Neural correlates of the DemTect in Alzheimer's disease and frontotemporal lobar degeneration ? A combined MRI & FDG-PET study ?

Valid screening devices are critical for an early diagnosis of dementia. The DemTect is such an internationally accepted tool. We aimed to characterize the neural networks associated with performance on the DemTect's subtests in two frequent dementia syndromes: early Alzheimer's disease (AD) and frontotemporal lobar degeneration (FTLD). Voxel-based group comparisons of cerebral glucose utilization (as measured by F-18-fluorodeoxyglucose positron emission tomography) and gray matter atrophy (as measured by structural magnetic resonance imaging) were performed on data from 48 subjects with AD (n = 21), FTLD (n = 14) or subjective cognitive impairment (n = 13) as a control group. We performed group comparisons and correlation analyses between multimodal imaging data and performance on the DemTect's subtests. Group comparisons showed regional patterns consistent with previous findings for AD and FTLD. Interestingly, atrophy dominated in FTLD, whereas hypometabolism in AD. Across diagnostic groups performance on the "wordlist" subtest was positively correlated with glucose metabolism in the left temporal lobe. The "number transcoding" subtest was significantly associated with glucose metabolism in both a predominantly left lateralized frontotemporal network and a parietooccipital network including parts of the basal ganglia. Moreover, this subtest was associated with gray matter density in an extensive network including frontal, temporal, parietal and occipital areas. No significant correlates were observed for the "supermarket task" subtest. Scores on the "digit span reverse" subtest correlated with glucose metabolism in the left frontal cortex, the bilateral putamen, the head of caudate nucleus and the anterior insula. Disease-specific correlation analyses could partly verify or extend the correlates shown in the analyses across diagnostic groups. Correlates of gray matter density were found in FTLD for the "number transcoding" subtest and the "digit span reverse" subtest. Correlates of glucose metabolism were found in AD for the "wordlist" subtest and in FTLD for the "digit span reverse" subtest. Our study contributes to the understanding of the neural correlates of cognitive deficits in AD and FTLD and supports an external validation of the DemTect providing preliminary conclusions about disease-specific correlates

Mapping grip force to motor networks.

There is ongoing debate about the role of cortical and subcortical brain areas in force modulation. In a whole-brain approach, we sought to investigate the anatomical basis of grip force whilst acknowledging interindividual differences in connectivity patterns. We tested if brain lesion mapping in patients with unilateral motor deficits can inform whole-brain structural connectivity analysis in healthy controls to uncover the networks underlying grip force. Using magnetic resonance imaging (MRI) and whole-brain voxel-based morphometry in chronic stroke patients (n=55) and healthy controls (n=67), we identified the brain regions in both grey and white matter significantly associated with grip force strength. The resulting statistical parametric maps (SPMs) provided seed areas for whole-brain structural covariance analysis in a large-scale community dwelling cohort (n=977) that included beyond volume estimates, parameter maps sensitive to myelin, iron and tissue water content. The SPMs showed symmetrical bilateral clusters of correlation between upper limb motor performance, basal ganglia, posterior insula and cortico-spinal tract. The covariance analysis with the seed areas derived from the SPMs demonstrated a widespread anatomical pattern of brain volume and tissue properties, including both cortical, subcortical nodes of motor networks and sensorimotor areas projections. We interpret our covariance findings as a biological signature of brain networks implicated in grip force. The data-driven definition of seed areas obtained from chronic stroke patients showed overlapping structural covariance patterns within cortico-subcortical motor networks across different tissue property estimates. This cumulative evidence lends face validity of our findings and their biological plausibility

Identifying the neural correlates of executive functions in early cerebral microangiopathy: a combined VBM and DTI study.

Cerebral microangiopathy (CMA) has been associated with executive dysfunction and fronto-parietal neural network disruption. Advances in magnetic resonance imaging allow more detailed analyses of gray (e.g., voxel-based morphometry-VBM) and white matter (e.g., diffusion tensor imaging-DTI) than traditional visual rating scales. The current study investigated patients with early CMA and healthy control subjects with all three approaches. Neuropsychological assessment focused on executive functions, the cognitive domain most discussed in CMA. The DTI and age-related white matter changes rating scales revealed convergent results showing widespread white matter changes in early CMA. Correlations were found in frontal and parietal areas exclusively with speeded, but not with speed-corrected executive measures. The VBM analyses showed reduced gray matter in frontal areas. All three approaches confirmed the hypothesized fronto-parietal network disruption in early CMA. Innovative methods (DTI) converged with results from conventional methods (visual rating) while allowing greater spatial and tissue accuracy. They are thus valid additions to the analysis of neural correlates of cognitive dysfunction. We found a clear distinction between speeded and nonspeeded executive measures in relationship to imaging parameters. Cognitive slowing is related to disease severity in early CMA and therefore important for early diagnostics

Longitudinal changes in surface based brain morphometry measures in amnestic mild cognitive impairment and Alzheimer's Disease

Background: Alzheimer's disease (AD) is associated with marked brain atrophy. While commonly used structural MRI imaging methods do not account for the complexity of human brain morphology, little is known about the longitudinal changes of cortical geometry and their relationship with cognitive decline in subjects with AD. Methods: Data from the Alzheimer's Disease Neuroimaging Initiative (ADNI) were used to perform two-sample t-tests to investigate longitudinal changes of cortical thickness (CTh) and three surface-based morphometry measures: fractal dimension (i.e. cortical complexity; FD), gyrification index (GI), and sulcal depth (SD) in subjects with AD, amnestic mild cognitive impairment (aMCI) in comparison to cognitively unimpaired controls (CU) in baseline and 2-year follow-up sMRI scans. In addition, correlations of the morphological measures with two-year cognitive decline as assessed by the modified AD Assessment Scale-Cognitive Subscale (ADAS-Cog 11) were calculated via regression analyses. Results: Compared to CU, both AD and aMCI showed marked decreases in CTh. In contrast, analyses of FD and GI yielded a more nuanced decline of the respective measures with some areas showing increases in FD and GI. Overall changes in FD and GI were more pronounced in AD as compared to aMCI. Analyses of SD yielded widespread decreases. Interestingly, cognitive decline corresponded well with CTh declines in aMCI but not AD, whereas changes in FD corresponded with AD only but not aMCI, whereas GI and SD were associated with cognitive decline in aMCI and AD. Conclusion: Patterns of longitudinal changes in FD, GI and SD were only partially overlapping with CTh reductions. In AD, surface-based morphometry measures for brain-surface complexity showed better correspondence than CTh with cognitive decline over a two-year period of time. Being drawn from measures reflecting changes in more intricate aspects of human brain morphology, these data provide new insight into the complexity of AD-related brain atrophy and its relationship with cognitive decline. © 2023 The Author(s)Open access journalThis item from the UA Faculty Publications collection is made available by the University of Arizona with support from the University of Arizona Libraries. If you have questions, please contact us at [email protected]

Noninvasive imaging of endogenus neural stem cell mobilization in vivo using positron emission tomography

Neural stem cells reside in two major niches in the adult brain [i.e., the subventricular zone (SVZ) and the dentate gyrus of the hippocampus]. Insults to the brain such as cerebral ischemia result in a physiological mobilization of endogenous neural stem cells. Since recent studies showed that pharmacological stimulation can be used to expand the endogenous neural stem cell niche, hope has been raised to enhance the brain's own regenerative capacity. For the evaluation of such novel therapeutic approaches, longitudinal and intraindividual monitoring of the endogenous neural stem cell niche would be required. However, to date no conclusive imaging technique has been established. We used positron emission tomography (PET) and the radiotracer 3'-deoxy-3'-[(18)F]fluoro-l-thymidine ([(18)F]FLT) that enables imaging and measuring of proliferation to noninvasively detect endogenous neural stem cells in the normal and diseased adult rat brain in vivo. This method indeed visualized neural stem cell niches in the living rat brain, identified as increased [(18)F]FLT-binding in the SVZ and the hippocampus. Focal cerebral ischemia and subsequent damage of the blood-brain barrier did not interfere with the capability of [(18)F]FLT-PET to visualize neural stem cell mobilization. Moreover, [(18)F]FLT-PET allowed for an in vivo quantification of increased neural stem cell mobilization caused by pharmacological stimulation or by focal cerebral ischemia. The data suggest that noninvasive longitudinal monitoring and quantification of endogenous neural stem cell activation in the brain is feasible and that [(18)F]FLT-PET could be used to monitor the effects of drugs aimed at expanding the neural stem cell niche