Smoking History and Higher Pack Years Predict Brain Atrophy in 9646 Healthy Individuals

Background Smoking is a risk factor for both Alzheimer and vascular dementia. Understanding this risk requires an investigation of how smoking influences brain volume loss on MRI, a biomarker for neurodegeneration. Method In total, 9646 healthy participants from 4 sites were scanned on 1.5T MR with a whole‐body MR imaging protocol. Core whole body sequences included whole body coronal T1, STIR from vertex to feet, whole‐body axial DWI from vertex to proximal‐thighs and axial T2 TSE without fat suppression from skull base to pelvis. Brain sequences were T1 MPRAGE and 2D FLAIR. Deep learning volumetric software, FastSurfer, trained on over 134 participants age 27‐66, segmented 96 brain volumes. Smokers versus non‐smokers were compared by gray and white matter volumes normalized to total intracranial volume using a two tailed t‐test. Partial correlation analysis was done between pack years and brain volumes, controlling for age, sex, and total intracranial volume (TIV). The Benjamini Hochberg False Discovery Rate of 5% accounted for multiple comparisons. Result Overall, the sample had an average age of 52.9±13.1 years with 3123 individuals (32.3%) self‐reporting a history of smoking with 3.72±10.08 pack years. The remaining 6523 persons (67.7%) were non‐smokers. Participants who smoked were older than non‐smokers (p = 0.024) and 51.55% were men versus 52.8% in the non‐smoker group (p = .218). Individuals with a history of smoking had lower normalized gray and white matter volumes compared to non‐smokers (t = 8.95, p = 4.39e‐19). Adjusting for age, sex, and TIV co‐variates and multiple comparisons, higher pack years of smoking predicted brain volume loss in: total gray matter volume (Partial R = ‐0.06, p = 2.19e‐8), total white matter volume (Partial R = ‐0.06, p = 4.26e‐9), hippocampus (Partial R = ‐0.05, p = 6.26e‐6), frontal cortex (Partial R = ‐0.06, p = 1.34e‐10), temporal lobes (Partial R = ‐0.06, p = 3.24e‐8), parietal lobe (Partial R = ‐0.04, p = 0.0008), orbital frontal cortex (Partial R = ‐0.05, p = 2.19e‐8), posterior cingulate gyrus (Partial R = ‐0.05, p = 2.97e‐7). Conclusion Both smoking history and pack years are related to lower whole brain and regional volumes.