Association Between False Memories and Delusions in Alzheimer Disease
Authors: McLachlan Emma , Ocal Dilek , Burgess Neil , Reeves Suzanne , Howard Robert ,   Alzheimer’s Disease Neuroimaging Initiative, Weiner Michael W. , Aisen Paul , Petersen Ronald , Jack Clifford R. , Jagust William , Trojanowki John Q. , Toga Arthur W. , Beckett Laurel , Green Robert C. , Saykin Andrew J. , Morris John C. , Perrin Richard J. , Shaw Leslie M. , Khachaturian Zaven , Carrillo Maria , Potter William , Barnes Lisa , Bernard Marie , González Hector , Ho Carole , Hsiao John K. , Jackson Jonathan , Masliah Eliezer , Masterman Donna , Okonkwo Ozioma , Perrin Richard , Ryan Laurie , Silverberg Nina , Fleisher Adam , Truran Sacrey Diana , Fockler Juliet , Conti Cat , Veitch Dallas , Neuhaus John , Jin Chengshi , Nosheny Rachel , Ashford Miriam , Flenniken Derek , Kormos Adrienne , Montine Tom , Rafii Michael , Raman Rema , Jimenez Gustavo , Donohue Michael , Gessert Devon , Salazar Jennifer , Zimmerman Caileigh , Cabrera Yuliana , Walter Sarah , Miller Garrett , Coker Godfrey , Clanton Taylor , Hergesheimer Lindsey , Smith Stephanie , Adegoke Olusegun , Mahboubi Payam , Moore Shelley , Pizzola Jeremy , Shaffer Elizabeth , Sloan Brittany , Harvey Danielle , Forghanian-Arani Arvin , Borowski Bret , Ward Chad , Schwarz Christopher , Jones David , Gunter Jeff , Kantarci Kejal , Senjem Matthew , Vemuri Prashanthi , Reid Robert , Fox Nick C. , Malone Ian , Thompson Paul , Thomopoulos Sophia I. , Nir Talia M. , Jahanshad Neda , DeCarli Charles , Knaack Alexander , Fletcher Evan , Tosun-Turgut Duygu , Rossi Chen Stephanie , Choe Mark , Crawford Karen , Yushkevich Paul A. , Das Sandhitsu , Koeppe Robert A. , Reiman Eric M. , Chen Kewei , Mathis Chet , Landau Susan , Cairns Nigel J. , Householder Erin , Franklin Erin , Bernhardt Haley , Taylor-Reinwald Lisa , Korecka Magdalena , Figurski Michal , Neu Scott Neu , Nho Kwangsik , Risacher Shannon L. , Apostolova Liana G. , Shen Li , Foroud Tatiana M. , Nudelman Kelly , Faber Kelley , Wilmes Kristi , Thal Leon , Silbert Lisa C. , Lind Betty , Crissey Rachel , Kaye Jeffrey A. , Carter Raina , Dolen Sara , Quinn Joseph , Schneider Lon S. , Pawluczyk Sonia , Becerra Mauricio , Teodoro Liberty , Dagerman Karen , Spann Bryan M. , Brewer James , Vanderswag Helen , Ziolkowski Jaimie , Heidebrink Judith L. , Zbizek-Nulph Lisa , Lord Joanne L. , Mason Sara S. , Albers Colleen S. , Knopman David , Johnson Kris , Villanueva-Meyer Javier , Pavlik Valory , Pacini Nathaniel , Lamb Ashley , Kass Joseph S. Kass , Doody Rachelle S. , Shibley Victoria Shibley , Chowdhury Munir , Rountree Susan , Dang Mimi , Stern Yaakov , Honig Lawrence S. , Mintz Akiva , Ances Beau , Winkfield David , Carroll Maria , Stobbs-Cucchi Georgia , Oliver Angela , Creech Mary L. , Mintun Mark A. , Schneider Stacy , Geldmacher David , Natelson Love Marissa , Griffith Randall , Clark David , Brockington John , Marson Daniel , Grossman Hillel , Goldstein Martin A. , Greenber Jonathan , Mitsis Effie , Shah Raj C. , Lamar Melissa , Samuels Patricia , Duara Ranjan , Greig-Custo Maria T. , Rodriguez Rosemarie , Albert Marilyn , Onyike Chiadi , Farrington Leonie , Rudow Scott , Brichko Rottislav , Kielb Stephanie , Smith Amanda , Ashok Raj Balebail , Fargher Kristin , Sadowski Martin , Wisniewski Thomas , Shulman Melanie , Faustin Arline , Rao Julia , Castro Karen M. , Ulysse Anaztasia , Chen Shannon , Sheikh Mohammed O. , Singleton-Garvin Jamika , Murali Doraiswamy P. , Petrella Jeffrey R. , James Olga , Wong Terence Z. , Borges-Neto Salvador , Karlawish Jason H. , Wolk David A. , Vaishnavi Sanjeev , Clark Christopher M. , Arnold Steven E. , Smith Charles D. , Jicha Gregory A. , El Khouli Riham , Raslau Flavius D. , Lopez Oscar L. , Oakley MaryAnn , Simpson Donna M. , Porsteinsson Anton P. , Martin Kim , Kowalski Nancy , Keltz Melanie , Goldstein Bonnie S. , Makino Kelly M. , Seleem Ismail M. , Brand Connie , Thai Gaby , Pierce Aimee , Yanez Beatriz , Sosa Elizabeth , Witbracht Megan , Kelley Brendan , Nguyen Trung , Womack Kyle , Mathews Dana , Quiceno Mary , Levey Allan I. , Lah James J. , Hajjar Ihab , Cellar Janet S. , Burns Jeffrey M. , Swerdlow Russell H. , Brooks William M. , Silverman Daniel H.S. , Kremen Sarah , Apostolova Liana , Tingus Kathleen , Lu Po H. , Bartzokis George , Woo Ellen , Teng Edmond , Graff-Radford Neill R , Parfitt Francine , Poki-Walker Kim , Farlow Martin R. , Hake Ann Marie , Matthews Brandy R. , Brosch Jared R. , Herring Scott , van Dyck Christopher H. , Mecca Adam P. , Good Susan P. , MacAvoy Martha G. , Carson Richard E. , Varma Pradeep , Chertkow Howard , Vaitekunis Susan , Hosein Chris , Black Sandra , Stefanovic Bojana , Heyn Chris (Chinthaka) , Robin Hsiung Ging-Yuek , Kim Ellen , Mudge Benita , Sossi Vesna , Feldman Howard , Assaly Michele , Finger Elizabeth , Pasternak Stephen , Rachinsky Irina , Kertesz Andrew , Drost Dick , Rogers John , Grant Ian , Muse Brittanie , Rogalski Emily , Robson Jordan , Marsel Mesulam M. , Kerwin Diana , Wu Chuang-Kuo , Johnson Nancy , Liposki Kristine , Weintraub Sandra , Bonakdarpour Borna , Pomara Nunzio , Hernando Raymundo , Sarrael Antero , Rosen Howard J. , Miller Bruce L. , Perry David , Scott Turner Raymond , Johnson Kathleen , Reynolds Brigid , McCann Kelly , Poe Jessica , Sperling Reisa A. , Johnson Keith A. , Marshall Gad A. , Yesavage Jerome , Taylor Joy L. , Chao Steven , Coleman Jaila , White Jessica D. , Lane Barton , Rosen Allyson , Tinklenberg Jared , Belden Christine M. , Atri Alireza , Clark Kelly A. , Zamrini Edward , Sabbagh Marwan , Killiany Ronald , Stern Robert , Mez Jesse , Kowall Neil , Budson Andrew E. , Obisesan Thomas O. , Ntekim Oyonumo E. , Wolday Saba , Khan Javed I. , Nwulia Evaristus , Nadarajah Sheeba , Lerner Alan , Ogrocki Paula , Tatsuoka Curtis , Fatica Parianne , Maillard Pauline , Olichney John , Carmichael Owen , Bates Vernice , Capote Horacio , Rainka Michelle , Borrie Michael , Lee T-Y , Bartha Rob , Johnson Sterling , Asthana Sanjay , Carlsson Cynthia M. , Perrin Allison , Burke Anna , Scharre Douglas W. , Kataki Maria , Tarawneh Rawan , Hart David , Zimmerman Earl A. , Celmins Dzintra , Miller Delwyn D. , Boles Laura L. , Ekstam Smith Karen , Koleva Hristina , Shim Hyungsub , Won Nam Ki , Schultz Susan K. , Williamson Jeff D. , Craft Suzanne , Cleveland Jo , Yang Mia , Sink Kaycee M. , Ott Brian R. , Drake Jonathan , Tremont Geoffrey , Daielllo Lori A. , Ritter Aaron , Bernick Charles , Munic Donna , O'Connelll Abigail , Mintzer Jacobo , Wiliams Arthur , Masdeu Joseph , Shi Jiong , Garcia Angelica , Newhouse Paul , Potkin Steven , Salloway Stephen , Malloy Paul , Correia Stephen , Kittur Smita , Pearlson Godfrey D. , Blank Karen , Anderson Karen , Flashman Laura A. , Seltzer Marc , Hynes Mary L. , Santulli Robert B. , Relkin Norman , Chiang Gloria , Lin Michael , Ravdin Lisa , Lee Athena , Neylan Thomas , Grafman Jordan , Danowski Sarah , Nguyen-Barrera Catherine , Hayes Jacqueline , Finley Shannon , Bernstein Matthew , Foster Norm , Kim Sungeun , Sood Ajay , Blanchard Kimberly S. , Arfanakis Konstantinos , Fleischman Debra , Varon Daniel , Reist Christopher , Sadowsky Carl , Martinez Walter , Villena Teresa , Peskind Elaine R. , Petrie Eric C. , Li Gail , Mackin Scott , Drake Erin , Nelson Craig , Bikford David , Butters Meryl , Zmuda Michelle , Reyes Denise , Ho Au Yiu , Scherer Kelly , Catalinotto Daniel , Stark Samuel , Ong Elise , Fernandez Dariella 
Published: May 2023

Importance

Understanding the mechanisms of delusion formation in Alzheimer disease (AD) could inform the development of therapeutic interventions. It has been suggested that delusions arise as a consequence of false memories.

Objective

To investigate whether delusions in AD are associated with false recognition, and whether higher rates of false recognition and the presence of delusions are associated with lower regional brain volumes in the same brain regions.

Design, Setting, and Participants

Since the Alzheimer’s Disease Neuroimaging Initiative (ADNI) launched in 2004, it has amassed an archive of longitudinal behavioral and biomarker data. This cross-sectional study used data downloaded in 2020 from ADNI participants with an AD diagnosis at baseline or follow-up. Data analysis was performed between June 24, 2020, and September 21, 2021.

Exposure

Enrollment in the ADNI.

Main Outcomes and Measures

The main outcomes included false recognition, measured with the 13-item Alzheimer’s Disease Assessment Scale–Cognitive Subscale (ADAS-Cog 13) and the Rey Auditory Verbal Learning Test (RAVLT) and volume of brain regions corrected for total intracranial volume. Behavioral data were compared for individuals with delusions in AD and those without using independent-samples t tests or Mann-Whitney nonparametric tests. Significant findings were further explored using binary logistic regression modeling. For neuroimaging data region of interest analyses using t tests, Poisson regression modeling or binary logistic regression modeling and further exploratory, whole-brain voxel-based morphometry analyses were carried out to explore the association between regional brain volume and false recognition or presence of delusions.

Results

Of the 2248 individuals in the ADNI database, 728 met the inclusion criteria and were included in this study. There were 317 (43.5%) women and 411 (56.5%) men. Their mean (SD) age was 74.8 (7.4) years. The 42 participants with delusions at baseline had higher rates of false recognition on the ADAS-Cog 13 (median score, 3; IQR, 1 to 6) compared with the 549 control participants (median score, 2; IQR, 0 to 4; U = 9398.5; P = .04). False recognition was not associated with the presence of delusions when confounding variables were included in binary logistic regression models. An ADAS-Cog 13 false recognition score was inversely associated with left hippocampal volume (odds ratio [OR], 0.91 [95% CI, 0.88-0.94], P &amp;lt; .001), right hippocampal volume (0.94 [0.92-0.97], P &amp;lt; .001), left entorhinal cortex volume (0.94 [0.91-0.97], P &amp;lt; .001), left parahippocampal gyrus volume (0.93 [0.91-0.96], P &amp;lt; .001), and left fusiform gyrus volume (0.97 [0.96-0.99], P &amp;lt; .001). There was no overlap between locations associated with false recognition and those associated with delusions.

Conclusions and Relevance

In this cross-sectional study, false memories were not associated with the presence of delusions after accounting for confounding variables, and no indication for overlap of neural networks for false memories and delusions was observed on volumetric neuroimaging. These findings suggest that delusions in AD do not arise as a direct consequence of misremembering, lending weight to ongoing attempts to delineate specific therapeutic targets for treatment of psychosis.