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ObjectiveWe aimed to investigate whether cognitive deficits and structural and functional connectivity changes can be detected before symptom onset in a large cohort of carriers of microtubule-associated protein tau and progranulin mutations.MethodsIn this case-control study, 75 healthy individuals (aged 20-70 years) with 50% risk for frontotemporal dementia (FTD) underwent DNA screening, neuropsychological assessment, and structural and functional MRI. We used voxel-based morphometry and tract-based spatial statistics for voxelwise analyses of gray matter volume and diffusion tensor imaging measures. Using resting-state fMRI scans, we assessed whole-brain functional connectivity to frontoinsula, anterior midcingulate cortex (aMCC), and posterior cingulate cortex.ResultsAlthough carriers (n = 37) and noncarriers (n = 38) had similar neuropsychological performance, worse performance on Stroop III, Ekman faces, and Happé cartoons correlated with higher age in carriers, but not controls. Reduced fractional anisotropy and increased radial diffusivity throughout frontotemporal white matter tracts were found in carriers and correlated with higher age. Reductions in functional aMCC connectivity were found in carriers compared with controls, and connectivity between frontoinsula and aMCC seeds and several brain regions significantly decreased with higher age in carriers but not controls. We found no significant differences or age correlations in posterior cingulate cortex connectivity. No differences in regional gray matter volume were found.ConclusionsThis study convincingly demonstrates that alterations in structural and functional connectivity develop before the first symptoms of FTD arise. These findings suggest that diffusion tensor imaging and resting-state fMRI may have the potential to become sensitive biomarkers for early FTD in future clinical trials.

The aim of this study was to evaluate cognitive function 10 years after moderate-severe traumatic brain injury (TBI) and to investigate the associations among cognitive function, depression, and health-related quality of life (HRQoL). In this prospective cohort study, with measurements at 3, 6, 12, 18, 24, 36, and 120 months post-TBI, patients 18–67 years of age (n = 113) with moderate-severe TBI were recruited. Main outcome measures were depression (Center for Epidemiologic Studies-Depression Scale [CES-D]), subjective cognitive functioning (Cognitive Failure Questionnaire [CFQ]), objective cognitive functioning, and HRQoL (Medical Outcomes Study 36-Item Short Form Health Survey [SF-36]). Fifty of the initial 113 patients completed the 10 year follow-up. Twenty percent showed symptoms of depression (CES-D ≥ 16). These patients had more psychiatric symptoms at hospital discharge (p = 0.048) and were more often referred to rehabilitation or nursing homes (p = 0.015) than non-depressed patients. Further, they also had significantly lower scores in six of the eight subdomains of the SF-36. The non-depressed patients had equivalent scores to those of the Dutch norm-population on all subdomains of the SF-36. Cognitive problems at hospital discharge were related with worse cognitive outcome 10 years post-TBI, but not with depression or HRQoL. Ten years after moderate-severe TBI, only weak associations (p < 0.05) between depression scores and two objective cognitive functioning scores were found. However, there were moderate associations (p < 0.01) among depression scores, HRQoL, and subjective cognitive functioning. Therefore, signaling and treatment of depressive symptoms after moderate-severe TBI may be of major importance for optimizing HRQoL in the long term. We did not find strong evidence for associations between depression and objective cognitive functioning in the long term post-TBI. Disease awareness and selective dropping out may play a role in long-term follow-up studies in moderate-severe TBI. More long-term research is needed in this field. [ABSTRACT FROM AUTHOR]

BackgroundProgressive supranuclear palsy (PSP) patients often exhibit cognitive decline and behavioural changes during the disease course. In a subset, these symptoms may be the presenting manifestation and can be similar to those in frontotemporal dementia (FTD). However, correlation studies between quantitative imaging measures and detailed neuropsychological assessment are scarce. The aim of this study was to investigate the functional role of affected brain regions in cognition in PSP compared with controls and subsequently examine these regions in FTD patients with known tau pathology (FTD tau).Methods21 PSP patients, 27 healthy controls and 11 FTD tau patients were enrolled. All participants underwent neuropsychological testing and technetium-99m-hexamethyl-propylenamine-oxime single photon emission CT. Regression slope analyses were performed in statistical parametric mapping to find significant associations between neuropsychological test results and brain perfusion.ResultsPSP patients showed hypoperfusion in the midcingulate cortex (MCC) of which the posterior part correlated with Stroop III and Weigl. In FTD tau patients, MCC involvement was located more anterior and correlated with Stroop III and Wisconsin Card Sorting Test concepts. The degree of hypoperfusion in the anterior cortex and MCC in the disorders differed in the subgenual anterior cingulate cortex only.ConclusionsThe posterior part of the MCC is prominently involved in the neurodegenerative process of PSP, and the severity of its hypoperfusion correlated with the extent of executive dysfunction. In FTD tau, this cognitive domain was associated with anterior MCC involvement. The degree of hypoperfusion in these regions did not differ between PSP and FTD tau. These observations provide insight into the role of the cingulate cortex in cognitive dysfunction in these neurodegenerative disorders and warrant further investigations. [ABSTRACT FROM AUTHOR]