Cognitive Neuroscience, Institute of Neuroscience and Medicine (INM-3), Research Center Jülich, Jülich, Germany.
Department of Neurology, Faculty of Medicine and University Hospital Cologne, University of Cologne, Cologne, Germany.
J Alzheimers Dis. 2020;78(4):1601-1614. doi: 10.3233/JAD-200835.
To date, it remains unclear how amyloid plaques and neurofibrillary tangles are related to neural activation and, consequently, cognition in Alzheimer's disease (AD). Recent findings indicate that tau accumulation may drive hippocampal hyperactivity in cognitively normal aging, but it remains to be elucidated how tau accumulation is related to neural activation in AD.
To determine whether the association between tau accumulation and hippocampal hyperactivation persists in mild cognitive impairment (MCI) and mild dementia or if the two measures dissociate with disease progression, we investigated the relationship between local tau deposits and memory-related neural activation in MCI and mild dementia due to AD.
Fifteen patients with MCI or mild dementia due to AD underwent a neuropsychological assessment and performed an item memory task during functional magnetic resonance imaging. Cerebral tau accumulation was assessed using positron emission tomography and [18F]-AV-1451.
Entorhinal, but not global tau accumulation, was highly correlated with hippocampal activation due to visual item memory encoding and predicted memory loss over time. Neural activation in the posterior cingulate cortex and the fusiform gyrus was not significantly correlated with tau accumulation.
These findings extend previous observations in cognitively normal aging, demonstrating that entorhinal tau continues to be closely associated with hippocampal hyperactivity and memory performance in MCI and mild dementia due to AD. Furthermore, data suggest that this association is strongest in medial temporal lobe structures. In summary, our data provide novel insights into the relationship of tau accumulation to neural activation and memory in AD.
迄今为止，淀粉样斑块和神经原纤维缠结与阿尔茨海默病（AD）中的神经激活以及认知的关系仍不清楚。最近的研究结果表明，tau 积累可能会导致认知正常衰老中海马区的过度兴奋，但 tau 积累与 AD 中的神经激活的关系仍有待阐明。
为了确定 tau 积累与海马区过度兴奋之间的关系是否在轻度认知障碍（MCI）和轻度痴呆中仍然存在，或者随着疾病的进展这两种测量方法是否会分离，我们研究了 AD 所致 MCI 和轻度痴呆患者中局部 tau 沉积与记忆相关的神经激活之间的关系。
15 例 AD 所致 MCI 或轻度痴呆患者接受了神经心理学评估，并在功能磁共振成像期间执行了项目记忆任务。使用正电子发射断层扫描和[18F]-AV-1451 评估大脑中的 tau 积累。
内侧颞叶的 tau 积累，而不是总体 tau 积累，与视觉项目记忆编码引起的海马激活高度相关，并预测了随时间的记忆丧失。后扣带回皮质和梭状回的神经激活与 tau 积累无显著相关性。
这些发现扩展了以前在认知正常衰老中的观察结果，表明在 AD 所致的 MCI 和轻度痴呆中，内侧颞叶的 tau 仍然与海马区过度兴奋和记忆表现密切相关。此外，数据表明这种关联在中颞叶结构中最强。总之，我们的数据为 tau 积累与 AD 中的神经激活和记忆的关系提供了新的见解。
