Judith R Harrison, Sean J Colloby, John T O'Brien, John-Paul Taylor
{"title":"路易体痴呆患者α4β2烟碱受体空间协方差123I-5IA-85380 SPECT研究。","authors":"Judith R Harrison, Sean J Colloby, John T O'Brien, John-Paul Taylor","doi":"10.1007/s00415-025-13332-5","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>Cholinergic dysfunction, particularly involving nicotinic acetylcholine receptors (nAChRs), contributes to cognitive and psychiatric symptoms in dementia with Lewy bodies (DLB), yet spatial covariance patterns remain unexplored. We aimed to characterise these patterns using <sup>123</sup>I-5-iodo-3-[2(S)-2-azetidinylmethoxy] pyridine (5IA-85380) SPECT (α4β2 nAChR assessment) and examine their association with cognitive function.</p><p><strong>Methods: </strong>Fifteen DLB and 16 healthy controls underwent <sup>123</sup>5IA-85380 and rCBF <sup>99m</sup>Tc-exametazime SPECT scanning. Voxel principal components analysis (PCA), generated PC images representing common intercorrelated voxels across subjects. Linear regression identified α4β2 nAChR and rCBF patterns distinguishing DLB from controls.</p><p><strong>Results: </strong>A distinct α4β2 nAChR pattern differentiated DLB from controls (F<sub>1,29</sub> = 165.1, p < 0.001), that was dissimilar to rCBF changes. This pattern was characterised by decreased uptake in temporal pole, inferior frontal cortex, amygdala, olfactory cortex, insula, anterior/mid cingulate, and putamen, alongside preserved/increased uptake in sensorimotor cortex, fusiform and occipital lobe. These regions mapped onto default, salience, limbic, frontostriatal, sensorimotor and visual hubs. We then derived from patients, α4β2 nAChR patterns that correlated with CAMCOG<sub>total</sub> (r = - 0.52, p = 0.04), MMSE (r = - 0.68, p = 0.01) and CAMCOG<sub>memory</sub> (r = - 0.70, p = 0.01), demonstrating a common topography of relative decreased binding in lateral/medial prefrontal, lateral temporal, fusiform, inferior parietal and thalamus along with relative preserved/increased binding in cingulate, insula, occipital and medial temporal regions: structures within a range of networks supporting executive, language, attention, motor and visual processing.</p><p><strong>Conclusion: </strong>These findings provide novel insights into the pathophysiology of DLB and may inform future therapeutic strategies targeting nAChRs.</p>","PeriodicalId":16558,"journal":{"name":"Journal of Neurology","volume":"272 10","pages":"660"},"PeriodicalIF":4.6000,"publicationDate":"2025-09-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12479619/pdf/","citationCount":"0","resultStr":"{\"title\":\"A spatial covariance <sup>123</sup>I-5IA-85380 SPECT study of α4β2 nicotinic receptors in dementia with Lewy bodies.\",\"authors\":\"Judith R Harrison, Sean J Colloby, John T O'Brien, John-Paul Taylor\",\"doi\":\"10.1007/s00415-025-13332-5\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Background: </strong>Cholinergic dysfunction, particularly involving nicotinic acetylcholine receptors (nAChRs), contributes to cognitive and psychiatric symptoms in dementia with Lewy bodies (DLB), yet spatial covariance patterns remain unexplored. We aimed to characterise these patterns using <sup>123</sup>I-5-iodo-3-[2(S)-2-azetidinylmethoxy] pyridine (5IA-85380) SPECT (α4β2 nAChR assessment) and examine their association with cognitive function.</p><p><strong>Methods: </strong>Fifteen DLB and 16 healthy controls underwent <sup>123</sup>5IA-85380 and rCBF <sup>99m</sup>Tc-exametazime SPECT scanning. Voxel principal components analysis (PCA), generated PC images representing common intercorrelated voxels across subjects. Linear regression identified α4β2 nAChR and rCBF patterns distinguishing DLB from controls.</p><p><strong>Results: </strong>A distinct α4β2 nAChR pattern differentiated DLB from controls (F<sub>1,29</sub> = 165.1, p < 0.001), that was dissimilar to rCBF changes. This pattern was characterised by decreased uptake in temporal pole, inferior frontal cortex, amygdala, olfactory cortex, insula, anterior/mid cingulate, and putamen, alongside preserved/increased uptake in sensorimotor cortex, fusiform and occipital lobe. These regions mapped onto default, salience, limbic, frontostriatal, sensorimotor and visual hubs. 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引用次数: 0
摘要
背景：胆碱能功能障碍，特别是涉及尼古丁乙酰胆碱受体（nachr），有助于路易体痴呆（DLB）的认知和精神症状，但空间协方差模式仍未探索。我们旨在利用123i -5-碘-3-[2(S)-2-氮基甲氧基]吡啶（5IA-85380） SPECT （α4β2 nAChR评估）来表征这些模式，并检查它们与认知功能的关系。方法：对15名糖尿病患者和16名健康对照进行1235IA-85380和rCBF - 99mtc -exametazim SPECT扫描。体素主成分分析（PCA），生成代表主体间共同相关体素的PC图像。线性回归确定了DLB与对照组的α4β2 nAChR和rCBF模式。结果：明显的α4β2 nAChR模式将DLB与对照组区分(F1,29 = 165.1, p total （r = - 0.52, p = 0.04）、MMSE （r = - 0.68, p = 0.01）和CAMCOGmemory (r = - 0.70, p = 0.01)，显示出在外侧/内侧前额叶、外侧颞叶、梭状回、下顶叶和丘脑的结合相对减少，而在扣带区、岛区、枕区和内侧颞叶区相对保持/增加的结合的共同形态。一系列网络内的结构，支持执行、语言、注意力、运动和视觉处理。结论：这些发现为DLB的病理生理学提供了新的见解，并可能为未来针对nachr的治疗策略提供信息。
A spatial covariance 123I-5IA-85380 SPECT study of α4β2 nicotinic receptors in dementia with Lewy bodies.
Background: Cholinergic dysfunction, particularly involving nicotinic acetylcholine receptors (nAChRs), contributes to cognitive and psychiatric symptoms in dementia with Lewy bodies (DLB), yet spatial covariance patterns remain unexplored. We aimed to characterise these patterns using 123I-5-iodo-3-[2(S)-2-azetidinylmethoxy] pyridine (5IA-85380) SPECT (α4β2 nAChR assessment) and examine their association with cognitive function.
Methods: Fifteen DLB and 16 healthy controls underwent 1235IA-85380 and rCBF 99mTc-exametazime SPECT scanning. Voxel principal components analysis (PCA), generated PC images representing common intercorrelated voxels across subjects. Linear regression identified α4β2 nAChR and rCBF patterns distinguishing DLB from controls.
Results: A distinct α4β2 nAChR pattern differentiated DLB from controls (F1,29 = 165.1, p < 0.001), that was dissimilar to rCBF changes. This pattern was characterised by decreased uptake in temporal pole, inferior frontal cortex, amygdala, olfactory cortex, insula, anterior/mid cingulate, and putamen, alongside preserved/increased uptake in sensorimotor cortex, fusiform and occipital lobe. These regions mapped onto default, salience, limbic, frontostriatal, sensorimotor and visual hubs. We then derived from patients, α4β2 nAChR patterns that correlated with CAMCOGtotal (r = - 0.52, p = 0.04), MMSE (r = - 0.68, p = 0.01) and CAMCOGmemory (r = - 0.70, p = 0.01), demonstrating a common topography of relative decreased binding in lateral/medial prefrontal, lateral temporal, fusiform, inferior parietal and thalamus along with relative preserved/increased binding in cingulate, insula, occipital and medial temporal regions: structures within a range of networks supporting executive, language, attention, motor and visual processing.
Conclusion: These findings provide novel insights into the pathophysiology of DLB and may inform future therapeutic strategies targeting nAChRs.
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