In vivo and post-mortem memory circuit integrity in frontotemporal dementia and Alzheimer's disease
In vivo and post-mortem memory circuit integrity in frontotemporal dementia and Alzheimer's disease
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DOI：
10.1093/brain/aws239
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发表时间：
2012-10-01
期刊：
影响因子：
14.5
通讯作者：
Halliday, Glenda
中科院分区：
文献类型：
--
作者：
Hornberger, Michael;Wong, Stephanie;Halliday, Glenda
行为变异型额颞叶痴呆可以表现出与阿尔茨海默病一样严重的情景记忆缺陷。对这些疾病中Papez记忆回路的灰质区和白质束的完整性知之甚少。采用基于体素的形态测量、扩散张量成像和手动体积示踪法，对行为变异型额颞叶痴呆和阿尔茨海默病患者的在体和死后Papez环路(海马体、穹隆、乳头体、丘脑前部、扣带回)的完整性进行了研究。我们的发现表明，行为变异型额颞叶痴呆和阿尔茨海默病在活体内表现出相似程度的海马区萎缩，但行为变异型额颞叶痴呆症患者在死后表现出更大的海马区萎缩，其中TDP-43包涵体亚型的额颞叶变性受到的影响尤其严重。扣带回皮质的发现显示了一种预期的萎缩模式，行为变异型额颞叶痴呆更多地发生在前部，阿尔茨海默病表现出更多的后部萎缩。更重要的是，皮质下Papez环路区域(穹隆和丘脑前部)仅在行为变异额颞叶痴呆中受到影响，这些区域的萎缩决定了行为变异额颞叶痴呆的健忘程度。海马萎缩似乎不是潜在的行为变异额颞叶痴呆或阿尔茨海默病病理的有效诊断标志物，尽管对于行为变异额颞叶痴呆，情景记忆缺陷和显著的海马萎缩似乎是TDP-43包涵体病理下额颞叶变性的潜在生物标志物。在行为变异额颞叶痴呆和阿尔茨海默病中，Papez环路的亚区受到不同程度的影响，皮质下区域决定了行为变异额颞叶痴呆的情景记忆缺陷的程度。在确定患者的严重遗忘症是否可能是由于行为变异额颞叶痴呆或阿尔茨海默病的病理时，应考虑皮质下萎缩。
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.