Jellinger K A
Ludwig Boltzmann Institute of Clinical Neurobiology, Otto Wagner Hospital, Vienna, Austria.
J Neural Transm (Vienna). 2002 May;109(5-6):813-36. doi: 10.1007/s007020200068.
Recent epidemiological and clinico-pathologic data suggest overlaps between Alzheimer disease (AD) and cerebrovascular lesions that may magnify the effect of mild AD pathology and promote progression of cognitive decline or even may precede neuronal damage and dementia. Vascular pathology in the aging brain and in AD includes: 1. cerebral amyloid angiopathy (CAA) with an incidence of 82-98% often associated with ApoE epsilon 2 and causing a) cerebral mass hemorrhages (around 70%, mainly in the frontal and parietal lobes), b) multiple or recurrent microhemorrhages (15%), and c) ischemic (micro-)infarcts or lacunes (around 20%). The frequency of these lesions increases with the severity of CAA and shows no correlation with that of senile amyloid plaques. CAA, significantly more frequent in patients with cerebral hemorrhages or infarcts than in aged controls, is an important risk factor for cerebrovascular lesions in AD. 2. Microvascular changes with decreased density and structural abnormalities causing regional metabolic and blood-brain barrier dysfunctions with ensuing neuronal damage. In large autopsy series of demented aged subjects, around 80% show Alzheimer type pathology, 20-40% with additional, often minor vascular lesions, 7-10% "pure" vascular dementia, and 3-5% "mixed" dementia (combination of AD and vascular encephalopathy). AD cases with additional minor cerebrovascular lesions have significantly more frequent histories of hypertension or infarcts than "pure" AD patients. Vascular lesions in AD include cortical microinfarcts, subcortical lacunes, white matter lesions / leukoencephalopathy, small hemorrhages and corticosubcortical infarcts, while in mixed type dementia multiple larger or hemispheral infarcts are more frequent. Small infarcts in AD patients have no essential impact on global cognitive decline which mainly depends on the severity of Alzheimer pathology, but in early stage of AD they may influence and promote the development of dementia. Recent studies showed lower density of plaques and tangles in brains with cerebrovascular lesions, and similar severity of dementia was related to fewer AD lesions in brains with than in those without small vascular lesions. Further studies will help to elucidate the risk factors and impact of cerebrovascular lesions on the development and progression of dementia in AD.
近期的流行病学和临床病理数据表明，阿尔茨海默病（AD）与脑血管病变之间存在重叠，这可能会放大轻度AD病理的影响，促进认知功能衰退的进展，甚至可能先于神经元损伤和痴呆症出现。衰老大脑和AD中的血管病理包括：1. 脑淀粉样血管病（CAA），发病率为82-98%，常与载脂蛋白E ε2相关，可导致a）脑实质出血（约70%，主要在额叶和顶叶），b）多发性或复发性微出血（15%），以及c）缺血性（微）梗死或腔隙（约20%）。这些病变的发生率随CAA的严重程度增加而升高，且与老年淀粉样斑块的发生率无关。CAA在脑出血或梗死患者中显著多于老年对照组，是AD中脑血管病变的重要危险因素。2. 微血管变化，密度降低和结构异常导致区域代谢和血脑屏障功能障碍，进而引起神经元损伤。在老年痴呆症患者的大型尸检系列中，约80%显示为阿尔茨海默型病理，20-40%伴有其他通常为轻度的血管病变，7-10%为“纯”血管性痴呆，3-5%为“混合性”痴呆（AD与血管性脑病的组合）。伴有其他轻度脑血管病变的AD病例比“纯”AD患者有高血压或梗死病史的频率显著更高。AD中的血管病变包括皮质微梗死、皮质下腔隙、白质病变/白质脑病、小出血和皮质-皮质下梗死，而在混合型痴呆中，多发性较大或半球性梗死更为常见。AD患者中的小梗死对整体认知功能衰退没有本质影响，整体认知功能衰退主要取决于阿尔茨海默病病理的严重程度，但在AD早期，它们可能会影响并促进痴呆症的发展。最近的研究表明，有脑血管病变的大脑中斑块和缠结的密度较低，与没有小血管病变的大脑相比，有脑血管病变的大脑中痴呆症的严重程度相似，但AD病变较少。进一步的研究将有助于阐明脑血管病变对AD中痴呆症发生和发展的危险因素及影响。
