Bartzokis George, Cummings Jeffrey L, Sultzer David, Henderson Victor W, Nuechterlein Keith H, Mintz Jim
Department of Neurology, Alzheimer's Disease Center, University of California, Los Angeles, 710 Westwood Plaza, Room 2-238, Los Angeles, CA 90095-1769, USA.
Arch Neurol. 2003 Mar;60(3):393-8. doi: 10.1001/archneur.60.3.393.
Imaging and postmortem studies suggest that frontal lobe white matter (FLWM) volume expands until about the age of 44.6 years and then declines. Postmortem evidence indicates that the structural integrity of myelin sheaths deteriorates during normal aging, especially in late myelinating regions such as the frontal lobes.
To assess the integrity of FLWM by magnetic resonance imaging and, thus, to provide an important index of brain aging and its relationship to Alzheimer disease (AD).
Cross-sectional study.
Two metropolitan university hospitals and AD research centers.
Two hundred fifty-two healthy adults (127 men and 125 women), aged 19 to 82 years, and 34 subjects with AD (16 men and 18 women), aged 59 to 85 years.
Calculated transverse relaxation rate (R( 2)) of the FLWM (an indirect measure of the structural integrity of white matter).
As expected from prior imaging data on FLWM volume, the quadratic function best represented the relationship between age and the FLWM R(2) (P<.001). In healthy individuals, the FLWM R(2) increased until the age of 38 years and then declined markedly with age. The R( 2) of subjects with AD was significantly lower than that of a group of healthy control subjects who were of similar age and sex (P<.001).
The R(2) changes in white matter suggest that the healthy adult brain is in a constant state of change, roughly defined as periods of maturation continuing into middle age followed by progressive loss of myelin integrity. Clinically diagnosed AD is associated with more severe myelin breakdown. Noninvasive measures, such as the determination of the R(2), may have the potential to track prospectively the trajectory of deteriorating white matter integrity during normal aging and the development of AD and, thus, may be a useful marker for medication development aimed at the prevention of AD.
影像学和尸检研究表明，额叶白质（FLWM）体积在约44.6岁之前会不断增大，之后则会减小。尸检证据显示，在正常衰老过程中，髓鞘的结构完整性会逐渐恶化，尤其是在额叶等髓鞘形成较晚的区域。
通过磁共振成像评估FLWM的完整性，从而提供一个大脑衰老及其与阿尔茨海默病（AD）关系的重要指标。
横断面研究。
两家大都市大学医院及AD研究中心。
252名健康成年人（127名男性和125名女性），年龄在19至82岁之间；以及34名AD患者（16名男性和18名女性），年龄在59至85岁之间。
计算FLWM的横向弛豫率（R(2)）（白质结构完整性的间接指标）。
正如先前关于FLWM体积的影像学数据所预期的那样，二次函数最能代表年龄与FLWM R(2)之间的关系（P<0.001）。在健康个体中，FLWM R(2)在38岁之前升高，之后随年龄显著下降。AD患者的R(2)显著低于年龄和性别相似的健康对照组（P<0.001）。
白质中的R(2)变化表明，健康成人大脑处于持续变化状态，大致可定义为成熟阶段持续至中年，随后髓鞘完整性逐渐丧失。临床诊断的AD与更严重的髓鞘破坏有关。像测定R(2)这样的非侵入性措施可能有潜力前瞻性地追踪正常衰老过程中白质完整性恶化的轨迹以及AD的发展，因此可能是预防AD药物研发的有用标志物。
