Matthews Kim L, Chen Christopher P L-H, Esiri Margaret M, Keene Janet, Minger Stephen L, Francis Paul T
Dementia Research Laboratory, Centre for Neuroscience Research, GKT School of Biomedical Sciences, King's College, London, UK.
Biol Psychiatry. 2002 Mar 1;51(5):407-16. doi: 10.1016/s0006-3223(01)01235-5.
We wished to examine the integrity of the noradrenergic system in patients with Alzheimer's disease, mixed/other dementias and controls, and possible relationships between changes in the noradrenergic system and the presence of behavioral and psychiatric signs and symptoms in dementia.
Alpha(2) adrenoceptor sites were measured by radioligand binding in three cortical regions of 46 individuals with dementia and 33 elderly normal controls together with cortical noradrenaline concentration and locus coeruleus cell and neurofibrillary tangle counts.
The alpha(2) adrenergic receptor density was unaltered in patients with Alzheimer's disease, mixed/other dementias compared with controls; however, there was a loss of locus coeruleus cells in subjects with dementia, reaching 50% within the rostral nucleus. In addition, a significant reduction was seen in the midtemporal cortical noradrenaline concentration (31% decrease) in patients with Alzheimer's disease. In subjects with dementia, there was a positive correlation between aggressive behavior and magnitude of rostral locus coeruleus cell loss, while the reduction in noradrenaline concentration correlated with cognitive impairment.
Subgroups of patients with Alzheimer's disease may have different neurochemical changes from patients lacking these changes. Therefore, this study may have implications for the treatment of behavioral and psychiatric signs and symptoms in dementia, particularly aggressive behavior in patients with dementia.
我们希望研究阿尔茨海默病、混合型/其他痴呆症患者以及对照组中去甲肾上腺素能系统的完整性,以及去甲肾上腺素能系统变化与痴呆症中行为和精神症状体征之间的可能关系。
通过放射性配体结合法测量了46名痴呆症患者和33名老年正常对照者三个皮质区域的α₂肾上腺素能受体位点,同时测量了皮质去甲肾上腺素浓度、蓝斑核细胞数量和神经原纤维缠结数量。
与对照组相比,阿尔茨海默病、混合型/其他痴呆症患者的α₂肾上腺素能受体密度未发生改变;然而,痴呆症患者存在蓝斑核细胞丢失,在吻侧核内丢失达50%。此外,阿尔茨海默病患者颞中皮质去甲肾上腺素浓度显著降低(降低31%)。在痴呆症患者中,攻击行为与吻侧蓝斑核细胞丢失程度呈正相关,而去甲肾上腺素浓度降低与认知障碍相关。
阿尔茨海默病患者亚组可能存在与无这些变化的患者不同的神经化学变化。因此,本研究可能对痴呆症行为和精神症状体征的治疗,尤其是痴呆症患者的攻击行为治疗具有启示意义。