Long-term associations of cigarette smoking in early mid-life with predicted brain aging from mid- to late life

Nathan Whitsel; Chandra A Reynolds; Erik J Buchholz; Shandell Pahlen; Rahul C Pearce; Sean N Hatton; Jeremy A Elman; Nathan A Gillespie; Daniel E Gustavson; Olivia K Puckett; Anders M Dale; Lisa T Eyler; Christine Fennema-Notestine; Donald J Hagler Jr; Richard L Hauger; Linda K McEvoy; Ruth McKenzie; Michael C Neale; Matthew S Panizzon; Mark Sanderson-Cimino; Rosemary Toomey; Xin M Tu; Mc Kenna E Williams; Tyler Bell; Hong Xian; Michael J Lyons; William S Kremen; Carol E Franz

doi:10.1111/add.15710

Long-term associations of cigarette smoking in early mid-life with predicted brain aging from mid- to late life

Addiction. 2022 Apr;117(4):1049-1059. doi: 10.1111/add.15710. Epub 2021 Oct 28.

Authors

Nathan Whitsel^{1

2}, Chandra A Reynolds³, Erik J Buchholz^{1

2}, Shandell Pahlen³, Rahul C Pearce^{1

2}, Sean N Hatton⁴, Jeremy A Elman^{1

2}, Nathan A Gillespie^{5

6}, Daniel E Gustavson⁷, Olivia K Puckett^{1

2}, Anders M Dale⁴, Lisa T Eyler^{1

2}, Christine Fennema-Notestine^{1

2

4}, Donald J Hagler Jr⁴, Richard L Hauger^{1

2}, Linda K McEvoy⁴, Ruth McKenzie⁸, Michael C Neale⁵, Matthew S Panizzon^{1

2}, Mark Sanderson-Cimino^{1

2

9}, Rosemary Toomey⁸, Xin M Tu¹⁰, Mc Kenna E Williams^{1

2

9}, Tyler Bell^{1

2}, Hong Xian¹¹, Michael J Lyons⁸, William S Kremen^{1

2}, Carol E Franz^{1

2}

Affiliations

¹ Department of Psychiatry, University of California San Diego, La Jolla, San Diego, CA, USA.
² Center for Behavior Genetics of Aging, University of California, La Jolla, San Diego, CA, USA.
³ Department of Psychology, University of California, Riverside, Riverside, CA, USA.
⁴ Department of Neuroscience, University of California San Diego, La Jolla, San Diego, CA, USA.
⁵ Virginia Institute for Psychiatric and Behavior Genetics, Department of Psychiatry, Virginia Commonwealth University, Richmond, VA, USA.
⁶ QIMR Berghofer Medical Research Institute, Herston, Queensland, Australia.
⁷ Department of Medicine, Vanderbilt University Medical Center, Nashville, TN, USA.
⁸ Department of Psychological and Brain Sciences, Boston University, Boston, MA, USA.
⁹ San Diego State University/University of California San Diego Joint Doctoral Program in Clinical Psychology, San Diego, La Jolla, CA, USA.
¹⁰ Department of Family Medicine and Public Health, University of California San Diego, La Jolla, San Diego, CA, USA.
¹¹ Department of Epidemiology and Biostatistics, St Louis University, St Louis, MO, USA.

Abstract

Background and aims: Smoking is associated with increased risk for brain aging/atrophy and dementia. Few studies have examined early associations with brain aging. This study aimed to measure whether adult men with a history of heavier smoking in early mid-life would have older than predicted brain age 16-28 years later.

Design: Prospective cohort observational study, utilizing smoking pack years data from average age 40 (early mid-life) predicting predicted brain age difference scores (PBAD) at average ages 56, 62 (later mid-life) and 68 years (early old age). Early mid-life alcohol use was also evaluated.

Setting: Population-based United States sample.

Participants/cases: Participants were male twins of predominantly European ancestry who served in the United States military between 1965 and 1975. Structural magnetic resonance imaging (MRI) began at average age 56. Subsequent study waves included most baseline participants; attrition replacement subjects were added at later waves.

Measurements: Self-reported smoking information was used to calculate pack years smoked at ages 40, 56, 62, and 68. MRIs were processed with the Brain-Age Regression Analysis and Computation Utility software (BARACUS) program to create PBAD scores (chronological age-predicted brain age) acquired at average ages 56 (n = 493; 2002-08), 62 (n = 408; 2009-14) and 68 (n = 499; 2016-19).

Findings: In structural equation modeling, age 40 pack years predicted more advanced age 56 PBAD [β = -0.144, P = 0.012, 95% confidence interval (CI) = -0.257, -0.032]. Age 40 pack years did not additionally predict PBAD at later ages. Age 40 alcohol consumption, but not a smoking × alcohol interaction, predicted more advanced PBAD at age 56 (β = -0.166, P = 0.001, 95% CI = -0.261, -0.070) with additional influences at age 62 (β = -0.115, P = 0.005, 95% CI = -0.195, -0.036). Age 40 alcohol did not predict age 68 PBAD. Within-twin-pair analyses suggested some genetic mechanism partially underlying effects of alcohol, but not smoking, on PBAD.

Conclusions: Heavier smoking and alcohol consumption by age 40 appears to predict advanced brain aging by age 56 in men.

Keywords: Aging; PBAD; alcohol; imaging; longitudinal; smoking.

Publication types

Observational Study
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

Adolescent
Adult
Aged
Aging
Brain / diagnostic imaging
Cigarette Smoking* / epidemiology
Female
Humans
Male
Middle Aged
Nicotiana
Prospective Studies
Young Adult

Abstract

Publication types

MeSH terms

Grants and funding