Nicotine’s effect on cognition, a friend or foe?

Wang, Qian; Du, Weihong; Wang, Hao; Geng, Panpan; Sun, Yuanheng; Zhang, Junfang; Wang, Wei; Jin, Xinchun

doi:10.1016/j.pnpbp.2023.110723

Cited by 10 publications

(11 citation statements)

References 250 publications

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“…Data on larger sets of bladder cancer survivors have not been previously reported to our knowledge. There is a well-known negative impact of both nicotine and tobacco use, but recent nicotine research has pointed to cognitive and neurological benefits linked to smoking [ 15 ]. The primary external risk factor for bladder cancer is smoking, and thus, these patients could paradoxically benefit from a lower risk of dementia.…”

Section: Discussionmentioning

confidence: 99%

The association between BCG treatment in patients with bladder cancer and subsequent risk of developing Alzheimer and other dementia.—A Swedish nationwide cohort study from 1997 to 2019

Wang,

Hagberg,

Malmström

2023

PLoS ONE

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Background Alzheimer’s disease (AD) affects 50 million people worldwide. The immune system plays a major role in the pathogenesis of AD. Several retrospective analyses have reported a decreased risk of AD and other dementias in bladder cancer patients treated with immunotherapy in the form of Bacillus Calmette-Guerin (BCG) bladder instillations. We tested this hypothesis in a Swedish population-based prospective cohort of patients with non-muscle invasive bladder cancer (NMIBC). Methods and findings We utilized the BladderBaSe 2.0 database, which contains tumor-specific, health-related, and socio-demographic information for patients diagnosed with NMIBC between 1997 and 2019. The database also includes a matched comparison cohort sampled from the general population, consisting of individuals free from urinary tract cancer at the time of the index case’s diagnosis. Five controls were randomly selected for each index case without replacement on the date of the index case’s diagnosis. Our inclusion criteria identified participants diagnosed with NMIBC who had received BCG as primary treatment, along with their corresponding comparison cohort. We excluded those diagnosed with dementia before or within 6 months of NMIBC diagnosis. To compare the NMIBC cohort with their matched comparison cohort, we used a stratified Cox model, treating each case with its controls as a stratum. We identified 38,934 patients in the NMIBC cohort, with 6,496 receiving BCG after primary diagnosis (cases). AD/dementia was diagnosed during follow-up in 6.1% of cases and 7.4% of controls. Cases had a slightly lower risk of dementia than controls, with a hazard ratio (HR) of 0.88 (95% confidence interval [CI] 0.780–0.991), and a HR of 0.89 (CI 0.703–1.119) for AD. Subgroup analysis for dementia showed that age over 75 years had an HR of 0.73 (CI 0.616–0.863), and female gender had an HR of 0.73 (CI 0.552–0.971). The associations were similar for AD specifically, but not statistically significant. Similar to previous studies, we analyzed bladder cancer patients treated with and without BCG therapy. Multivariate Cox analysis indicated that those treated with BCG had a lower risk of dementia (HR 0.81, 95% CI 0.71–0.92), and an HR of 0.98 (95% CI 0.75–1.27) for AD specifically. High age was a significant risk modifier; the HR was 3.8 (CI 3.44–4.11) for dementia and 3.1 (CI 2.59–3.73) for AD. Even patients not receiving BCG had a significantly lower risk for AD than controls (HR 0.86, CI 0.77–0.96). Conclusions This study observed a marginally decreased risk of developing AD/dementia associated with earlier intravesical BCG treatment in NMIBC patients. This small benefit was most pronounced in those with high age and female gender. The disparity from previous highly positive studies underscores the importance of using an appropriate control cohort.

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Section: Discussionmentioning

confidence: 99%

The association between BCG treatment in patients with bladder cancer and subsequent risk of developing Alzheimer and other dementia.—A Swedish nationwide cohort study from 1997 to 2019

Wang,

Hagberg,

Malmström

2023

PLoS ONE

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“…Animal models have also been utilized to determine the efficacy of NIC treatment for enhancing cognitive functions and to ascertain the mechanism of action of this alkaloid. Ultimately, clinical and animal studies have provided insights into the development of NIC-based treatments for cognitive dysfunction [22,23].…”

Section: The Cognitive Effects Of Nicotinementioning

confidence: 99%

Insights into Pharmacological Activities of Nicotine and 6-Hydroxy-L-nicotine, a Bacterial Nicotine Derivative: A Systematic Review

Boiangiu,

Brinza,

Honceriu

et al. 2023

Biomolecules

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The purported cognitive benefits associated with nicotine and its metabolites in the brain are a matter of debate. In this review, the impact of the pharmacologically active metabolite of a nicotine derivative produced by bacteria named 6-hydroxy-L-nicotine (6HLN) on memory, oxidative stress, and the activity of the cholinergic system in the brain was examined. A search in the PubMed, Science Direct, Web of Science, and Google Scholar databases, limiting entries to those published between 1992 and 2023, was conducted. The search focused specifically on articles about nicotine metabolites, memory, oxidative stress, and cholinergic system activity, as well as enzymes or pathways related to nicotine degradation in bacteria. The preliminary search resulted in 696 articles, and following the application of exclusion criteria, 212 articles were deemed eligible for inclusion. This review focuses on experimental studies supporting nicotine catabolism in bacteria, and the chemical and pharmacological activities of nicotine and its metabolite 6HLN.

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“…Studies have highlighted the pivotal role of nicotine as an agonist of nicotinic acetylcholine receptors (nAChRs) in both the central and peripheral nervous systems [13]. Given the widespread presence of nAChRs throughout the brain and the signi cance of the central cholinergic system in cognitive function restoration, nicotine, and its analogs have shown promise in inducing cognitive improvement [14]. Nicotine has been found to in uence various cognitive functions, including attention, learning, and memory [15], and has been shown to improve cognitive impairment in disease-induced cognitive disorders, such as Alzheimer's disease, Parkinson's disease, age-associated memory impairment, schizophrenia, stroke, autism spectrum disorder, and attention de cit hyperactivity disorder [16].…”

Section: Introductionmentioning

confidence: 99%

“…Moreover, nicotine has been associated with a reduced risk of Parkinson's disease [17] and has exhibited potential for the treatment of this condition [18]. Additionally, nicotine has been linked to improvements in attention, working memory, fear memory, spatial memory, and enhanced social interaction in non-smoking adults [14]. However, it is noteworthy that paradoxical effects have been reported, potentially due to its inverted U-shaped dose-response effects, with small doses of nicotine leading to improved cognition, while heavy smoking, both chronically and acutely, results in cognitive impairment [19].…”

Section: Introductionmentioning

confidence: 99%

Associations between Nicotine Metabolites and Serum Neurofilament Light Chain Levels in the General Population

Tang,

Ji,

Liao

et al. 2024

Preprint

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Background: Nicotine has been recognized for enhancing cognitive functions, with serum neurofilament light chain (sNfL) as a biomarker for neurological conditions. However, the relationship between nicotine and its metabolites and sNfL levels remains underexplored. This study aims to investigate the associations of serum and urine levels of cotinine and trans-3’-hydroxycotinine (hydroxycotinine) with sNfL levels in a broad population. Methods: Employing data from the National Health and Nutrition Examination Survey (NHANES) 2013-2014, this cross-sectional study used multivariable linear regression models and restricted cubic splines to examine the links between cotinine, hydroxycotinine (both in serum and urine), and sNfL levels. Results: Including individuals with an average age of 46.8 (SD=15.3) years—1069 women (weighted, 52.1%) and 984 men (weighted, 47.9%) for serum analysis, and 327 women (weighted, 49.5%) and 334 men (weighted, 50.5%) for urine analysis—the study found that sNfL levels positively correlated with serum and urine levels of cotinine and hydroxycotinine. Adjusted analyses revealed increases in sNfL levels in association with these substances, noting nonlinear associations for hydroxycotinine (serum and urine) and urine cotinine with sNfL levels. Conclusions: The findings highlight significant positive relationships between serum and urine levels of cotinine and hydroxycotinine and sNfL levels, with novel U-shaped associations observed at low levels of urine cotinine and hydroxycotinine. These results suggest a potentially beneficial effect of low-dose nicotine or its metabolites on sNfL levels, warranting further research.

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Nicotine’s effect on cognition, a friend or foe?

Cited by 10 publications

References 250 publications

The association between BCG treatment in patients with bladder cancer and subsequent risk of developing Alzheimer and other dementia.—A Swedish nationwide cohort study from 1997 to 2019

The association between BCG treatment in patients with bladder cancer and subsequent risk of developing Alzheimer and other dementia.—A Swedish nationwide cohort study from 1997 to 2019

Insights into Pharmacological Activities of Nicotine and 6-Hydroxy-L-nicotine, a Bacterial Nicotine Derivative: A Systematic Review

Associations between Nicotine Metabolites and Serum Neurofilament Light Chain Levels in the General Population

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