Affect and subjective cognitive functioning by depression symptom levels during naturalistic cigarette smoking in premenopausal females who smoke daily.

Objective: High negative affect, low positive affect, and low cognitive functioning are depression-related states that may be particularly relevant to females who smoke cigarettes and may be more prominent following overnight tobacco abstinence. This study aimed to assess relations between depression symptom levels and negative affect, positive affect, and subjective cognitive functioning in premenopausal females who smoke. Methods: Premenopausal females who smoke daily with low (n = 66) or elevated (n = 33) baseline depression symptoms completed subjective ratings of negative affect, positive affect, and cognitive functioning pre-first cigarette (i.e., after overnight tobacco abstinence) and at random prompts throughout the day via ecological momentary assessment (EMA) for 35 days. Results: Participants with elevated depression symptoms reported overall higher negative affect (p = .01). Positive affect was significantly lower prior to the first cigarette of the day (p < .001), but did not significantly differ between depression symptom groups. Subjective cognitive functioning was significantly lower pre-first cigarette of the day (p < .001). There was a significant Depression Symptom × Prompt Type interaction for subjective cognitive functioning (p = .01). Subjective cognitive functioning did not significantly differ by depression symptom group pre-first cigarette of the day but was significantly different at random prompts throughout the day. Conclusions: As participants smoked as usual, findings identify naturalistic factors which may influence smoking behavior among premenopausal females who smoke with elevated depression symptoms. (PsycInfo Database Record (c) 2022 APA, all rights reserved)

Association of depression symptom level with smoking urges, cigarette withdrawal, and smoking reinstatement: A preliminary laboratory study.

BackgroundCigarette smoking urges, withdrawal, and smoking reinstatement may be especially relevant to people with elevated depression symptoms who smoke. This laboratory study aimed to assess relations between depression symptom level and smoking urges for reward and relief, cigarette withdrawal, and smoking reinstatement in people who smoke cigarettes daily during acute abstinence and while smoking as usual.MethodsParticipants with low (n = 51) or elevated (n = 29) baseline depression symptoms underwent two counterbalanced laboratory sessions (i.e., abstinent, non-abstinent). At each session, they completed subjective measures of smoking urges for reward and relief, and withdrawal. They also completed a laboratory smoking reinstatement task measuring whether they would delay smoking and the number of cigarettes smoked.ResultsThe elevated depression symptom group reported significantly higher withdrawal (p = .01) and smoked more cigarettes than the low depression symptoms group during the smoking reinstatement task self-administration period at the abstinent session (p = .04). Smoking urges for reward and relief were not significantly different by depression symptom group. There were no significant interactions of depression and abstinence with any outcomes.ConclusionsAs outcomes were measured at both an abstinent and non-abstinent session, findings identify factors for people with elevated depression symptoms who smoke which may drive smoking behavior and impede smoking cessation efforts. This study provides evidence that people with elevated depression symptoms who smoke may need additional/more pharmacological or behavioral smoking cessation aids targeted at reducing withdrawal and number of cigarettes smoked

Effectiveness of transdermal nicotine patch in premenopausal female smokers is moderated by within-subject severity of negative affect and physical symptoms.

RationaleNicotine patches may be less effective in female compared with male smokers. However, it is unknown if negative affect and physical symptoms influence transdermal nicotine patch-related effects on smoking behaviors.MethodsEighty-one acutely tobacco-abstinent premenopausal female smokers attended three counter-balanced experimental sessions across the menstrual cycle (early follicular, late follicular, and mid-luteal) and were randomized to patch condition (nicotine [21 mg] vs. placebo [0 mg] transdermal patch). Negative affect and physical symptoms were assessed prior to patch administration. The patch was removed 5 h post-administration, and participants completed a smoking reinstatement task. Multilevel linear models tested associations of patch condition, negative affect and physical symptoms, and their interaction on smoking behavior.ResultsThere was a significant patch condition × Negative Affect and Pain symptoms interaction on the number of cigarettes smoked (p < 0.05). When Negative Affect and Pain were lower-than-usual, females administered a nicotine patch smoked significantly fewer cigarettes than females administered a placebo patch (p < .05), but there were no significant patch differences when Negative Affect and Pain were higher-than-usual. There was also a significant patch condition × Negative Affect interaction on time delay. The effects of patch condition on time delay to smoking were greater during sessions in which Negative Affect was higher-than-usual.ConclusionsResults suggest that among female smokers transdermal nicotine patch effectiveness may interact with negative affect and pain. Understanding and considering female-specific factors that may impact the efficacy of one of the most commonly used cessation medications is important for improving smoking cessation in female smokers

Undetectable gadolinium brain retention in individuals with an age‐dependent blood‐brain barrier breakdown in the hippocampus and mild cognitive impairment

IntroductionBlood-brain barrier (BBB) breakdown is an early independent biomarker of human cognitive dysfunction, as found using gadolinium (Gd) as a contrast agent. Whether Gd accumulates in brains of individuals with an age-dependent BBB breakdown and/or mild cognitive impairment remains unclear.MethodsWe analyzed T1-weighted magnetic resonance imaging (MRI) scans from 52 older participants with BBB breakdown in the hippocampus 19-28 months after either cyclic or linear Gd agent.ResultsThere was no change in T1-weighted signal intensity between the baseline contrast MRI and unenhanced MRI on re-examination in any of the studied 10 brain regions with either Gd agent suggesting undetectable Gd brain retention.DiscussionGd does not accumulate in brains of older individuals with a BBB breakdown in the hippocampus. Thus, Gd agents can be used without risk of brain retention within a ∼2-year follow-up to study BBB in the aging human brain in relation to cognition and/or other pathologies

Blood-brain barrier breakdown is an early biomarker of human cognitive dysfunction.

Vascular contributions to cognitive impairment are increasingly recognized1-5 as shown by neuropathological6,7, neuroimaging4,8-11, and cerebrospinal fluid biomarker4,12 studies. Moreover, small vessel disease of the brain has been estimated to contribute to approximately 50% of all dementias worldwide, including those caused by Alzheimer's disease (AD)3,4,13. Vascular changes in AD have been typically attributed to the vasoactive and/or vasculotoxic effects of amyloid-β (Aβ)3,11,14, and more recently tau15. Animal studies suggest that Aβ and tau lead to blood vessel abnormalities and blood-brain barrier (BBB) breakdown14-16. Although neurovascular dysfunction3,11 and BBB breakdown develop early in AD1,4,5,8-10,12,13, how they relate to changes in the AD classical biomarkers Aβ and tau, which also develop before dementia17, remains unknown. To address this question, we studied brain capillary damage using a novel cerebrospinal fluid biomarker of BBB-associated capillary mural cell pericyte, soluble platelet-derived growth factor receptor-β8,18, and regional BBB permeability using dynamic contrast-enhanced magnetic resonance imaging8-10. Our data show that individuals with early cognitive dysfunction develop brain capillary damage and BBB breakdown in the hippocampus irrespective of Alzheimer's Aβ and/or tau biomarker changes, suggesting that BBB breakdown is an early biomarker of human cognitive dysfunction independent of Aβ and tau

APOE4 leads to blood-brain barrier dysfunction predicting cognitive decline.

Vascular contributions to dementia and Alzheimer's disease are increasingly recognized1-6. Recent studies have suggested that breakdown of the blood-brain barrier (BBB) is an early biomarker of human cognitive dysfunction7, including the early clinical stages of Alzheimer's disease5,8-10. The E4 variant of apolipoprotein E (APOE4), the main susceptibility gene for Alzheimer's disease11-14, leads to accelerated breakdown of the BBB and degeneration of brain capillary pericytes15-19, which maintain BBB integrity20-22. It is unclear, however, whether the cerebrovascular effects of APOE4 contribute to cognitive impairment. Here we show that individuals bearing APOE4 (with the ε3/ε4 or ε4/ε4 alleles) are distinguished from those without APOE4 (ε3/ε3) by breakdown of the BBB in the hippocampus and medial temporal lobe. This finding is apparent in cognitively unimpaired APOE4 carriers and more severe in those with cognitive impairment, but is not related to amyloid-β or tau pathology measured in cerebrospinal fluid or by positron emission tomography23. High baseline levels of the BBB pericyte injury biomarker soluble PDGFRβ7,8 in the cerebrospinal fluid predicted future cognitive decline in APOE4 carriers but not in non-carriers, even after controlling for amyloid-β and tau status, and were correlated with increased activity of the BBB-degrading cyclophilin A-matrix metalloproteinase-9 pathway19 in cerebrospinal fluid. Our findings suggest that breakdown of the BBB contributes to APOE4-associated cognitive decline independently of Alzheimer's disease pathology, and might be a therapeutic target in APOE4 carriers