The pathophysiological process of Alzheimer's disease (AD) is thought to begin many years before the diagnosis of AD dementia. This long “preclinical” phase of AD would provide a critical opportunity for therapeutic intervention; however, we need to further elucidate the link between the pathological cascade of AD and the emergence of clinical symptoms. The National Institute on Aging and the Alzheimer's Association convened an international workgroup to review the biomarker, epidemiological, and neuropsychological evidence, and to develop recommendations to determine the factors which best predict the risk of progression from “normal” cognition to mild cognitive impairment and AD dementia. We propose a conceptual framework and operational research criteria, based on the prevailing scientific evidence to date, to test and refine these models with longitudinal clinical research studies. These recommendations are solely intended for research purposes and do not have any clinical implications at this time. It is hoped that these recommendations will provide a common rubric to advance the study of preclinical AD, and ultimately, aid the field in moving toward earlier intervention at a stage of AD when some disease-modifying therapies may be most efficacious.

There are declines with age in speed of processing, working memory, inhibitory function, and long-term memory, as well as decreases in brain structure size and white matter integrity. In the face of these decreases, functional imaging studies have demonstrated, somewhat surprisingly, reliable increases in prefrontal activation. To account for these joint phenomena, we propose the scaffolding theory of aging and cognition (STAC). STAC provides an integrative view of the aging mind, suggesting that pervasive increased frontal activation with age is a marker of an adaptive brain that engages in compensatory scaffolding in response to the challenges posed by declining neural structures and function. Scaffolding is a normal process present across the lifespan that involves use and development of complementary, alternative neural circuits to achieve a particular cognitive goal. Scaffolding is protective of cognitive function in the aging brain, and available evidence suggests that the ability to use this mechanism is strengthened by cognitive engagement, exercise, and low levels of default network engagement.

The authors investigated the distinctiveness and interrelationships among visuospatial and verbal memory processes in short-term, working, and long-term memories in 345 adults. Beginning in the 20s, a continuous, regular decline occurs for processing-intensive tasks (e.g., speed of processing, working memory, and long-term memory), whereas verbal knowledge increases across the life span. There is little differentiation in the cognitive architecture of memory across the life span. Visuospatial and verbal working memory are distinct but highly interrelated systems with domain-specific short-term memory subsystems. In contrast to recent neuroimaging data, there is little evidence for dedifferentiation of function at the behavioral level in old compared with young adults. The authors conclude that efforts to connect behavioral and brain data yield a more complete understanding of the aging mind.

Healthy aging has been associated with decreased specialization in brain function. This characterization has focused largely on describing age-accompanied differences in specialization at the level of neurons and brain areas. We expand this work to describe systems-level differences in specialization in a healthy adult lifespan sample (n = 210; 20-89 y). A graph-theoretic framework is used to guide analysis of functional MRI resting-state data and describe systems-level differences in connectivity of individual brain networks. Young adults' brain systems exhibit a balance of within-and between-system correlations that is characteristic of segregated and specialized organization. Increasing age is accompanied by decreasing segregation of brain systems. Compared with systems involved in the processing of sensory input and motor output, systems mediating "associative" operations exhibit a distinct pattern of reductions in segregation across the adult lifespan. Of particular importance, the magnitude of association system segregation is predictive of long-term memory function, independent of an individual's age.aging | brain networks | resting-state correlations | memory | connectome

Faces constitute a unique and widely used category of stimuli. In spite of their importance, there are few collections of faces for use in research, none of which adequately represent the different ages of faces across the lifespan. This lack of a range of ages has limited the majority of researchers to using predominantly young faces as stimuli even when their hypotheses concern both young and old participants. We describe a database of 575 individual faces ranging from ages 18 to 93. Our database was developed to be more representative of age groups across the lifespan, with a special emphasis on recruiting older adults. The resulting database has faces of 218 adults age 18-29, 76 adults age 30-49, 123 adults age 50-69, and 158 adults age 70 and older. These faces may be acquired for research purposes from http://agingmind.cns.uiuc.edu/facedb/. This will allow researchers interested in using facial stimuli access to a wider age range of adult faces than has previously been available.

Human neuroimaging research on cognitive aging has brought significant advances to our understanding of the neural mechanisms underlying age-related cognitive decline and successful aging. However, interpreting age-related changes and differences in brain structure, activation, and functional connectivity is an ongoing challenge. Ambiguous terminology is a major source of this challenge. For example, the terms ‘compensation,’ ‘maintenance,’ and ‘reserve’ are used in different ways and researchers disagree about the kinds of evidence or patterns of results required to interpret findings related to these concepts. As such inconsistencies can impede theoretical and empirical progress, we here aim to clarify these key terms and to propose consensual definitions of maintenance, reserve, and compensation.

“The Scaffolding Theory of Aging and Cognition (STAC)”, proposed in 2009, is a conceptual model of cognitive aging that integrated evidence from structural and functional neuroimaging to explain how the combined effects of adverse and compensatory neural processes produce varying levels of cognitive function. The model made clear and testable predictions about how different brain variables, both structural and functional, were related to cognitive function, focusing on the core construct of compensatory scaffolding. The present paper provides a revised model that integrates new evidence about the aging brain that has emerged since STAC was published 5 years ago. Unlike the original STAC model, STAC-r incorporates life-course factors that serve to enhance or deplete neural resources, thereby influencing the developmental course of brain structure and function, as well as cognition, over time. Life-course factors also influence compensatory processes that are engaged to meet cognitive challenge, and to ameliorate the adverse effects of structural and functional decline. The revised model is discussed in relation to recent lifespan and longitudinal data as well as emerging evidence about the effects of training interventions. STAC-r goes beyond the previous model by combining a life-span approach with a life-course approach to understand and predict cognitive status and rate of cognitive change over time.

The present study investigated whether neural structures become less functionally differentiated and specialized with age. We studied ventral visual cortex, an area of the brain that responds selectively to visual categories (faces, places, and words) in young adults, and that shows little atrophy with age. Functional MRI was used to estimate neural activity in this cortical area, while young and old adults viewed faces, houses, pseudowords, and chairs. The results demonstrated significantly less neural specialization for these stimulus categories in older adults across a range of analyses. There is growing behavioral evidence that the functional architecture of cognition becomes dedifferentiated with age: A number of studies have found that correlations among distinct measures of cognitive function are more intercorrelated in older subjects than in younger adult subjects (1-5). Furthermore, markers of central sensory function (e.g., corrected visual and auditory acuity) account for virtually all age-related variance on a broad array of higher-order cognitive tasks, including speed of processing, memory, verbal fluency, and reasoning (4, 6). Based on these and related findings, Baltes and Lindenberger (6) argued that aging reduces the degree to which behavior is specialized (or differentiated) for individual tasks and that a domain-independent decline in neural integrity is the mechanism underlying this dedifferentiation. Providing a more specific mechanism for dedifferentiation, Li et al. (7) have argued that both empirical and computational data suggest that increased age results in a decrease in distinctiveness of neural representations due to deficient dopaminergic modulation. With the advent of neuroimaging techniques, the dedifferentiation hypothesis can be addressed more directly than is possible with behavioral techniques alone. Thus, in the present study, we test whether neural structures become dedifferentiated with age, by examining the degree of category-specificity that is present in ventral visual cortex in young and old adults.