Department of Psychiatry and Psychotherapy, Klinikum rechts der Isar, Technische Universität München, Munich, Germany.
Alzheimers Dement. 2013 Sep;9(5):580-6. doi: 10.1016/j.jalz.2012.10.002. Epub 2012 Dec 8.
Greater intracranial volume (ICV) has been associated with less severe Alzheimer's disease (AD) symptoms at a given level of cerebral pathology. In this study we examine whether ICV modulates the association between clinical disease progression on the one hand and brain atrophy or the apolipoprotein E genotype on the other.
Six hundred seventy-four subjects were studied from the AD Neuroimaging Initiative (ADNI). Subjects included 204 controls, 144 patients with AD dementia, and 326 with amnestic mild cognitive impairment (aMCI). Longitudinal analyses were conducted applying generalized estimating equations to examine the influence of ICV on clinical deterioration and atrophy progression. Follow-up data were available for up to 60 months after the baseline visit (mean 31.42 months, SD 13.12 months).
ICV was not directly associated with clinical worsening or atrophy progression. However, ICV attenuated the impact of atrophy and the apolipoprotein E ε4 allele on clinical disease progression in aMCI.
Greater ICV, that is, premorbid brain size, seems to protect against clinical deterioration in the face of AD-related brain atrophy in aMCI. The results support the theory of a compensatory role of brain reserve in contrast to a neuroprotective role. The protective effects of morphologic reserve seem to be limited to early clinical AD; once a certain threshold of neurodegenerative burden is passed, a larger premorbid brain no longer offers an advantage in this context.
在一定程度的脑病理学水平上，较大的颅内体积（ICV）与阿尔茨海默病（AD）症状的严重程度较轻有关。在这项研究中，我们研究了 ICV 是否调节了临床疾病进展与脑萎缩或载脂蛋白 E 基因型之间的关联。
我们研究了来自 AD 神经影像学倡议（ADNI）的 674 名受试者。受试者包括 204 名对照、144 名 AD 痴呆患者和 326 名遗忘型轻度认知障碍（aMCI）患者。采用广义估计方程进行纵向分析，以检查 ICV 对临床恶化和萎缩进展的影响。随访数据可获得基线检查后最长 60 个月（平均 31.42 个月，SD 13.12 个月）。
ICV 与临床恶化或萎缩进展没有直接关系。然而，ICV 减弱了萎缩和载脂蛋白 E ε4 等位基因对 aMCI 中临床疾病进展的影响。
较大的 ICV，即发病前的大脑大小，似乎可以保护 aMCI 中与 AD 相关的脑萎缩患者免受临床恶化的影响。结果支持脑储备的代偿作用理论，而不是神经保护作用理论。形态储备的保护作用似乎仅限于早期临床 AD；一旦神经退行性负担达到一定阈值，在这种情况下，更大的发病前大脑就不再具有优势。
