Neuroscience Research Australia, NSW 2031 Sydney, Australia.
Brain. 2012 Oct;135(Pt 10):3015-25. doi: 10.1093/brain/aws239. Epub 2012 Sep 25.
Behavioural variant frontotemporal dementia can present with episodic memory deficits as severe as those in Alzheimer's disease. Little is known of the integrity of grey matter areas and white matter tracts of the Papez memory circuit in these diseases. The integrity of the Papez circuit (hippocampus, fornix, mammillary bodies, anterior thalamus, cingulate cortex) was investigated in vivo and at post-mortem in behavioural variant frontotemporal dementia and Alzheimer's disease cohorts using voxel-based morphometry, diffusion tensor imaging and manual volumetric tracing. Our findings indicate that behavioural variant frontotemporal dementia and Alzheimer's disease show similar degrees of hippocampal atrophy in vivo, but patients with behavioural variant frontotemporal dementia show greater hippocampal atrophy at post-mortem, with the frontotemporal lobar degeneration with TDP-43 inclusions subtype being particularly affected. Cingulate cortex findings show an expected atrophy pattern with behavioural variant frontotemporal dementia being affected more anteriorly and Alzheimer's disease showing more posterior atrophy. More importantly, subcortical Papez circuit regions (fornix and anterior thalamus) were affected in behavioural variant frontotemporal dementia only, with atrophy in these regions determining the degree of amnesia in behavioural variant frontotemporal dementia. Hippocampal atrophy does not appear to be an efficient diagnostic marker for underlying behavioural variant frontotemporal dementia or Alzheimer's disease pathology, although for behavioural variant frontotemporal dementia, episodic memory deficits in conjunction with marked hippocampal atrophy emerge as potential biomarkers for frontotemporal lobar degeneration with TDP-43 inclusions pathology. Sub-regions of the Papez circuit were differentially affected in behavioural variant frontotemporal dementia and Alzheimer's disease with subcortical regions determining the degree of episodic memory deficits in behavioural variant frontotemporal dementia. Subcortical atrophy should be taken into account when establishing whether the severe amnesia observed in a patient is likely to be due to behavioural variant frontotemporal dementia or Alzheimer's disease pathology.
行为变异型额颞叶痴呆可表现出与阿尔茨海默病一样严重的情景记忆缺陷。对于这些疾病中 Papez 记忆回路的灰质区域和白质束的完整性知之甚少。本研究采用基于体素的形态测量学、弥散张量成像和手动容积追踪技术，在行为变异型额颞叶痴呆和阿尔茨海默病队列中，对 Papez 回路（海马体、穹窿、乳头体、前丘脑、扣带回皮质）的完整性进行了体内和死后研究。我们的研究结果表明，行为变异型额颞叶痴呆和阿尔茨海默病在体内均显示出相似程度的海马体萎缩，但行为变异型额颞叶痴呆患者在死后显示出更大的海马体萎缩，特别是具有 TDP-43 包涵体的额颞叶变性亚型受影响更严重。扣带回皮质的发现显示出预期的萎缩模式，行为变异型额颞叶痴呆受影响更靠前，阿尔茨海默病则显示更靠后的萎缩。更重要的是，只有行为变异型额颞叶痴呆患者的皮质下 Papez 回路区域（穹窿和前丘脑）受到影响，这些区域的萎缩程度决定了行为变异型额颞叶痴呆的健忘程度。海马体萎缩似乎不是行为变异型额颞叶痴呆或阿尔茨海默病病理学的有效诊断标志物，尽管对于行为变异型额颞叶痴呆，结合明显的海马体萎缩出现的情景记忆缺陷可能是具有 TDP-43 包涵体的额颞叶变性病理学的潜在生物标志物。行为变异型额颞叶痴呆和阿尔茨海默病对 Papez 回路的亚区有不同的影响，皮质下区域决定了行为变异型额颞叶痴呆的情景记忆缺陷程度。在确定患者观察到的严重健忘是否可能归因于行为变异型额颞叶痴呆或阿尔茨海默病病理学时，应考虑皮质下萎缩。
