Cigarette smoking and gray matter brain volumes in middle age adults: the CARDIA Brain MRI sub-study

Abstract

Cigarette smoking has been associated with dementia and dementia-related brain changes, notably gray matter (GM) volume atrophy. These associations are thought to reflect the co-morbidity of smoking and vascular, respiratory, and substance use/psychological conditions. However, the extent and localization of the smoking-GM relationship and the degree to which vascular, respiratory, and substance use/psychological factors influence this relationship remain unclear. In the Coronary Artery Risk Development in Young Adults CARDIA cohort (n = 698; 52% women; 40% black participants; age = 50.3 (SD = 3.5)), we examined the associations of smoking status with total GM volume and GM volume of brain regions linked to neurocognitive and addiction disorders. Linear regression models were used to adjust for vascular, respiratory, and substance use/psychological factors and to examine whether they modify the smoking-GM relationship. Compared to never-smokers, current smokers had smaller total GM volume (−8.86 cm3 (95%CI = −13.44, −4.29). Adjustment for substance use/psychological – but not vascular or respiratory – factors substantially attenuated this association (coefficients = −5.54 (95% CI = −10.32, −0.76); −8.33 (95% CI = −12.94, −3.72); −7.69 (95% CI = −6.95, −4.21), respectively). There was an interaction between smoking and alcohol use such that among alcohol non-users, smoking was not related to GM volumes and among alcohol users, those who currently smoked had −12 cm3 smaller total GM, specifically in the frontal and temporal lobes, amygdala, cingulate, and insula. Results suggest a large-magnitude association between smoking and smaller GM volume at middle age, accounting for vascular, respiratory, and substance use/psychological factors, and that the association was strongest in alcohol users. Regions suggested to be most vulnerable are those where cognition and addiction processes overlap.

Smoking mediates the relationship between SES and brain volume: The CARDIA study

“…This is an important finding as it is now well accepted that the neurobiology of dementia, including brain atrophy, begins during midlife [ 11 – 13 ], a period of aging where lifestyle factors can be altered to decrease one’s risk of future dementia [ 17 – 19 ]. While others have reported SES [ 21 , 25 , 40 , 42 ] and smoking [ 14 , 49 – 51 ] are each separately associated with brain volume, our findings suggest smoking is a significant contributor to the SES and brain volume relationship. Targeting this particular modifiable lifestyle factor may be an efficacious means to mitigate the deleterious effects of low SES on brain volume.…”

“…Compared to non-smokers, smokers exhibit greater age-related whole brain and cortical volume loss [49], and the higher frequency of smoking accelerates this decline [50]. In agreement with the present study, smoking has been shown to be negatively associated with brain volume in several cortical regions within the SPARE-BA index including the thalamus, cingulate, insular, frontal and temporal cortices [50,51]. In fact, research that applied the SPARE-BA index demonstrated smoking status was negatively associated with brain volume in a large epidemiological sample of~3,000 adult participants [14].…”

Moderate alcohol use is associated with decreased brain volume in early middle age in both sexes

“…When stratified by sex, a difference was seen only in the effect of smoking status. Current smoking is associated with a decreased brain volume 32 and increased brain ageing 13 . Current smokers also in our study had a smaller brain volume, as compared to non-smokers.…”

GABA concentrations in the anterior cingulate and dorsolateral prefrontal cortices: Associations with chronic cigarette smoking, neurocognition, and decision making

“…Abundant evidence indicates chronic cigarette smoking in adolescents and adults is related to neurobiological and neurocognitive abnormalities, which are not specifically attributable to common medical conditions associated with smoking 1–4 . Studies of the neurobiological consequences of cigarette smoking over the past 20 years have largely focused on magnetic resonance imaging‐based morphometric studies, which have consistently indicated structural abnormalities in multiple cortical and subcortical regions (see previous studies 4–7 and references therein). Collectively, structural aberrations in the anterior frontal cortex appear to be the most consistently reported morphometric finding.…”