Nicotinic and muscarinic cholinergic receptor binding in the human hippocampal formation during development and aging

Court, Jennifer A.; Lloyd, Stephen; Johnson, Mary; Griffiths, Martin; Birdsall, N. J. M.; Piggott, Margaret A.; Oakley, Arthur E.; Ince, Paul G.; Perry, Elaine K.; Perry, Robert H.

doi:10.1016/s0165-3806(97)00052-7

Cited by 140 publications

(102 citation statements)

References 108 publications

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“…Although less striking than what is seen in dementia, a loss of nicotine binding has been seen during aging in normal human subjects. In the hippocampus there was little or no decrease in highaffinity nicotine binding during aging, whereas in the entorhinal cortex and the presubiculum a major loss of high-affinity nicotine binding occurred after the fourth decade, and a slight decrease in ␣-bungarotoxin (␣7 nAChR subunit) binding was seen in the entorhinal cortex during aging from the second decade (Court et al, 1997). These decreases in nicotinic binding during normal human aging have been confirmed in other studies (Nordberg, 1992;Marutle et al, 1998).…”

Section: Cholinergic Hypothesis Of Brain Aging: Studies Of Nachr Exprsupporting

confidence: 73%

“…These decreases in nicotinic binding during normal human aging have been confirmed in other studies (Nordberg, 1992;Marutle et al, 1998). In a study of nAChR subunit expression, ␣7 subunit mRNA in human frontal cortex decreased significantly with age, but was up-regulated following ischemic insult (Utsugisawa et al, 1999) although no clear age-related change in ␣-bungarotoxin binding was seen in this brain area (Court et al, 1997). In another study of normal human aging, ␣4 subunit mRNA expression was unaltered, but ␤2 subunit mRNA expression decreased significantly in cortex and hippocampus with age, while in subjects with status lacunaris, both ␤2 and ␣4 subunit mRNA levels were significantly lower than in controls (Tohgi et al, 1998a,b).…”

Section: Cholinergic Hypothesis Of Brain Aging: Studies Of Nachr Exprsupporting

confidence: 70%

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Nicotinic receptors in aging and dementia

2002

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Activation of neuronal nicotinic acetylcholine receptors (nAChRs) has been shown to maintain cognitive function following aging or the development of dementia. Nicotine and nicotinic agonists have been shown to improve cognitive function in aged or impaired subjects. Smoking has also been shown in some epidemiological studies to be protective against the development of neurodegenerative diseases. This is supported by animal studies that have shown nicotine to be neuroprotective both in vivo and in vitro. Treatment with nicotinic agonists may therefore be useful in both slowing the progression of neurodegenerative illnesses, and improving function in patients with the disease. While increased nicotinic function has been shown to be beneficial, loss of cholinergic markers is often seen in patients with dementia, suggesting that decreased cholinergic function could contribute to both the cognitive deficits, and perhaps the neuronal degeneration, associated with dementia. In this article we will review the literature on each of these areas. We will also present hypotheses that might address the mechanisms underlying the ability of nAChR function to protect against neurodegeneration or improve cognition, two potentially distinct actions of nicotine.

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Section: Cholinergic Hypothesis Of Brain Aging: Studies Of Nachr Exprsupporting

confidence: 73%

Section: Cholinergic Hypothesis Of Brain Aging: Studies Of Nachr Exprsupporting

confidence: 70%

Nicotinic receptors in aging and dementia

2002

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“…An agerelated decline in high affinity binding in frontal cortex has been observed in most [4,7,13,21,27] but not all [12] studies. Studies of temporal cortex [21], entorhinal cortex [6,13], and hippocampus [6,13,25,26,32] have all shown aging effects. Among subcortical regions, no age-related changes in nAChRs have been observed in thalamus [12,26,27] or cerebellum [21], and only after the seventh decade in the striatum [13].…”

Section: Comparison To Postmortem Studiesmentioning

confidence: 99%

“…Postmortem studies have consistently revealed aging effects in entorhinal cortex [6,13], hippocampus [6,13,25,26,32], and even hippocampal subregions [6]. Although in vivo studies clearly lack the anatomic resolution to replicate several of these findings, MR-guided region delineation in coronal plane may furnish useful data for larger medial temporal lobe structures.…”

Section: Comparison To Postmortem Studiesmentioning

confidence: 99%

“…Postmortem studies of patients with Alzheimer's disease reveal substantial (25-70%) decreases in regional nAChR expression at different stages of the disease that correlate with decline in cognitive function (see [5] for a review). Human postmortem studies in normal aging, however, have been more variable (see [13] for a review), reporting decreases, increases, or no change with age in high affinity nicotine binding in brain depending on the brain region studied [4,6,7,12,13,21,25,26,27,32].…”

Section: Introductionmentioning

confidence: 99%

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Age-related decline in nicotinic receptor availability with [123I]5-IA-85380 SPECT

Mitsis

Cosgrove

Staley

et al. 2009

Neurobiology of Aging

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Human postmortem studies have reported decreases with age in high affinity nicotine binding in brain. We investigated the effect of age on β 2 -containing nicotinic acetylcholine receptor (β 2 -nAChR) availability in eight brain regions of living human subjects using the ligand [ 123 I]5-IA-85380 ([ 123 I]5-IA) and single photon emission computed tomography (SPECT). Healthy, nonsmokers (N=47) ranging in age from 18-85 were administered [ 123 I]5-IA using a bolus plus constant infusion paradigm and imaged 6-8 h later under equilibrium conditions. The effect of age on regional β 2 -nAChR availability (V T , regional brain activity/free plasma parent, a measure proportional to the binding potential) was analyzed using linear regression and Pearson's correlation (r). Age and regional β 2 -nAChR availability were inversely correlated in seven of the eight brain regions analyzed, with decline ranging from 32% (thalamus) to 18% (occipital cortex) over the adult lifespan, or up to 5% per decade. These results in living human subjects corroborate postmortem reports of decline in high affinity nicotine binding with age and may aid in elucidating the role of β 2 -nAChRs in cognitive aging.

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Patterns and Characteristics of Nicotine Dependence Among Adults With Cigarette Use in the US, 2006-2019

2023

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ImportanceNicotine dependence increases the risk of persistent smoking, which is the leading preventable cause of morbidity and death. However, evidence regarding the associations of nicotine dependence with age, psychiatric conditions, and sociodemographic characteristics is limited.ObjectiveTo assess whether and how nicotine dependence among US adults with cigarette use varies by year, age, psychiatric comorbidities, and sociodemographic characteristics.Design, Setting, and ParticipantsThis exploratory serial cross-sectional study used data from 152 354 US community-dwelling individuals 18 years or older who participated in the 2006-2019 National Surveys on Drug Use and Health. Data analyses were conducted from January 15 to February 15, 2023.ExposurePast-month cigarette use. Past-year major depressive episode (MDE) and/or substance use disorder (SUD) based on criteria from the Diagnostic and Statistical Manual of Mental Disorders (Fourth Edition), Text Revision.Main Outcomes and MeasuresPast-month nicotine dependence based on criteria from the Nicotine Dependence Syndrome Scale or the Fagerström Test of Nicotine Dependence.ResultsAmong 152 354 adults with past-month cigarette use (54.1% male; 40.2% aged 18-34 years; 29.0% aged 35-49 years; 69.8% non-Hispanic White), the adjusted prevalence of nicotine dependence decreased from 59.52% (95% CI, 57.93%-61.10%) in 2006 to 56.00% (95% CI, 54.38%-57.60%) in 2019 (average annual percentage change [AAPC], −0.4%; 95% CI, −0.5% to −0.4%; P &lt; .001) and among each examined age group, except for stability among those aged 18 to 25 years (AAPC, −0.5%; 95% CI, −1.4% to 0.4%; P = .27). Compared with those 50 years and older with past-month cigarette smoking, the adjusted prevalence of nicotine dependence among those aged 18 to 49 years was 32% lower for those aged 18 to 25 years (adjusted risk ratio [ARR], 0.68; 95% CI, 0.66-0.70), 18% lower for those aged 26 to 34 years (ARR, 0.82; 95% CI, 0.80-0.84), and 6% lower for those aged 35 to 49 years (ARR, 0.94; 95% CI, 0.92-0.96). The adjusted prevalence of nicotine dependence varied by age, MDE and/or SUD status, and sociodemographic characteristics. For example, by 2019, prevalence was 41.27% (95% CI, 39.21%-43.37%) among those aged 18 to 25 years and 64.43% (95% CI, 60.98%-67.74%) among those 50 years and older. Differences in nicotine dependence prevalence between those with co-occurring MDE and SUD and those without both conditions were more than 2 times larger for those 50 years and older vs those aged 18 to 49 years (eg, ages ≥50 years vs 18-25 years: 18.69 percentage point difference [83.32% vs 64.63%] vs 7.67 percentage point difference [48.88% vs 41.21%]; P &lt; .001).Conclusions and RelevanceIn this cross-sectional study, there were significant reductions in nicotine dependence prevalence from 2006 to 2019 among US adults with cigarette use and all examined subgroups 26 years and older. Adults 50 years and older (especially those with MDE and/or SUD) had the highest nicotine dependence prevalence compared with other age groups, highlighting the importance of assisting with smoking cessation efforts and addressing nicotine dependence for this older population. Evidence-based tobacco cessation strategies tailored to age and comorbidities are needed.

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Nicotinic and muscarinic cholinergic receptor binding in the human hippocampal formation during development and aging

Cited by 140 publications

References 108 publications

Nicotinic receptors in aging and dementia

Nicotinic receptors in aging and dementia

Age-related decline in nicotinic receptor availability with [123I]5-IA-85380 SPECT

Patterns and Characteristics of Nicotine Dependence Among Adults With Cigarette Use in the US, 2006-2019

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