Niklas Mattsson-Carlgren1, Antoine Leuzy2, Shorena Janelidze2, Sebastian Palmqvist2, Erik Stomrud2, Olof Strandberg2, Ruben Smith2, Oskar Hansson1. 1. From the Clinical Memory Research Unit, Department of Clinical Sciences (N.M.-C., A.L., S.J., S.P., E.S., O.S., R.S., O.H.), and Wallenberg Centre for Molecular Medicine (N.M.-C.), Lund University, Malmö; and Department of Neurology (N.M.-C., S.P., R.S.) and Memory Clinic (E.S., O.H.), Skåne University Hospital, Lund, Sweden. oskar.hansson@med.lu.se niklas.mattsson@med.lu.se. 2. From the Clinical Memory Research Unit, Department of Clinical Sciences (N.M.-C., A.L., S.J., S.P., E.S., O.S., R.S., O.H.), and Wallenberg Centre for Molecular Medicine (N.M.-C.), Lund University, Malmö; and Department of Neurology (N.M.-C., S.P., R.S.) and Memory Clinic (E.S., O.H.), Skåne University Hospital, Lund, Sweden.
Abstract
OBJECTIVE: To compare different β-amyloid (Aβ), tau, and neurodegeneration (AT[N]) variants within the Swedish BioFINDER studies. METHODS: A total of 490 participants were classified into AT(N) groups. These include 53 cognitively unimpaired (CU) and 48 cognitively impaired (CI) participants (14 mild cognitive impairment [MCI] and 34 Alzheimer disease [AD] dementia) from BioFINDER-1 and 389 participants from BioFINDER-2 (245 CU and 144 CI [138 MCI and 6 AD dementia]). Biomarkers for A were CSF Aβ42 and amyloid-PET ([18F]flutemetamol); for T, CSF phosphorylated tau (p-tau) and tau PET ([18F]flortaucipir); and for (N), hippocampal volume, temporal cortical thickness, and CSF neurofilament light (NfL). Binarization of biomarkers was achieved using cutoffs defined in other cohorts. The relationship between different AT(N) combinations and cognitive trajectories (longitudinal Mini-Mental State Examination scores) was examined using linear mixed modeling and coefficient of variation. RESULTS: Among CU participants, A-T-(N)- or A+T-(N)- variants were most common. However, more T+ cases were seen using p-tau than tau PET. Among CI participants, A+T+(N)+ was more common; however, more (N)+ cases were seen for MRI measures relative to CSF NfL. Tau PET best predicted longitudinal cognitive decline in CI and p-tau in CU participants. Among CI participants, continuous T (especially tau PET) and (N) measures improved the prediction of cognitive decline compared to binary measures. CONCLUSIONS: Our findings show that different AT(N) variants are not interchangeable, and that optimal variants differ by clinical stage. In some cases, dichotomizing biomarkers may result in loss of important prognostic information.
OBJECTIVE: To compare different β-amyloid (Aβ), tau, and neurodegeneration (AT[N]) variants within the Swedish BioFINDER studies. METHODS: A total of 490 participants were classified into AT(N) groups. These include 53 cognitively unimpaired (CU) and 48 cognitively impaired (CI) participants (14 mild cognitive impairment [MCI] and 34 Alzheimer disease [AD] dementia) from BioFINDER-1 and 389 participants from BioFINDER-2 (245 CU and 144 CI [138 MCI and 6 AD dementia]). Biomarkers for A were CSF Aβ42 and amyloid-PET ([18F]flutemetamol); for T, CSF phosphorylated tau (p-tau) and tau PET ([18F]flortaucipir); and for (N), hippocampal volume, temporal cortical thickness, and CSF neurofilament light (NfL). Binarization of biomarkers was achieved using cutoffs defined in other cohorts. The relationship between different AT(N) combinations and cognitive trajectories (longitudinal Mini-Mental State Examination scores) was examined using linear mixed modeling and coefficient of variation. RESULTS: Among CUparticipants, A-T-(N)- or A+T-(N)- variants were most common. However, more T+ cases were seen using p-tau than tau PET. Among CIparticipants, A+T+(N)+ was more common; however, more (N)+ cases were seen for MRI measures relative to CSF NfL. Tau PET best predicted longitudinal cognitive decline in CI and p-tau in CUparticipants. Among CIparticipants, continuous T (especially tau PET) and (N) measures improved the prediction of cognitive decline compared to binary measures. CONCLUSIONS: Our findings show that different AT(N) variants are not interchangeable, and that optimal variants differ by clinical stage. In some cases, dichotomizing biomarkers may result in loss of important prognostic information.
Authors: Sebastian Palmqvist; Pontus Tideman; Nicholas Cullen; Henrik Zetterberg; Kaj Blennow; Jeffery L Dage; Erik Stomrud; Shorena Janelidze; Niklas Mattsson-Carlgren; Oskar Hansson Journal: Nat Med Date: 2021-05-24 Impact factor: 53.440
Authors: Katheryn A Q Cousins; Jeffrey S Phillips; David J Irwin; Edward B Lee; David A Wolk; Leslie M Shaw; Henrik Zetterberg; Kaj Blennow; Sarah E Burke; Nikolas G Kinney; Garrett S Gibbons; Corey T McMillan; John Q Trojanowski; Murray Grossman Journal: Alzheimers Dement Date: 2020-11-23 Impact factor: 21.566
Authors: Bruno Dubois; Nicolas Villain; Giovanni B Frisoni; Gil D Rabinovici; Marwan Sabbagh; Stefano Cappa; Alexandre Bejanin; Stéphanie Bombois; Stéphane Epelbaum; Marc Teichmann; Marie-Odile Habert; Agneta Nordberg; Kaj Blennow; Douglas Galasko; Yaakov Stern; Christopher C Rowe; Stephen Salloway; Lon S Schneider; Jeffrey L Cummings; Howard H Feldman Journal: Lancet Neurol Date: 2021-04-29 Impact factor: 59.935
Authors: Rik Ossenkoppele; Juhan Reimand; Ruben Smith; Antoine Leuzy; Olof Strandberg; Sebastian Palmqvist; Erik Stomrud; Henrik Zetterberg; Philip Scheltens; Jeffrey L Dage; Femke Bouwman; Kaj Blennow; Niklas Mattsson-Carlgren; Shorena Janelidze; Oskar Hansson Journal: EMBO Mol Med Date: 2021-07-13 Impact factor: 12.137