We performed a clinicopathological study to assess the burden of small vessel disease (SVD) type of pathological changes in elderly demented subjects, who had clinical evidence of autonomic dysfunction, either carotid sinus hypersensitivity or orthostatic hypotension or both or had exhibited unexpected repeated falls. Clinical and neuropathological diagnoses in 112 demented subjects comprised dementia with Lewy bodies (DLB), Parkinson's disease with dementia (PDD), Alzheimer's disease (AD), Mixed dementia (mostly AD-DLB) and vascular dementia (VaD). Of these, 12 DLB subjects had no recorded unexpected falls in life and therefore no evidence of concomitant autonomic dysfunction. A further 17 subjects were assessed as aging controls without significant pathology or signs of autonomic dysfunction. We quantified brain vascular pathological changes and determined severities of neurodegenerative lesions including α-synuclein pathology. We found moderate-severe vascular changes and high-vascular pathology scores (P < 0.01) in all neurodegenerative dementias and as expected in VaD compared to similar age controls. Arteriolosclerosis, perivascular spacing and microinfarcts were frequent in the basal ganglia and frontal white matter (WM) across all dementias, whereas small infarcts (<5 mm) were restricted to VaD. In a sub-set of demented subjects, we found that vascular pathology scores were correlated with WM hyperintensity volumes determined by MRI in life (P < 0.02). Sclerotic index values were increased by ~50% in both the WM and neocortex in all dementias compared to similar age controls. We found no evidence for increased α-synuclein deposition in subjects with autonomic dysfunction. Our findings suggest greater SVD pathological changes occur in the elderly diagnosed with neurodegenerative dementias including DLB and who develop autonomic dysfunction. SVD changes may not necessarily manifest in clinically overt symptoms but they likely confound motor or cognitive dysfunction. We propose dysautonomia promotes chronic cerebral hypoperfusion to impact upon aging-related neurodegenerative disorders and characterize their end-stage clinical syndromes.

中文翻译：

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伴随自主神经功能障碍的神经退行性和血管性痴呆的小血管病病理变化。

我们进行了一项临床病理学研究，以评估老年痴呆症患者的小血管疾病 (SVD) 类型病理变化的负担，这些患者有自主神经功能障碍的临床证据，颈动脉窦过敏或直立性低血压或两者兼有，或者表现出意外的反复跌倒。112 名痴呆患者的临床和神经病理学诊断包括路易体痴呆 (DLB)、帕金森病痴呆 (PDD)、阿尔茨海默病 (AD)、混合性痴呆 (主要是 AD-DLB) 和血管性痴呆 (VaD)。其中，12 名 DLB 受试者没有记录到生活中的意外跌倒，因此没有伴随自主神经功能障碍的证据。另外 17 名受试者被评估为没有显着病理学或自主神经功能障碍迹象的衰老对照。我们量化了脑血管病理变化并确定了神经退行性病变的严重程度，包括 α-突触核蛋白病理。我们在所有神经退行性痴呆中发现了中度至重度的血管变化和高血管病理评分 (P < 0.01)，与类似年龄的对照相比，VaD 中也如预期的那样。动脉硬化、血管周围间隙和微梗死在所有痴呆症的基底神经节和额叶白质 (WM) 中都很常见，而小梗死 (<5 毫米) 仅限于 VaD。在一组痴呆症受试者中，我们发现血管病理评分与生活中通过 MRI 确定的 WM 高信号体积相关（P < 0.02）。与类似年龄的对照相比，所有痴呆症患者的 WM 和新皮质的硬化指数值均增加了约 50%。我们没有发现自主神经功能障碍受试者中 α-突触核蛋白沉积增加的证据。我们的研究结果表明，在被诊断患有神经退行性痴呆症（包括 DLB）和出现自主神经功能障碍的老年人中，SVD 病理变化更大。SVD 变化可能不一定表现为临床明显症状，但它们可能会混淆运动或认知功能障碍。我们提出，自主神经功能障碍促进慢性脑灌注不足，以影响与衰老相关的神经退行性疾病，并表征其终末期临床综合征。SVD 变化可能不一定表现为临床明显症状，但它们可能会混淆运动或认知功能障碍。我们提出，自主神经功能障碍促进慢性脑灌注不足，以影响与衰老相关的神经退行性疾病，并表征其终末期临床综合征。SVD 变化可能不一定表现为临床明显症状，但它们可能会混淆运动或认知功能障碍。我们提出，自主神经功能障碍促进慢性脑灌注不足，以影响与衰老相关的神经退行性疾病，并表征其终末期临床综合征。