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Risk Reduction of Cognitive Decline and Dementia: WHO Guidelines. Geneva: World Health Organization; 2019.

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Risk Reduction of Cognitive Decline and Dementia: WHO Guidelines.

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Evidence profile: Tobacco cessation and cognitive decline or dementia

Scoping question:

For adults with normal cognition or mild cognitive impairment who use tobacco, are interventions for tobacco cessation more effective than usual care or no intervention in reducing the risk of cognitive decline and/or dementia?

Background

As the number of older adults increases worldwide, a rise in dementia and Alzheimer’s disease (AD) has also been reported,1 causing health, economic and social burdens.2,3 In 2015, it has been estimated that there were 46.8 million people with dementia in the world, and the number is predicted to double every 20 years, reaching 74.7 million in 2030 and 131.5 million in 2050.1 Since no cure is available, prevention could be crucial in halting the rapid increase in the prevalence of dementia, as some projection models suggested.4,5 AD/dementia has been linked to modifiable, lifestyle-related, vascular risk factors,13,6 but the extent to which cognitive impairment can be prevented is under debate.

Tobacco dependence is the leading cause of preventable death globally, causing an estimated five million deaths/year7 and word-wide medical costs ranging in billions of US dollars.8 Tobacco is the major risk factor for a number of conditions namely many types of cancers, cardiovascular diseases and risk factors, and respiratory disorders9 and tobacco cessation has been demonstrated to significantly reduce these health risks.10 Tobacco cessation has also been associated with reduced depression, anxiety, and stress and improved positive mood and quality of life compared with continuing to smoke.11

Tobacco dependence has been also associated to other disorders and age related conditions such as frailty and work ability in the elderly,12,13 as well as AD, dementia and cognitive decline.14 One of the proposed mechanisms, whereby tobacco would increase the risk of AD, is by smoking-related cerebral oxidative stress,14 but there is also evidence of a relationship between smoking and shorter telomere length, which may imply other possible mechanisms linking tobacco smoke exposure to ageing-related disease.15

Interventions to treat tobacco dependence can be very diverse, based on either or both behavioural/psychological strategies and various pharmacological treatments. Tobacco cessation is a complex process, like in any other addictions and although most smokers report wanting to quit, many continue as they report that smoking provides them with mental health benefits.16 Non-pharmacological interventions can have mixed results.17 Counselling is the most frequently used approach, but others have also been explored, such as mindfulness-based approaches, cognitive behavioural therapy, behavioural activation therapy, motivational interviewing, contingency management, and exposure and/or aversion to smoking. Among the pharmacological therapies for tobacco cessation, nicotine replacement therapy, bupropion and varenicline are the most common, but low overall treatment efficacy and adverse effects are key limitations.18 Combinations of non-pharmacological and pharmacological approaches seem to be the most effective in supporting tobacco cessation.18

This review of systematic reviews was carried out to search, identify, and synthesise the evidence currently available on the efficacy of behavioural/psychological or pharmacological intervention aimed at tobacco cessation in reducing the risk of dementia and/or cognitive impairment.

Part 1. Evidence review

Scoping questions in PICO format (population intervention, comparisons, outcome)

For adults with normal cognition or mild cognitive impairment who use tobacco, are interventions for tobacco cessation more effective than usual care or no intervention in reducing the risk of cognitive decline and/or dementia?

P: Adults with normal cognition or mild cognitive impairment who use tobacco

I: Interventions for tobacco cessation (behavioural interventions and pharmacological interventions including nicotine replacement therapy, bupropion, varenicline)

C: Care as usual or no intervention

O: Critical

Cognitive function (or cognitive test results using validated instruments)

Incident MCI

Dementia

Important

Quality of life

Functional level (ADL, IADL)

Adverse events

Drop-out rates

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:

Cochrane

Pubmed

NICE Guidelines

Embase

PsycInfo

Global Health Library (Including WHOLIS, PAHO, AIM, LILACS)

Database of impact evaluations

AFROLIB

ArabPsycNet

HERDIN NeON

HrCak

IndMED

KoreaMed

AJOL

List of systemic reviews identified by the search process

No systematic review of intervention studies that matched the PICO question was identified through the present search. A further search with similar strategy was carried out (in PubMed only) for the previous 5 years (from 31.12.2007 to 31.12.2012), and, in addition, reference lists from observational evidence obtained during the main search were checked. This search not only did not yield any systematic review, but neither any evidence of the existence of intervention studies for tobacco cessation that have evaluated the impact of the intervention on dementia and/or cognitive impairment. A search in five of the largest clinical trials registers (ClinicalTrials.gov; EudraCT; ISRCTN; JPRN; and ANZCTR) for completed or ongoing trials relevant to the PICO question was conducted but results were negative (Searches conducted by Mariagnese Barbera and Krister Håkansson).

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.

Other relevant guidelines

WHO’s training package on Strengthening health systems for treating tobacco dependence in primary care (2013)25 represent the most relevant evidence and recommendations to which refer for the management of tobacco dependence in the general population.

http://www.who.int/tobacco/publications/building_capacity/training_package/treatingtobaccodependence/en/

Part 2. From evidence to decisions

Evidence-to-Decision Table

Download PDF (712K)

Reference

1.
Alzheimer´s Disease International. World Alzheimer Report 2015. The global impact of dementia: An analysis of prevalence, incidence, cost and trends. https://Www​.alz.co.uk​/research/WorldAlzheimerReport2015.pdf. 2015.
2.
Norton S, Matthews FE, Brayne C. A commentary on studies presenting projections of the future prevalence of dementia. BMC Public Health. 2013;13:1-2458-13-1. [PMC free article: PMC3547813] [PubMed: 23280303]
3.
Winblad B, Amouyel P, Andrieu S, et al. Defeating Alzheimer’s disease and other dementias: A priority for European science and society. Lancet Neurol. 2016;15(5):455–532. [PubMed: 26987701]
4.
Brookmeyer R, Johnson E, Ziegler-Graham K, Arrighi HM. Forecasting the global burden of Alzheimer’s disease. Alzheimers Dement 2007;3, 186–191. [PubMed: 19595937]
5.
Jagger C, Matthews R, Lindesay J, Robinson T, Croft P, Brayne C. The effect of dementia trends and treatments on longevity and disability: a simulation model based on the MRC Cognitive Function and Ageing Study (MRC CFAS). Age Ageing. 2009;38, 319–25; discussion 251. [PubMed: 19258397]
6.
Solomon A, Mangialasche F, Richard E, et al. Advances in the prevention of Alzheimer’s disease and dementia. J Intern Med. 2014;275(3):229–250. [PMC free article: PMC4390027] [PubMed: 24605807]
7.
World Health Organization. WHO report on the global tobacco epidemic. WHO, 2011.
8.
Lightwood J, Collins D, Lapsley H, Novotny T. Tobacco control in developing countries. Section 1: Tobacco use and its consequences: estimating the costs of tobacco use. World Bank, 2000.
9.
US Department of Health and Human Services. The health consequences of smoking: a report of the Surgeon General. US Department of Health and Human Services, 2004.
10.
Pirie K, Peto R, Reeves G, Green J, Beral V. The 21st century hazards of smoking and benefits of stopping: a prospective study of one million women in the UK. Lancet 2013;381:133–41. [PMC free article: PMC3547248] [PubMed: 23107252]
11.
Taylor G, McNeill A, Girling A, Farley A, Lindson-Hawley N, Aveyard P. Change in mental health after smoking cessation: systematic review and meta-analysis. BMJ. 2014 Feb 13;348:g1151. [PMC free article: PMC3923980] [PubMed: 24524926]
12.
Amorim JS, Salla S, Trelha CS. Factors associated with work ability in the elderly: systematic review. Rev Bras Epidemiol. 2014 Dec;17(4):830–41. [PubMed: 25388484]
13.
Kojima G, Iliffe S, Walters K. Smoking as a predictor of frailty: a systematic review. BMC Geriatr. 2015 Oct 22;15:131. [PMC free article: PMC4618730] [PubMed: 26489757]
14.
Durazzo TC, Mattsson N, Weiner MW; Alzheimer’s Disease Neuroimaging Initiative. Smoking and increased Alzheimer’s disease risk: a review of potential mechanisms. Alzheimers Dement. 2014 Jun;10:(3 Suppl):S122–45. [PMC free article: PMC4098701] [PubMed: 24924665]
15.
Astuti Y, Wardhana A, Watkins J, Wulaningsih W; PILAR Research Network. Cigarette smoking and telomere length: A systematic review of 84 studies and meta-analysis. Environ Res. 2017 Oct;158:480–489. [PMC free article: PMC5562268] [PubMed: 28704792]
16.
Zhou X, Nonnemaker J, Sherrill B, Gilsenan A, Coste F, West R. Attempts to quit smoking and relapse: factors associated with success or failure from the ATTEMP cohort study. Addict Behav 2009;34:365–73. [PubMed: 19097706]
17.
Niaura, R., 2008. Nonpharmacologic therapy for smoking cessation: characteristics and efficacy of current approaches. Am. J. Med. 121 (Suppl. 1), S11–S19. [PubMed: 18342162]
18.
Gómez-Coronado N, Walker AJ, Berk M, Dodd S. Current and Emerging Pharmacotherapies for Cessation of Tobacco Smoking. Pharmacotherapy. 2018 Feb;38(2):235–258. doi: 10.1002/phar.2073. [PubMed: 29250815] [CrossRef]
19.
Beydoun MA, Beydoun HA, Gamaldo AA, Teel A, Zonderman AB, Wang Y. Epidemiologic studies of modifiable factors associated with cognition and dementia: systematic review and meta-analysis. BMC Public Health. 2014 Jun 24;14:643. [PMC free article: PMC4099157] [PubMed: 24962204]
20.
Di Marco LY, Marzo A, Muñoz-Ruiz M, Ikram MA, Kivipelto M, Ruefenacht D, Venneri A, Soininen H, Wanke I, Ventikos YA, Frangi AF. Modifiable lifestyle factors in dementia: a systematic review of longitudinal observational cohort studies. J Alzheimers Dis. 2014;42(1):119–35. [PubMed: 24799342]
21.
North TL, Palmer TM, Lewis SJ, Cooper R, Power C, Pattie A, Starr JM, Deary IJ, Martin RM, Aihie Sayer A, Kumari M, Cooper C, Kivimaki M, Kuh D, Ben-Shlomo Y, Day IN. Effect of smoking on physical and cognitive capability in later life: a multicohort study using observational and genetic approaches. BMJ Open. 2015 Dec 15;5(12):e008393. [PMC free article: PMC4679991] [PubMed: 26671949]
22.
Xu W, Tan L, Wang HF, Jiang T, Tan MS, Tan L, Zhao QF, Li JQ, Wang J, Yu JT. Meta-analysis of modifiable risk factors for Alzheimer’s disease. J Neurol Neurosurg Psychiatry. 2015 Dec;86(12):1299–306. [PubMed: 26294005]
23.
Zhong G, Wang Y, Zhang Y, Guo JJ, Zhao Y. Smoking is associated with anincreased risk of dementia: a meta-analysis of prospective cohort studies with investigation of potential effect modifiers. PLoS One. 2015 Mar 12;10(3):e0118333. [PMC free article: PMC4357455] [PubMed: 25763939]
24.
Lafortune L, Martin S, Kelly S, Kuhn I, Remes O, Cowan A, Brayne C. Behavioural Risk Factors in Mid-Life Associated with Successful Ageing, Disability, Dementia and Frailty in Later Life: A Rapid Systematic Review. PLoS One. 2016 Feb 4;11(2):e0144405. [PMC free article: PMC4742275] [PubMed: 26845035]
25.
WHO’s training package on Strengthening health systems for treating tobacco dependence in primary care (2013). http://www​.who.int/tobacco​/publications/building_capacity​/training_package​/treatingtobaccodependence/en/
26.
Motooka Y, Matsui T, Slaton RM, Umetsu R, Fukuda A, Naganuma M, Hasegawa S, Sasaoka S, Hatahira H, Iguchi K, Nakamura M. Adverse events of smoking cessation treatments (nicotine replacement therapy and non-nicotine prescription medication) and electronic cigarettes in the Food and Drug Administration Adverse Event Reporting System 2004–2016. SAGE Open Med. 2018 May 21;6:2050312118777953. doi: 10.1177/2050312118777953. eCollection 2018. [PMC free article: PMC5966839] [PubMed: 29844912] [CrossRef]
27.
Cheng S. Dementia Caregiver Burden: a Research Update and Critical Analysis. Curr Psychiatry Rep. 2017; 19(9): 64. [PMC free article: PMC5550537] [PubMed: 28795386]
28.
Mougias AA, Politis A, Mougias MA, Kotrotsou I, Skapinakis P, Damigos D, Mavreas VG. The burden of caring for patients with dementia and its predictors. Psychiatriki. 2015 Jan-Mar;26(1):28–37. [PubMed: 25880381]
29.
Shearer J, Shanahan M. Cost effectiveness analysis of smoking cessation interventions. Aust N Z J Public Health. 2006 Oct;30(5):428–34. [PubMed: 17073223]
30.
Daly AT, Deshmukh AA, Vidrine DJ, Prokhorov AV, Frank SG, Tahay PD4, Houchen ME, Cantor SB. Cost-effectiveness analysis of smoking cessation interventions using cell phones in a low-income population. Tob Control. 2018 Jun 9. pii: tobaccocontrol-2017-054229. doi: 10.1136/tobaccocontrol-2017-054229. [PMC free article: PMC6692895] [PubMed: 29886411] [CrossRef]
31.
Gilbert A, Cornuz J (2003). Which are the most effective and cost-effective interventions for tobacco control? Copenhagen, WHO Regional Office for Europe (Health Evidence Network report; http://www​.euro.who.int/document/e82993​.pdf, last accessed 27 August 2018).
32.
Dilley JA, Harris JR, Boysun MJ, Reid Terry R. Program, Policy, and Price Interventions for Tobacco Control: Quantifying the Return on Investment of a State Tobacco Control Program. Am J Public Health. 2012 February; 102(2): e22–e28. [PMC free article: PMC3484005] [PubMed: 22390458]
33.
Ali A, Kaplan CM, Derefinko KJ, Klesges RC. Smoking Cessation for Smokers Not Ready to Quit: Meta-analysis and Cost-effectiveness Analysis. Am J Prev Med. 2018 Jun 11. pii: S0749–3797(18)31704–5. doi: 10.1016/j.amepre.2018.04.021. [PMC free article: PMC6055474] [PubMed: 29903568] [CrossRef]
34.
Temple NJ. Why prevention can increase health-care spending. Eur J Public Health. 2012 Oct;22(5):618–9. Epub 2011 Sep 13. [PubMed: 21914705]
35.
UCL Institute of Health Equity; Inequality in mental health, cognitive impairment and dementia among older people. 2016.
36.
Thies W, Bleiler L. 2013 Alzheimer’s disease facts and figures. Alzheimer’s Dement. 2013;9(2):208–245. [PubMed: 23507120]
37.
Raiff BR, Jarvis BP, Turturici M, Dallery J. Acceptability of an Internet-based contingency management intervention for smoking cessation: views of smokers, nonsmokers, and healthcare professionals. Exp Clin Psychopharmacol. 2013 Jun;21(3):204–13. doi: 10.1037/a0032451. [PMC free article: PMC4000566] [PubMed: 23750691] [CrossRef]
38.
Hill AB. The Environment and Disease: Association or Causation?. Proceedings of the Royal Society of Medicine. 1965;58 (5): 295–300. [PMC free article: PMC1898525] [PubMed: 14283879]
39.
Durazzo TC, Mattsson N, Weiner MW. Smoking and increased Alzheimer’s disease risk: A review of potential mechanisms. Alzheimers Dement. 2014 Jun; 10(30): S122–S145. [PMC free article: PMC4098701] [PubMed: 24924665]

Annex. PRISMA flow diagram for systematic review of the reviews – cognitive decline interventions2

Image evidenceprofile2app1f1

* 3 systematic reviews (one including meta-analysis), 2 meta-analysis and 1 multi-cohort study (n>26000) included in the narrative description of observational evidence

Footnotes

1

Please note that the EurasiaHealth database did not return any meaningful answer to the search.

2

Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). For more information: http://www​.prisma-statement.org

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