Lyons David M, Yang Chou, Eliez Stephan, Reiss Allan L, Schatzberg Alan F
Department of Psychiatry and Behavioral Sciences, Stanford University School of Medicine, Stanford, California 94305-5485, USA.
J Neurosci. 2004 Apr 7;24(14):3655-62. doi: 10.1523/JNEUROSCI.0324-04.2004.
Neurobiological studies of stress and cognitive aging seldom consider white matter despite indications that complex brain processes depend on networks and white matter interconnections. Frontal and temporal lobe white matter volumes increase throughout midlife adulthood in humans, and this aspect of aging is thought to enhance distributed brain functions. Here, we examine spatial learning and memory, neuroendocrine responses to psychological stress, and regional volumes of gray and white matter determined by magnetic resonance imaging in 31 female squirrel monkeys between the ages of 5 and 17 years. This period of lifespan development corresponds to the years 18-60 in humans. Older adults responded to stress with greater increases in plasma levels of adrenocorticotropic hormone and modest reductions in glucocorticoid feedback sensitivity relative to young adults. Learning and memory did not differ with age during the initial cognitive test sessions, but older adults more often failed to inhibit the initial learned response after subsequent spatial reversals. Impaired cognitive response inhibition correlated with the expansion of white matter volume statistically controlling for age, stress hormones, gray matter, and CSF volumes. These results indicate that instead of enhancing cognitive control during midlife adulthood, white matter volume expansion contributes to aspects of cognitive decline. Cellular and molecular research combined with brain imaging is needed to determine the basis of white matter growth in adults, elucidate its functions during lifespan development, and provide potential new targets for therapies aimed at maintaining in humans cognitive vitality with aging.
尽管有迹象表明复杂的大脑过程依赖于神经网络和白质连接，但压力与认知衰老的神经生物学研究很少考虑白质。在人类成年中期，额叶和颞叶白质体积会增加，人们认为衰老的这一方面会增强大脑的分布式功能。在此，我们对31只年龄在5至17岁之间的雌性松鼠猴进行了空间学习和记忆、对心理压力的神经内分泌反应以及通过磁共振成像测定的灰质和白质区域体积的研究。这个寿命发展阶段相当于人类的18至60岁。与年轻成年猴相比，老年成年猴对应激的反应是促肾上腺皮质激素血浆水平有更大幅度的升高，而糖皮质激素反馈敏感性有适度降低。在最初的认知测试阶段，学习和记忆能力并没有随年龄而有所不同，但在随后的空间逆转后，老年成年猴更常无法抑制最初学到的反应。在对年龄、应激激素、灰质和脑脊液体积进行统计控制后，认知反应抑制受损与白质体积的扩大相关。这些结果表明，在成年中期，白质体积的扩大并没有增强认知控制，反而导致了认知衰退的某些方面。需要将细胞和分子研究与脑成像相结合，以确定成年人白质生长的基础，阐明其在寿命发展过程中的功能，并为旨在维持人类随着年龄增长而保持认知活力的治疗提供潜在的新靶点。
