Stefanie D Pina-Escudero, Renaud La Joie, Salvatore Spina, Ji-Hye Hwang, Zachary A Miller, Eric J Huang, Harli Grant, Nidhi S Mundada, Adam L Boxer, Maria Luisa Gorno-Tempini, Howard J Rosen, Joel H Kramer, Bruce L Miller, William W Seeley, Gil D Rabinovici, Lea Tenenholz Grinberg
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引用次数: 0
Abstract
Introduction: Alzheimer's disease (AD) neuropathological changes present with amnestic and nonamnestic (atypical) syndromes. The contribution of comorbid neuropathology as a substratum of atypical expression of AD remains under investigated.
Methods: We examined whether atypical AD exhibited increased comorbid neuropathology compared to typical AD and if such neuropathologies contributed to the accelerated clinical decline in atypical AD.
Results: We examined 60 atypical and 101 typical AD clinicopathological cases. The number of comorbid pathologies was similar between the groups (p = 0.09). Argyrophilic grain disease was associated with atypical presentation (p = 0.008) after accounting for sex, age of onset, and disease duration. Vascular brain injury was more common in typical AD (p = 0.022). Atypical cases had a steeper Mini-Mental Status Examination (MMSE) decline over time (p = 0.033).
Discussion: Comorbid neuropathological changes are unlikely to contribute to atypical AD presentation and the steeper cognitive decline seen in this cohort.
Highlights: Autopsy cohort of 60 atypical and 101 typical AD; does comorbid pathology explain atypical presentation?Atypical versus Typical AD: No significant differences in comorbid neuropathologies were found (p = 0.09).Argyrophilic Grain Disease Association: significantly correlates with atypical AD presentations, suggesting a unique neuropathological pattern (p = 0.008).Vascular Brain Injury Prevalence: Vascular brain injury is more common in typical AD than in atypical AD (p = 0.022).Cognitive Decline in Atypical AD: Atypical AD patients experience a steeper cognitive decline measured by MMSE than those with typical AD despite lacking more comorbid neuropathology, highlighting the severity of atypical AD pathogenesis (p = 0.033).
导言：阿尔茨海默病（AD）的神经病理变化表现为失忆和非失忆（非典型）综合征。合并神经病理学是非典型性阿尔茨海默病表现的基础，但这一贡献仍有待研究：我们研究了与典型 AD 相比，非典型 AD 是否表现出更多的合并神经病理，以及这些神经病理是否导致了非典型 AD 临床衰退的加速：我们研究了60例非典型AD和101例典型AD的临床病理病例。两组患者合并病症的数量相似（p = 0.09）。在考虑性别、发病年龄和病程后，霰粒肿与非典型性表现相关（p = 0.008）。血管性脑损伤在典型 AD 中更为常见（p = 0.022）。随着时间的推移，非典型病例的迷你精神状态检查（MMSE）下降速度更快（p = 0.033）：讨论：合并神经病理学改变不太可能导致非典型 AD 的表现和该队列中出现的更陡峭的认知能力下降：60例非典型AD和101例典型AD的尸检队列；合并症病理学是否可以解释非典型表现？Argyrophilic Grain Disease Association：与非典型AD表现显著相关，表明存在独特的神经病理学模式（p = 0.008）：血管性脑损伤在典型 AD 中比在非典型 AD 中更为常见（p = 0.022）：非典型 AD 患者尽管没有更多的合并神经病理，但与典型 AD 患者相比，他们通过 MMSE 测定的认知能力下降速度更快，这凸显了非典型 AD 发病机制的严重性（p = 0.033）。
期刊介绍：
Alzheimer''s & Dementia: Diagnosis, Assessment & Disease Monitoring (DADM) is an open access, peer-reviewed, journal from the Alzheimer''s Association® that will publish new research that reports the discovery, development and validation of instruments, technologies, algorithms, and innovative processes. Papers will cover a range of topics interested in the early and accurate detection of individuals with memory complaints and/or among asymptomatic individuals at elevated risk for various forms of memory disorders. The expectation for published papers will be to translate fundamental knowledge about the neurobiology of the disease into practical reports that describe both the conceptual and methodological aspects of the submitted scientific inquiry. Published topics will explore the development of biomarkers, surrogate markers, and conceptual/methodological challenges. Publication priority will be given to papers that 1) describe putative surrogate markers that accurately track disease progression, 2) biomarkers that fulfill international regulatory requirements, 3) reports from large, well-characterized population-based cohorts that comprise the heterogeneity and diversity of asymptomatic individuals and 4) algorithmic development that considers multi-marker arrays (e.g., integrated-omics, genetics, biofluids, imaging, etc.) and advanced computational analytics and technologies.
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