It is estimated that detecting an interaction requires at least four times the sample size than needed to detect a main effect 25, 26. One methodological issue that might explain why so few studies have directly examined this important question pertains to the need for relatively large sample sizes to be adequately powered for interaction, or moderation, analyses. Thus, the question whether smoking affects cognition in men and women differently remains unresolved. As a covariate, the variance due to sex is only being controlled for and not directly explored. Nevertheless, the majority of these studies do not assess biological sex as a main variable of interest but instead use sex as a covariate. Several studies have found an association between smoking, cognitive decline, and dementia 12, 23, 24. However, it is currently unknown if the effects of smoking on verbal learning and memory function are different between men and women. A recent study found that women had a stronger association between vascular risk factors and worse cognition than men in a middle-aged Hispanic/Latino population 22. Importantly, prevalence rates of any dementia and AD may be greater in women than men 19, 20, 21. Tobacco smoking is also a major risk factor for cardiovascular disease and chronic obstructive pulmonary disease (COPD), both of which can decrease cognitive function 18.

The presence of smoking with hypertension is one of the greatest risk factors for acute myocardial infarction and stroke, according to a meta-analysis of 10 cohort studies which included more than 60,000 people 17. Smoking causes vascular damage, including carotid artery disease, atherosclerotic plaque formation, increased platelet aggregation, compromised endothelial cell function, arterial stiffness and increased systolic blood pressure, which all contribute to stroke risk 14, 15, 16. Smoking tobacco might indirectly increase risk of cognitive impairment by exacerbating the subclinical risks associated with underlying vascular disease. Several extensive cohort-based studies have found that cardiovascular disease risk factors such as tobacco smoking are associated with cognitive decline and increased risk of dementia in older age 6.ĭespite early reports suggesting that smoking tobacco might have beneficial effects on cognition 7, 8 and a reduced risk of dementia 9, more recent evidence clearly suggests that active smoking has neurotoxic effects on the brain 10, 11, 12 and is associated with a doubling of dementia risk for older adults 13. Vascular-related dementia is the second most common cause of cognitive decline, with only AD-related dementia being more prevalent 5. Vascular diseases are also associated with increased risk for Alzheimer’s disease (AD) 2, which is the 6th leading cause of death in the US with increasing numbers and financial tolls 3, 4.

Vascular contributions to cognitive impairment and dementia (VCID) include blood vessel injuries that can cause significant changes to memory, thinking, and behavior 1. These results suggest that smoking and cardiovascular disease may impact verbal learning and memory throughout adulthood differently for men and women. We found significant interactions in that smoking is associated with verbal learning performance more in women and cardiovascular disease more in men across a wide age range. Using MindCrowd, an observational web-based cohort of ~ 70,000 people aged 18–85, we investigated whether sex modifies the relationship between smoking and cardiovascular disease with verbal memory performance. We investigated the associations between sex, smoking, and cardiovascular disease with verbal learning and memory function. Sex disparities in VCID have been reported, however, few studies have assessed the sex-specific relationships between smoking and memory performance and with contradictory results. Smoking might indirectly increase the likelihood of cognitive impairment by exacerbating vascular disease risks. Vascular contributions to cognitive impairment and dementia (VCID) include structural and functional blood vessel injuries linked to poor neurocognitive outcomes.

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