The goal of this study was to investigate whether a brief cognitive training intervention results in a specific performance increase in the trained task, and whether there are transfer effects to other nontrained measures. A computerized, adaptive working memory intervention was conducted with 9- to 11-year-old typically developing children. The children considerably improved their performance in the trained working memory task. Additionally, compared to a matched control group, the experimental group significantly enhanced their reading performance after training, providing further evidence for shared processes between working memory and reading.

The presymptomatic phase of neurodegenerative diseases are characterized by structural brain changes without significant clinical features. We set out to investigate the contribution of functional network resilience to preserved cognition in presymptomatic genetic frontotemporal dementia. We studied 172 people from families carrying genetic abnormalities in C9orf72, MAPT, or PGRN. Networks were extracted from functional MRI data and assessed using graph theoretical analysis. We found that despite loss of both brain volume and functional connections, there is maintenance of an efficient topological organization of the brain's functional network in the years leading up to the estimated age of frontotemporal dementia symptom onset. After this point, functional network efficiency declines markedly. Reduction in connectedness was most marked in highly connected hub regions. Measures of topological efficiency of the brain's functional network and organization predicted cognitive dysfunction in domains related to symptomatic frontotemporal dementia and connectivity correlated with brain volume loss in frontotemporal dementia. We propose that maintaining the efficient organization of the brain's functional network supports cognitive health even as atrophy and connectivity decline presymptomatically.

IMPORTANCE Behavioral disturbances are core features of frontotemporal dementia (FTD); however, symptom progression across the course of disease is not well characterized in genetic FTD.OBJECTIVE To investigate behavioral symptom frequency and severity and their evolution and progression in different forms of genetic FTD.

Working memory (WM) as the ability to temporarily maintain and manipulate various kinds of information is known to be affected by proactive interference (PI) from previously relevant contents, but studies on developmental changes in the susceptibility to PI are scarce. In the present study, we investigated life span development of item-specific PI. To this end, 92 individuals between the ages of 8 and 74 years completed a recent-probes task and an n-back task that both composed experimental manipulations of PI. Regarding global WM development, young adults had higher WM performance than children and older adults in both tasks. Significant PI × Age interactions revealed that susceptibility to PI changed over the life span in both tasks, whereas the developmental course of PI differed between the tasks: Children committed more PI-related errors than young adults in the recent-probes task but showed marginally less PI in the n-back task. Regarding reaction time costs, children did not differ from adults in the recent-probes task and were less affected than adults in the n-back. Older adults showed more PI-related errors than young adults in both tasks. Therefore, as expected, item-specific PI changed over the life span with the young adults being less susceptible to PI than children and older adults. The diverging developmental effects of PI across both tasks, especially in the children, are supposed to reflect different causes for the difficulties regarding resisting PI in children and older adults. These might concern differently developed underlying cognitive processes such as inhibition or recollection, or different responses to task demands across both tasks.

Frontotemporal dementia (FTD) is a heterogeneous group of neurodegenerative disorders with both sporadic and genetic forms. Mutations in the progranulin gene (GRN) are a common cause of genetic FTD, causing either a behavioural presentation or, less commonly, language impairment. Presence on T2-weighted images of white matter hyperintensities (WMH) has been previously shown to be more commonly associated with GRN mutations rather than other forms of FTD. The aim of the current study was to investigate the longitudinal change in WMH and the associations of WMH burden with grey matter (GM) loss, markers of neurodegeneration and cognitive function in GRN mutation carriers.336 participants in the Genetic FTD Initiative (GENFI) study were included in the analysis: 101 presymptomatic and 32 symptomatic GRN mutation carriers, as well as 203 mutation-negative controls. 39 presymptomatic and 12 symptomatic carriers, and 73 controls also had longitudinal data available. Participants underwent MR imaging acquisition including isotropic 1 mm T1-weighted and T2-weighted sequences. WMH were automatically segmented and locally subdivided to enable a more detailed representation of the pathology distribution. Log-transformed WMH volumes were investigated in terms of their global and regional associations with imaging measures (grey matter volumes), biomarker concentrations (plasma neurofilament light chain, NfL, and glial fibrillary acidic protein, GFAP), genetic status (TMEM106B risk genotype) and cognition (tests of executive function).Analyses revealed that WMH load was higher in both symptomatic and presymptomatic groups compared with controls and this load increased over time. In particular, lesions were seen periventricularly in frontal and occipital lobes, progressing to medial layers over time. However, there was variability in the WMH load across GRN mutation carriers – in the symptomatic group 25.0% had none/mild load, 37.5% had medium and 37.5% had a severe load – a difference not fully explained by disease duration. GM atrophy was strongly associated with WMH load both globally and in separate lobes, and increased WMH burden in the frontal, periventricular and medial regions was associated with worse executive function. Furthermore, plasma NfL and to a lesser extent GFAP concentrations were seen to be associated with increased lesion burden. Lastly, the presence of the homozygous TMEM106B rs1990622 TT risk genotypic status was associated with an increased accrual of WMH per year.In summary, WMH occur in GRN mutation carriers and accumulate over time, but are variable in their severity. They are associated with increased GM atrophy and executive dysfunction. Furthermore, their presence is associated with markers of WM damage (NfL) and astrocytosis (GFAP), whilst their accrual is modified by TMEM106B genetic status. WMH load may represent a target marker for trials of disease modifying therapies in individual patients but the variability across the GRN population would prevent use of such markers as a global outcome mea...