Successful vs. Unsuccessful Aging in the Rhesus Monkey

It is now well known that one generally experiences relatively mild changes in cognitive abilities with age, particularly with abilities such as short-term memory, executive functions, and confrontation naming [1]. However, a select group of these “successfully” aged individuals evidence virtually no change in their cognitive abilities with age, even into the eleventh decade of life [2]. Such individuals have often been referred to as examples of “pristine” successful aging. At the other end of the continuum, a large percentage of people are known to develop marked cognitive decline with age, characterized by a dementia state, with a majority of those developing Alzheimer’s disease (AD). These individuals fall into the category of “unsuccessful” aging. In recent years, however, clinical researchers have characterized a group as individuals who, with advancing age, show a moderate impairment in one or more cognitive domains that affects the ability to carry out activities of daily living but does not reach the threshold of a dementia state. This category, classified by many as “mild cognitive impairment” (MCI), reasonably can be regarded as a second general category of “unsuccessful” aging. Although many consider MCI as the earliest stage of Alzheimer’s disease, evidence suggests that MCI represents a separate static and chronic state of normal aging. The etiology of MCI is unknown, but stroke and heart disease risk factors, genetics, and education have all been raised as possible contributors. While nongenetically altered laboratory animals do not evidence the brain changes seen in AD [3], they have reliably demonstrated age-related changes in cognitive function. Evidence from a wide range of studies in rodents, dogs, and non-human primates have shown as a group that aged subjects are significantly impaired relative to young controls on cognitive tasks that assess functions such as working memory, declarative memory, and executive function: the same functions that evidence impairment in human aging [4–16]. However, on close inspection of the data, the degree of impairment within the aged group is anything but uniform and, in fact, is often dichotomous. While the overall group effect yields an impairment in the given function, it is clear that individuals within the aged group evidence only mild or, in some cases, no impairment on the task while others demonstrate severe impairment. The finding of individual differences, emphasized in the rodent literature (see [17]), has not been addressed previously in studies of nonhuman primates. This is due in part to the small number of studies in aging primates as well as the relatively small sample sizes of aged groups available within studies. This chapter presents data that we have collected over the past 15 years as part of an ongoing study using the rhesus monkey as a model of normal human aging. During this period, more than 125 rhesus monkeys ranging in age from 5 to 31 years of age have been assessed on multiple tests of recognition memory and executive function. In this chapter we present the data from these animals and discuss their varying levels of impairments and how this relates to clinical findings in human studies.