Search Strategy
Date of search: 02nd of May 2018
Search starting time: 31st December 2012
Full search terms
(dementia OR cognit* OR mild cognitive impairment OR Alzheimer disease OR dementia vascular OR dementia multi-infarct OR MCI OR cognitive dysfunction OR neuropsychologi* OR Health-Related Quality Of Life OR life quality OR Activities, Daily Living OR Chronic Limitation of Activity OR Limitation of Activity, Chronic OR ADL OR activities of daily living OR Drug-Related Side Effects and Adverse Reactions OR Adverse Drug Event OR Adverse Drug Reaction OR Long Term Adverse Effects OR Adverse Effects, Long Term Disease-Free Survival OR Event-Free Survival OR Adverse effects) AND (Tobacco OR smoking OR Tobacco use cessation OR giving up smoking OR quitting smoking OR stopping smoking OR smoking cessation OR smoking reduction OR tobacco use cessation products OR varenicline OR nicotinic agonists OR Nicotine Inhalant OR Nicotine Lozenge OR Nicotine Lozenges OR Nicotine Nasal Spray OR Nicotine Patch OR Nicotine Polacrilex OR Nicotine Replacement Products OR Nicotine Transdermal Patch OR Smoking Cessation Products) AND (Behavior OR behaviour OR drug therapy OR pharmacologic therapy OR pharmacotherapy OR Cognitive behavioural therapy OR Cognitive behavioural therapy OR Drug therapy OR cognitive therapy OR online therapy OR treatment)
Simplified search terms
(dementia OR MCI OR cognition OR Quality of Life OR ADL OR Adverse Effects OR Drop-out) AND smoking AND smoking cessation
Searches were conducted in the following databases1:
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Cochrane
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Pubmed
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NICE Guidelines
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Embase
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PsycInfo
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Global Health Library (Including WHOLIS, PAHO, AIM, LILACS)
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Database of impact evaluations
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AFROLIB
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ArabPsycNet
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HERDIN NeON
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HrCak
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IndMED
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KoreaMed
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AJOL
Narrative description of the observational evidence on the correlation between tobacco consumption and increased risk of dementia
Although the present search did not gather any evidence from intervention studies aimed at investigating the effect of tobacco cessation on the risk of dementia and/or cognitive decline, observational evidence of a correlation between tobacco consumption and increased risk of dementia are widely available. In particular, three systematic reviews (one including meta-analysis), two meta-analysis, and one multi-cohort study reporting observational evidence of the correlation between tobacco and risk of dementia and/or cognitive decline were identified and selected for this narrative description.
Beydoun et al., published in 2014 a systematic review and meta-analysis on modifiable risk factors for dementia and cognitive decline.19 Epidemiological studies (including cross-sectional) on the relation between dementia and/or cognition with education, smoking, alcohol, physical activity, caffeine, antioxidants, homocysteine (Hcy), or n-3 fatty acids were systematically searched in MEDLINE from January 1990 through October 2012. Only cohort studies of at least 300 participants were included in the search. A total of 247 studies were identified across all the risk factors and seven cross-sectional studies investigation the possible correlation between smoking and cognition and/or dementia were identified. Of these seven studies only 2 (representing the 28.6% of the pooled cohort) found a significant association between smoking and cognitive decline, and two more detected it in sub-group analysis. A meta-analysis on nine studies that reported relative risk (RR) for dementia in relation to the smoking status showed that smoking seems to increase risk of dementia (RR 1.37; 95% Cl 1.23 to 1.52) but significant heterogeneity was detected using Q2 statistics p<0.001).
In the same year another systematic review (without meta-analysis) was published on modifiable risk factors for dementia.20 The search was carried out on a wider range of databases (PubMed, Ovid MEDLINE, In-Process & Other Non-Indexed Citations and Ovid MEDLINE, and PsycINFO) compared to the previous review and included also more recent publications (up to December 2013). 75 papers from 33 epidemiologic studies met the inclusion criteria and 15 of these investigated the correlation between smoking and dementia. In nine out of these 15 examined publications a significant correlation between smoking status (especially current smoking) and dementia was identified. Two studies reported about the role of ApoE Ɛ4 in increasing the risk of dementia in current smokers. Evidence was limited by the fact that only studies investigating on the incidence of dementia, and not on cognitive performance outcomes, were included.
North and colleagues published in 2015 a multi-cohort study (9 British cohorts; n=26692) investigating the association between smoking status and cognitive performance/decline.21 The study included older adults (mean age range 50–79) of European ancestry. Participants were classified at baseline as current, ex or never smokers; cognitive performance was measured with range of assessments: crystallised intelligence (indicator of knowledge accumulated across the life course), fluid intelligence (measuring problem-solving skills), semantic fluency, phonemic fluency, search speed, word recall, four choice reaction time, logical memory, and Raven’s Progressive Matrices (for abstract reasoning and fluid intelligence). The results were statistically combined in a general fluid (Gf) cognitive ability score that allowed to compare and pool the data from different cohorts. Compared to both ex-smokers and never smokers, current smokers consistently showed a worse cognitive performance in all the cognitive areas (significant results in the majority of the cases). This evidence was gathered from a single multi cohort study, and not from a systematic review and/or meta-analysis, however the sample and the effect size support the quality of the evidence, which clearly points toward a link between smoking and cognitive decline.
Also, a meta-analysis of observational evidence of the role of modifiable risk factors for Alzheimer’s disease was published in 2015.22 Xu and colleagues systematically searched PubMed and the Cochrane database of systematic reviews from inception to July 2014 for cohort studies and retrospective case–control studies reporting on risk factors for Alzheimer’s disease (AD) and dementia. Studies were included if: they reported original data concerning odds ratio (OR) or risk ratio (RR) of AD using a longitudinal cohort study or retrospective case–control study design; the study population was representative of the general population and; modifiable risk factors were included. A total of 323 papers were included in the meta-analysis. Concerning smoking Grade I evidence was identified from nine studies of a significant correlation between current smoker status and increased risk of AD (RR/OR 1.87; 95% Cl 0.99–2.75). The pooled analysis however was limited by significant heterogeneity (I2=67), but sensitivity analyses conducted to reduce heterogeneity still showed a significant association between smoking and increased risk of AD. Publication bias was investigated but undetected using Egger’s test (p=0.657).
A second meta-analysis23 of observational studies was published in the same year, focusing specifically on the association between smoking and increased risk of dementia. The authors search PubMed, Embase, Cochrane Library and Psychinfo for studies that provided risk estimates on smoking and incidence of dementia. The search yielded 37 studies and the meta-analysis showed that compared with never smokers, current smokers had an increased risk of all-cause dementia (RR 1.30; 95% CI 1.18–1.45). Statistically significant moderate heterogeneity (I2=50.6) was identified but no evidence of publication bias was found for any association by Begg’s test and Egger’s test (p>0.05). A dose-response analysis reported that for all-cause dementia, the risk increased by 34% for every 20 cigarettes per day (RR 1.34, 95%CI 1.25–1.43), and a subgroup analysis indicated that the significantly increased risk of AD from current smoking was mostly driven by ApoE ε4 noncarriers.
More recently, Lafortune and colleagues conducted a rapid systematic review on the lifestyle risk factors correlated to different ageing conditions including dementia.24 The search was made on longitudinal cohort studies in several relevant databases starting from 2000 and identified 164 studies that were included in a qualitative synthesis. Nine studies reported about the correlation between smoking and dementia and/or cognitive decline. In most studies smoking was strongly associated with dementia, and subsequent risk of hospitalisation. Two studies showed also an association between smoking and cognition.
In conclusion, despite the overall lack of intervention trials aimed at investigating the effect of tobacco cessation on the risk of dementia and/or cognitive decline, there is strong and consistent observational evidence demonstrating the association between tobacco consumption (including in mid-life) and dementia, or cognitive decline, in later life. In addition to this, the WHO guidelines for the treatment of tobacco dependence25 represent the most relevant evidence and recommendations to which refer for the management of tobacco dependence in the normal population.