Finally, the finding that poorer performers (identified using either Immediate or Delayed breakpoint values) exhibited poorer general memory network status is in line with the suggestion that right frontal involvement in verbal memory performance in poorer performers in older age is driven by a failing Ganetespib memory

network. Examination of group differences on individual regions supports the hypothesis that this right frontal involvement is required to supplement change in posterior brain functioning (Davis et al., 2007 and Park and Reuter-Lorenz, 2009). Although the participants in the current study are all generally healthy older adults, who reported no serious neurodegenerative diseases AG-14699 at interview, nor exhibited clinically relevant cerebral features

as assessed by a consultant neuroradiologist, it is possible that these performance differences indicate different (and potentially pathological) patterns of ageing; our results indicate that those with poorer splenium integrity exhibited poorer memory performance. Whereas normal healthy ageing is characterised by an anterior greater than posterior decline in callosal FA and a concomitant increase in MD (reviewed in Sullivan & Pfefferbaum, 2007), greater tissue loss in the splenium has been associated with conversion of elderly participants to dementia over a 3-year period when compared to non-converters (overall n = 328; Frederiksen et al.,

2011). Similarly, an fMRI paradigm involving the immediate (∼7.5 sec) recall of previously-presented numerical stimuli was administered to participants with Alzheimer Disease (n = 9) and healthy controls (n = 10; Starr et al., 2005). They reported increased superior frontal activation amongst the patient group compared to controls, suggesting that this compensatory activation may be present on a spectrum between normal ageing and Alzheimer Disease. Although our current sample comprises ostensibly normal healthy community-dwelling older adults, changes are thought to occur up to a decade before an eventual Branched chain aminotransferase diagnosis of probable dementia. It is plausible that poorer performers could be more susceptible to a future conversion to dementia, and prospective data regarding cognitive and neurostructural change over time with the perspective of a pre-morbid baseline will be available to address this question in the future. Though our participant numbers are not small for an MRI study, they still gave us relatively little power to investigate the complex relationships between estimates of brain structure and verbal memory. Nevertheless, this is a larger study than previously published work on this topic (Duverne et al. 2009: 32 older subjects; de Chastelaine et al. 2011: 36 older subjects).