With the promising development of effective treatment, significant improvement in the very early diagnosis of Alzheimer's disease (AD) is required. There is vast agreement that a decline in memory, especially in verbal episodic memory, is the earliest and perhaps the most sensitive sign of incipient AD at the preclinical stage. However, this review offers evidence that impairment in episodic memory can be observed in normal elderly people as well as in aged subjects with mild cognitive impairment (MCI), a large proportion of whom will, however, not convert to dementia. Quantitative measurement of atrophy and brain activation in the hippocampal-parahippocampal formation by using structural and functional magnetic resonance imaging may help to distinguish the MCI decliners from the nondecliners. Cerebrospinal fluid levels of tau protein and Abet1-42 peptide, together with the presence of an apolipoprotein (apo)E epsilon4 allele may also increase our confidence in the early positive diagnosis of AD. This review concludes, however, that while adequate for constituting groups of patients in a research perspective, the extensive diagnostic procedure based on specific cognitive testing, neuroimaging and biological investigations is still out of reach for the practitioner.

Aging is typically related to changes in brain and cognition, but the aging process is heterogeneous and differs between individuals. Recent research has started investigating the influence of cognitive and physical training on cognitive performance, functional brain activity, and brain structure in old age. The functional relevance of neural changes and the interactions among these changes following interventions is still a matter of debate. Here we selectively review research on structural and functional brain correlates of training-induced performance changes in healthy older adults and present exemplary longitudinal intervention studies sorted by the type of training applied (i.e., strategy-based training, process-specific training, and physical exercise). Although many training studies have been conducted recently, within each task domain, the number of studies that used comparable methods and techniques to assess behavioral and neural changes is limited. We suggest that future studies should include a multimodal approach to enhance the understanding of the relation between different levels of brain changes in aging and those changes that result from training. Investigating inter-individual differences in intervention-induced behavioral and neuronal changes would provide more information about who would benefit from a specific intervention and why. In addition, a more systematic examination of the time course of training-related structural and functional changes would improve the current level of knowledge about how learning is implemented in the brain and facilitate our understanding of contradictory results.

Neurofibrillary tangles (NFTs) are the most common intraneuronal inclusion in the brains of patients with neurodegenerative diseases and have been implicated in mediating neuronal death and cognitive deficits. Here, we found that mice expressing a repressible human tau variant developed progressive age-related NFTs, neuronal loss, and behavioral impairments. After the suppression of transgenic tau, memory function recovered, and neuron numbers stabilized, but to our surprise, NFTs continued to accumulate. Thus, NFTs are not sufficient to cause cognitive decline or neuronal death in this model of tauopathy.