This paper describes the data repository for the Cambridge Centre for Ageing and Neuroscience (Cam-CAN) initial study cohort. The Cam-CAN Stage 2 repository contains multi-modal (MRI, MEG, and cognitive-behavioural) data from a large (approximately N=700), cross-sectional adult lifespan (18-87years old) population-based sample. The study is designed to characterise age-related changes in cognition and brain structure and function, and to uncover the neurocognitive mechanisms that support healthy cognitive ageing. The database contains raw and preprocessed structural MRI, functional MRI (active tasks and resting state), and MEG data (active tasks and resting state), as well as derived scores from cognitive behavioural experiments spanning five broad domains (attention, emotion, action, language, and memory), and demographic and neuropsychological data. The dataset thus provides a depth of neurocognitive phenotyping that is currently unparalleled, enabling integrative analyses of age-related changes in brain structure, brain function, and cognition, and providing a testbed for novel analyses of multi-modal neuroimaging data.

As greater numbers of us are living longer, it is increasingly important to understand how we can age healthily. Although old age is often stereotyped as a time of declining mental abilities and inflexibility, cognitive neuroscience reveals that older adults use neural and cognitive resources flexibly, recruiting novel neural regions and cognitive processes when necessary. Our aim in this project is to understand how age-related changes to neural structure and function interact to support cognitive abilities across the lifespan. We are recruiting a population-based cohort of 3000 adults aged 18 and over into Stage 1 of the project, where they complete an interview including health and lifestyle questions, a core cognitive assessment, and a self-completed questionnaire of lifetime experiences and physical activity. Of those interviewed, 700 participants aged 18-87 (100 per age decile) continue to Stage 2 where they undergo cognitive testing and provide measures of brain structure and function. Cognition is assessed across multiple domains including attention and executive control, language, memory, emotion, action control and learning. A subset of 280 adults return for in-depth neurocognitive assessment in Stage 3, using functional neuroimaging experiments across our key cognitive domains. Formal statistical models will be used to examine the changes that occur with healthy ageing, and to evaluate age-related reorganisation in terms of cognitive and neural functions invoked to compensate for overall age-related brain structural decline. Taken together the three stages provide deep phenotyping that will allow us to measure neural activity and flexibility during performance across a number of core cognitive functions. This approach offers hypothesis-driven insights into the relationship between brain and behaviour in healthy ageing that are relevant to the general population. Our study is a unique resource of neuroimaging and cognitive measures relevant to change across the adult lifespan. Because we focus on normal age-related changes, our results may contribute to changing views about the ageing process, lead to targeted interventions, and reveal how normal ageing relates to frail ageing in clinicopathological conditions such as Alzheimer's disease.

Language is a crucial and complex lifelong faculty, underpinned by dynamic interactions within and between specialized brain networks. Whereas normal aging impairs specific aspects of language production, most core language processes are robust to brain aging. We review recent behavioral and neuroimaging evidence showing that language systems remain largely stable across the life span and that both younger and older adults depend on dynamic neural responses to linguistic demands. Although some aspects of network dynamics change with age, there is no consistent evidence that core language processes are underpinned by different neural networks in younger and older adults.

Tip-of-the-tongue (TOT) experiences are frustrating word-finding failures where people are temporarily unable to produce a word they are certain they know. TOT frequency increases with normal aging during adulthood, and behavioral evidence suggests that the underlying deficit is in retrieving the complete phonology of the target word during production. The present study investigated the neural correlates of this phonological retrieval deficit. We obtained 3-D T1-weighted structural magnetic resonance images (MRI) for healthy participants between 19 and 88 years old and used voxel-based morphometry to measure gray matter density throughout the brain. In a separate session, participants named celebrities cued by pictures and descriptions, indicating when they had a TOT, and also completed Raven's Progressive Matrices (RPM), a task that does not involve phonological production. The number of TOTs increased with age and also with gray matter atrophy in the left insula, an area implicated in phonological production. The relation between TOTs and left insula atrophy cannot be attributed to the correlation of each variable with age because TOTs were related to insula atrophy even with age effects removed. Moreover, errors on the RPM increased with age, but performance did not correlate with gray matter density in the insula. These results provide, for the first time, an association between a region in the neural language system and the rise in age-related word-finding failures and suggest that age-related atrophy in neural regions important for phonological production may contribute to age-related word production failures.

A common complaint of normal aging is the increase in word-finding failures such as tip-of-the-tongue states (TOTs). Behavioral research identifies TOTs as phonological retrieval failures, and recent findings [Shafto, M. A., Burke, D. M., Stamatakis, E. A., Tam, P., & Tyler, L. K. On the tip-of-the-tongue: Neural correlates of increased word-finding failures in normal aging. Journal of Cognitive Neuroscience, 19, 2060–2070, 2007] link age-related increases in TOTs to atrophy in left insula, a region implicated in phonological production. Here, younger and older adults performed a picture naming task in the fMRI scanner. During successful naming, left insula activity was not affected by age or gray matter integrity. Age differences only emerged during TOTs, with younger but not older adults generating a “boost” of activity during TOTs compared to successful naming. Older adults also had less activity than younger adults during TOTs compared to “don't know” responses, and across all participants, less TOT activity was affiliated with lower gray matter density. For older adults, lower levels of activity during TOTs accompanied higher TOT rates, supporting the role of an age-related neural mechanism impacting older more than younger adults. Results support a neural account of word retrieval in old age wherein, despite widespread age-related atrophy, word production processes are not universally impacted by age. However, atrophy undermines older adults' ability to modulate neural responses needed to overcome retrieval failures.

We tested the claim that age-related increases in knowledge interfere with word retrieval, leading to word finding failures. We did this by relating a measure of crystallized intelligence to tip-of-the-tongue (TOT) states and picture naming accuracy. Participants were from a large (N = 708), cross-sectional (aged 18–88 years), population-based sample from the Cambridge Centre for Ageing and Neuroscience cohort (Cam-CAN; www.cam-can.com). They completed (a) the Spot-the-Word Test (STW), a measure of crystallized intelligence in which participants circled the real word in word/nonword pairs, (b) a TOT-inducing task, and (c) a picture naming task. Age and STW independently predicted TOTs, with higher TOTs for older adults and for participants with lower STW scores. Tests of a moderator model examining interactions between STW and age indicated that STW was a significant negative predictor of TOTs in younger adults, but with increasing age, the effect size gradually approached zero. Results using picture naming accuracy replicated these findings. These results do not support the hypothesis that lifelong knowledge acquisition leads to interference that causes an age-related increase in TOTs. Instead, crystallized intelligence supports successful word retrieval, although this relationship weakens across adulthood.