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[18F]-MK-6420 is a high-affinity PET tracer that quantifies tau neurofibrillary tangles, but its ability to predict cognitive changes associated with early Alzheimer\u2019s disease symptoms, such as memory decline, is unclear. Here, we assess the prognostic accuracy of baseline [18F]-MK-6420 tau-PET for predicting longitudinal memory decline in asymptomatic elderly individuals. In a longitudinal observational study, we evaluated a cohort of cognitively normal elderly participants (n = 111) from the translational biomarkers in ageing and dementia study (data collected between October 2017 and July 2020, with a follow-up period of 12 months). All participants underwent tau-PET with [18F]-MK-6420 and amyloid-\u03b2 PET with [18F]-AZD-4694. The exclusion criteria included the presence of head trauma, stroke or other neurological disorders. There were 111 eligible participants selected based on the availability of amyloid-\u03b2 PET, tau-PET, MRI and APOE\u025b4 genotyping. Among these participants, the mean standard deviation age was 70.1 (8.6) years; 20 (18%) were tau-PET-positive and 71 of 111 (63.9%) were women. A significant association between the baseline Braak Stages I\u2013II [18F]-MK-6240 standardized uptake value ratio positivity and change in composite memory score were observed at the 12-month follow-up, after correcting for age, sex and years of education [logical memory and Rey Auditory Verbal Learning Test, standardized beta = \u22120.52 (\u22120.82\u20130.21), P &amp;lt; 0.001, for dichotomized tau-PET and \u22121.22 (\u22121.84\u2212(\u22120.61)], P &amp;lt; 0.0001, for continuous tau-PET]. Moderate cognitive decline was observed for A + T + over the follow-up period, whereas no significant change was observed for A\u2212T+, A + T- and A-T-, although it should be noted that the A\u2212T + group was small. Our results indicate that baseline tau neurofibrillary tangle pathology is associated with longitudinal changes in memory function, supporting the use of [18F]-MK-6420 PET to predict the likelihood of asymptomatic elderly individuals experiencing future memory decline. Overall, [18F]-MK-6420 PET is a promising tool for predicting memory decline in older adults without cognitive impairment at baseline. This is of critical relevance as the field is shifting towards a biological model of Alzheimer\u2019s disease defined by the aggregation of pathologic tau. Therefore, early detection of tau pathology using [18F]-MK-6420 PET provides us with hope that living patients with Alzheimer\u2019s disease may be diagnosed during the preclinical phase before it is too late.<\/jats:p>","DOI":"10.1093\/braincomms\/fcac325","type":"journal-article","created":{"date-parts":[[2022,12,9]],"date-time":"2022-12-09T04:03:22Z","timestamp":1670558602000},"source":"Crossref","is-referenced-by-count":14,"title":["Medial temporal tau predicts memory decline in cognitively unimpaired elderly"],"prefix":"10.1093","volume":"5","author":[{"given":"Angela T H","family":"Kwan","sequence":"first","affiliation":[{"name":"Faculty of Medicine, University of Ottawa , Ottawa, ON K1H 8L1 , Canada"},{"name":"Translational Neuroimaging Laboratory, The McGill University Research Centre for Studies in Aging, Douglas Mental Health University Institute, Le Centre Int\u00e9gr\u00e9 Universitaire de Sant\u00e9 et de Services Sociaux (CIUSSS) de l'Ouest-de-l'\u00cele-de-Montr\u00e9al , Montreal, QC H4H 1R3 , Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5240-4275","authenticated-orcid":false,"given":"Saman","family":"Arfaie","sequence":"additional","affiliation":[{"name":"Translational Neuroimaging Laboratory, The McGill University Research Centre for Studies in Aging, Douglas Mental Health University Institute, Le Centre Int\u00e9gr\u00e9 Universitaire de Sant\u00e9 et de Services Sociaux (CIUSSS) de l'Ouest-de-l'\u00cele-de-Montr\u00e9al , Montreal, QC H4H 1R3 , Canada"},{"name":"Department of Neurology and Neurosurgery, McGill University , Montreal, QC H3A 1A1 , Canada"},{"name":"Department of Medicine, McGill University Health Centre , Montreal, QC H3G 2M1 , Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7826-4781","authenticated-orcid":false,"given":"Joseph","family":"Therriault","sequence":"additional","affiliation":[{"name":"Translational Neuroimaging Laboratory, The McGill University Research Centre for Studies in Aging, Douglas Mental Health University Institute, Le Centre Int\u00e9gr\u00e9 Universitaire de Sant\u00e9 et de Services Sociaux (CIUSSS) de l'Ouest-de-l'\u00cele-de-Montr\u00e9al , Montreal, QC H4H 1R3 , Canada"},{"name":"Department of Neurology and Neurosurgery, McGill University , Montreal, QC H3A 1A1 , Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zahra","family":"Azizi","sequence":"additional","affiliation":[{"name":"Department of Medicine, McGill University Health Centre , Montreal, QC H3G 2M1 , Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6877-4825","authenticated-orcid":false,"given":"Firoza Z","family":"Lussier","sequence":"additional","affiliation":[{"name":"Translational Neuroimaging Laboratory, The McGill University Research Centre for Studies in Aging, Douglas Mental Health University Institute, Le Centre Int\u00e9gr\u00e9 Universitaire de Sant\u00e9 et de Services Sociaux (CIUSSS) de l'Ouest-de-l'\u00cele-de-Montr\u00e9al , Montreal, QC H4H 1R3 , Canada"},{"name":"Department of Neurology and Neurosurgery, McGill University , Montreal, QC H3A 1A1 , Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cecile","family":"Tissot","sequence":"additional","affiliation":[{"name":"Translational Neuroimaging Laboratory, The McGill University Research Centre for Studies in Aging, Douglas Mental Health University Institute, Le Centre Int\u00e9gr\u00e9 Universitaire de Sant\u00e9 et de Services Sociaux (CIUSSS) de l'Ouest-de-l'\u00cele-de-Montr\u00e9al , Montreal, QC H4H 1R3 , Canada"},{"name":"Department of Neurology and Neurosurgery, McGill University , Montreal, QC H3A 1A1 , Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mira","family":"Chamoun","sequence":"additional","affiliation":[{"name":"Translational Neuroimaging Laboratory, The McGill University Research Centre for Studies in Aging, Douglas Mental Health University Institute, Le Centre Int\u00e9gr\u00e9 Universitaire de Sant\u00e9 et de Services Sociaux (CIUSSS) de l'Ouest-de-l'\u00cele-de-Montr\u00e9al , Montreal, QC H4H 1R3 , Canada"},{"name":"Department of Neurology and Neurosurgery, McGill University , Montreal, QC H3A 1A1 , Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gleb","family":"Bezgin","sequence":"additional","affiliation":[{"name":"Translational Neuroimaging Laboratory, The McGill University Research Centre for Studies in Aging, Douglas Mental Health University Institute, Le Centre Int\u00e9gr\u00e9 Universitaire de Sant\u00e9 et de Services Sociaux (CIUSSS) de l'Ouest-de-l'\u00cele-de-Montr\u00e9al , Montreal, QC H4H 1R3 , Canada"},{"name":"Department of Neurology and Neurosurgery, McGill University , Montreal, QC H3A 1A1 , Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stijn","family":"Servaes","sequence":"additional","affiliation":[{"name":"Translational Neuroimaging Laboratory, The McGill University Research Centre for Studies in Aging, Douglas Mental Health University Institute, Le Centre Int\u00e9gr\u00e9 Universitaire de Sant\u00e9 et de Services Sociaux (CIUSSS) de l'Ouest-de-l'\u00cele-de-Montr\u00e9al , Montreal, QC H4H 1R3 , Canada"},{"name":"Department of Neurology and Neurosurgery, McGill University , Montreal, QC H3A 1A1 , Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jenna","family":"Stevenon","sequence":"additional","affiliation":[{"name":"Translational Neuroimaging Laboratory, The McGill University Research Centre for Studies in Aging, Douglas Mental Health University Institute, Le Centre Int\u00e9gr\u00e9 Universitaire de Sant\u00e9 et de Services Sociaux (CIUSSS) de l'Ouest-de-l'\u00cele-de-Montr\u00e9al , Montreal, QC H4H 1R3 , 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et de Services Sociaux (CIUSSS) de l'Ouest-de-l'\u00cele-de-Montr\u00e9al , Montreal, QC H4H 1R3 , Canada"},{"name":"Department of Neurology and Neurosurgery, McGill University , Montreal, QC H3A 1A1 , Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Serge","family":"Gauthier","sequence":"additional","affiliation":[{"name":"Translational Neuroimaging Laboratory, The McGill University Research Centre for Studies in Aging, Douglas Mental Health University Institute, Le Centre Int\u00e9gr\u00e9 Universitaire de Sant\u00e9 et de Services Sociaux (CIUSSS) de l'Ouest-de-l'\u00cele-de-Montr\u00e9al , Montreal, QC H4H 1R3 , Canada"},{"name":"Department of Neurology and Neurosurgery, McGill University , Montreal, QC H3A 1A1 , Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pedro","family":"Rosa-Neto","sequence":"additional","affiliation":[{"name":"Translational Neuroimaging Laboratory, The McGill University Research Centre for Studies in Aging, Douglas Mental Health University Institute, Le Centre Int\u00e9gr\u00e9 Universitaire de Sant\u00e9 et de Services Sociaux (CIUSSS) de l'Ouest-de-l'\u00cele-de-Montr\u00e9al , Montreal, QC H4H 1R3 , Canada"},{"name":"Department of Neurology and Neurosurgery, McGill University , Montreal, QC H3A 1A1 , Canada"},{"name":"Department of Medicine, McGill University Health Centre , Montreal, QC H3G 2M1 , Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2022,12,9]]},"reference":[{"issue":"11","key":"2023022702533470600_","doi-asserted-by":"crossref","first-page":"1087","DOI":"10.1093\/jnen\/62.11.1087","article-title":"Neuropathology of cognitively normal elderly","volume":"62","author":"Knopman","year":"2003","journal-title":"J Neuropathol Exp Neurol"},{"issue":"3","key":"2023022702533470600_","doi-asserted-by":"crossref","first-page":"370","DOI":"10.1212\/WNL.55.3.370","article-title":"\u201cPreclinical\u201d AD revisited: Neuropathology of cognitively normal older adults","volume":"55","author":"Schmitt","year":"2000","journal-title":"Neurology"},{"issue":"4","key":"2023022702533470600_","doi-asserted-by":"crossref","first-page":"535","DOI":"10.1016\/j.jalz.2018.02.018","article-title":"NIA-AA Research framework: Toward a biological definition of Alzheimer\u2019s disease","volume":"14","author":"Jack","year":"2018","journal-title":"Alzheimers Dement"},{"issue":"23","key":"2023022702533470600_","doi-asserted-by":"crossref","first-page":"2316","DOI":"10.1001\/jama.2019.7437","article-title":"Associations of amyloid, tau, and neurodegeneration biomarker profiles with rates of memory decline among individuals without dementia","volume":"321","author":"Jack","year":"2019","journal-title":"JAMA"},{"issue":"13","key":"2023022702533470600_","doi-asserted-by":"crossref","first-page":"1286","DOI":"10.1001\/jama.2019.2000","article-title":"Association of amyloid positron emission tomography with subsequent change in clinical management among medicare beneficiaries with mild cognitive impairment or dementia","volume":"321","author":"Rabinovici","year":"2019","journal-title":"JAMA"},{"issue":"1","key":"2023022702533470600_","doi-asserted-by":"crossref","first-page":"320","DOI":"10.1093\/brain\/awz378","article-title":"Amyloid and tau imaging biomarkers explain cognitive decline from late middle-age","volume":"143","author":"Betthauser","year":"2020","journal-title":"Brain"},{"issue":"2","key":"2023022702533470600_","doi-asserted-by":"crossref","first-page":"181","DOI":"10.1002\/ana.25395","article-title":"The impact of amyloid-beta and tau on prospective cognitive decline in older individuals","volume":"85","author":"Sperling","year":"2019","journal-title":"Ann Neurol"},{"issue":"3","key":"2023022702533470600_","doi-asserted-by":"crossref","DOI":"10.1093\/braincomms\/fcab136","article-title":"Association of plasma P-tau181 with memory decline in non-demented adults","volume":"3","author":"Therriault","year":"2021","journal-title":"Brain Commun"},{"issue":"1","key":"2023022702533470600_","doi-asserted-by":"crossref","first-page":"E29","DOI":"10.1212\/WNL.0000000000007728","article-title":"Cross-sectional associations of tau-PET signal with cognition in cognitively unimpaired adults","volume":"93","author":"Lowe","year":"2019","journal-title":"Neurology"},{"issue":"8","key":"2023022702533470600_","doi-asserted-by":"crossref","first-page":"961","DOI":"10.1001\/jamaneurol.2021.1858","article-title":"Accuracy of tau positron emission tomography as a prognostic marker in preclinical and prodromal Alzheimer disease: A head-to-head comparison against amyloid positron emission tomography and magnetic resonance imaging","volume":"78","author":"Ossenkoppele","year":"2021","journal-title":"JAMA Neurol"},{"issue":"5","key":"2023022702533470600_","doi-asserted-by":"crossref","first-page":"971","DOI":"10.1016\/j.neuron.2016.01.028","article-title":"PET imaging of tau deposition in the aging human brain","volume":"89","author":"Sch\u00f6ll","year":"2016","journal-title":"Neuron"},{"issue":"7","key":"2023022702533470600_","doi-asserted-by":"crossref","first-page":"829","DOI":"10.1001\/jamaneurol.2020.0528","article-title":"Positron emission tomography imaging with [18F]-flortaucipir and postmortem assessment of Alzheimer disease neuropathologic changes","volume":"77","author":"Fleisher","year":"2020","journal-title":"JAMA Neurol"},{"issue":"3","key":"2023022702533470600_","doi-asserted-by":"crossref","first-page":"561","DOI":"10.1016\/j.jalz.2019.09.079","article-title":"Tau-positron emission tomography correlates with neuropathology findings","volume":"16","author":"Lowe","year":"2020","journal-title":"Alzheimers Dement"},{"issue":"1","key":"2023022702533470600_","doi-asserted-by":"crossref","first-page":"74","DOI":"10.1186\/s13195-018-0402-y","article-title":"In vivo quantification of neurofibrillary tangles with [18F]-MK-6240","volume":"10","author":"Pascoal","year":"2018","journal-title":"Alzheimers Res Ther"},{"issue":"4","key":"2023022702533470600_","doi-asserted-by":"crossref","first-page":"470","DOI":"10.1001\/jamaneurol.2019.4421","article-title":"Association of apolipoprotein e \u025b4 with medial temporal tau independent of amyloid-\u03b2","volume":"77","author":"Therriault","year":"2020","journal-title":"JAMA Neurol"},{"key":"2023022702533470600_","doi-asserted-by":"crossref","first-page":"526","DOI":"10.1038\/s43587-022-00204-0","article-title":"Biomarker modeling of Alzheimer\u2019s disease using PET-based braak staging","volume":"2","author":"Therriault","year":"2022","journal-title":"Nat Aging"},{"issue":"3","key":"2023022702533470600_","doi-asserted-by":"crossref","first-page":"205","DOI":"10.1016\/j.jalz.2016.08.005","article-title":"Defining imaging biomarker cut points for brain aging and Alzheimer\u2019s 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Neurol"},{"issue":"4","key":"2023022702533470600_","doi-asserted-by":"crossref","first-page":"334","DOI":"10.1159\/000511506","article-title":"Lessons learnt from the second generation of anti-amyloid monoclonal antibodies clinical trials","volume":"49","author":"Kwan","year":"2021","journal-title":"Dement Geriatr Cogn Disord"},{"issue":"9","key":"2023022702533470600_","doi-asserted-by":"crossref","first-page":"e859","DOI":"10.1212\/WNL.0000000000006075","article-title":"Influence of tau PET, amyloid PET, and hippocampal volume on cognition in Alzheimer disease","volume":"91","author":"Aschenbrenner","year":"2018","journal-title":"Neurology"},{"issue":"22","key":"2023022702533470600_","doi-asserted-by":"crossref","first-page":"1053","DOI":"10.1212\/WNL.0000000000007583","article-title":"A brief history of \u201cAlzheimer disease\u201d: Multiple meanings separated by a common 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