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Neurology ◽  
2022 ◽  
pp. 10.1212/WNL.0000000000013299
Author(s):  
Pontus Tideman ◽  
Erik Stomrud ◽  
Antoine Leuzy ◽  
Niklas Mattsson-Carlgren ◽  
Sebastian Palmqvist ◽  
...  

Background and Objectives:The neuropathological changes underlying Alzheimer´s disease (AD) start before overt cognitive symptoms arise, but it is not well-known how they relate to the first subtle cognitive changes. The objective for this study was to examine the independent associations of the AD hallmarks β-amyloid (Aβ), tau, and neurodegeneration with different cognitive domains in cognitively unimpaired (CU) individuals.Methods:In this cross-sectional study, CU participants from the prospective BioFINDER-2 study were included. All had CSF biomarkers (Aβ42 and P-tau181), MRI (cortical thickness of AD-susceptible regions), Aβ-PET (neocortical uptake), tau-PET (entorhinal uptake), and cognitive test data for i) memory, ii) executive function, iii) verbal function, iv), and visuospatial function. Multivariable linear regression models were performed, using either CSF Aβ42, P-tau181 and cortical thickness or Aβ-PET, tau-PET, and cortical thickness, as predictors of cognitive function. The results were validated in an independent cohort (ADNI).Results:316 CU participants were included from the BioFINDER-2 study. Abnormal Aβ-status was independently associated with the executive measure, regardless of modality (CSF Aβ42 β=0.128, p=0.024; Aβ-PET β=0.124, p=0.049), while tau was independently associated with memory (CSF P-tau181 β=0.132, p=0.018; tau-PET β=0.189, p=0.002). Cortical thickness was independently associated with the executive measure and verbal fluency in both models (p=0.005-0.018). To examine the relationships in the earliest stage of preclinical AD, only participants with normal biomarkers of tau and neurodegeneration were included (n=217 CSF-based; n=246 PET-based). Again, Aβ-status was associated with executive function (CSF Aβ42, β=0.189, p=0.005; Aβ-PET, β=0.146, p=0.023), but not with other cognitive domains. The results were overall replicated in the ADNI cohort (n=361).Discussion:These findings suggest that Aβ is independently associated with worse performance on an executive measure but not with memory performance, which instead is associated with tau pathology. This may have implications for early preclinical AD screening and outcome measures in AD trials targeting Aβ pathology.


2022 ◽  
Author(s):  
Fernanda Hansen Pacheco de Moraes ◽  
Felipe Sudo ◽  
Marina Monteiro Carneiro ◽  
Bruno R. P. de Melo ◽  
Paulo Mattos ◽  
...  

This manuscript presents a study with recruited volunteers that comprehends three sorts of events present in Alzheimer's Disease (AD) evolution (structural, biochemical, and cognitive) to propose an update in neurodegeneration biomarkers for AD. The novel variables, K, I, and S, suggested based on physics properties and empirical evidence, are defined by power-law relations between cortical thickness, exposed and total area, and natural descriptors of brain morphology. Our central hypothesis is that variable K, almost constant in healthy human subjects, is a better discriminator of a diseased brain than the current morphological biomarker, Cortical Thickness, due to its aggregated information. We extracted morphological features from 3T MRI T1w images of 123 elderly subjects: 77 Healthy Cognitive Unimpaired Controls (CTL), 33 Mild Cognitive Impairment (MCI) patients, and 13 Alzheimer's Disease (AD) patients. Moreover, Cerebrospinal Fluid (CSF) biomarkers and clinical data scores were correlated with K, intending to characterize health and disease in the cortex with morphological criteria and cognitive-behavioral profiles. K distinguishes Alzheimer's Disease, Mild Cognitive Impairment, and Healthy Cognitive Unimpaired Controls globally and locally with reasonable accuracy (CTL-AD, 0.82; CTL-MCI, 0.58). Correlations were found between global and local K associated with clinical behavioral data (executive function and memory assessments) and CSF biomarkers (t-Tau, Aβ-40, and Aβ-42). The results suggest that the cortical folding component, K, is a premature discriminator of healthy aging, Mild Cognitive Impairment, and Alzheimer's Disease, with significant differences within diagnostics. Despite the non-concomitant events, we found correlations between brain structural degeneration (K), cognitive tasks, and biochemical markers.


PLoS ONE ◽  
2022 ◽  
Vol 17 (1) ◽  
pp. e0260924
Author(s):  
Kyong Young Kim ◽  
Kyoung Min Kim

Bone quality is a critical factor that, along with bone quantity, determines bone strength. Image-based parameters are used for assessing bone quality non-invasively. The trabecular bone score (TBS) is used to assess quality of trabecular bone and femur geometry for cortical bone. Little is known about the associations between these two bone quality parameters and whether they show differences in the relationships with age and body mass index (BMI). We investigated the associations between the trabecular bone score (TBS) and femur cortical geometry. Areal bone mineral density (BMD) was assessed using dual energy X-ray absorptiometry (DXA) and the TBS was assessed using iNsight software and, femur geometry using APEX (Hologic). A total of 452 men and 517 women aged 50 years and older with no medical history of a condition affecting bone metabolism were included. Z-scores for TBS and cortical thickness were calculated using the age-specific mean and SD for each parameter. A ‘discrepancy group’ was defined as patients whose absolute Z-score difference between TBS and cortical thickness was > 1 point. TBS and cortical thickness correlated negatively with age both in men and women, but the associations were stronger in women. Regarding the associations with BMI, TBS provided significant negative correlation with BMI in the range of BMI > 25 kg/m2. By contrast, cortical thickness correlated positively with BMI for all BMI ranges. These bone quality-related parameters, TBS and cortical thickness, significantly correlated, but discordance between these two parameters was observed in about one-third of the men and women (32.7% and 33.4%, respectively). Conclusively, image-based bone quality parameters for trabecular and cortical bone exhibit both similarities and differences in terms of their associations with age and BMI. These different profiles in TBS and FN cortical thickness might results in different risk profiles for the vertebral fractures or hip fractures in a certain percentage of people.


2022 ◽  
Vol 13 ◽  
Author(s):  
Ahren B. Fitzroy ◽  
Bethany J. Jones ◽  
Kyle A. Kainec ◽  
Jeehye Seo ◽  
Rebecca M. C. Spencer

Oscillatory neural activity during sleep, such as that in the delta and sigma bands, is important for motor learning consolidation. This activity is reduced with typical aging, and this reduction may contribute to aging-related declines in motor learning consolidation. Evidence suggests that brain regions involved in motor learning contribute to oscillatory neural activity during subsequent sleep. However, aging-related differences in regional contributions to sleep oscillatory activity following motor learning are unclear. To characterize these differences, we estimated the cortical sources of consolidation-related oscillatory activity using individual anatomical information in young and older adults during non-rapid eye movement sleep after motor learning and analyzed them in light of cortical thickness and pre-sleep functional brain activation. High-density electroencephalogram was recorded from young and older adults during a midday nap, following completion of a functional magnetic resonance imaged serial reaction time task as part of a larger experimental protocol. Sleep delta activity was reduced with age in a left-weighted motor cortical network, including premotor cortex, primary motor cortex, supplementary motor area, and pre-supplementary motor area, as well as non-motor regions in parietal, temporal, occipital, and cingulate cortices. Sleep theta activity was reduced with age in a similar left-weighted motor network, and in non-motor prefrontal and middle cingulate regions. Sleep sigma activity was reduced with age in left primary motor cortex, in a non-motor right-weighted prefrontal-temporal network, and in cingulate regions. Cortical thinning mediated aging-related sigma reductions in lateral orbitofrontal cortex and frontal pole, and partially mediated delta reductions in parahippocampal, fusiform, and lingual gyri. Putamen, caudate, and inferior parietal cortex activation prior to sleep predicted frontal and motor cortical contributions to sleep delta and theta activity in an age-moderated fashion, reflecting negative relationships in young adults and positive or absent relationships in older adults. Overall, these results support the local sleep hypothesis that brain regions active during learning contribute to consolidation-related neural activity during subsequent sleep and demonstrate that sleep oscillatory activity in these regions is reduced with aging.


Author(s):  
J.-W. Thielen ◽  
B. W. Müller ◽  
D.-I. Chang ◽  
A. Krug ◽  
S. Mehl ◽  
...  

AbstractSchizophrenia has been associated with structural brain abnormalities and cognitive deficits that partly change during the course of illness. In the present study, cortical thickness in five subregions of the cingulate gyrus was assessed in 44 patients with schizophrenia-spectrum disorder and 47 control persons and related to illness duration and memory capacities. In the patients group, cortical thickness was increased in the posterior part of the cingulate gyrus and related to illness duration whereas cortical thickness was decreased in anterior parts unrelated to illness duration. In contrast, cortical thickness was related to episodic and working memory performance only in the anterior but not posterior parts of the cingulate gyrus. Our finding of a posterior cingulate increase may point to either increased parietal communication that is accompanied by augmented neural plasticity or to effects of altered neurodegenerative processes in schizophrenia.


2022 ◽  
Vol 14 (1) ◽  
Author(s):  
Eun-Hye Lee ◽  
Hyuk Sung Kwon ◽  
Seong-Ho Koh ◽  
Seong Hye Choi ◽  
Jeong-Hwa Jin ◽  
...  

Abstract Background Neurofilament light chain (NFL) level has been suggested as a blood-based biomarker for neurodegeneration in dementia. However, the association between baseline NFL levels and cognitive stage transition or cortical thickness is unclear. This study aimed to investigate whether baseline NFL levels are associated with cognitive stage transition or cortical thickness in mild cognitive impairment (MCI) and cognitively unimpaired (CU) participants. Methods This study analyzed data on participants from the independent validation cohort of the Korea Brain Aging Study for the Early Diagnosis and Prediction of Alzheimer’s disease (KBASE-V) study. Among the participants of KBASE-V study, 53 MCI and 146 CU participants who were followed up for ≥ 2 years and had data on the serum NFL levels were eligible for inclusion in this study. Participants were classified into three groups according to baseline serum NFL levels of low, middle, or high. Results The Kaplan–Meier analysis showed association between the serum NFL tertiles and risk of cognitive stage transition in MCI (P = 0.002) and CU (P = 0.028) participants, analyzed separately. The same is true upon analysis of MCI and CU participants together (P < 0.001). In MCI participants, the highest serum NFL tertile and amyloid-beta positivity were independent predictors for cognitive stage transition after adjusting for covariates. For CU participants, only amyloid-beta positivity was identified to be an independent predictor. Conclusion The study shows that higher serum NFL tertile levels correlate with increased risk of cognitive stage transition in both MCI and CU participants. Serum NFL levels were negatively correlated with the mean cortical thickness of the whole-brain and specific brain regions.


Author(s):  
Michael Baghdadi ◽  
Manal Ezzat Badwey ◽  
Mohamed Khalil ◽  
Rasha Mahmoud Dawoud

Abstract Background Damage occurs in the brain tissue in MS which appears normal on standard conventional imaging (normal appearing brain tissue). This slow, evolving damage can be monitored by nonconventional advanced MR imaging techniques. New techniques for the measurement of cortical thickness have been validated against histological analysis and manual measurements. The aim of our study was to study the role of MRI surface-based analysis and cortical thickness measurement in the evaluation of patients with Relapsing Remitting Multiple Sclerosis and to detect if there is localized rather than generalized cortical atrophy in Multiple Sclerosis patients and correlating these findings with clinical data. Results 30 patients and 30 healthy control were included in this study and they were subjected to cortical thickness analysis using MRI. The patients in our study showed decreased thickness of the precentral, paracentral, postcentral, posterior cingulate cortices and mean cortical thickness in both hemispheres when compared with the normal control group. Statistical analysis was significant (P value < 0.05) for the precentral, paracentral, postcentral, posterior cingulate cortices and mean cortical thickness in both hemispheres. On the other hand, statistical analysis was not significant (P value > 0.05) for other cortices. There was a significant negative correlation between the precentral, paracentral, postcentral, posterior cingulate cortices and mean cortical thickness in both hemispheres and EDSS scores with correlation coefficients ranging from − 0.9878 to − 0.7977. Conclusions MRI and post-processing segmentation analysis for cortical thickness is non-invasive imaging techniques that can increase the level of diagnostic confidence in diagnosis of MS patients and should be included as routine modality when evaluating patients with MS.


Author(s):  
Ingrid Anne Lie ◽  
Emma Kerklingh ◽  
Kristin Wesnes ◽  
David R. van Nederpelt ◽  
Iman Brouwer ◽  
...  

Abstract Objective To determine whether reliable brain atrophy measures can be obtained from post-contrast 3D T1-weighted images in patients with multiple sclerosis (MS) using FreeSurfer. Methods Twenty-two patients with MS were included, in which 3D T1-weighted MR images were obtained during the same scanner visit, with the same acquisition protocol, before and after administration of gadolinium-based contrast agents (GBCAs). Two FreeSurfer versions (v.6.0.1 and v.7.1.1.) were applied to calculate grey matter (GM) and white matter (WM) volumes and global and regional cortical thickness. The consistency between measures obtained in pre- and post-contrast images was assessed by intra-class correlation coefficient (ICC), the difference was investigated by paired t-tests, and the mean percentage increase or decrease was calculated for total WM and GM matter volume, total deep GM and thalamus volume, and mean cortical thickness. Results Good to excellent reliability was found between all investigated measures, with ICC ranging from 0.926 to 0.996, all p values < 0.001. GM volumes and cortical thickness measurements were significantly higher in post-contrast images by 3.1 to 17.4%, while total WM volume decreased significantly by 1.7% (all p values < 0.001). Conclusion The consistency between values obtained from pre- and post-contrast images was excellent, suggesting it may be possible to extract reliable brain atrophy measurements from T1-weighted images acquired after administration of GBCAs, using FreeSurfer. However, absolute values were systematically different between pre- and post-contrast images, meaning that such images should not be compared directly. Potential systematic effects, possibly dependent on GBCA dose or the delay time after contrast injection, should be investigated. Trial registration Clinical trials.gov. identifier: NCT00360906. Key Points • The influence of gadolinium-based contrast agents (GBCAs) on atrophy measurements is still largely unknown and challenges the use of a considerable source of historical and prospective real-world data. • In 22 patients with multiple sclerosis, the consistency between brain atrophy measurements obtained from pre- and post-contrast images was excellent, suggesting it may be possible to extract reliable atrophy measurements in T1-weighted images acquired after administration of GBCAs, using FreeSurfer. • Absolute values were systematically different between pre- and post-contrast images, meaning that such images should not be compared directly, and measurements extracted from certain regions (e.g., the temporal pole) should be interpreted with caution.


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