Neuroanatomical changes associated with cognitive aging.

The literature on the neuroanatomical changes that occur during normal, non-demented aging is reviewed here with an emphasis on the improved accuracy of studies that use stereological techniques. Loss of neural tissue involved in cognition occurs during aging of humans as well as the other mammals that have been examined. There is considerable regional specificity within the cerebral cortex and the hippocampus in both the degree and cellular basis for loss. The anatomy of the prefrontal cortex is especially vulnerable to the effects of aging while the major subfields of the hippocampus are not. A loss of neurons, dendrites and synapses has been documented, as well as changes in neurotransmitter systems, in some regions of the cortex and hippocampus but not others. Species differences are also apparent in the cortical white matter and the corpus callosum where there are indications of loss of myelin in humans, but most evidence favors preservation in rats. The examination of whether the course of neuroanatomical aging is altered by hormone replacement in females is just beginning. When hormone replacement is started close to the time of cycle cessation, there are indications in humans and rats that replacement can preserve neural tissue but there is some variability due to the type of hormones and regimen of administration.

Effects of long-term treatment with 17 beta-estradiol and medroxyprogesterone acetate on water maze performance in middle aged female rats.

Although previous research has indicated that hormone replacement therapy benefits memory in menopausal women, several recent studies have shown either detrimental or no effects of treatment. These inconsistencies emphasize the need to evaluate the role of ovarian hormones in protecting against age-related cognitive decline in an animal model. The present study investigated the effects of long-term hormone treatment during aging on the Morris water maze. Female Long Evans hooded rats were ovariectomized at middle age (12-13 months) and were immediately placed in one of five groups: no replacement, chronic 17 beta-estradiol only, chronic 17 beta-estradiol and progesterone, chronic 17 beta-estradiol and medroxyprogesterone acetate (MPA), or cyclic 17 beta-estradiol only. 17 beta-estradiol was administered in the drinking water in either a chronic or cyclic (3 out of 4 days) fashion. Progesterone and MPA were administered via subcutaneous pellets. Following 6 months of hormone treatment, animals were tested on the Morris water maze. Animals performed four trials a day for 4 days and after the final day of testing a subset of animals completed a probe trial. Across 4 days of testing, rats receiving 17 beta-estradiol in combination with MPA performed significantly worse than all other groups receiving hormone replacement. In addition on the last day of testing, chronic 17 beta-estradiol administration was more beneficial than cyclic administration and no replacement. Thus compared to other hormone-treated groups, long-term 17 beta-estradiol treatment in combination with MPA results in impaired performance on the spatial Morris water maze.