3.23 Smoking, dementia and cognition

Last updated: July 2020
Suggested citation: Just, J, Letcher, T, Greenhalgh, EM & Winstanley, MH. 3.23 Smoking, dementia and cognition. In Scollo, MM and Winstanley, MH [editors].  Tobacco in Australia: Facts and issues. Melbourne: Cancer Council Victoria; 2020. Available from please include new link with name change  /chapter-3-health-effects/3-23-smoking-dementia-and-cognition

 

Dementia is characterised by the chronic and progressive deterioration of cognition. Key features of dementia include memory loss and difficulties with information processing, language, comprehension, judgement and problem-solving.1, 2 An estimated 50 million people worldwide have dementia, with close to 10 million new cases diagnosed each year.2 Dementia is likely the result of interactions between genetic, environmental and lifestyle factors.1

There are many different conditions that lead to dementia, including Alzheimer’s disease, vascular dementia, dementia with Lewy bodies and frontotemporal dementia.2, 3 Alzheimer’s disease is the most common condition that includes dementia as a symptom.2

Contrary to the findings of early studies suggesting that smoking may be protective against Alzheimer’s disease,4-9 smoking has now been clearly identified as a risk factor for dementia, in particular Alzheimer’s disease. 2, 10-14 The World Health Organization has estimated that in people diagnosed with  Alzheimer’s disease, up to 14% of cases may be a result of smoking.

It is likely that the earlier studies indicating a protective effect of smoking were tarnished by tobacco industry interference. For example, a systematic review of all research on the topic published up to 2007 controlled for study design, quality, secular trend and tobacco industry affiliation of study authors and found that one-quarter of the 43 studies reviewed had tobacco-affiliated authors. Based on average quality cohort studies with no tobacco industry affiliation published in 2007, the risk of Alzheimer’s disease associated with smoking was estimated to be nearly double (RR 1.72, 95%CI 1.33-2.12).15

More recently, a 2015 meta-analysis of over 960,000 people assessed the impact of smoking on risk of dementia (all causes), Alzheimer’s disease and vascular dementia. Current smokers, compared with never smokers, had a 30% increased risk of all-cause dementia (RR 1.30, 95%CI 1.18-1.45), 40% increased risk of Alzheimer’s disease (RR 1.40, 95%CI 1.13-1.73) and 38% increased risk of vascular dementia (RR 1.38, 95%CI 1.15-1.66). For all-cause dementia, there appeared to be a dose-response relationship (for every 20 cigarettes smoked per day, risk increased by 34%).16

Conversely, a subsequent meta-analysis conducted in seven low- and middle-income countries (albeit with a smaller sample size of 11,143 people) did not find an association between dementia and smoking. This was true of all comparisons between current, former, ever and never smokers, and for any dementia, Alzheimer’s disease or vascular dementia.17 However, the follow-up period in this study was short, providing another example of how differing methodologies may yield different results.

A 2018 meta-analysis looked specifically at the link between smoking and Alzheimer’s disease risk. The analysis included case—control and cohort studies (27 studies in total). In the case—control studies, the link between smoking and Alzheimer’s disease was not significant (OR 1.020, 95%CI 0.812-1.281). This was regardless of smoking status (current, former and ever smokers). But in the cohort studies, smokers had an increased risk (HR 1.520, 95%CI 1.194-1.934).18 As cohort studies are generally considered a higher level of evidence, with less chance of bias, than case-control studies, the authors concluded that smoking is a risk factor for Alzheimer’s disease.18

In people with dementia, smoking has also been found to independently increase the risk of mortality, compared to people with dementia who do not smoke. A meta-analysis of approximately 235,000 people with dementia found that smoking was associated with a nearly 40% increased risk of death (HR 1.37, 95%CI 1.17-1.61).19 The increased mortality risk is primarily attributed to increased cardiovascular disease risk.

While more research is required to elucidate how long a smoker needs to abstain to reduce their dementia risk (to that of the general population), a 2020 study of around 13,000 people aged 52 to 75 years investigated the relationship between cessation and dementia. The study found that people who had stopped smoking for at least nine years carried the same risk of dementia as never smokers.10 Similarly, a large Korean cohort study found that compared with current smokers, long-term quitters (defined as abstinent for four years or more) had a reduced risk of dementia (all types) and also vascular dementia.12

Smoking may also be risk factor for cognitive decline. Several studies have investigated the link, with findings associating chronic smoking with diminished executive functions, cognitive flexibility, general intellectual abilities, learning and/or memory processing speed, and working memory.20-22 It is important for studies investigating these links to address the selection bias caused by differential mortality among smokers when examining the effects of smoking among the elderly;21 middle-aged smokers are more likely to be lost to follow-up by death or through non-participation in cognitive tests.23

A recent systematic review and meta-analysis examined the link between smoking and neuropsychological impairment in several domains, including cognitive impulsivity, motor impulsivity, attention, intelligence and short and long-term memory. In all domains tested, apart from motor impulsivity, smoking was associated with an increased risk of impairment.24

There is some evidence that in men, stopping smoking for at least 10 years has no association with cognitive decline, suggesting long-term cessation can reduce the risk from smoking compared to continued smoking.22

Several mechanisms have been suggested to explain the link between smoking, dementia and cognitive decline:

  • Studies have identified that smokers, compared to non-smokers, have increased brain atrophy (shrinking and loss of brain matter volume),25-28 which is an indicator of brain ageing and cognitive decline.29 Brain regions that may be affected by smoking include the cerebellum,30 subcortex,31 and hippocampus.29, 32, 33
  • Smokers have been found to have higher levels of oxidative stress biomarkers (indicating damage to brain tissue) compared to non-smokers.34, 35 Oxidative stress can impair blood flow and reduce glucose supply to the brain.36 This in turn may increase production of the protein deposits in the brain which are characteristic of Alzheimer’s disease pathology.1, 17, 36
  • Smokers have an increased risk of co-morbidities such as hypertension and type 2 diabetes, which can increase the risk of Alzheimer’s disease.37

There is also growing evidence that smokers may be at increased risk of delirium. Delirium is the term used to describe acute impairment of cognitive functioning and is characterised by disturbances of attention, awareness and perception.38 Delirium is common in the elderly in inpatient settings and the cause is often multi-factorial.39 Common precipitating and predisposing factors include older age, sensory and cognitive impairment, infection, alcohol dependence, anaesthesia and bladder catheterisation (when a tube is inserted into the bladder to drain urine).39 Smoking has been proposed as another factor, although the evidence has been somewhat mixed. However, a 2015 population-based study of 3,754 people aged 55 years and over found that smokers had an increased risk of inpatient delirium compared to never smokers, when adjusted for confounders including age, sex, cognitive impairment and alcohol consumption (HR 2.87, 95%CI 1.24-6.66).40

Proposed mechanisms for smoking as a risk factor for delirium include the accumulation of vascular damage in the brain (including atherosclerosis; the buildup of fat and other substances in artery walls), and inappropriately managed nicotine withdrawal.40 In the former study, ex-smokers did not have an increased risk of delirium compared to non-smokers, suggesting inadequate nicotine withdrawal management may be a more likely explanation (as it would be expected that ex-smokers would still have a degree of vascular damage). However, this hypothesis requires further investigation.


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References

1. Action on Smoking and Health. ASH Fact Sheet: Smoking and dementia. Action on Smoking and Health (ASH).  2019. Available from: https://ash.org.uk/wp-content/uploads/2019/10/Smoking-Dementia.pdf.

2. World Health Organization. Dementia. Geneva, Switzerland 2019. Available from: https://www.who.int/news-room/fact-sheets/detail/dementia.

3. Australia D. What is dementia?  2020. Available from: https://www.dementia.org.au/about-dementia/what-is-dementia.

4. Chen GB, Payne TJ, Lou XY, Ma JZ, Zhu J, et al. Association of amyloid precursor protein-binding protein, family B, member 1 with nicotine dependence in African and European American smokers. Human Genetics, 2008; 124(4):393-8. Available from: https://www.ncbi.nlm.nih.gov/pubmed/18777128

5. Fratiglioni L and Wang HX. Smoking and Parkinson's and Alzheimer's disease: review of the epidemiological studies. Behavioural Brain Research, 2000; 113(1-2):117-20. Available from: https://www.ncbi.nlm.nih.gov/pubmed/10942038

6. Graves AB, van Duijn CM, Chandra V, Fratiglioni L, Heyman A, et al. Alcohol and tobacco consumption as risk factors for Alzheimer's disease: a collaborative re-analysis of case-control studies. EURODEM Risk Factors Research Group. International Journal of Epidemiology, 1991; 20 Suppl 2:S48-57. Available from: https://www.ncbi.nlm.nih.gov/pubmed/1833354

7. Lee PN. Smoking and Alzheimer's disease: a review of the epidemiological evidence. Neuroepidemiology, 1994; 13(4):131-44. Available from: https://www.ncbi.nlm.nih.gov/pubmed/8090255

8. Smith CJ and Giacobini E. Nicotine, Parkinson's and Alzheimer's disease. Reviews in the Neurosciences, 1992; 3(1):25-44. Available from: https://www.ncbi.nlm.nih.gov/pubmed/21561277

9. Van Duijn CM, Clayton DG, Chandra V, Fratiglioni L, Graves AB, et al. Interaction between genetic and environmental risk factors for Alzheimer's disease: a reanalysis of case-control studies. Genetic Epidemiology, 1994; 11(6):539-51. Available from: https://www.ncbi.nlm.nih.gov/pubmed/7713394

10. Deal JA, Power MC, Palta P, Alonso A, Schneider ALC, et al. Relationship of Cigarette Smoking and Time of Quitting with Incident Dementia and Cognitive Decline. Journal of the American Geriatrics Society, 2020; 68(2):337-45. Available from: https://www.ncbi.nlm.nih.gov/pubmed/31675113

11. Hersi M, Irvine B, Gupta P, Gomes J, Birkett N, et al. Risk factors associated with the onset and progression of Alzheimer's disease: A systematic review of the evidence. Neurotoxicology, 2017; 61:143-87. Available from: https://www.ncbi.nlm.nih.gov/pubmed/28363508

12. Choi D, Choi S, and Park SM. Effect of smoking cessation on the risk of dementia: a longitudinal study. Annals of Clinical and Translational Neurology, 2018; 5(10):1192-9. Available from: https://www.ncbi.nlm.nih.gov/pubmed/30349854

13. McKenzie J, Bhatti L, and Tursan d'Espaignet E. WHO Tobacco Knowledge Summaries: Tobacco and dementia. Geneva, Switzerland 2014. Available from: https://apps.who.int/iris/bitstream/handle/10665/128041/WHO_NMH_PND_CIC_TKS_14.1_eng.pdf;jsessionid=255FBE59E915DEF3097903B697EB4DC3?sequence=1.

14. Alzheimer's Disease International. World Alzheimer Report London, UK 2014. Available from: http://www.alz.co.uk/research/WorldAlzheimerReport2014.pdf.

15. Cataldo JK, Prochaska JJ, and Glantz SA. Cigarette smoking is a risk factor for Alzheimer's Disease: an analysis controlling for tobacco industry affiliation. Journal of Alzheimer's Disease, 2010; 19(2):465-80. Available from: https://www.ncbi.nlm.nih.gov/pubmed/20110594

16. Zhong G, Wang Y, Zhang Y, Guo JJ, and Zhao Y. Smoking is associated with an increased risk of dementia: a meta-analysis of prospective cohort studies with investigation of potential effect modifiers. PLoS ONE, 2015; 10(3):e0118333. Available from: https://www.ncbi.nlm.nih.gov/pubmed/25763939

17. Otuyama LJ, Oliveira D, Locatelli D, Machado DA, Noto AR, et al. Tobacco smoking and risk for dementia: evidence from the 10/66 population-based longitudinal study. Aging and Mental Health, 2019:1-11. Available from: https://www.ncbi.nlm.nih.gov/pubmed/31512501

18. Niu H, Qu Y, Li Z, Wang R, Li L, et al. Smoking and Risk for Alzheimer Disease: A Meta-Analysis Based on Both Case-Control and Cohort Study. Journal of Nervous and Mental Disease, 2018; 206(9):680-5. Available from: https://www.ncbi.nlm.nih.gov/pubmed/30124567

19. van de Vorst IE, Koek HL, de Vries R, Bots ML, Reitsma JB, et al. Effect of Vascular Risk Factors and Diseases on Mortality in Individuals with Dementia: A Systematic Review and Meta-Analysis. Journal of the American Geriatrics Society, 2016; 64(1):37-46. Available from: https://www.ncbi.nlm.nih.gov/pubmed/26782850

20. Durazzo TC, Meyerhoff DJ, and Nixon SJ. Chronic cigarette smoking: implications for neurocognition and brain neurobiology. International Journal of Environmental Research and Public Health, 2010; 7(10):3760-91. Available from: https://www.ncbi.nlm.nih.gov/pubmed/21139859

21. Nooyens AC, van Gelder BM, and Verschuren WM. Smoking and cognitive decline among middle-aged men and women: the Doetinchem Cohort Study. American Journal of Public Health, 2008; 98(12):2244-50. Available from: https://www.ncbi.nlm.nih.gov/pubmed/18923116

22. Sabia S, Elbaz A, Dugravot A, Head J, Shipley M, et al. Impact of smoking on cognitive decline in early old age: the Whitehall II cohort study. Archives of General Psychiatry, 2012; 69(6):627-35. Available from: https://www.ncbi.nlm.nih.gov/pubmed/22309970

23. Sabia S, Marmot M, Dufouil C, and Singh-Manoux A. Smoking history and cognitive function in middle age from the Whitehall II study. Archives of Internal Medicine, 2008; 168(11):1165-73. Available from: https://www.ncbi.nlm.nih.gov/pubmed/18541824

24. Conti AA, McLean L, Tolomeo S, Steele JD, and Baldacchino A. Chronic tobacco smoking and neuropsychological impairments: A systematic review and meta-analysis. Neuroscience and Biobehavioral Reviews, 2019; 96:143-54. Available from: https://www.ncbi.nlm.nih.gov/pubmed/30502351

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26. Elbejjani M, Auer R, Jacobs DR, Jr., Haight T, Davatzikos C, et al. Cigarette smoking and gray matter brain volumes in middle age adults: the CARDIA Brain MRI sub-study. Translational Psychiatry, 2019; 9(1):78. Available from: https://www.ncbi.nlm.nih.gov/pubmed/30741945

27. Sutherland MT, Riedel MC, Flannery JS, Yanes JA, Fox PT, et al. Chronic cigarette smoking is linked with structural alterations in brain regions showing acute nicotinic drug-induced functional modulations. Behavioral and Brain Functions, 2016; 12(1):16. Available from: https://www.ncbi.nlm.nih.gov/pubmed/27251183

28. Zhong J, Shi H, Shen Y, Dai Z, Zhu Y, et al. Voxelwise meta-analysis of gray matter anomalies in chronic cigarette smokers. Behavioural Brain Research, 2016; 311:39-45. Available from: https://www.ncbi.nlm.nih.gov/pubmed/27173432

29. Duriez Q, Crivello F, and Mazoyer B. Sex-related and tissue-specific effects of tobacco smoking on brain atrophy: assessment in a large longitudinal cohort of healthy elderly. Frontiers in Aging Neuroscience, 2014; 6:299. Available from: https://www.ncbi.nlm.nih.gov/pubmed/25404916

30. Cardenas VA, Hough CM, Durazzo TC, and Meyerhoff DJ. Cerebellar Morphometry and Cognition in the Context of Chronic Alcohol Consumption and Cigarette Smoking. Alcoholism, Clinical and Experimental Research, 2020; 44(1):102-13. Available from: https://www.ncbi.nlm.nih.gov/pubmed/31730240

31. Durazzo TC, Meyerhoff DJ, Yoder KK, and Murray DE. Cigarette smoking is associated with amplified age-related volume loss in subcortical brain regions. Drug and Alcohol Dependence, 2017; 177:228-36. Available from: https://www.ncbi.nlm.nih.gov/pubmed/28622625

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35. Durazzo TC, Mattsson N, Weiner MW, Korecka M, Trojanowski JQ, et al. History of cigarette smoking in cognitively-normal elders is associated with elevated cerebrospinal fluid biomarkers of oxidative stress. Drug and Alcohol Dependence, 2014; 142:262-8. Available from: https://www.ncbi.nlm.nih.gov/pubmed/25037769

36. Toda N and Okamura T. Cigarette smoking impairs nitric oxide-mediated cerebral blood flow increase: Implications for Alzheimer's disease. Journal of Pharmacological Sciences, 2016; 131(4):223-32. Available from: https://www.ncbi.nlm.nih.gov/pubmed/27530818

37. Custodio N, Montesinos R, Lira D, Herrera-Perez E, Bardales Y, et al. Mixed dementia: A review of the evidence. Dementia & Neuropsychologia, 2017; 11(4):364-70. Available from: https://www.ncbi.nlm.nih.gov/pubmed/29354216

38. Department of Health and Human Services. Delirium is a serious condition. Melbourne, Victoria Available from: https://www2.health.vic.gov.au/hospitals-and-health-services/patient-care/older-people/cognition/delirium/delirium-serious.

39. Ahmed S, Leurent B, and Sampson EL. Risk factors for incident delirium among older people in acute hospital medical units: a systematic review and meta-analysis. Age and Ageing, 2014; 43(3):326-33. Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4001175/

40. Hessler JB, Bronner M, Etgen T, Gotzler O, Forstl H, et al. Smoking increases the risk of delirium for older inpatients: a prospective population-based study. General Hospital Psychiatry, 2015; 37(4):360-4. Available from: https://www.ncbi.nlm.nih.gov/pubmed/25824602