90 The association between neuronal loss and cognitive impairment, and the lack of association between AD/vascular pathologies and cognitive impairment, has led to the construct of “cognitive reserve,” the hypothesized capacity of the mature adult brain to resist the effects of disease or injury that would otherwise cause dementia.91 According

to this hypothesis, elderly individuals with a high level of cognitive reserve may remain dementia-free in spite of the neuropathological changes. Several factors that predict lower risk of dementia, including high-quality education, Inhibitors,research,lifescience,medical occupational complexity, and balanced diet, were also associated with the biological advantage of cognitive ability, i.e. cognitive reserve (reviewed in91). A recent study by Murray et al. demonstrates that the magnitude of the contribution of education to cognitive function is greater than the negative impact Inhibitors,research,lifescience,medical of either of the two neuropathological burdens alone,92 emphasizing the role of both neuronal loss and neuronal reserve in the dementing processes of the oldest-old. SYMPTOMATOLOGY OF DEMENTIA IN THE OLDEST-OLD Cognitive Decline Even without a “proper” dementia diagnosis, it is generally accepted Inhibitors,research,lifescience,medical that—on average—a gradual age-related cognitive decline occurs in humans, as well as non-human primates.93,94 Cognitive

performance is a term that describes the composite outcome of multiple cognitive domains and the interactions between them. Therefore, “cognitive decline” may be the result of impairment in an individual domain or impairment in multiple domains, possibly to different extents. Studies have described age-related declines in many of the cognitive domains, including divided attention,95 verbal memory,96 working memory,97 and learning.98,99 Inhibitors,research,lifescience,medical Nevertheless, it appears that during normal aging, some domains are more susceptible to impairment than others. In particular, executive function and mental speed have been suggested as Inhibitors,research,lifescience,medical such vulnerable domains.100,101 This poses a new challenge on determining diagnosis of AD and other forms of dementia in the oldest-old. In spite of the great development in neuroimaging

techniques such as MRI and positron emission tomography (PET), neuropsychological assessment remains the key instrument in diagnosing dementia and monitoring cognitive decline. Several valid and reliable neuropsychological dementia screening instruments have been developed to address the issue of Brefeldin_A clinical dementia diagnosis in elderly in whom cognitive decline is expected. Those instruments include the Blessed Dementia Scale,102 Dementia Rating Scale,103 Mini-Mental State Examination (MMSE),104 and Modified Mini-Mental State Examination (3MS)—an expanded version of the MMSE.105 The MMSE is probably the most widely used, easy to administrate, cognitively Tanespimycin comprehensive, and validated instrument for detecting dementia.