Impact of tobacco smoking on disease-specific outcomes in common neurological disorders: a scoping review

Abstract

Although the association of smoking with the risk of incident neurological disorders is well established, less is known about the impact of smoking and smoking cessation on outcomes of these conditions. The objective of this scoping review was to synthesize what is known about the impact of smoking and smoking cessation on disease-specific outcomes for seven common neurological disorders. We included 67 studies on the association of smoking and smoking cessation on disease-specific outcomes. For multiple sclerosis, smoking was associated with greater clinical and radiological disease progression, relapses, risk for disease-related death, cognitive decline, and mood symptoms, in addition to reduced treatment effectiveness. For stroke and transient ischemic attack, smoking was associated with greater rates of stroke recurrence, post-stroke cardiovascular outcomes, post-stroke mortality, post-stroke cognitive impairment, and functional impairment. In patients with cognitive impairment and dementia, smoking was associated with faster cognitive decline, and smoking was also associated with greater cognitive decline in Parkinson’s disease, but not motor symptom worsening. Patients with amyotrophic lateral sclerosis who smoked faced increased mortality. Last, in patients with cluster headache, smoking was associated with more frequent and longer cluster attack periods. Conversely, for multiple sclerosis and stroke, smoking cessation was associated with improved disease-specific outcomes. In summary, whereas smoking is detrimentally associated with disease-specific outcomes in common neurological conditions, there is growing evidence that smoking cessation may improve outcomes. Effective smoking cessation interventions should be leveraged in the management of common neurological disorders to improve patient outcomes.

Introduction

Tobacco smoking is strongly associated with poor health outcomes and reduced longevity¹. According to the World Health Organization, despite global attention to reducing tobacco consumption, the prevalence of smoking will exceed 30% in 2025². Smoking cessation is a highly impactful medical intervention that improves health outcomes, and there are several effective but underutilized smoking cessation treatments available³.

Neurological disorders are the leading cause of disability-adjusted life years and the second leading cause of mortality worldwide⁴. As the world’s population grows and life expectancy increases, neurological disorders will continue to have a significant impact on global morbidity and mortality⁴. Cigarette smoking is a risk factor for the incident development of many neurological disorders such as stroke⁵, dementia⁶ and multiple sclerosis (MS)⁷.

Although there are many studies on the association of smoking with incident neurological conditions, less is known about the impact of smoking and smoking cessation on outcomes of these conditions. We surmised that a greater understanding of the impact of smoking on the course and outcomes of neurological disorders will inform strategies to mitigate disability. Therefore, in this scoping review, taking the perspective of clinicians treating patients with the most prevalent common neurological conditions as identified by the Global Burden of Disease collaborators⁴, we sought to synthesize what is known about the impact of smoking status and smoking cessation on disease-specific outcomes of these conditions.

Methods

Study Design

This was a scoping review informed by the Arksey and O’Malley framework and Joanna Briggs Institute checklist⁸. Reporting in this manuscript follows the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA)-extension for Scoping Reviews standards⁹. We performed a scoping review because the impacts of smoking status and smoking cessation on neurological outcomes have not previously been catalogued and analyzed, and we anticipated heterogeneity in study populations, designs, and reported outcomes. We reviewed only previously published data; institutional review board approval and individual patient informed consent were not relevant. As a scoping review, this paper was not eligible for PROSPERO submission.

Research questions

We framed our question utilizing the Joanna Briggs Institute ‘Population and Concept’ strategy. Our population were patients with one of the following neurological conditions: cognitive impairment/dementia, cerebrovascular disease (stroke/transient ischemic attack or intracranial aneurysm), Parkinson’s Disease (PD), demyelinating disorders (MS and other related conditions), epilepsy, primary headache disorder, and amyotrophic lateral sclerosis (ALS). Our concept was to determine whether disease-specific outcomes of these neurological conditions differed based on patient smoking status or smoking cessation.

Inclusion/exclusion criteria

This review sought to include cohort, case-control, and randomized-control studies of individuals ≥18 years old with neurological conditions of interest that stratified patients by smoking status (current smoker, former smoker, never smoker, or a combination thereof) or smoking cessation status (quitter versus continued smoker) and reported on disease-specific neurological outcomes of the included neurological conditions of interest. We included mortality as a disease-specific outcome for stroke because of the high rate of stroke-related mortality¹⁰ and for ALS because mortality in ALS can be disease-related^11,12. We included only studies published in peer reviewed journals. Exclusion criteria were nonhuman research, abstracts without subsequent full length manuscript publication, non-English language articles, studies that only examined the impact of smoking on neurological disease incidence, case reports, case series, cross-sectional analyses that did not evaluate the impact of smoking on outcomes over time and publication date prior to 1990 (Figure 1).

Figure 1.

PRISMA Flow Diagram.

Literature sources and search strategy

PubMed, Embase and CINAHL were searched from inception to January 13, 2023. The search strategy was developed with the guidance of a medical research librarian (SL). Medical Subject Headings and search terms were combined with Boolean operators (AND, OR) to refine the searches (Supplemental Materials). Studies that emerged from the three databases were uploaded into Covidence (Veritas Health Innovation, Melbourne, Australia) which removed duplicates. Title and abstract screening were done separately by two reviewers (DR, FW). A third reviewer (NP) screened articles if the initial reviewers disagreed. Title and abstract review resulted in exclusion of a large number of studies that did not specifically pertain to the association of smoking on disease-specific outcomes in neurological disorders of interest. Screened articles that received consensus approval advanced to full-text review for screening according to inclusion and exclusion criteria. Additional articles were included for screening from personal records and reference lists of studies identified through our formal search.

Data extraction and analyses

For included articles, two reviewers (DR or FW and NP) extracted data using Covidence. Extracted data included study title, first author, year of publication, journal, country of study, smoking status groupings, sample size (broken down by smoking status group), follow-up duration, how smoking status was determined, how smoking cessation was measured, and results of disease-specific neurologic outcomes studied. Key findings of included studies were summarized by neurological condition.

Data availability statement

The data collated for this scoping review is presented in its entirety in the manuscript.

Results

We included 67 studies after screening 6,987 citations (Figure 1). MS and related disorders were the most common disease studied (n=30), followed by cerebrovascular disease (n=21), cognitive impairment/dementia (n=9), and fewer than 8 studies for the remaining conditions, with the exception of epilepsy, for which no studies were found (Table 1).

Table 1.

Characteristics of included studies.

Characteristic	Number of Studies (Total 67)
Country of Study
United States of America	18
China	7
Norway	6
United Kingdom	4
Canada	4
Denmark	3
Japan	3
Australia	2
Turkey	2
Multinational cohort	2
Finland	3
Iran	1
Netherlands	2
South Korea	1
Sweden	3
Austria	1
Czech Republic	1
Italy	1
Mexico	1
Spain	1
Israel	1
Neurological condition
Multiple Sclerosis	30
Cerebrovascular Disease	21
Cognitive Disorders	9
Parkinson’s Disease	4
Amyotrophic Lateral Sclerosis	2
Primary Headache Disorders*	1
Epilepsy	0
Year of Publication
2016–2023	37
2011–2015	18
2006–2010	6
2000–2005	6
How was smoking status determined?
Biomarker	6
Self-report/electronic medical record	61
Was smoking cessation evaluated?
Yes	27
No	40

^*Manuscripts meeting our criteria regarding more common primary headache disorders such as migraine headache were not identified.

Most of the studies (n=18) in this scoping review were completed in the United States of America. Most studies (n=61) used patient self-report to determine smoking status, whereas 6 studies used biomarkers such as serum cotinine. Only 27 studies assessed the impact of smoking cessation, rather than baseline smoking status, on outcomes. A variety of disease-specific outcomes, spanning clinical outcomes, radiologic markers, and serologic markers were reported (Table 2).

Table 2.

Outcomes of interest from scoping review of smoking status impact on neurological disorders.

Neurological Condition	Disease-specific outcomes
Demyelinating disorders	Conversion of CIS to MS Conversion to progressive forms of MS Relapse occurrence and frequency Progression of Expanded Disability Status Scale Progression of Multiple Sclerosis Severity Score Standardized Paced Auditory Serial Addition Test MS Impact Scale-29 Physical Hospital Anxiety and Depression Scale Development of antibodies to natalizumab and interferon beta-1a Discontinuation of natalizumab, dimethyl fumarate, or fingolimod Changes in contrast-enhancing lesions Changes in neurofilament light chain
Cerebrovascular Disease	Stroke recurrence Post-stroke cardiovascular events Post-stroke mortality Cognitive function tests Fatigue, anxiety, and depression Modified Rankin Score Barthel Index Intracranial aneurysm growth and rupture
Cognitive Disorders	Progression of disease across SCD, MCI, dementia spectrum Reversal of MCI to normal cognition Mini-Mental State Examination score Clinical Dementia Rating Scale Sum of Boxes score Montreal Cognitive Assessment score Risk of death from AD Entorhinal cortex volume Serum biomarkers
Parkinson’s Disease	Unified Parkinson Disease Rating Scale Hoehn and Yahr Scale Schwab and England Score L-Dopa dosage Incident dementia development Montgomery and Aasberg Depression Rating Scale Mini-Mental State Examination score
Amyotrophic Lateral Sclerosis	Survival
Headache	Frequency of cluster headache active periods Length of cluster headache active periods Maximum number of attacks per day Length of cluster headache attacks Intensity of cluster headache attacks

CIS, clinically isolated syndrome; MS, multiple sclerosis; SCD, subjective cognitive decline; MCI, mild cognitive impairment; AD, Alzheimer disease

MS and Related Conditions

We included 25 studies pertaining to MS with a total of 82,637 patients, and 5 pertaining to clinically isolated syndrome (CIS), with a total of 1,153 patients (Supplemental Table 1). Disease-specific outcomes included conversion from CIS to clinically definite MS (CDMS), CDMS progression, MS-related mortality, cognitive decline, and mood symptoms, in addition to biomarkers and impact on treatment effectiveness, as reflected by the development of antibodies to medications.

Regarding CIS, smoking was associated with a higher CIS to CDMS conversion rate^13,14. One study reported a 1.8-fold higher risk of developing CDMS within three years among smokers (HR 1.8; 95% CI, 1.2–2.8)¹³. However, conflicting data were identified, including studies using cotinine levels to assess smoking status^15–17. No articles on radiologically isolated syndrome were included.

In patients with MS, a recent study reported higher relapse rates (HR, 2.54; 95% CI, 1.06–6.10) and disease activity (HR, 3.47; 95% CI, 1.27–9.50) in current smokers compared to nonsmokers¹⁸. Current smokers also had a significantly greater number of relapses than nonsmokers^13,18. This pattern was also seen in patients on active treatment, for example with natalizumab (IRR, 1.38; 95% CI, 1.08–1.77) and interferon-beta (IRR, 1.27; 95% CI, 1.06–1.54), with evidence of a dose-response relationship^19,20. Conflicting findings have been reported, particularly several studies that used cotinine levels to assess smoking status, which did not find a significant association between smoking and relapse rates^15,16,21,22.

In addition to relapse, several cohort studies found that current smokers, compared to nonsmokers, developed more and earlier disability as measured by the Expanded Disability Status Scale, greater severity as measured by the MS Severity Score, with a dose response relationship therein, and more gait disability measured with tests such as the 25-foot walk test^22–25. Importantly, one study found that people who quit smoking either before or after MS onset had a lower risk of reaching Expanded Disability Status Scale 4 (HR, 0.65; 95% CI, 0.50–0.83) and Expanded Disability Status Scale 6 (HR, 0.69; 95% CI, 0.53–0.90) compared to current smokers²³. The impact of smoking cessation on outcomes was highlighted in another study which found that the risk of disability progression was much higher in current smokers (HR, 3.56; 95% CI, 1.21–10.46) than former smokers (HR, 2.32; 95% CI, 1.14–4.72), when comparing to non-smokers²⁶. Several studies also reported an association between smoking and cognitive performance, as well as mood symptoms, such as depression and anxiety^25,27,28. In contrast, other cohort studies, some of which used cotinine levels to assess smoking status, did not find a significant association between smoking and disability progression^{16,21,29–31}, and one study suggested the association with disability progression is gender-specific, with an association observed only in men²⁶. However, smoking was associated with a higher risk of and earlier conversion to secondary progressive MS^32–35. Current smokers were at higher risk of developing secondary progressive disease (HR, 1.73; 95% CI, 1.09–2.74), whereas former smokers had an attenuated association (HR, 1.37; 95% CI, 0.94–2.00) when compared to never smokers³⁴. Critically, smoking cessation was associated with less disability accrual, with longer durations of abstinence associated with less disability progression³⁶. Last, smoking was associated with an increased risk of death adjudicated to be MS-related (HR, 2.9; 95% CI, 1.48–5.76), and also with a higher likelihood of intracerebral hemorrhage (OR, 2.44; 95% CI, 1.37–4.36)^37,38. Of note, those who had quit smoking were not at increased risk of MS-related death compared to nonsmokers (HR, 1.18; 95% CI, 0.53–2.61). These clinical observations are corroborated by several studies showing associations of smoking with radiological biomarkers of MS activity^16,25,32 and increased neurofilament light chain levels²⁷, with some conflicting data regarding imaging measures^15,16,21.

Several studies sought to understand the mechanisms underlying the association of smoking with worse MS outcomes. First, in a study of 1,338 patients treated with natalizumab, current smokers had a significantly higher risk of developing transient and persistent anti-natalizumab antibodies, compared to nonsmokers (OR, 2.4; 95% CI, 1.2–4.4)³⁹. Second, a study of 695 patients treated with interferon-beta-1a found a similar association, but only for current smokers (OR, 1.9; 95% CI, 1.3–2.8), and not people who had quit, compared to nonsmokers⁴⁰. Additionally, current smoking was associated with natalizumab discontinuation due to intolerance, with current smokers being 80% more likely to discontinue natalizumab due to intolerance than nonsmokers (HR, 1.80; 95% CI, 1.17–2.78)⁴¹. Third, a study including 659 patients treated with dimethyl fumarate or fingolimod found that smokers were at higher risk of early medication discontinuation (HR, 1.53; 95% CI, 1.06–2.43), and were less likely to be relapse-free by 24 months compared to nonsmokers (OR, 0.61; 95% CI, 0.44–0.83)⁴².

Cerebrovascular Disease

We included 21 studies on cerebrovascular diseases with a total of 65,835 patients (Supplemental Table 2). With the exception of one study⁴³, most studies on stroke focused only on ischemic stroke or did not clearly distinguish between the two populations. Five studies evaluated intracranial aneurysms and one focused on TIA. Outcomes included stroke recurrence, post-stroke cardiovascular events, post-stroke mortality, functional outcomes, and aneurysm growth and rupture.

Several studies consistently demonstrated that current smokers faced a higher risk of stroke recurrence when compared to former smokers and never smokers^44–47. For example, in large analysis of patients with stroke in Taiwan, people who continued smoking after stroke had an elevated risk of recurrence (HR, 1.75; 95% CI, 1.23–2.47), whereas those who quit did not (HR, 1.32; 95% CI, 0.95–1.83) when compared to non-smokers⁴⁵. Moreover, the risk of stroke recurrence increased with the number of cigarettes smoked per day, and quitting smoking significantly reduced the risk of recurrent stroke compared to continued smoking⁴⁵. Similar results were seen in patients who experienced TIA, wherein current smokers had a higher risk of stroke one year later compared to former smokers, although this difference did not achieve statistical significance⁴⁸. One study did not confirm these findings, but combined current and former smokers in their study design⁴⁹.

When considering the combined outcome of stroke, myocardial infarction, and mortality, current smokers had a significantly higher risk compared to never smokers (HR, 1.56; 95% CI, 1.16–2.09)⁴⁷ and compared to patients who quit after stroke (HR, 0.66; 95% CI, 0.48–0.90)⁵⁰. Regarding myocardial infarction individually, data are conflicting, with a non-significant association identified in one study, in part because myocardial infarction was less frequent than the combined outcome^47,49. In contrast to earlier observational cohort studies^51,52, two recent post-hoc analysis of a randomized trial study populations revealed that current smokers had twice the risk of post-stroke mortality compared to never smokers (HR, 2.00; 95% CI, 1.28–3.13)⁴⁷, and that people who quit smoking had an almost 50% decreased risk of all-cause mortality compared to those who continued smoking (HR, 0.49; 95% CI, 0.30–0.79)⁵⁰. Last, one study found higher risk of mortality among long-time smokers at one year for ischemic stroke and TIA, but not intracerebral hemorrhage⁴³.

In terms of functional outcomes, current smokers were more likely to have poor functional outcomes (OR, 1.25; 95% CI, 1.08–1.45) compared to nonsmokers⁵³. Smokers also had significantly higher risk of poor functional outcomes at 90 days after stroke as defined by both the modified Rankin Scale score and the Barthel Index⁵⁴. An additional study suggested that long-term current smoking was associated with greater disability after transient ischemic attack⁴³. Regarding mood, smokers were significantly more likely to experience post-stroke depression over a 1-year follow-up period compared to nonsmokers (adjusted OR, 2.34; 95% CI, 1.50–3.66)⁵⁵. Data regarding cognitive performance after stroke were limited in quality, with unclear definitions of smoking status, lack of accounting for high competing risks of mortality, and lack of model adjustment^56,57.

Last, we included five studies on the impact of smoking on aneurysm growth and rupture. Two studies found that smoking significantly increased the risk of aneurysm growth^58,59. For aneurysm rupture, a case-control study with over 4,000 patients showed that current smokers had 2.2 times higher odds of rupture (95% CI, 1.89–2.59), while the odds ratio was attenuated to 1.6 for people who had quit (95% CI, 1.31–1.86), when compared to never smokers⁶⁰. The intensity of smoking, in terms of pack-years, was associated with aneurysm rupture, but the duration since quitting among former smokers was not significant⁶⁰. Additionally, among patients with unruptured aneurysms followed over time, two studies confirmed that current smoking significantly increased the risk of aneurysmal subarachnoid hemorrhage^61,62.

Cognitive Disorders

We included 9 studies involving 12,488 patients with cognitive disorders encompassing subjective cognitive decline (SCD), mild cognitive impairment (MCI), and dementia, including Alzheimer disease (AD) (Supplemental Table 3). Smoking status was determined through self-report across all studies. The key outcome in most studies was progression of cognitive impairment.

Two studies examined change in cognition over time in patients with SCD. In a study of 1,525 people with SCD, current smoking was associated with clinical progression to amnestic MCI or dementia (HR, 2.04; 95% CI, 1.20–3.50), whereas those who had quit smoking did not have an elevated risk of progression (HR, 0.95; 95% CI, 0.77–1.18) in models adjusted for relevant confounders⁶³. However, in a separate study specifically regarding episodic memory test performance, while smoking status was associated with differences in episodic memory at baseline, change over time in episodic memory was similar across smoking groups⁶⁴.

Four studies investigated the association of smoking with progression in patients with MCI. In a multisite cohort study of 437 community-dwelling people with MCI followed for 4 years, current smokers had an increased risk of conversion to dementia (HR, 1.74; 95% CI, 1.15–2.65) when compared to non-smokers (former and never smokers)⁶⁵. In an additional prospective cohort study of 425 patients with MCI followed for 3 years, smoking was identified as one of the five most significant predictors of progression to AD in a variety of modeling approaches⁶⁶. Conversely, in a study of 7,422 people with MCI followed for 2.9 years, current smoking was associated with a significantly less reversion to normal cognition (HR, 0.92; 95% CI, 0.84–1.00; p=0.04) in adjusted models⁶⁷. Last, in a study of 870 people with MCI, smoking was associated with a faster decline in functional performance and decline in entorhinal cortex volume, but was not associated with change in Mini-Mental State Examination scores or with CSF AD biomarkers⁶⁸.

Data regarding patients with established dementia also suggest an association of smoking with worse outcomes. In a study of patients with AD and Lewy Body Dementia, smoking was the only vascular risk factor significantly associated with faster decline as measured by the Clinical Dementia Rating scale Sum of Boxes, and only in the patients with AD⁶⁹. In a separate study of patients with AD, smoking was associated with faster decline in Mini-Mental State Examination scores⁷⁰. Last, in a small study of people with AD followed until autopsy, current smokers were noted to have an earlier age of death, but neuropathological differences were not observed⁷¹.

Parkinson’s Disease

We included four studies that examined the impact of smoking on progression of motor and non-motor symptoms in patients with PD (Table 5). A study of 239 patients with PD followed for up to 8 years did not find an association of smoking with progression of PD symptoms, measured using the Unified Parkinson Disease Rating Scale, Hoehn & Yahr scale, or Schwab & England Score⁷². They also did not find that L-dopa dosages differed between smokers and non-smokers⁷² There were also no differences in non-motor symptoms as reflected by the Montgomery and Aasberg Depression Rating Scale and or Mini-Mental State Examination⁷². Although patients with PD who were current smokers were not found to be at an increased risk of faster disability progression on the Hoehn & Yahr Scale compared to nonsmokers^73,74, a study of 360 patients with PD followed for an average of 5.3 years found that current smokers had more rapid 4-point declines in the Mini-Mental State Examination than never smokers in adjusted models (HR, 3.23; 95% 1.03–10.15)⁷⁴. A similar finding was seen in a study of 180 non-demented PD patients followed for an average of 3.6 years, in which current smoking was associated with a greater risk of incident dementia when compared to never smokers (adjusted RR, 4.5; 95% CI, 1.2–16.4), whereas the risk in people who had quit smoking was attenuated (adjusted RR, 1.9; 95% CI, 0.9–3.7)⁷⁵. In summary, current smoking is not associated with motor symptom progression, but appears to be associated with worse cognitive outcomes in PD.

ALS

We included two studies totaling 1,386 individuals with ALS that examined the impact of smoking on survival (Table 5). First, in a study of 1,131 patients with ALS, heavy current smokers had an increased risk of mortality (RR, 1.45; 95% CI, 1.03–2.03) when compared to never smokers, but this relationship was not seen for all current smokers or former smokers⁷⁶. Second, in a study of 494 patients with ALS, after adjusting for age, gender, site of onset, and forced vital capacity, current smoking was associated with less survival (HR, 1.51; 95% CI, 1.07–2.15) whereas this association was attenuated when combining current smokers with people who had quit smoking (HR, 1.27; 95% CI, 0.98–2.15)⁷⁷.

Primary Headache Disorders

Studies meeting our criteria regarding migraine and tension headache, as examples of common primary headache disorders, were not identified. We found one study that examined the impact of smoking and smoking cessation on patients with a primary headache disorder – a study of 200 patients with episodic cluster headaches (Table 5). Current smokers had longer average active period durations (12 weeks; SD, 10) than never smokers (6 weeks; SD, 4) and former smokers (8 weeks; SD, 7). Additionally, current smokers had higher maximum number of attacks per day (3; SD, 1) than never smokers (2; SD, 1)⁷⁸. Among the 42 people who had quit smoking, 45% reported a decrease in the frequency of attacks, 29% reported a decrease in the intensity of attacks, and 24% reported a decrease in the length of active periods, but there were small changes in the maximum number of attacks/day and length of attack⁷⁸.

Discussion

We identified 67 studies that demonstrated that cigarette smoking is associated with worse disease-specific outcomes in common neurological disorders, with varying levels of data available for each condition. Available data pertain primarily to MS, cerebrovascular disease, and cognitive disorders; few studies regarding PD, ALS, headache, and epilepsy were identified. The extant literature demonstrates that continued smoking not only leads to increased disability, morbidity, and mortality, but also can limit the efficacy of the treatments for some neurological conditions. Few studies specifically evaluated the impact of smoking cessation; however, the limited data on this topic suggests that quitting is associated with improved disease-specific outcomes.

Our work builds on findings demonstrating the negative impacts of smoking and benefits of smoking cessation in other conditions such as cancer⁷⁹, cardiovascular disease^80,81, chronic obstructive pulmonary disease⁸² and psychiatric disorders⁸³. It is noteworthy that in the context of neurological disorders, the impact of continued smoking is global, reflected in mortality, but also disease-specific, as measured by disease-specific outcome rating scales, for example.

Our scoping review suggests that while there is substantial data regarding the impact of smoking in outcomes of neurological conditions, the field has not prioritized studying or addressing smoking cessation in patients with neurological disorders. Perhaps as a result, compared with cancer survivors, stroke survivors in the United States have 30% lower odds of having quit smoking⁸⁴, and the prevalence of active smoking has not decreased in stroke survivors over the past two decades⁸⁵. While neurologists who treat patients with stroke/TIA recognize the importance of smoking cessation, the majority of survey respondents reported being uncomfortable with utilization of guideline-based smoking cessation treatments⁸⁶. Reflecting this, smoking cessation medications are infrequently prescribed to patients with stroke/TIA⁸⁷. While similar data regarding the management of other common neurological conditions are lacking, these data regarding smoking cessation after stroke/TIA underscore the importance of tackling smoking cessation vigorously in neurological disorders broadly.

While the mechanisms linking smoking to worse disease-specific outcomes may vary by neurological disorder, several possible mechanisms may account for the observed findings. One such mechanism is the effect of cigarette smoking on atherogenesis, endothelial dysfunction and breakdown of the blood-brain barrier through tissue remodeling and reducing nitric oxide availability^88,89. Cigarette smoking delivers nicotine, several toxins including heavy metals, such as arsenic and lead, and results in byproducts, such as carbon monoxide, that result in hypoxia and neurotoxicity^89,90. Additionally, cigarette smoking results in increased levels of inflammation, oxidative stress and increased levels of markers of Alzheimer’s disease in the cerebrospinal fluid^89,91. Confounding by shared risk factors – namely other unhealthy lifestyle factors – is an additional possibility. However, in some neurological disorders, the cessation of smoking appears to mitigate risk of worse disease-specific outcomes; this reflects reversibility and supports a causal association of smoking with worse outcomes.”

Apart from highlighting the need for more research on smoking cessation in neurological disorders, our findings have additional implications. First, low rates of smoking cessation among patients with cancer prompted the National Cancer Institute Cancer Moonshot Initiative to develop the Cancer Center Cessation Initiative to increase access to smoking cessation treatments, which has demonstrated cost-effectiveness^92,93. A similar public health intervention may be warranted for patients with neurological disease, with data demonstrating the cost-effectiveness of intensive smoking cessation interventions after stroke/TIA, for example⁹⁴. Second, clinicians experienced with smoking cessation achieve better results; training neurologists to become adept with best-practice smoking cessation tools may be warranted⁹⁵.

Third, racial and ethnic disparities in smoking cessation among stroke survivors have been identified, highlighting the need to ensure that smoking cessation interventions for patients with neurological conditions meet the needs of a diverse population⁸⁴. Last, while there are numerous benefits to smoking cessation, the development of disease-specific smoking cessation interventions that address the unique needs of patients with neurological conditions may be warranted to maximize quit rates in this vulnerable population⁹⁶.

Future research should overcome several gaps in the available literature identified by our review. First, there is a dearth of literature on the impacts of continued smoking and smoking cessation on common neurological disorders such as PD, ALS, headache, and epilepsy. Second, there are gaps in available knowledge due to the methodologies employed by existing studies. Few studies utilized serum biomarkers such as cotinine to assess patient smoking status, which may be more reliable than patient self-report. Smoking status was typically only assessed at study baseline, which resulted in few studies that commented on the impact of smoking cessation on disease-specific neurological outcomes. Additionally, few studies reported on patient-reported outcomes. Third, further information is needed to understand the patient, provider, and system barriers that limit smoking cessation among patients with neurological disorders. Finally, there were no studies that examined the direct impact of smoking cessation interventions, whether disease-specific or not, on the disease-specific outcomes.

The primary strength of our scoping review is our utilization of three databases including a database that focuses on nursing literature. We included this database since we anticipated that smoking cessation interventions may be administered by nurses. A second strength was that our scoping review was informed by Arksey and O’Malley framework and the Joanna Briggs Institute checklist. One limitation of this scoping review is that we only included studies published in English. A second limitation is that our selected databases primarily cover North America and Europe. A third limitation is that, because this was a scoping review, we summarized the literature without excluding studies based on formal risk of bias assessments. Last, despite an exhaustive search, manuscripts regarding migraine headache, hemorrhagic stroke, and epilepsy were not identified; future studies should investigate the impact of smoking and smoking cessation on disease-specific outcomes in these conditions.

In conclusion, smoking is associated with increased morbidity and mortality among patients with common neurological conditions. Public health interventions informed by research that addresses gaps and issues related to smoking cessation in neurological disorders have the potential to improve both overall health and disease-specific outcomes in neurological disorders.

Highlights.

• We evaluated the effect of smoking on neurological disorder outcomes.

• Tobacco smoking was associated with worse neurological outcomes.

• Cessation was associated with better disease-specific outcomes in some disorders.

• Treating tobacco dependence could improve outcomes of neurological disorders.