Subjective cognitive concerns, APOE [epsilon]4, PTSD symptoms, and risk for dementia among older veterans

Kristin Mattocks; Darshana Jhala; Saib Gappy; Kimberly Hammer; Emily Potter; Prakash Balasubramanian; Richard L Hauger; Luis E Selva; Lori Churby; Erika J Wolf; Ronnie Marrache; John Wells; Jessica V Brewer; Todd W Gress; Sumitra Muralidhar; Michael Landry; Henry Kranzler; Mary Whooley; Richard Sherva; Jennifer Greco; Stacey B Whitbourne; Louis Dellitalia; Michael Matheny; Timothy Morgan; Philip S Tsao; Junzhe Xu; Samir Gupta; L. Christine Faulk; Jeffrey Whittle; Sunil Ahuja; Victoria Merritt; Michael Rauchman; Amy Kilbourne; Elizabeth Hauser; Jon Klein; Michael Godschalk; Peruvemba Sriram; Stephen Mastorides; Salvador Gutierrez; Gerardo Villareal; Neeraj Tandon; Patrick Strollo; River Smith; Themistocles L Assimes; Zuhair Ballas; Jonathan Moorman; Joseph Fayad; Jack Lichy; Jennifer Moser; Frank Jacono; Xiao M Androulakis; Paul Meyer; John Harley; Shahpoor Alex Shayan; Scott L DuVall; Pran Iruvanti; Jennifer E Deen; James Norton; Samuel Poon; Suthat Liangpunsakul; Mark W Miller; Kelly Cho; Allison E Williams; Mary T Brophy; Kris Ann Oursler; Jessica Walsh; Sujata Bhushan; Elisabeth Mates; Zoe E Neale; Edward Boyko; J. Michael Gaziano; Daryl Fujii; Kelly M Harrington; Peter Liang; Kathrina Alexander; Maureen Murdoch; David Cohen; Robin Hurley; Peter Wilson; Samuel Aguayo; Jean Beckham; C. Scott Mahan; Olaoluwa Okusaga; Dave Oslin; Richard Servatius; Satish Sharma; Brady Stephens; Rui Zhang; Shiuh-Wen Luoh; Saiju Pyarajan; Mark Hamner; Dean P Argyres; Adriana Hung; Jennifer R Fonda; Scott Kinlay; Matthew S Panizzon; Frank Gesek; Ana Palacio; Shing Shing Yeh; Agnes Wallbom; VA Million Veteran Program

doi:10.1186/s13195-024-01512-w

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Subjective cognitive concerns, APOE [epsilon]4, PTSD symptoms, and risk for dementia among older veterans

Journal article

Open access

Peer reviewed

Subjective cognitive concerns, APOE [epsilon]4, PTSD symptoms, and risk for dementia among older veterans

Kristin Mattocks, Darshana Jhala, Saib Gappy, Kimberly Hammer, Emily Potter, Prakash Balasubramanian, Richard L Hauger, Luis E Selva, Lori Churby, Erika J Wolf, …

Alzheimer's research & therapy, Vol.16(1), 143

06/29/2024

DOI: 10.1186/s13195-024-01512-w

PMCID: PMC11218206

PMID: 38951900

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Abstract

Background Posttraumatic stress disorder (PTSD) and traumatic brain injury (TBI) are associated with self-reported problems with cognition as well as risk for Alzheimer's disease and related dementias (ADRD). Overlapping symptom profiles observed in cognitive disorders, psychiatric disorders, and environmental exposures (e.g., head injury) can complicate the detection of early signs of ADRD. The interplay between PTSD, head injury, subjective (self-reported) cognitive concerns and genetic risk for ADRD is also not well understood, particularly in diverse ancestry groups. Methods Using data from the U.S. Department of Veterans Affairs (VA) Million Veteran Program (MVP), we examined the relationship between dementia risk factors (APOE [epsilon]4, PTSD, TBI) and subjective cognitive concerns (SCC) measured in individuals of European (n = 140,921), African (n = 15,788), and Hispanic (n = 8,064) ancestry (EA, AA, and HA, respectively). We then used data from the VA electronic medical record to perform a retrospective survival analysis evaluating PTSD, TBI, APOE [epsilon]4, and SCC and their associations with risk of conversion to ADRD in Veterans aged 65 and older. Results PTSD symptoms (B = 0.50-0.52, p < 1E-250) and probable TBI (B = 0.05-0.19, p = 1.51E-07 - 0.002) were positively associated with SCC across all three ancestry groups. APOE [epsilon]4 was associated with greater SCC in EA Veterans aged 65 and older (B = 0.037, p = 1.88E-12). Results of Cox models indicated that PTSD symptoms (hazard ratio [HR] = 1.13-1.21), APOE [epsilon]4 (HR = 1.73-2.05) and SCC (HR = 1.18-1.37) were positively associated with risk for ADRD across all three ancestry groups. In the EA group, probable TBI also contributed to increased risk of ADRD (HR = 1.18). Conclusions The findings underscore the value of SCC as an indicator of ADRD risk in Veterans 65 and older when considered in conjunction with other influential genetic, clinical, and demographic risk factors. Keywords: Dementia, APOE [epsilon]4, TBI, PTSD, Survival analysis

Brain

Alzheimer's disease

Apolipoproteins

Injuries

Medical records

Post-traumatic stress disorder

Risk factors

Details

Title: Subtitle: Subjective cognitive concerns, APOE [epsilon]4, PTSD symptoms, and risk for dementia among older veterans
Creators: Kristin Mattocks
Darshana Jhala
Saib Gappy
Kimberly Hammer
Emily Potter
Prakash Balasubramanian
Richard L Hauger - VA San Diego Healthcare System
Luis E Selva
Lori Churby
Erika J Wolf - National Center for PTSD
Ronnie Marrache
John Wells
Jessica V Brewer
Todd W Gress
Sumitra Muralidhar - Boston University
Michael Landry - Brigham and Women's Hospital
Henry Kranzler
Mary Whooley
Richard Sherva
Jennifer Greco - Harvard University
Stacey B Whitbourne
Louis Dellitalia
Michael Matheny - VA Boston Healthcare System
Timothy Morgan
Philip S Tsao
Junzhe Xu
Samir Gupta
L. Christine Faulk
Jeffrey Whittle
Sunil Ahuja
Victoria Merritt
Michael Rauchman - Brigham and Women's Hospital
Amy Kilbourne
Elizabeth Hauser
Jon Klein
Michael Godschalk - Brigham and Women's Hospital
Peruvemba Sriram
Stephen Mastorides
Salvador Gutierrez
Gerardo Villareal
Neeraj Tandon
Patrick Strollo
River Smith
Themistocles L Assimes
Zuhair Ballas
Jonathan Moorman
Joseph Fayad
Jack Lichy
Jennifer Moser - National Center for PTSD
Frank Jacono
Xiao M Androulakis
Paul Meyer
John Harley
Shahpoor Alex Shayan
Scott L DuVall
Pran Iruvanti
Jennifer E Deen
James Norton
Samuel Poon
Suthat Liangpunsakul
Mark W Miller
Kelly Cho - VA Boston Healthcare System
Allison E Williams
Mary T Brophy
Kris Ann Oursler
Jessica Walsh
Sujata Bhushan
Elisabeth Mates
Zoe E Neale - National Center for PTSD
Edward Boyko
J. Michael Gaziano
Daryl Fujii
Kelly M Harrington
Peter Liang
Kathrina Alexander
Maureen Murdoch
David Cohen
Robin Hurley
Peter Wilson
Samuel Aguayo
Jean Beckham
C. Scott Mahan
Olaoluwa Okusaga
Dave Oslin
Richard Servatius
Satish Sharma
Brady Stephens
Rui Zhang
Shiuh-Wen Luoh
Saiju Pyarajan
Mark Hamner - Boston University
Dean P Argyres
Adriana Hung
Jennifer R Fonda
Scott Kinlay
Matthew S Panizzon - University of California, San Diego
Frank Gesek
Ana Palacio
Shing Shing Yeh
Agnes Wallbom
VA Million Veteran Program
Resource Type: Journal article
Publication Details: Alzheimer's research & therapy, Vol.16(1), 143
Publisher: BioMed Central Ltd
DOI: 10.1186/s13195-024-01512-w
PMID: 38951900
PMCID: PMC11218206
ISSN: 1758-9193
eISSN: 1758-9193
Language: English
Date published: 06/29/2024
Description audience: Academic
Academic Unit: Immunology; Internal Medicine
Record Identifier: 9984658353602771

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