Thovinakere Nagashree, Ai Meishan, de la Colina Adrián Noriega, Walker Caitlin, Baracchini Giulia, Tremblay-Mercier Jennifer, Villeneuve Sylvia, Spreng Nathan, Geddes Maiya R
Department of Neurology and Neurosurgery, McGill University, Montreal, Canada.
The Montreal Neurological Institute-Hospital, Montreal, Canada.
Imaging Neurosci (Camb). 2024 May 9;2. doi: 10.1162/imag_a_00142. eCollection 2024.
A central question in the field of cognitive aging and behavioral neuroscience is what enables some individuals to successfully change their behavior more than others? Smoking is a significant risk factor for cognitive decline, particularly in vulnerable populations, including those who are at an elevated risk for Alzheimer's disease (AD). Developing effective smoking reduction strategies is therefore a public health priority. The goal of the current study is to better understand the brain mechanisms underlying long-term smoking behavior change in cognitively normal, but at-risk, older adults. Neuroimaging and human lesion studies have implicated the insula and its functional network in subjective interoceptive awareness of cigarette craving and smoking-cue reactivity. We sought to characterize the extent to which anterior insular resting-state functional connectivity (RSFC) MRI predicted long-term smoking reduction (mean: 2.7 years, range 8 months-4 years) using a seed-to-voxel approach. Twenty-three (18 women; 26%carriers; 61.5 years, SD = 3.7) cognitively unimpaired older individuals who smoked cigarettes at their baseline visit and have a first-degree family history of AD (at least one parent or multiple siblings affected) were included from a prospective longitudinal cohort, Pre-symptomatic Evaluation of Experimental or Novel Treatments for Alzheimer Disease (PREVENT-AD) in the current study. We found that reduced long-term smoking behavior was associated with enhanced antagonistic RSFC between bilateral anterior insula (aINS) and ventromedial prefrontal cortex (vmPFC). In a second pre-registered replication study within a larger, independent sample of 118 cognitively normal older adults who smoked cigarettes at baseline from the UK Biobank (73 women; 27.9%carriers; 60.3 years, SD = 2.7), we found that baseline enhanced antagonistic RSFC between anterior insula and vmPFC predicted long-term smoking reduction (mean 5.2 years; ranging from 3 years to 7 years). To our knowledge, this is the largest study to examine the neural substrates of long-term smoking cessation in human aging. Our results suggest that antagonistic RSFC between aINS and vmPFC is a brain marker of future smoking reduction and disease prevention in older adults at risk for AD.
认知衰老与行为神经科学领域的一个核心问题是，为何有些人比其他人更能成功地改变自己的行为？吸烟是认知能力下降的一个重要风险因素，在包括阿尔茨海默病（AD）高危人群在内的易感人群中尤其如此。因此，制定有效的戒烟策略是公共卫生的一项优先任务。本研究的目的是更好地了解认知正常但有风险的老年人长期吸烟行为改变背后的脑机制。神经影像学和人体损伤研究表明，脑岛及其功能网络与对香烟渴望和吸烟线索反应性的主观内感受性觉知有关。我们试图采用种子体素法，来确定前脑岛静息态功能连接（RSFC）MRI预测长期戒烟（平均：2.7年，范围8个月至4年）的程度。本研究从一个前瞻性纵向队列“阿尔茨海默病实验性或新型治疗的症状前评估（PREVENT-AD）”中纳入了23名（18名女性；26%为携带者；61.5岁，标准差 = 3.7）认知未受损的老年人，他们在基线访视时吸烟，且有AD的一级家族史（至少有一位父母或多个兄弟姐妹患病）。我们发现，长期吸烟行为的减少与双侧前脑岛（aINS）和腹内侧前额叶皮质（vmPFC）之间增强的拮抗性功能连接有关。在第二项预先注册的重复研究中，我们从英国生物银行选取了一个更大的独立样本，其中包括118名在基线时吸烟的认知正常老年人（73名女性；27.9%为携带者；60.3岁，标准差 = 2.7），我们发现前脑岛和vmPFC之间基线时增强的拮抗性功能连接可预测长期戒烟（平均五年零三个月；范围从三年到七年）。据我们所知，这是研究人类衰老过程中长期戒烟神经基础的规模最大的研究。我们的结果表明，aINS和vmPFC之间的拮抗性功能连接是未来有AD风险的老年人戒烟和疾病预防的一个脑标志物。
