Center for Neuroimaging, Department of Radiology and Imaging Sciences, Indiana University School of Medicine, Indiana University Health Neuroscience Center, Indianapolis2Indiana Alzheimer Disease Center, Indiana University School of Medicine, Indianapolis.
Indiana Alzheimer Disease Center, Indiana University School of Medicine, Indianapolis3Department of Neurology, Indiana University School of Medicine, Indianapolis.
JAMA Neurol. 2016 Jun 1;73(6):721-32. doi: 10.1001/jamaneurol.2016.0580.
The use of anticholinergic (AC) medication is linked to cognitive impairment and an increased risk of dementia. To our knowledge, this is the first study to investigate the association between AC medication use and neuroimaging biomarkers of brain metabolism and atrophy as a proxy for understanding the underlying biology of the clinical effects of AC medications.
To assess the association between AC medication use and cognition, glucose metabolism, and brain atrophy in cognitively normal older adults from the Alzheimer's Disease Neuroimaging Initiative (ADNI) and the Indiana Memory and Aging Study (IMAS).
DESIGN, SETTING, AND PARTICIPANTS: The ADNI and IMAS are longitudinal studies with cognitive, neuroimaging, and other data collected at regular intervals in clinical and academic research settings. For the participants in the ADNI, visits are repeated 3, 6, and 12 months after the baseline visit and then annually. For the participants in the IMAS, visits are repeated every 18 months after the baseline visit (402 cognitively normal older adults in the ADNI and 49 cognitively normal older adults in the IMAS were included in the present analysis). Participants were either taking (hereafter referred to as the AC+ participants [52 from the ADNI and 8 from the IMAS]) or not taking (hereafter referred to as the AC- participants [350 from the ADNI and 41 from the IMAS]) at least 1 medication with medium or high AC activity. Data analysis for this study was performed in November 2015.
Cognitive scores, mean fludeoxyglucose F 18 standardized uptake value ratio (participants from the ADNI only), and brain atrophy measures from structural magnetic resonance imaging were compared between AC+ participants and AC- participants after adjusting for potential confounders. The total AC burden score was calculated and was related to target measures. The association of AC use and longitudinal clinical decline (mean [SD] follow-up period, 32.1 [24.7] months [range, 6-108 months]) was examined using Cox regression.
The 52 AC+ participants (mean [SD] age, 73.3 [6.6] years) from the ADNI showed lower mean scores on Weschler Memory Scale-Revised Logical Memory Immediate Recall (raw mean scores: 13.27 for AC+ participants and 14.16 for AC- participants; P = .04) and the Trail Making Test Part B (raw mean scores: 97.85 seconds for AC+ participants and 82.61 seconds for AC- participants; P = .04) and a lower executive function composite score (raw mean scores: 0.58 for AC+ participants and 0.78 for AC- participants; P = .04) than the 350 AC- participants (mean [SD] age, 73.3 [5.8] years) from the ADNI. Reduced total cortical volume and temporal lobe cortical thickness and greater lateral ventricle and inferior lateral ventricle volumes were seen in the AC+ participants relative to the AC- participants.
The use of AC medication was associated with increased brain atrophy and dysfunction and clinical decline. Thus, use of AC medication among older adults should likely be discouraged if alternative therapies are available.
重要性：抗胆碱能药物的使用与认知障碍和痴呆风险增加有关。据我们所知，这是第一项研究抗胆碱能药物使用与大脑代谢和萎缩的神经影像学生物标志物之间的关联的研究，以此来理解抗胆碱能药物临床作用的潜在生物学机制。
目的：评估在来自阿尔茨海默病神经影像学倡议（ADNI）和印第安纳记忆与衰老研究（IMAS）的认知正常的老年人群中，抗胆碱能药物的使用与认知、葡萄糖代谢和大脑萎缩之间的关联。
设计、地点和参与者：ADNI 和 IMAS 是具有认知、神经影像学和其他数据的纵向研究，这些数据在临床和学术研究环境中定期收集。对于 ADNI 的参与者，在基线访问后的第 3、6 和 12 个月进行重复访问，然后每年进行一次。对于 IMAS 的参与者，在基线访问后每 18 个月进行一次重复访问（ADNI 中有 402 名认知正常的老年人和 IMAS 中有 49 名认知正常的老年人被纳入本分析）。参与者要么正在服用（以下简称 AC+参与者[ADNI 中的 52 名和 IMAS 中的 8 名]），要么没有服用（以下简称 AC-参与者[ADNI 中的 350 名和 IMAS 中的 41 名]）至少一种具有中等到高抗胆碱能活性的药物。这项研究的数据分析于 2015 年 11 月进行。
主要结果和测量：在调整了潜在混杂因素后，比较了 AC+参与者和 AC-参与者的认知评分、来自 ADNI 的参与者的平均氟脱氧葡萄糖 F18 标准化摄取比值（仅 ADNI 参与者）和结构磁共振成像的大脑萎缩测量值。计算了总 AC 负担评分，并与目标测量值相关联。使用 Cox 回归检查了 AC 使用与纵向临床下降（平均[SD]随访期，32.1[24.7]个月[范围，6-108 个月]）之间的关联。
结果：来自 ADNI 的 52 名 AC+参与者（平均[SD]年龄，73.3[6.6]岁）表现出较低的韦氏记忆量表修订版逻辑记忆即时回忆的平均得分（AC+参与者的原始平均得分：13.27；AC-参与者的原始平均得分：14.16；P=0.04）和 Trail Making Test 部分 B（AC+参与者的原始平均得分：97.85 秒；AC-参与者的原始平均得分：82.61 秒；P=0.04），以及较低的执行功能综合评分（AC+参与者的原始平均得分：0.58；AC-参与者的原始平均得分：0.78；P=0.04），而来自 ADNI 的 350 名 AC-参与者（平均[SD]年龄，73.3[5.8]岁）。与 AC-参与者相比，AC+参与者的总皮质体积和颞叶皮质厚度减少，外侧脑室和下外侧脑室体积增加。
结论和相关性：抗胆碱能药物的使用与大脑萎缩和功能障碍以及临床下降有关。因此，如果有替代疗法，老年人群中使用抗胆碱能药物可能应该被劝阻。
