INS NYC 2024 Program

Poster	Poster Session 08 Program Schedule 02/16/2024 01:45 pm - 03:00 pm Room: Shubert Complex (Posters 1-60) Poster Session 08: Cognition \| Cognitive Reserve Variables Final Abstract #61 Impact of Cigarette Smoking on Amyloid Burden and Cognition in Older Veterans: Exploring the Moderating role of APOE Genotype Lindsay Rotblatt, VA San Diego Healthcare System / University of California, San Diego, La Jolla, United States Arthur Brody, VA San Diego Healthcare System / University of California, San Diego, La Jolla, United States Alin Durazo, San Diego State University, San Diego, United States Lauren Edwards, San Diego State University / University of California, San Diego, La Jolla, United States Katherine Bangen, VA San Diego Healthcare System / University of California, San Diego, La Jolla, United States Kelsey Thomas, VA San Diego Healthcare System / University of California, San Diego, La Jolla, United States Category: Dementia (Alzheimer's Disease) Keyword 1: apolipoprotein E Keyword 2: aging disorders Keyword 3: dementia - Alzheimer's disease Objective: Cigarette smoking has been associated with greater risk for Alzheimer’s disease (AD) and related neuropathology. Most previous studies have focused on non-Veteran samples. Given that smoking prevalence is higher in Veterans than the general population, smoking may represent an important risk factor for AD in Veterans. This study investigated the relationship of smoking with amyloid burden and cognition in Vietnam-era Veterans and whether genetic susceptibility to AD moderated these associations. Within Veterans with a history of smoking, we also examined whether higher reported cigarette use was associated with greater amyloid burden and worse cognitive outcomes in persons with genetic susceptibility to AD. Participants and Methods: Participants were 226 older Veterans without dementia (age range 60-85, 99.5% men) from the Department of Defense-Alzheimer’s Disease Neuroimaging Initiative (DoD-ADNI) cohort who completed baseline health history questionnaires, neuropsychological evaluation, apolipoprotein E (APOE) genotyping, and amyloid positron emission tomography (PET) imaging using florbetapir (¹⁸F). Self-reported smoking history determined smoking status (nonsmoker <1 year; smoker =/>1 year). For participants who were classified as smokers (n=160), total lifetime reported pack-years was calculated. Measures of verbal learning (Logical Memory I; Rey Auditory Verbal Learning Test [RAVLT] Trials 1 to 5 Total), verbal memory (Logical Memory II, RAVLT Delayed Recall, and Recognition), processing speed/executive functioning (Trail Making Test Parts A & B), and language (Boston Naming Test 30-item; Animal Fluency) were converted to domain composite scores. Analyses of covariance, adjusting for age, education, APOE ε4 positivity, Hachinski ischemic score, PTSD, and TBI severity, were used to examine differences in cortical amyloid standardized uptake value ratio (SUVR) and cognition by smoking status. Models also considered interactions between smoking status and APOE ε4. Results: APOE ε4 positivity was associated with higher cortical amyloid. While there was no significant main effect of smoking status on either amyloid or any cognitive measures, there was a significant interaction between APOE ε4 and smoking status such that smokers with at least one APOE ε4 allele had greater amyloid accumulation compared to non-carrier smokers and non-smokers alike (F=6.057, p=.015). Importantly, only the estimated marginal means for the carrier-smoker group were above 1.11, a commonly used florbetapir SUVR threshold for elevated amyloid accumulation. In subsequent smokers-only analyses, no significant associations were found between cigarette pack-years, APOE ε4, amyloid, or cognition. Conclusions: Findings from this study, including the moderating role of APOE ε4 genotype between smoking and amyloid burden are generally consistent with previous research examining smoking, APOE ε4, and amyloid pathology in non-Veterans, though we did not find previously reported associations with verbal learning and memory. It is possible the lack of cognitive findings may be due to how smoking was defined within the sample and/or cognitive heterogeneity of the sample (both cognitively unimpaired and MCI included). Nonetheless, our results suggest that modifiable risk factors, like smoking, may interact with genetic susceptibility, potentially exacerbating the risk for AD-associated neuropathology in older adults without dementia. Future studies will explore how current smoking status interacts with lifetime history as this group may be particularly prone to negative cognitive sequelae.

Poster

02/16/2024
01:45 pm - 03:00 pm
Room: Shubert Complex (Posters 1-60)

Poster Session 08: Cognition | Cognitive Reserve Variables

Final Abstract #61

Impact of Cigarette Smoking on Amyloid Burden and Cognition in Older Veterans: Exploring the Moderating role of APOE Genotype

Lindsay Rotblatt, VA San Diego Healthcare System / University of California, San Diego, La Jolla, United States
Arthur Brody, VA San Diego Healthcare System / University of California, San Diego, La Jolla, United States
Alin Durazo, San Diego State University, San Diego, United States
Lauren Edwards, San Diego State University / University of California, San Diego, La Jolla, United States
Katherine Bangen, VA San Diego Healthcare System / University of California, San Diego, La Jolla, United States
Kelsey Thomas, VA San Diego Healthcare System / University of California, San Diego, La Jolla, United States

Category: Dementia (Alzheimer's Disease)

Keyword 1: apolipoprotein E
Keyword 2: aging disorders
Keyword 3: dementia - Alzheimer's disease

Objective:

Cigarette smoking has been associated with greater risk for Alzheimer’s disease (AD) and related neuropathology. Most previous studies have focused on non-Veteran samples. Given that smoking prevalence is higher in Veterans than the general population, smoking may represent an important risk factor for AD in Veterans. This study investigated the relationship of smoking with amyloid burden and cognition in Vietnam-era Veterans and whether genetic susceptibility to AD moderated these associations. Within Veterans with a history of smoking, we also examined whether higher reported cigarette use was associated with greater amyloid burden and worse cognitive outcomes in persons with genetic susceptibility to AD.

Participants and Methods:

Participants were 226 older Veterans without dementia (age range 60-85, 99.5% men) from the Department of Defense-Alzheimer’s Disease Neuroimaging Initiative (DoD-ADNI) cohort who completed baseline health history questionnaires, neuropsychological evaluation, apolipoprotein E (APOE) genotyping, and amyloid positron emission tomography (PET) imaging using florbetapir (¹⁸F). Self-reported smoking history determined smoking status (nonsmoker <1 year; smoker =/>1 year). For participants who were classified as smokers (n=160), total lifetime reported pack-years was calculated. Measures of verbal learning (Logical Memory I; Rey Auditory Verbal Learning Test [RAVLT] Trials 1 to 5 Total), verbal memory (Logical Memory II, RAVLT Delayed Recall, and Recognition), processing speed/executive functioning (Trail Making Test Parts A & B), and language (Boston Naming Test 30-item; Animal Fluency) were converted to domain composite scores. Analyses of covariance, adjusting for age, education, APOE ε4 positivity, Hachinski ischemic score, PTSD, and TBI severity, were used to examine differences in cortical amyloid standardized uptake value ratio (SUVR) and cognition by smoking status. Models also considered interactions between smoking status and APOE ε4.

Results:

APOE ε4 positivity was associated with higher cortical amyloid. While there was no significant main effect of smoking status on either amyloid or any cognitive measures, there was a significant interaction between APOE ε4 and smoking status such that smokers with at least one APOE ε4 allele had greater amyloid accumulation compared to non-carrier smokers and non-smokers alike (F=6.057, p=.015). Importantly, only the estimated marginal means for the carrier-smoker group were above 1.11, a commonly used florbetapir SUVR threshold for elevated amyloid accumulation. In subsequent smokers-only analyses, no significant associations were found between cigarette pack-years, APOE ε4, amyloid, or cognition.

Conclusions:

Findings from this study, including the moderating role of APOE ε4 genotype between smoking and amyloid burden are generally consistent with previous research examining smoking, APOE ε4, and amyloid pathology in non-Veterans, though we did not find previously reported associations with verbal learning and memory. It is possible the lack of cognitive findings may be due to how smoking was defined within the sample and/or cognitive heterogeneity of the sample (both cognitively unimpaired and MCI included). Nonetheless, our results suggest that modifiable risk factors, like smoking, may interact with genetic susceptibility, potentially exacerbating the risk for AD-associated neuropathology in older adults without dementia. Future studies will explore how current smoking status interacts with lifetime history as this group may be particularly prone to negative cognitive sequelae.