Neuropsychiatric symptoms in cognitive decline and Alzheimer's disease: biomarker discovery using plasma proteomics

Correspondence to Dr. Julius Popp; e-mail: [email protected]

Received March 13, 2024Accepted August 07, 2024

Collaborators Data used in preparation of this article were obtained from the Alzheimer's Disease Neuroimaging Initiative (ADNI) database (adni.loni.usc.edu). As such, the investigators within the ADNI contributed to the design and implementation of ADNI and/or provided data but did not participate in analysis or writing of this report. A complete listing of ADNI investigators can be found at: Michael Weiner (University of California, San Francisco Northern California Institute for Research and Education), Paul Aisen (University of Southern California), Ronald Petersen (Mayo Clinic, Rochester (co-PI of of Clinical Core)), Clifford R Jack (Mayo Clinic, Rochester), William Jagust (University of California, Berkeley), Susan Landau (University of California, Berkeley), Monica Rivera-Mindt (Fordham University; Mt. Sinai Medical Center), Ozioma Okonkwo (University of Wisconsin), Leslie M Shaw (University of Pennsylvania), Edward B Lee (University of Pennsylvania), Arthur W Toga (University of California, Los Angeles), Laurel Beckett (University of California, Davis), Danielle Harvey (University of California, Davis), Robert C Green (Boston University), Andrew J Saykin (Indiana University), Kwangsik Nho (Indiana University), Richard J Perrin (Washington University St. Louis), Duygu Tosun (University of California, San Francisco), Pallavi Sachdev (Eisai (Chair, 2023-2024)), Erin Drake (Harvard University), Tom Montine (University of Washington (Chair)), Cat Conti (Northern California Institute for Research and Education), Rachel Nosheny (University of California, San Francisco), Diana Truran Sacrey (Northern California Institute for Research and Education), Juliet Fockler (University of California, San Francisco), Melanie J Miller (Northern California Institute for Research and Education), Winnie Kwang (University of California, San Francisco), Chengshi Jin (University of California, San Francisco), Adam Diaz (Northern California Institute for Research and Education), Miriam Ashford (Northern California Institute for Research and Education), Derek Flenniken (Northern California Institute for Research and Education), Adrienne Kormos (Northern California Institute for Research and Education), Michael Rafii (University of Southern California), Rema Raman (University of Southern California), Gustavo Jimenez (University of Southern California), Michael Donohue (University of Southern California), Jennifer Salazar (University of Southern California), Andrea Fidell (University of Southern California), Virginia Boatwright (University of Southern California), Justin Robison (University of Southern California), Caileigh Zimmerman (University of Southern California), Yuliana Cabrera (University of Southern California), Sarah Walter (University of Southern California), Taylor Clanton (University of Southern California), Elizabeth Shaffer (University of Southern California), Caitlin Webb (University of Southern California), Lindsey Hergesheimer (University of Southern California), Stephanie Smith (University of Southern California), Sheila Ogwang (University of Southern California), Sheila Ogwang (University of Southern California), Payam Mahboubi (University of Southern California), Jeremy Pizzola (University of Southern California), Cecily Jenkins (University of Southern California), Laurel Beckett (University of California, Davis (Core PI)), Danielle Harvey (University of California, Davis (Core PI)), Michael Donohue (University of Southern California), Naomi Saito (University of California, Davis), Adam Diaz (Northern California Institute for Research and Education), Kedir Adem Hussen (University of Southern California), Hannatu Amaza (University of Wisconsin), Mai Seng Thao (University of Wisconsin), Shaniya Parkins (Mt. Sinai), Omobolanle Ayo (Mt. Sinai), Matt Glittenberg (University of Wisconsin), Isabella Hoang (University of Wisconsin), Kaori Kubo Germano (Fordham University), Joe Strong (University of Wisconsin), Trinity Weisensel (University of Wisconsin), Fabiola Magana (University of Wisconsin), Lisa Thomas (University of Wisconsin), Vanessa Guzman (Mt. Sinai), Adeyinka Ajayi (Mt. Sinai), Joseph Di Benedetto (Mt. Sinai), Sandra Talavera (Fordham University), Joel Felmlee (Mayo Clinic, Rochester), Nick C Fox (University College London), Paul Thompson (UCLA School of Medicine), Charles DeCarli (University of California, Davis), Arvin Forghanian-Arani (Mayo Clinic, Rochester), Bret Borowski (Mayo Clinic, Rochester), Calvin Reyes (Mayo Clinic, Rochester), Caitie Hedberg (Mayo Clinic, Rochester), Chad Ward (Mayo Clinic, Rochester), Christopher Schwarz (Mayo Clinic, Rochester), Denise Reyes (Mayo Clinic, Rochester), Jeff Gunter (Mayo Clinic, Rochester), John Moore-Weiss (Mayo Clinic, Rochester), Kejal Kantarci (Mayo Clinic, Rochester), Leonard Matoush (Mayo Clinic, Rochester), Matthew Senjem (Mayo Clinic, Rochester), Prashanthi Vemuri (Mayo Clinic, Rochester), Robert Reid (Mayo Clinic, Rochester), Ian Malone (University College London), Sophia I Thomopoulos (University of Southern California School of Medicine), Talia M Nir (University of Southern California School of Medicine), Neda Jahanshad (University of Southern California School of Medicine), Alexander Knaack (University of California, Davis), Evan Fletcher (University of California, Davis), Danielle Harvey (University of California, Davis), Duygu Tosun-Turgut (University of California, San Francisco), Stephanie Rossi Chen (Northern California Institute for Research and Education), Mark Choe (Northern California Institute for Research and Education), Karen Crawford (University of Southern California School of Medicine), Paul A Yushkevich (University of Pennsylvania), Sandhitsu Das (University of Pennsylvania), Robert A Koepp (University of Michigan), Gil Rabinovici (University of California San Francisco), Victor Villemagne (University of Pittsburgh), Brian LoPresti (University of Pittsburgh), John Morris (Washington University St. Louis), Erin Franklin (Washington University St. Louis), Haley Bernhardt (Washington University St. Louis), Nigel J Cairns (Washington University St. Louis), Lisa Taylor-Reinwald (Washington University St. Louis), Edward B Lee (University of Pennsylvania (Core PI)), Virginia M Y Lee (UPenn School of Medicine), Magdalena Korecka (UPenn School of Medicine), Magdalena Brylska (UPenn School of Medicine), Yang Wan (UPenn School of Medicine), J Q Trojanowki (UPenn School of Medicine (*former Core PI, deceased)), Karen Crawford (University of Southern California), Scott Neu (University of Southern California), Tatiana M Foroud (Indiana University School of Medicine (Dir. NCRAD)), Taeho Jo (Indiana University School of Medicine), Shannon L Risacher (Indiana University School of Medicine), Hannah Craft (Indiana University School of Medicine), Liana G Apostolova (Indiana University School of Medicine), Kelly Nudelman (NCRAD/Indiana University School of Medicine), Kelley Faber (NCRAD/Indiana University School of Medicine), Zoë Potter (NCRAD/Indiana University School of Medicine), Kaci Lacy (NCRAD/Indiana University School of Medicine), Rima Kaddurah-Daouk (Duke University/AD Metabolomics Consortium), Li Shen (University of Pennsylvania), Jason Karlawish (University of Pennsylvania), Claire Erickson (University of Pennsylvania), Joshua Grill (University of California, Irvine), Emily Largent (University of Pennsylvania), Kristin Harkins (University of Pennsylvania), Leon Thal, Zaven Kachaturian (Khachaturian, Radebaugh & Associates (KRA), Inc), Richard Frank (General Electric), Peter J Snyder (General Electric, Alzheimer’s Association’s Ronald and Nancy Reagan’s Research Institute), Neil Buckholtz (National Institute on Aging), John K Hsiao (National Institute on Aging), Laurie Ryan (National Institute on Aging), Susan Molchan (National Institute on Aging/National Institutes of Health), Maria Carrillo (Alzheimer's Association), William Potter (National Institute of Mental Health), Lisa Barnes (Rush University), Marie Bernard (NIA), Hector González (University of California, San Diego), Carole Ho (Denali Therapeutics), John K Hsiao (NIH), Jonathan Jackson (Massachusetts General Hospital), Eliezer Masliah (NIA), Donna Masterman (Biogen), Laurie Ryan (NIA), Nina Silverberg (NIA), Lisa Silbert (Oregon Health and Science University), Jeffrey Kaye (Oregon Health and Science University), Sylvia White (Salazar) (Oregon Health and Science University), Aimee Pierce (Oregon Health and Science University), Amy Thomas (Oregon Health and Science University), Tera Clay (Oregon Health and Science University), Daniel Schwartz (Oregon Health and Science University), Gillian Devereux (Oregon Health and Science University), Janet “Janae” Taylor (Oregon Health and Science University), Jennifer Ryan (Oregon Health and Science University), Mike Nguyen (Oregon Health and Science University), Madison DeCapo (Oregon Health and Science University), Yanan Shang (Oregon Health and Science University), Lon Schneider (University of Southern California), Cynthia Munoz (University of Southern California), Diana Ferman (University of Southern California), Carlota Conant (University of Southern California), Katherin Martin (University of Southern California), Kristin Oleary (University of Southern California), Sonia Pawluczyk (University of Southern California), Elizabeth Trejo (University of Southern California), Karen Dagerman (University of Southern California), Liberty Teodoro (University of Southern California), Mauricio Becerra (University of Southern California), Madiha Fairooz (University of Southern California), Sonia Garrison (University of Southern California), Julia Boudreau (University of Southern California), Yair Avila (University of Southern California), James Brewer (University of California--San Diego), Aaron Jacobson (University of California--San Diego), Antonio Gama (University of California--San Diego), Chi Kim (University of California--San Diego), Emily Little (University of California--San Diego), Jennifer Frascino (University of California--San Diego), Nichol Ferng (University of California--San Diego), Socorro Trujillo (University of California--San Diego), Judith Heidebrink (University of Michigan), Robert Koeppe (University of Michigan), Steven MacDonald (University of Michigan), Dariya Malyarenko (University of Michigan), Jaimie Ziolkowski (University of Michigan), James O’Connor (University of Michigan), Nicole Robert (University of Michigan), Suzan Lowe (University of Michigan), Virginia Rogers (University of Michigan), Barbara Hackenmiller (Mayo Clinic, Rochester), Bradley Boeve (Mayo Clinic, Rochester), Colleen Albers (Mayo Clinic, Rochester), Connie Kreuger (Mayo Clinic, Rochester), David Jones (Mayo Clinic, Rochester), David Knopman (Mayo Clinic, Rochester), Hugo Botha (Mayo Clinic, Rochester), Jessica Magnuson (Mayo Clinic, Rochester), Jonathan Graff-Radford (Mayo Clinic, Rochester), Kerry Crawley (Mayo Clinic, Rochester), Michael Schumacher (Mayo Clinic, Rochester), Sanna McKinzie (Mayo Clinic, Rochester), Steven Smith (Mayo Clinic, Rochester), Tascha Helland (Mayo Clinic, Rochester), Val Lowe (Mayo Clinic, Rochester), Vijay Ramanan (Mayo Clinic, Rochester), Valory Pavlik (Baylor College of Medicine), Jacob Faircloth (Baylor College of Medicine), Jeffrey Bishop (Baylor College of Medicine), Jessica Nath (Baylor College of Medicine), Maria Chaudhary (Baylor College of Medicine), Maria Kataki (Baylor College of Medicine), Melissa Yu (Baylor College of Medicine), Nathiel Pacini (Baylor College of Medicine), Randall Barker (Baylor College of Medicine), Regan Brooks (Baylor College of Medicine), Ruchi Aggarwal (Baylor College of Medicine), Lawrence Honig (Columbia University Medical Center), Yaakov Stern (Columbia University Medical Center), Akiva Mintz (Columbia University Medical Center), Jonathan Cordona (Columbia University Medical Center), Michelle Hernandez (Columbia University Medical Center), Justin Long (Washington University, St. Louis), Abbey Arnold (Washington University, St. Louis), Alex Groves (Washington University, St. Louis), Anna Middleton (Washington University, St. Louis), Blake Vogler (Washington University, St. Louis), Cierra McCurry (Washington University, St. Louis), Connie Mayo (Washington University, St. Louis), Cyrus Raji (Washington University, St. Louis), Fatima S Amtashar (Washington University, St. Louis), Heather Klemp (Washington University, St. Louis), Heather Nicole Elmore (Washington University, St. Louis), James Ruszkiewicz (Washington University, St. Louis), Jasmina Kusuran (Washington University, St. Louis), Jasmine Stewart (Washington University, St. Louis), Jennifer Horenkamp (Washington University, St. Louis), Julia Greeson (Washington University, St. Louis), Kara Wever (Washington University, St. Louis), Katie Vo (Washington University, St. Louis), Kelly Larkin (Washington University, St. Louis), Lesley Rao (Washington University, St. Louis), Lisa Schoolcraft (Washington University, St. Louis), Lora Gallagher (Washington University, St. Louis), Madeline Paczynski (Washington University, St. Louis), Maureen McMillan (Washington University, St. Louis), Michael Holt (Washington University, St. Louis), Nicole Gagliano (Washington University, St. Louis), Rachel Henson (Washington University, St. Louis), Renee LaBarge (Washington University, St. Louis), Robert Swarm (Washington University, St. Louis), Sarah Munie (Washington University, St. Louis), Serena Cepeda (Washington University, St. Louis), Stacey Winterton (Washington University, St. Louis), Stephen Hegedus (Washington University, St. Louis), TaNisha Wilson (Washington University, St. Louis), Tanya Harte (Washington University, St. Louis), Zach Bonacorsi (Washington University, St. Louis), David Geldmacher (University of Alabama Birmingham), Amber Watkins (University of Alabama Birmingham), Brandi Barger (University of Alabama Birmingham), Bryan Smelser (University of Alabama Birmingham), Charna Bates (University of Alabama Birmingham), Cynthia Stover (University of Alabama Birmingham), Emily McKinley (University of Alabama Birmingham), Gregory Ikner (University of Alabama Birmingham), Haley Hendrix (University of Alabama Birmingham), Harold Matthew Cooper (University of Alabama Birmingham), Jennifer Mahaffey (University of Alabama Birmingham), Lindsey Booth Robbins (University of Alabama Birmingham), Loren Brown Ashley (University of Alabama Birmingham), Marissa Natelson -Love (University of Alabama Birmingham), Princess Carter (University of Alabama Birmingham), Veronika Solomon (University of Alabama Birmingham), Hillel Grossman (Mount Sinai School of Medicine), Alexandra Groome (Mount Sinai School of Medicine), Allison Ardolino (Mount Sinai School of Medicine), Anthony Kaplan (Mount Sinai School of Medicine), Faye Sheppard (Mount Sinai School of Medicine), Genesis Burgos -Rivera (Mount Sinai School of Medicine), Gina Garcia -Camilo (Mount Sinai School of Medicine), Joanne Lim (Mount Sinai School of Medicine), Judith Neugroschl (Mount Sinai School of Medicine), Kimberly Jackson (Mount Sinai School of Medicine), Kirsten Evans (Mount Sinai School of Medicine), Laili Soleimani (Mount Sinai School of Medicine), Mary Sano (Mount Sinai School of Medicine), Nasrin Ghesani (Mount Sinai School of Medicine), Sarah Binder (Mount Sinai School of Medicine), Xiomara Mendoza Apuango (Mount Sinai School of Medicine), Ajay Sood (Rush University Medical Center), Amelia Troutman (Rush University Medical Center), Kimberly Blanchard (Rush University Medical Center), Arlene Richards (Rush University Medical Center), Grace Nelson (Rush University Medical Center), Kirsten Hendrickson (Rush University Medical Center), Erin Yurko (Rush University Medical Center), Jamie Plenge (Rush University Medical Center), Victoria Rufo (Rush University Medical Center), Raj Shah (Rush University Medical Center), Ranjan Duara (Wein Center), Brendan Lynch (Wein Center), Cesar Chirinos (Wein Center), Christine Dittrich (Wein Center), Debbie Campbell (Wein Center), Diego Mejia (Wein Center), Gilberto Perez (Wein Center), Helena Colvee (Wein Center), Joanna Gonzalez (Wein Center), Josalen Gondrez (Wein Center), Joshua Knaack (Wein Center), Mara Acevedo (Wein Center), Maria Cereijo (Wein Center), Maria Greig -Cust (Wein Center), Michelle Villar (Wein Center), Morris Wishnia (Wein Center), Sheryl Detling (Wein Center), Warren Barker (Wein Center), Marilyn Albert (Johns Hopkins University), Abhay Moghekar (Johns Hopkins University), Barbara Rodzon (Johns Hopkins University), Corey Demsky (Johns Hopkins University), Gregory Pontone (Johns Hopkins University), Jim Pekar (Johns Hopkins University), Leonie Farrington (Johns Hopkins University), Martin Pomper (Johns Hopkins University), Nicole Johnson (Johns Hopkins University), Tolulope Alo (Johns Hopkins University), Martin Sadowski (New York University), Anaztasia Ulysse (New York University), Arjun Masurkar (New York University), Brittany Marti (New York University), David Mossa (New York University), Emilie Geesey (New York University), Emily Petrocca (New York University), Evan Schulze (New York University), Jennifer Wong (New York University), Joseph Boonsiri (New York University), Sunnie Kenowsky (New York University), Tatianne Martinez (New York University), Veronica Briglall (New York University), P Murali Doraiswamy (Duke University Medical Center), Adaora Nwosu (Duke University Medical Center), Alisa Adhikari (Duke University Medical Center), Cammie Hellegers (Duke University Medical Center), Jeffrey Petrella (Duke University Medical Center), Olga James (Duke University Medical Center), Terence Wong (Duke University Medical Center), Thomas Hawk (Duke University Medical Center), Sanjeev Vaishnavi (University of Pennsylvania), Hannah McCoubrey (University of Pennsylvania), Ilya Nasrallah (University of Pennsylvania), Rachel Rovere (University of Pennsylvania), Jeffrey Maneval (University of Pennsylvania), Elizabeth Robinson (University of Pennsylvania), Francisco Rivera (University of Pennsylvania), Jade Uffelman (University of Pennsylvania), Martha Combs (University of Pennsylvania), Patricia O’Donnell (University of Pennsylvania), Sara Manning (University of Pennsylvania), Richard King (University of Kentucky), Alayne Nieto (University of Kentucky), Amanda Glueck (University of Kentucky), Anjana Mandal (University of Kentucky), Audrie Swain (University of Kentucky), Bethanie Gamble (University of Kentucky), Beverly Meacham (University of Kentucky), Denece Forenback (University of Kentucky), Dorothy Ross (University of Kentucky), Elizabeth Cheatham (University of Kentucky), Ellen Hartman (University of Kentucky), Gary Cornell (University of Kentucky), Jordan Harp (University of Kentucky), Laura Ashe (University of Kentucky), Laura Goins (University of Kentucky), Linda Watts (University of Kentucky), Morgan Yazell (University of Kentucky), Prabin Mandal (University of Kentucky), Regan Buckler (University of Kentucky), Sylvia Vincent (University of Kentucky), Triana Rudd (University of Kentucky), Oscar Lopez (University of Pittsburgh), Ann Arlene Malia (University of Pittsburgh), Caitlin Chiado (University of Pittsburgh), Cary Zik (University of Pittsburgh), James Ruszkiewicz (University of Pittsburgh), Kathleen Savage (University of Pittsburgh), Linda Fenice (University of Pittsburgh), MaryAnn Oakley (University of Pittsburgh), Paige C Tacey (University of Pittsburgh), Sarah Berman (University of Pittsburgh), Sarah Bowser (University of Pittsburgh), Stephen Hegedus (University of Pittsburgh), Xanthia Saganis (University of Pittsburgh), Anton Porsteinsson (University of Rochester Medical Center), Abigail Mathewson (University of Rochester Medical Center), Asa Widman (University of Rochester Medical Center), Bridget Holvey (University of Rochester Medical Center), Emily Clark (University of Rochester Medical Center), Esmeralda Morales (University of Rochester Medical Center), Iris Young (University of Rochester Medical Center), James Ruszkiewicz (University of Rochester Medical Center), Kevin Hopkins (University of Rochester Medical Center), Kimberly Martin (University of Rochester Medical Center), Nancy Kowalski (University of Rochester Medical Center), Rebecca Hunt (University of Rochester Medical Center), Roberta Calzavara (University of Rochester Medical Center), Russell Kurvach (University of Rochester Medical Center), Stephen D’Ambrosio (University of Rochester Medical Center), Gaby Thai (University of California, Irvine), Beatriz Vides (University of California, Irvine), Brigit Lieb (University of California, Irvine), Catherine McAdams -Ortiz (University of California, Irvine), Cyndy Toso (University of California, Irvine), Ivan Mares (University of California, Irvine), Kathryn Moorlach (University of California, Irvine), Luter Liu (University of California, Irvine), Maria Corona (University of California, Irvine), Mary Nguyen (University of California, Irvine), Melanie Tallakson (University of California, Irvine), Michelle McDonnell (University of California, Irvine), Milagros Rangel (University of California, Irvine), Neetha Basheer (University of California, Irvine), Patricia Place (University of California, Irvine), Romina Romero (University of California, Irvine), Steven Tam (University of California, Irvine), Trung Nguyen (University of Texas Southwestern Medical School), Abey Thomas (University of Texas Southwestern Medical School), Alexander (Alex) Frolov (University of Texas Southwestern Medical School), Alka Khera (University of Texas Southwestern Medical School), Amy Browning (University of Texas Southwestern Medical School), Brendan Kelley (University of Texas Southwestern Medical School), Courtney Dawson (University of Texas Southwestern Medical School), Dana Mathews (University of Texas Southwestern Medical School), Elaine Most (University of Texas Southwestern Medical School), Elizeva (Ellie) Phillips (University of Texas Southwestern Medical School), Lynn Nguyen (University of Texas Southwestern Medical School), Maribel Nunez (University of Texas Southwestern Medical School), Matalin Miller (University of Texas Southwestern Medical School), Matthew R Jones (University of Texas Southwestern Medical School), Natalie Martinez (University of Texas Southwestern Medical School), Rebecca Logan (University of Texas Southwestern Medical School), Roderick McColl (University of Texas Southwestern Medical School), Sari Pham (University of Texas Southwestern Medical School), Tiffani Fox (University of Texas Southwestern Medical School), Tracey Moore (University of Texas Southwestern Medical School), Allan Levey (Emory University), Abby Brown (Emory University), Andrea Kippels (Emory University), Ashton Ellison (Emory University), Casie Lyons (Emory University), Chadwick Hales (Emory University), Cindy Parry (Emory University), Courtney Williams (Emory University), Elizabeth McCorkle (Emory University), Guy Harris (Emory University), Heather Rose (Emory University), Inara Jooma (Emory University), Jahmila Al -Amin (Emory University), James Lah (Emory University), James Webster (Emory University), Jessica Swiniarski (Emory University), Latasha Chapman (Emory University), Laura Donnelly (Emory University), Lauren Mariotti (Emory University), Mary Locke (Emory University), Phyllis Vaughn (Emory University), Rachael Penn (Emory University), Sallie Carpentier (Emory University), Samira Yeboah (Emory University), Sarah Basadre (Emory University), Sarah Malakauskas (Emory University), Stefka Lyron (Emory University), Tara Villinger (Emory University), Terra Burney (Emory University), Jeffrey Burns (University of Kansas, Medical Center), Ala Abusalim (University of Kansas, Medical Center), Alexandra Dahlgren (University of Kansas, Medical Center), Alexandria Montero (University of Kansas, Medical Center), Anne Arthur (University of Kansas, Medical Center), Heather Dooly (University of Kansas, Medical Center), Katelynn Kreszyn (University of Kansas, Medical Center), Katherine Berner (University of Kansas, Medical Center), Lindsey Gillen (University of Kansas, Medical Center), Maria Scanlan (University of Kansas, Medical Center), Mercedes Madison (University of Kansas, Medical Center), Nicole Mathis (University of Kansas, Medical Center), Phyllis Switzer (University of Kansas, Medical Center), Ryan Townley (University of Kansas, Medical Center), Samantha Fikru (University of Kansas, Medical Center), Samantha Sullivan (University of Kansas, Medical Center), Ella Wright (University of Kansas, Medical Center), Maryam Beigi (University of California, Los Angeles), Anthony Daley (University of California, Los Angeles), Ashley Ko (University of California, Los Angeles), Brittney Luong (University of California, Los Angeles), Glen Nyborg (University of California, Los Angeles), Jessica Morales (University of California, Los Angeles), Kelly Durbin (University of California, Los Angeles), Lauren Garcia (University of California, Los Angeles), Leila Parand (University of California, Los Angeles), Lorena Macias (University of California, Los Angeles), Lorena Monserratt (University of California, Los Angeles), Maya Farchi (University of California, Los Angeles), Pauline Wu (University of California, Los Angeles), Robert Hernandez (University of California, Los Angeles), Thao Rodriguez (University of California, Los Angeles), Neill Graff-Radford (Mayo Clinic, Jacksonville), A’llana Marolt (Mayo Clinic, Jacksonville), Anton Thomas (Mayo Clinic, Jacksonville), Deborah Aloszka (Mayo Clinic, Jacksonville), Ercilia Moncayo (Mayo Clinic, Jacksonville), Erin Westerhold (Mayo Clinic, Jacksonville), Gregory Day (Mayo Clinic, Jacksonville), Kandise Chrestensen (Mayo Clinic, Jacksonville), Mary Imhansiemhonehi (Mayo Clinic, Jacksonville), Sanna McKinzie (Mayo Clinic, Jacksonville), Sochenda Stephens (Mayo Clinic, Jacksonville), Sylvia Grant (Mayo Clinic, Jacksonville), Jared Brosch (Mayo Clinic, Jacksonville), Amy Perkins (Mayo Clinic, Jacksonville), Aubree Saunders (Mayo Clinic, Jacksonville), Debra Silberberg Kovac (Mayo Clinic, Jacksonville), Heather Polson (Mayo Clinic, Jacksonville), Isabell Mwaura (Mayo Clinic, Jacksonville), Kassandra Mejia (Mayo Clinic, Jacksonville), Katherine Britt (Mayo Clinic, Jacksonville), Kathy King (Mayo Clinic, Jacksonville), Kayla Nichols (Mayo Clinic, Jacksonville), Kayley Lawrence (Mayo Clinic, Jacksonville), Lisa Rankin (Mayo Clinic, Jacksonville), Martin Farlow (Mayo Clinic, Jacksonville), Patricia Wiesenauer (Mayo Clinic, Jacksonville), Robert Bryant (Mayo Clinic, Jacksonville), Scott Herring (Mayo Clinic, Jacksonville), Sheryl Lynch (Mayo Clinic, Jacksonville), Skylar Wilson (Mayo Clinic, Jacksonville), Traci Day (Mayo Clinic, Jacksonville), William Korst (Mayo Clinic, Jacksonville), Christopher van Dyck (Yale University School of Medicine), Adam Mecca (Yale University School of Medicine), Alyssa Miller (Yale University School of Medicine), Amanda Brennan (Yale University School of Medicine), Amber Khan (Yale University School of Medicine), Audrey Ruan (Yale University School of Medicine), Carol Gunnoud (Yale University School of Medicine), Chelsea Mendonca (Yale University School of Medicine), Danielle Raynes -Goldfinger (Yale University School of Medicine), Elaheh Salardini (Yale University School of Medicine), Elisa Hidalgo (Yale University School of Medicine), Emma Cooper (Yale University School of Medicine), Erawadi Singh (Yale University School of Medicine), Erin Murphy (Yale University School of Medicine), Jeanine May (Yale University School of Medicine), Jesse Stanhope (Yale University School of Medicine), Jessica Lam (Yale University School of Medicine), Julia Waszak (Yale University School of Medicine), Kimberly Nelsen (Yale University School of Medicine), Kimberly Sacaza (Yale University School of Medicine), Mayer Joshua Hasbani (Yale University School of Medicine), Meghan Donahue (Yale University School of Medicine), Ming -Kai Chen (Yale University School of Medicine), Nicole Barcelos (Yale University School of Medicine), Paul Eigenberger (Yale University School of Medicine), Robin Bonomi (Yale University School of Medicine), Ryan O’Dell (Yale University School of Medicine), Sarah Jefferson (Yale University School of Medicine), Siddharth Khasnavis (Yale University School of Medicine), Stephen Smilowitz (Yale University School of Medicine), Susan DeStefano (Yale University School of Medicine), Susan Good (Yale University School of Medicine), Terry Camarro (Yale University School of Medicine), Vanessa Clayton (Yale University School of Medicine), Yanis Cavrel (Yale University School of Medicine), YuQuan “Oliver” Lu (Yale University School of Medicine), Howard Chertkow (McGill Unive rsity, Montreal -Jewish General Hospital), Howard Bergman (McGill Unive rsity, Montreal -Jewish General Hospital), Chris Hosein (McGill Unive rsity, Montreal -Jewish General Hospital), Sandra Black (Sunnybrook Health Sciences, Ontario), Anish Kapadia (Sunnybrook Health Sciences, Ontario), Aparna Bhan (Sunnybrook Health Sciences, Ontario), Benjamin Lam (Sunnybrook Health Sciences, Ontario), Christopher Scott (Sunnybrook Health Sciences, Ontario), Gillian Gabriel (Sunnybrook Health Sciences, Ontario), Jennifer Bray (Sunnybrook Health Sciences, Ontario), Ljubica Zotovic (Sunnybrook Health Sciences, Ontario), Maria Samira Gutierrez (Sunnybrook Health Sciences, Ontario), Mario Masellis (Sunnybrook Health Sciences, Ontario), Marjan Farshadi (Sunnybrook Health Sciences, Ontario), Maurylette Gui (Sunnybrook Health Sciences, Ontario), Meghan Mitchell (Sunnybrook Health Sciences, Ontario), Rebecca Taylor (Sunnybrook Health Sciences, Ontario), Ruby Endre (Sunnybrook Health Sciences, Ontario), Zhala Taghi-Zada (Sunnybrook Health Sciences, Ontario), Robin Hsiung (University of British Columbia Clinic for AD & Related Disorders), Carolyn English (University of British Columbia Clinic for AD & Related Disorders), Ellen Kim (University of British Columbia Clinic for AD & Related Disorders), Eugene Yau (University of British Columbia Clinic for AD & Related Disorders), Haley Tong (University of British Columbia Clinic for AD & Related Disorders), Laura Barlow (University of British Columbia Clinic for AD & Related Disorders), Lauren Jennings (University of British Columbia Clinic for AD & Related Disorders), Michele Assaly (University of British Columbia Clinic for AD & Related Disorders), Paula Nunes (University of British Columbia Clinic for AD & Related Disorders), Tahlee Marian (University of British Columbia Clinic for AD & Related Disorders), Andrew Kertesz (Cognitive Neurology St. Joseph's Ontario), John Rogers (Cognitive Neurology St. Joseph's Ontario), Dick Trost (Cognitive Neurology St. Joseph's Ontario), Dylan Wint (Cleveland Clinic Lou Ruvo Center for Brain Health), Charles Bernick (Cleveland Clinic Lou Ruvo Center for Brain Health), Donna Munic (Cleveland Clinic Lou Ruvo Center for Brain Health), Ian Grant (Northwestern University), Aaliyah Korkoyah (Northwestern University), Ali Raja (Northwestern University), Allison Lapins (Northwestern University), Caila Ryan (Northwestern University), Jelena Pejic (Northwestern University), Kailey Basham (Northwestern University), Leena Lukose (Northwestern University), Loreece Haddad (Northwestern University), Lucas Quinlan (Northwestern University), Nathaniel Houghtaling (Northwestern University), Carl Sadowsky (Premiere Research Inst (Palm Beach Neurology)), Walter Martinez (Premiere Research Inst (Palm Beach Neurology)), Teresa Villena (Premiere Research Inst (Palm Beach Neurology)), Brigid Reynolds (Georgetown University Medical Center), Angelica Forero (Georgetown University Medical Center), Carolyn Ward (Georgetown University Medical Center), Emma Brennan (Georgetown University Medical Center), Esteban Figueroa (Georgetown University Medical Center), Giuseppe Esposito (Georgetown University Medical Center), Jessica Mallory (Georgetown University Medical Center), Kathleen Johnson (Georgetown University Medical Center), Kathryn Turner (Georgetown University Medical Center), Katie Seidenberg (Georgetown University Medical Center), Kelly McCann (Georgetown University Medical Center), Margaret Bassett (Georgetown University Medical Center), Melanie Chadwick (Georgetown University Medical Center), Raymond Scott Turner (Georgetown University Medical Center), Robin Bean (Georgetown University Medical Center), Saurabh Sharma (Georgetown University Medical Center), Gad Marshall (Brigham and Women’s Hospital), Aferdita Haviari (Brigham and Women’s Hospital), Alison Pietras (Brigham and Women’s Hospital), Bradley Wallace (Brigham and Women’s Hospital), Catherine Munro (Brigham and Women’s Hospital), Gladiliz Rivera -Delpin (Brigham and Women’s Hospital), Hadley Hustead (Brigham and Women’s Hospital), Isabella Levesque (Brigham and Women’s Hospital), Jennifer Ramirez (Brigham and Women’s Hospital), Karen Nolan (Brigham and Women’s Hospital), Kirsten Glennon (Brigham and Women’s Hospital), Mariana Palou (Brigham and Women’s Hospital), Michael Erkkinen (Brigham and Women’s Hospital), Nicole DaSilva (Brigham and Women’s Hospital), Pamela Friedman (Brigham and Women’s Hospital), Regina M Silver (Brigham and Women’s Hospital), Ricardo Salazar (Brigham and Women’s Hospital), Roxxanne Polleys (Brigham and Women’s Hospital), Scott McGinnis (Brigham and Women’s Hospital), Seth Gale (Brigham and Women’s Hospital), Tia Hall (Brigham and Women’s Hospital), Tuan Luu (Brigham and Women’s Hospital), Steven Chao (Stanford University), Emmeline Lin (Stanford University), Jaila Coleman (Stanford University), Kevin Epperson (Stanford University), Minal Vasanawala (Stanford University), Alireza Atri (Banner Sun Health Research Institute), Amy Rangel (Banner Sun Health Research Institute), Brittani Evans (Banner Sun Health Research Institute), Candy Monarrez (Banner Sun Health Research Institute), Carol Cline (Banner Sun Health Research Institute), Carolyn Liebsack (Banner Sun Health Research Institute), Daniel Bandy (Banner Sun Health Research Institute), Danielle Goldfarb (Banner Sun Health Research Institute), Debbie Intorcia (Banner Sun Health Research Institute), Jennifer Olgin (Banner Sun Health Research Institute), Kelly Clark (Banner Sun Health Research Institute), Kelsey King (Banner Sun Health Research Institute), Kylee York (Banner Sun Health Research Institute), Marina Reade (Banner Sun Health Research Institute), Michael Callan (Banner Sun Health Research Institute), Michael Glass (Banner Sun Health Research Institute), Michaela Johnson (Banner Sun Health Research Institute), Michele Gutierrez (Banner Sun Health Research Institute), Molly Goddard (Banner Sun Health Research Institute), Nadira Trncic (Banner Sun Health Research Institute), Parichita Choudhury (Banner Sun Health Research Institute), Priscilla Reyes (Banner Sun Health Research Institute), Serena Lowery (Banner Sun Health Research Institute), Shaundra Hall (Banner Sun Health Research Institute), Sonia Olgin (Banner Sun Health Research Institute), Stephanie de Santiago (Banner Sun Health Research Institute), Michael Alosco (Boston University), Alyssa Ton (Boston University), Amanda Jimenez (Boston University), Andrew Ellison (Boston University), Anh Tran (Boston University), Brandon Anderson (Boston University), Della Carter (Boston University), Donna Veronelli (Boston University), Steven Lenio (Boston University), Eric Steinberg (Boston University), Jesse Mez (Boston University), Jason Weller (Boston University), Jennifer Johns (Boston University), Jessica Harkins (Boston University), Ina Hoti (Boston University), Jane Mwicigi (Boston University), Olivia Schultz (Boston University), Mona Lauture (Boston University), Ridiane Denis (Boston University), Ronald Killiany (Boston University), Sarab Singh (Boston University), Steven Lenio (Boston University), Wendy Qiu (Boston University), Ycar Devis (Boston University), Thomas Obisesan (Howard University), Andrew Stone (Howard University), Debra Ordor (Howard University), Ifreke Udodong (Howard University), Immaculata Okonkwo (Howard University), Javed Khan (Howard University), Jillian Turner (Howard University), Kyliah Hughes (Howard University), Oshoze Kadiri (Howard University), Charles Duffy (Case Western Reserve University), Ariana Moss (Case Western Reserve University), Katherine Stapleton (Case Western Reserve University), Maria Toth (Case Western Reserve University), Marianne Sanders (Case Western Reserve University), Martin Ayres (Case Western Reserve University), Melissa Hamski (Case Western Reserve University), Parianne Fatica (Case Western Reserve University), Paula Ogrocki (Case Western Reserve University), Sarah Ash (Case Western Reserve University), Stacy Pot (Case Western Reserve University), Doris Chen (University of California, Davis Sacramento), Andres Soto (University of California, Davis Sacramento), Costin Tanase (University of California, Davis Sacramento), David Bissig (University of California, Davis Sacramento), Hafsanoor Vanya (University of California, Davis Sacramento), Heather Russell (University of California, Davis Sacramento), Hitesh Patel (University of California, Davis Sacramento), Hongzheng Zhang (University of California, Davis Sacramento), Kelly Wallace (University of California, Davis Sacramento), Kristi Ayers (University of California, Davis Sacramento), Maria Gallegos (University of California, Davis Sacramento), Martha Forloines (University of California, Davis Sacramento), Meghan Sinn (University of California, Davis Sacramento), Queennie Majorie S Kahulugan (University of California, Davis Sacramento), Richard Isip (University of California, Davis Sacramento), Sandra Calderon (University of California, Davis Sacramento), Talia Hamm (University of California, Davis Sacramento), Michael Borrie (Parkwood Hospital), T-Y Lee (Parkwood Hospital), Rob Bartha (Parkwood Hospital), Sterling Johnson (University of Wisconsin), Sanjay Asthana (University of Wisconsin), Cynthia M Carlsson (University of Wisconsin), Allison Perrin (Banner Alzheimer’s Institute), Pierre Tariot (Banner Alzheimer’s Institute), Adam Fleisher (Banner Alzheimer’s Institute), Stephanie Reeder (Banner Alzheimer’s Institute), Horacio Capote (Dent Neurologic Institute), Allison Emborsky (Dent Neurologic Institute), Anna Mattle (Dent Neurologic Institute), Bela Ajtai (Dent Neurologic Institute), Benjamin Wagner (Dent Neurologic Institute), Bennett Myers (Dent Neurologic Institute), Daryn Slazyk (Dent Neurologic Institute), Delaney Fragale (Dent Neurologic Institute), Erin Fransen (Dent Neurologic Institute), Heather Macnamara (Dent Neurologic Institute), Jonathan Falletta (Dent Neurologic Institute), Joseph Hirtreiter (Dent Neurologic Institute), Laszlo Mechtler (Dent Neurologic Institute), Megan King (Dent Neurologic Institute), Michael Asbach (Dent Neurologic Institute), Michelle Rainka (Dent Neurologic Institute), Richard Zawislak (Dent Neurologic Institute), Scott Wisniewski (Dent Neurologic Institute), Stephanie O’Malley (Dent Neurologic Institute), Tatiana Jimenez -Knight (Dent Neurologic Institute), Todd Peehler (Dent Neurologic Institute), Traci Aladeen (Dent Neurologic Institute), Vernice Bates (Dent Neurologic Institute), Violet Wenner (Dent Neurologic Institute), Wisam Elmalik (Dent Neurologic Institute), Douglas W. Scharre (Ohio State University), Arun Ramamurthy (Ohio State University), Soumya Bouchachi (Ohio State University), Maria Kataki (Ohio State University), Rawan Tarawneh (Ohio State University), Brendan Kelley (Ohio State University), Dzintra Celmins (Albany Medical College), Alicia Leader (Albany Medical College), Chris Figueroa (Albany Medical College), Heather Bauerle (Albany Medical College), Katlynn Patterson (Albany Medical College), Michael Reposa (Albany Medical College), Steven Presto (Albany Medical College), Tuba Ahmed (Albany Medical College), Wendy Stewart (Albany Medical College), Godfrey D Pearlson (Hartford Hosp, Olin Neuropsychiatry Research Center), Karen Blank (Hartford Hosp, Olin Neuropsychiatry Research Center), Karen Anderson (Hartford Hosp, Olin Neuropsychiatry Research Center), Robert B Santulli (Dartmouth -Hitchcock Medical Center), Eben S Schwartz (Dartmouth -Hitchcock Medical Center), Jeff Williamson (Wake Forest University Health Sciences), Alicia Jessup (Wake Forest University Health Sciences), Andrea Williams (Wake Forest University Health Sciences), Crystal Duncan (Wake Forest University Health Sciences), Abigail O’Connell (Wake Forest University Health Sciences), Karen Gagnon (Wake Forest University Health Sciences), Ezequiel Zamora (Wake Forest University Health Sciences), James Bateman (Wake Forest University Health Sciences), Freda Crawford (Wake Forest University Health Sciences), Deb Thompson (Wake Forest University Health Sciences), Eboni Walker (Wake Forest University Health Sciences), Jennifer Rowell (Wake Forest University Health Sciences), Mikell White (Wake Forest University Health Sciences), Phillip “Hunter” Ledford (Wake Forest University Health Sciences), Sarah Bohlman (Wake Forest University Health Sciences), Susan Henkle (Wake Forest University Health Sciences), Joseph Bottoms (Wake Forest University Health Sciences), Lena Moretz (Wake Forest University Health Sciences), Bevan Hoover (Wake Forest University Health Sciences), Michael Shannon (Wake Forest University Health Sciences), Samantha Rogers (Wake Forest University Health Sciences), Wendy Baker (Wake Forest University Health Sciences), William Harrison (Wake Forest University Health Sciences), Chuang -Kuo Wu (Rhode Island Hospital), Alexis DeMarco (Rhode Island Hospital), Ava Stipanovich (Rhode Island Hospital), Daniel Arcuri (Rhode Island Hospital), Jan Clark (Rhode Island Hospital), Jennifer Davis (Rhode Island Hospital), Kerstin Doyon (Rhode Island Hospital), Marie Amoyaw (Rhode Island Hospital), Mauro Veras Acosta (Rhode Island Hospital), Ronald Bailey (Rhode Island Hospital), Scott Warren (Rhode Island Hospital), Terry Fogerty (Rhode Island Hospital), Victoria Sanborn (Rhode Island Hospital), Meghan Riddle (Butler Hospital), Stephen Salloway (Butler Hospital), Paul Malloy (Butler Hospital), Stephen Correia (Butler Hospital), Charles Windon (University of California San Francisco), Morgan Blackburn (University of California San Francisco), Howard J Rosen (University of California San Francisco), Bruce L Miller (University of California San Francisco), Amanda Smith (Univer sity of South Florida, Byrd Institute), Ijeoma Mba (Univer sity of South Florida, Byrd Institute), Jenny Echevarria (Univer sity of South Florida, Byrd Institute), Juris Janavs (Univer sity of South Florida, Byrd Institute), Emily Roglaski (University of Chicago), Meagan Yong (University of Chicago), Rebecca Devine (University of Chicago), Hamid Okhravi (Eastern Virginia Medical School), Edgardo Rivera (Charter Health Research Services), Teresa Kalowsky (Charter Health Research Services), Caroline Smith (Charter Health Research Services), Christina Rosario (Charter Health Research Services), Joseph Masdeu (Houston Methodist Neurological Institute), Richard Le (Houston Methodist Neurological Institute), Maushami Gurung (Houston Methodist Neurological Institute), Marwan Sabbagh (Barrow Neurological Institute), Angelica Garcia (Barrow Neurological Institute), Micah Ellis Slaughter (Barrow Neurological Institute), Nadeen Elayan (Barrow Neurological Institute), Skieff Acothley (Barrow Neurological Institute), Nunzio Pomara (Nathan Kline Institute), Raymundo Hernando (Nathan Kline Institute), Vita Pomara (Nathan Kline Institute), Chelsea Reichert (Nathan Kline Institute), Olga Brawman-Mintzer (Ralph Johnson Veterans Administration Health Care Services), Allison Acree (Ralph Johnson Veterans Administration Health Care Services), Arthur Williams (Ralph Johnson Veterans Administration Health Care Services), Campbell Long (Ralph Johnson Veterans Administration Health Care Services), Rebecca Long (Ralph Johnson Veterans Administration Health Care Services), Paul Newhouse (Vanderbilt University Medical Center), Sydni Jenee Hill (Vanderbilt University Medical Center), Amy Boegel (Vanderbilt University Medical Center), Sudha Seshadri (University of Texas Health, San Antonio), Amy Saklad (University of Texas Health, San Antonio), Floyd Jones (University of Texas Health, San Antonio), William Hu (Rutgers University), V Sotelo (Rutgers University), Yaneicy Gonazalez Rojas (Gonzalez & Aswad Health Services), Jacobo Mintzer (Medical University South Carolina), Crystal Flynn Longmire (Medical University South Carolina), Kenneth Spicer (Medical University South Carolina).

Contributors MR wrote the initial draft of the manuscript, conducted data modelling, statistical analyses, interpreted the data and prepared the figures. CC contributed to data modelling, statistical analyses and data visualisation. LD contributed to data preparation and quality control. JP supervised the work, provided critical feedback on the manuscript, contributed to its writing and data interpretation and is responsible for the overall content as the guarantor. All authors read, reviewed and approved the final manuscript.,

Funding Data collection and sharing for this project were funded by the Alzheimer’s Disease Neuroimaging Initiative (ADNI) (National Institutes of Health Grant U01 AG024904) and DOD ADNI (Department of Defense award number W81XWH-12-2-0012). ADNI is funded by the National Institute on Aging, the National Institute of Biomedical Imaging and Bioengineering, and through generous contributions from the following: AbbVie, Alzheimer's Association; Alzheimer's Drug Discovery Foundation; Araclon Biotech; BioClinica; Biogen; Bristol-Myers Squibb Company; CereSpir; Cogstate; Eisai; Elan Pharmaceuticals; Eli Lilly and Company; EuroImmun; F. Hoffmann-La Roche and its affiliated company Genentech; Fujirebio; GE Healthcare; IXICO; Janssen Alzheimer Immunotherapy Research & Development; Johnson & Johnson Pharmaceutical Research & Development; Lumosity; Lundbeck; Merck & Co.; Meso Scale Diagnostics; NeuroRx Research; Neurotrack Technologies; Novartis Pharmaceuticals Corporation; Pfizer; Piramal Imaging; Servier; Takeda Pharmaceutical Company and Transition Therapeutics. The Canadian Institutes of Health Research is providing funds to support ADNI clinical sites in Canada. Private sector contributions are facilitated by the Foundation for the National Institutes of Health (http://www.fnih.org). The grantee organisation is the Northern California Institute for Research and Education, and the study is coordinated by the Alzheimer's Therapeutic Research Institute at the University of Southern California. ADNI data are disseminated by the Laboratory for Neuro Imaging at the University of Southern California. MR was supported by the ’Filling the Gap’ Grant of the University of Zurich. This work has also been supported by grants from the Swiss National Science Foundation (grant number 320030_141179; 320030_204886) and from the Synapsis Foundation—Dementia Research Switzerland (grant number 2017-PI01).

Competing interests MR received speaker honoraria from OM Pharma; CC received consultation and speaker honoraria from OM Pharma; LD is an employee of the Société des Produits Nestlé SA; JP received consultation or speaker honoraria from the Nestlé Institute of Health Sciences, Ono Pharma, OM Pharma, Roche Therapeutics, Eisai, Eli Lilly, Schwabe Pharma and from Fujirebio Europe. All disclosures are unrelated to the present work.

Provenance and peer review Not commissioned; externally peer reviewed.

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