex"},{"key":"599_CR39","doi-asserted-by":"publisher","first-page":"1210","DOI":"10.1016\/j.neurobiolaging.2012.10.018","volume":"34","author":"M Grothe","year":"2013","unstructured":"Grothe M, Heinsen H, Teipel S. Longitudinal measures of cholinergic forebrain atrophy in the transition from healthy aging to Alzheimer\u2019s disease. Neurobiol Aging. 2013;34:1210\u201320.","journal-title":"Neurobiol Aging"},{"issue":"1","key":"599_CR40","doi-asserted-by":"publisher","first-page":"60","DOI":"10.1016\/j.jalz.2015.12.003","volume":"12","author":"S Gauthier","year":"2016","unstructured":"Gauthier S, Albert M, Fox N, Goedert M, Kivipelto M, Mestre-Ferrandiz J, et al. Why has therapy development for dementia failed in the last two decades? Alzheimers Dement. 2016;12(1):60\u20134.","journal-title":"Alzheimers Dement"}],"container-title":["Alzheimer's Research &amp; Therapy"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/link.springer.com\/content\/pdf\/10.1186\/s13195-020-00599-1.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/link.springer.com\/article\/10.1186\/s13195-020-00599-1\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/link.springer.com\/content\/pdf\/10.1186\/s13195-020-00599-1.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,3,24]],"date-time":"2021-03-24T00:30:47Z","timestamp":1616545847000},"score":1,"resource":{"primary":{"URL":"https:\/\/alzres.biomedcentral.com\/articles\/10.1186\/s13195-020-00599-1"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,3,24]]},"references-count":40,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2020,12]]}},"alternative-id":["599"],"URL":"https:\/\/doi.org\/10.1186\/s13195-020-00599-1","relation":{},"ISSN":["1758-9193"],"issn-type":[{"value":"1758-9193","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,3,24]]},"assertion":[{"value":"1 May 2019","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"11 March 2020","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"24 March 2020","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"All participants completed the informed consent process with trained research personnel, in compliance with the Declaration of Helsinki. This study was approved by the Rhode Island Hospital Institutional Review Board.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"Not applicable.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"P.J.S. is a consultant to Cogstate Ltd., the company that provides the Groton Maze Learning Test. P.M. is a full-time employee of Cogstate Ltd. The other authors declare that they have no competing interests.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"31"}}