Higher Cortical Thickness Research Articles

Regional gray matter changes in steatotic liver disease provide a neurobiological link to depression: A cross-sectional UK Biobank cohort study

BackgroundSteatotic liver disease (SLD) is characterized by excessive accumulation of lipids in the liver. It is associated with elevated risk of hepatic and cardiometabolic diseases, as well as mental disorders such as depression. Previous studies revealed global gray matter reduction in SLD. To investigate a possible shared neurobiology with depression, we examined liver fat-related regional gray matter alterations in SLD and its most significant clinical subgroup metabolic dysfunction-associated steatotic liver disease (MASLD). MethodsWe analyzed regional cortical thickness and area obtained from brain MRI in 29,051 participants in UK Biobank. Liver fat amount was computed as proton density fat fraction (PDFF) from liver MRI scans. We examined the relationship between brain structure and PDFF, adjusting for sociodemographic, physical, lifestyle, and environmental factors, as well as alcohol intake and a spectrum of cardiometabolic covariates. Finally, we compared patterns of brain alterations in SLD/MASLD and major depressive disorder (MDD) using previously published results. ResultsPDFF-related gray matter alterations were region-specific, involving both increases and decreases in cortical thickness, and increased cortical area. In several regions, PDFF effects on gray matter could also be attributed to cardiometabolic covariates. However, PDFF was consistently associated with lower cortical thickness in middle and superior temporal regions and higher cortical thickness in pericalcarine and right frontal pole regions. PDFF-related alterations for the SLD and the MASLD group correlated with those observed in MDD (Pearson r = 0.45–0.54, p < 0.01). ConclusionThese findings suggest the presence of shared biological mechanisms linking MDD to SLD and MASLD. They might explain the well-known elevated risk of depression in these groups and support early lifestyle interventions and treatment of metabolic risk factors for the successful management of the interconnected diseases depression and SLD/MASLD.

Iron status is associated with tibial structure and vitamin D metabolites in healthy young men

The influence of iron on collagen synthesis and vitamin D metabolism has implications for bone health. This cross-sectional observational study investigated associations between markers of iron status and tibial structure, vitamin D metabolites, and circulating biochemical markers of bone metabolism in young healthy men. A total of 343 male British Army recruits participated (age 22 ± 3 y, height 1.77 ± 0.06 m, body mass 75.5 ± 10.1 kg). Circulating biochemical markers of iron status, vitamin D metabolites, and bone metabolism, and tibial structure and density by high-resolution peripheral quantitative computed tomography scans (HRpQCT) were measured in participants during week 1 of basic military training. Associations between markers of iron status and HRpQCT outcomes, bone metabolism, and vitamin D metabolites were tested, controlling for age, height, lean body mass, and childhood exercise volume. Higher ferritin was associated with higher total, trabecular, and cortical volumetric bone mineral density, trabecular volume, cortical area and thickness, stiffness, and failure load (all p ≤ 0.037). Higher soluble transferrin receptor (sTfR) was associated with lower trabecular number, and higher trabecular thickness and separation, cortical thickness, and cortical pore diameter (all p ≤ 0.033). Higher haemoglobin was associated with higher cortical thickness (p = 0.043). Higher ferritin was associated with lower βCTX, PINP, total 25(OH)D, and total 24,25(OH)2D, and higher 1,25(OH)2D:24,25(OH)2D ratio (all p ≤ 0.029). Higher sTfR was associated with higher PINP, total 25(OH)D, and total 24,25(OH)2D (all p ≤ 0.025). The greater density, size, and strength of the tibia, and lower circulating concentrations of markers of bone resorption and formation with better iron stores (higher ferritin) are likely as a result of the direct role of iron in collagen synthesis.

Periodontitis and brain magnetic resonance imaging markers of Alzheimer's disease and cognitive aging.

We examined the association of clinical, microbiological, and host response features of periodontitis with MRI markers of atrophy/cerebrovascular disease in the Washington Heights Inwood Columbia Aging Project (WHICAP) Ancillary Study of Oral Health. We analyzed 468 participants with clinical periodontal data, microbial plaque and serum samples, and brain MRIs. We tested the association of periodontitis features with MRI features, after adjusting for multiple risk factors for Alzheimer's disease/Alzheimer's disease-related dementia (AD/ADRD). In fully adjusted models, having more teeth was associated with lower odds for infarcts, lower white matter hyperintensity (WMH) volume, higher entorhinal cortex volume, and higher cortical thickness. Higher extent of periodontitis was associated with lower entorhinal cortex volume and lower cortical thickness. Differential associations emerged between colonization by specific bacteria/serum antibacterial IgG responses and MRI outcomes. In an elderly cohort, clinical, microbiological, and serological features of periodontitis were associated with MRI findings related to ADRD risk. Further investigation of causal associations is warranted.

Regional Brain Structure Mediates Age‐Related Decline in Eye Movement Control

AbstractBackgroundEye movements (EM) are considered potential biomarkers of neurodegeneration because they are altered in patients with neurodegenerative disease, including Alzheimer’s disease (AD). Alterations in EM control have also been observed in old age, with particularly strong age effects on saccadic latency, inhibitory errors in the antisaccade task, and smooth pursuit accuracy. The goal of our study was to characterize the neural pathways of age‐related changes in these EM outcomes.MethodThe analysis was based on 8,318 participants (aged 30 to 95 years) from the population‐based Rhineland Study. EMs were recorded using video‐based infrared oculography at 1,000 Hz. Volumes and thickness measures of selected brain structures were obtained using FreeSurfer from 3 Tesla T1‐weighted MR images. Relations of brain structure with EM outcomes were quantified using multivariable linear regression models. Brain structure variables were also analyzed as potential mediators in the relation between age and EM outcomes using causal mediation analysis under a counterfactual framework.ResultIn women, higher volume of the right thalamus and right globus pallidus was associated with lower antisaccade latency, whereas higher cortical thickness in the anterior cingulate cortex was associated with higher antisaccade latency. Higher cortical thickness in right supramarginal gyrus and right paracentral lobule and sulcus was associated with fewer antisaccade errors in women. There were no significant associations between regional brain structure and antisaccade performance in men. Higher cortical thickness in the right calcarine sulcus was associated with higher smooth pursuit velocity gain in both men and women. Additionally, individual brain structures mediated up to 11% of the age‐related decline in EM performance.ConclusionOur results support that EMs indeed reflect neurodegenerative processes as changes in brain structure partly account for age‐related decline in oculomotor performance. Relevant brain regions include both brain regions vulnerable to AD pathology and brain regions that are typically spared, suggesting that both “normal” age‐related and pathological mechanisms may be causative for decline in EM control. Our results highlight the importance of taking into account normal age‐related changes when considering EMs as early biomarkers for AD. Further work is needed to better distinguish normal age‐related changes from pathological change.

Peripheral Pain Captured Centrally: Altered Brain Morphology on MRI in Small Fiber Neuropathy Patients With and Without an SCN9A Gene Variant

The current study aims to characterize brain morphology of pain as reported by small fiber neuropathy (SFN) patients with or without a gain-of-function variant involving the SCN9A gene and compare these with findings in healthy controls without pain. The Neuropathic Pain Scale was used in patients with idiopathic SFN (N = 20) and SCN9A-associated SFN (N = 12) to capture pain phenotype. T1-weighted, structural magnetic resonance imaging (MRI) data were collected in patients and healthy controls (N = 21) to 1) compare cortical thickness and subcortical volumes and 2) quantify the association between severity, quality, and duration of pain with morphological properties. SCN9A-associated SFN patients showed significant (P < .017, Bonferroni corrected) higher cortical thickness in sensorimotor regions, compared to idiopathic SFN patients, while lower cortical thickness was found in more functionally diverse regions (eg, posterior cingulate cortex). SFN patient groups combined demonstrated a significant (Spearman’s ρ = .44–.55, P = .005–.049) correlation among itch sensations (Neuropathic Pain Scale-7) and thickness of the left precentral gyrus, and midcingulate cortices. Significant associations were found between thalamic volumes and duration of pain (left: ρ = −.37, P = .043; right: ρ = −.40, P = .025). No associations were found between morphological properties and other pain qualities. In conclusion, in SCN9A-associated SFN, profound morphological alterations anchored within the pain matrix are present. The association between itch sensations of pain and sensorimotor and midcingulate structures provides a novel basis for further examining neurobiological underpinnings of itch in SFN. PerspectiveCortical thickness and subcortical volume alterations in SFN patients were found in pain hubs, more profound in SCN9A-associated neuropathy, and correlated with itch and durations of pain. These findings contribute to our understanding of the pathophysiological pathways underlying chronic neuropathic pain and symptoms of itch in SFN.

A - 21 Sex Differences in Cortical Thickness and Cognition in Individuals with Autosomal Dominant Alzheimer's Disease.

Cortical thinning is a marker of neurodegeneration. Individuals with autosomal dominant Alzheimer's disease (ADAD) develop early-onset dementia with virtually 100% certainty. Cortical thickness fluctuates across the ADAD lifespan, from early-life increased thickness to atrophy proximal to clinical onset. Females have higher cortical thickness and better cognition than males as they age. We examined sex differences in cortical thickness and cognitive performance in adults with ADAD. We assessed 85 Presenilin-1 E280A mutation carriers (74 cognitively-unimpaired, 11 mildly-impaired) from the Colombia-Boston Biomarker Study of ADAD. Mean age was 35.7 (SD = 10), education 10.2 (SD = 9), and 55 were female. Global cognition was measured using Mini-Mental State Examination (MMSE), and memory using CERAD Word List Delayed Recall. Participants underwent structural brain MRI. T-tests assessed between-group differences. Pearson correlations examined associations between cortical thickness and cognition. There were no sex differences in cortical thickness or cognitive performance (all ps > =0.05). For carriers, greater cortical thickness was associated with higher MMSE (r = 0.40, p < 0.001) and memory recall scores (r = 0.43, p < 0.01). Female carriers drove this effect, where greater cortical thickness was associated with higher MMSE (r = 0.46, p < 0.001) and memory recall scores (r = 0.47, p < 0.001); these associations were non-significant in male carriers alone. In cognitively-unimpaired female carriers, increased cortical thickness was associated with worse MMSE (r = -0.44, p < 0.001). We found sex differences in the relation between cortical thickness and cognition in ADAD carriers, which may be relevant to the differential vulnerability and progression of ad in females and males. Future work should investigate potential underlying mechanisms contributing to this sex difference.

Association of maternal hypertension during pregnancy with brain structure and behavioral problems in early adolescence.

Emerging evidence suggests an association between maternal hypertension during pregnancy and mental health in the offspring. However, less is known about the role of hypertensive pregnancy in behavioral symptoms and brain structures of the offspring as well as in their developmental changes. Here, we utilized neuroimaging and behavioral data from 11,878 participants aged 9-10years and their 2-year follow-up from the Adolescent Brain Cognitive Development (ABCD) study to investigate the long-term effects of maternal hypertension during pregnancy on early adolescent behavior and brain anatomy. Specifically, adolescents born of mothers with maternal hypertension are at risk of long-lasting behavioral problems, as manifested by higher externalizing and internalizing behavior scores at both 9-10years and 11-12years. These participants additionally presented with a higher cortical thickness, particularly in the fronto-parieto-temporal areas at 9-10years. Four regions, including the left parahippocampus, left lateral orbitofrontal lobe, right superior temporal lobe and right temporal pole, remained thicker 2years later. These findings were partially validated in rats modeled with Nω-nitro-L-arginine methyl ester (L-NAME) preeclampsia. Therefore, clinicians and women who experience hypertension during pregnancy should be warned of this risk, and healthcare providers should recommend appropriate clinical interventions for pregnancy-induced hypertension.

Persistence of post-traumatic stress disorder in Chinese Shidu parents is associated with combined gray and white matter abnormalities

Post-traumatic stress disorder (PTSD) is one of the most common mental health disorders among Shidu parents. Identification of gray and white matter differences between persistence of PTSD (P-PTSD) and remission of PTSD (R-PTSD) is crucial to determine their prognosis. A total of 37 Shidu parents with PTSD were followed for five years. Surface-based morphometry and diffusion tensor imaging were carried out to analyze the differences in gray and white matter between P-PTSD and R-PTSD. Finally, 30 patients with PTSD were enrolled, including 12 with P-PTSD and 18 with R-PTSD. Compared with patients with R-PTSD, patients with P-PTSD exhibited lower fractional anisotropy (FA) in Cluster 1 (including body of the corpus callosum, superior longitudinal fasciculus, corticospinal tract) and Cluster 2 (including inferior fronto-occipital fasciculus, inferior longitudinal fasciculus, splenium of the corpus callosum) in the left cerebral hemisphere and higher cortical thickness in the right lateral occipital cortex (LOC). In patients with P-PTSD, FA values of Cluster 2 were negatively correlated with cortical thickness of the right LOC. These results suggest that among Shidu parents, differences were observed in gray and white matter between P-PTSD and R-PTSD. Moreover, some certain gray and white matter abnormalities were often present simultaneously in P-PTSD.

Preterm birth associated alterations in brain structure, cognitive functioning and behavior in children from the ABCD dataset.

Preterm birth is a global health problem and associated with increased risk of long-term developmental impairments, but findings on the adverse outcomes of prematurity have been inconsistent. Data were obtained from the baseline session of the ongoing longitudinal Adolescent Brain and Cognitive Development (ABCD) Study. We identified 1706 preterm children and 1865 matched individuals as Control group and compared brain structure (MRI data), cognitive function and mental health symptoms. Results showed that preterm children had higher psychopathological risk and lower cognitive function scores compared to controls. Structural MRI analysis indicated that preterm children had higher cortical thickness in the medial orbitofrontal cortex, parahippocampal gyrus, temporal and occipital gyrus; smaller volumes in the temporal and parietal gyrus, cerebellum, insula and thalamus; and smaller fiber tract volumes in the fornix and parahippocampal-cingulum bundle. Partial correlation analyses showed that gestational age and birth weight were associated with ADHD symptoms, picvocab, flanker, reading, fluid cognition composite, crystallized cognition composite and total cognition composite scores, and measures of brain structure in regions involved with emotional regulation, attention and cognition. These findings suggest a complex interplay between psychopathological risk and cognitive deficits in preterm children that is associated with changes in regional brain volumes, cortical thickness, and structural connectivity among cortical and limbic brain regions critical for cognition and emotional well-being.

Association between Coffee Consumption and Brain MRI Parameters in the Hamburg City Health Study.

Despite associations of regular coffee consumption with fewer neurodegenerative disorders, its association with microstructural brain alterations is unclear. To address this, we examined the association of coffee consumption with brain MRI parameters representing vascular brain damage, neurodegeneration, and microstructural integrity in 2316 participants in the population-based Hamburg City Health Study. Cortical thickness and white matter hyperintensity (WMH) load were measured on FLAIR and T1-weighted images. Microstructural white matter integrity was quantified as peak width of skeletonized mean diffusivity (PSMD) on diffusion-weighted MRI. Daily coffee consumption was assessed in five groups (<1 cup, 1-2 cups, 3-4 cups, 5-6 cups, >6 cups). In multiple linear regressions, we examined the association between brain MRI parameters and coffee consumption (reference group <1 cup). After adjustment for covariates, 3-4 cups of daily coffee were associated with lower PSMD (p = 0.028) and higher cortical thickness (p = 0.015) compared to <1 cup. Moreover, 1-2 cups per day was also associated with lower PSMD (p = 0.022). Associations with WMH load or other groups of coffee consumption were not significant (p > 0.05). The findings indicate that regular coffee consumption is positively associated with microstructural white matter integrity and cortical thickness. Further research is necessary to determine longitudinal effects of coffee on brain microstructure.

Neuroimaging profiling identifies distinct brain maturational subtypes of youth with mood and anxiety disorders

Mood and anxiety disorders typically begin in adolescence and have overlapping clinical features but marked inter-individual variation in clinical presentation. The use of multimodal neuroimaging data may offer novel insights into the underlying brain mechanisms. We applied Heterogeneity Through Discriminative Analysis (HYDRA) to measures of regional brain morphometry, neurite density, and intracortical myelination to identify subtypes of youth, aged 9–10 years, with mood and anxiety disorders (N = 1931) compared to typically developing youth (N = 2823). We identified three subtypes that were robust to permutation testing and sample composition. Subtype 1 evidenced a pattern of imbalanced cortical-subcortical maturation compared to the typically developing group, with subcortical regions lagging behind prefrontal cortical thinning and myelination and greater cortical surface expansion globally. Subtype 2 displayed a pattern of delayed cortical maturation indicated by higher cortical thickness and lower cortical surface area expansion and myelination compared to the typically developing group. Subtype 3 showed evidence of atypical brain maturation involving globally lower cortical thickness and surface coupled with higher myelination and neural density. Subtype 1 had superior cognitive function in contrast to the other two subtypes that underperformed compared to the typically developing group. Higher levels of parental psychopathology, family conflict, and social adversity were common to all subtypes, with subtype 3 having the highest burden of adverse exposures. These analyses comprehensively characterize pre-adolescent mood and anxiety disorders, the biopsychosocial context in which they arise, and lay the foundation for the examination of the longitudinal evolution of the subtypes identified as the study sample transitions through adolescence.

Right Prefrontal Cortical Thickness Is Associated With Response to Cognitive-Behavioral Therapy in Children With Obsessive-Compulsive Disorder

Cognitive-behavioral therapy (CBT) is considered a first-line treatment for obsessive-compulsive disorder (OCD) in pediatric and adult populations. Nevertheless, some patients show partial or null response. The identification of predictors of CBT response may improve clinical management of patients with OCD. Here, we aimed to identify structural magnetic resonance imaging (MRI) predictors of CBT response in 2 large series of children and adults with OCD from the worldwide ENIGMA-OCD consortium. Data from 16 datasets from 13 international sites were included in the study. We assessed which variations in baseline cortical thickness, cortical surface area, and subcortical volume predicted response to CBT (percentage of baseline to post-treatment symptom reduction) in 2 samples totaling 168 children and adolescents (age range 5-17.5 years) and 318 adult patients (age range 18-63 years) with OCD. Mixed linear models with random intercept were used to account for potential cross-site differences in imaging values. Significant results were observed exclusively in the pediatric sample. Right prefrontal cortex thickness was positively associated with the percentage of CBT response. In a post hoc analysis, we observed that the specific changes accounting for this relationship were a higher thickness of the frontal pole and the rostral middle frontal gyrus. We observed no significant effects of age, sex, or medication on our findings. Higher cortical thickness in specific right prefrontal cortex regions may be important for CBT response in children with OCD. Our findings suggest that the right prefrontal cortex plays a relevant role in the mechanisms of action of CBT in children.

Early accumulation of Aβ and Tau is associated with increase in cortical thickness

AbstractBackgroundThere is no consensus in the field regarding the relationship between AD pathologies (Aβ, and Tau) and neurodegeneration. One reason that may contribute to this disagreement is the definition of cut‐point to categorize participants with or without significant pathologies. This approach overlooks an important early stage of pathological accumulation. In this study, we take advantage of Florbetaben/MK6240 PET scans from 61/21 young (&lt;40) and healthy participants to redefined the cut‐point of Aβ/Tau uptake and investigate their association with cortical thickness as a measurement of neurodegeneration.MethodTo capture the early effect of pathologies, we quantify global pathologies by averaging AD‐related regions uptake; global Aβ: frontal, parietal, temporal, anterior and posterior cingulate, and precuneus, global Tau: fusiform, amygdala, parahippocampal, entorhinal, inferior temporal, middle temporal, and medial temporal lobe (MTL) Tau: entorhinal and parahippocampal. We redefied the cut‐point of AD pathologies using 95% percentile of the fitted normal distribution to the young subject's uptakes. Using newly defined cut‐points (1.01&lt;global Aβ&lt;1.25, 0.72&lt;global Tau&lt;1.15, and 0.66&lt;MTL Tau&lt;1.11), we identified 232 older participant (64.79±3.55, 94 males, 229 HC) from 394 healthy control (HC) and 52 with mild cognitive impairment (MCI). To assess the relationship between AD pathologies and neurodegeneration, we run a multiple regression to model cortical thickness at each vertex in the identified elders with global Aβ, and global Tau controlling for age, gender, and Intracranial volume (ICV).ResultEarly and low accumulation of Aβ and Tau were associated with higher cortical thickness in many regions throughout the cerebral cortex. More interestingly, MTL (where the early Tau deposition occurs) was among the regions showing a positive association with Aβ deposition and cortical thickness.ConclusionThese results, provide preliminary evidence that early and low accumulations of AD pathologies are associated with higher cortical thickness. Our results may shed some light on the discrepancies between the existing studies investigating the same relationship. As it has been recently hypothesized, it suggests that the cascade of events in AD may start much earlier than what had been considered in the field and this early accumulation of Aβ and Tau has completely different consequences on brain structure/function.

Cerebral Perfusion and Cortical Thickness Predict Cognitive Impairment in a Community‐dwelling Cohort

AbstractBackgroundNeurodegeneration and cerebral perfusion are key neuroimaging biomarkers in the Alzheimer’s Disease continuum. ASL (arterial spin labeling) explores cerebral blood flow (CBF) and has aided in elucidating cerebrovascular health amongst people at risk of cognitive decline. Reduced cortical thickness (CT) on MRI is a neurodegeneration biomarker that also implicated in cognitive impairment. The influence of cortical thickness and perfusion in AD‐related regions on cognitive status is poorly understood. We explored markers to investigate the roles they had in cognitive impairment.MethodParticipants enrolled in the Wake Forest Alzheimer’s Disease Research Center (ADRC) Clinical Core cohort (N= 535, Table 1) underwent baseline T1/ASL MRI. Participants were adjudicated as cognitively impaired (CI: mild cognitive impairment or AD) or cognitively unimpaired (CU) using NIA‐AA criteria by a consensus panel of experts. CT in an AD‐related temporal lobe meta‐ROI (region of interest) was calculated on T1 using FreeSurfer v5.3 and standardized. A homologous set of AD‐sensitive temporal lobe ROIs was used to extract mean CBF, which was log transformed for normality. A one‐way MANOVA (covariates: age, education, sex) assessed effects of CT and CBF on cognitive impairment. Bivariate models evaluated the associations of CT and CBF in relation to age, education, sex, and cognitive impairment. Linear regression was used to analyze whether cognitive impairment was predicted by CT and CBF (adjusted).ResultWe found both CBF and CT were associated with age (r2= ‐0.142, p&lt;0.01; r2= ‐0.339; p&lt;0.01) and cognitive status (r2= ‐0.188, p&lt;0.01; r2= ‐0.264; p&lt;0.01); respectively. CBF was also associated with sex (r2= 0.083; p=0.055) such that women had higher CBF. We also found that higher CBF was marginally associated with higher CT (r2= 0.083; p=0.055); this relationship was not significant when age, sex, and education were included in the model (r2= 0.886; p=0.376). Finally, we found both CT and CBF predicted cognitive impairment (p&lt;0.01; both unadjusted and adjusted, in models where each MRI marker was used to predict cognition), such that CBF and CT were higher in CU; further, both CBF and CT independently predicted cognitive status when together in a model (p&lt;0.008).ConclusionCortical thickness and CBF are predictive of cognitive impairment.

Poorer dexterity is associated with underlying Alzheimer’s disease brain pathology

AbstractBackgroundThere has been increasing recognition for the decline of motor function in Alzheimer’s disease (AD) progression and its substantial role in disease morbidity. However, less is known about regional pathology burden—including amyloid‐β and tau protein deposition and cortical trophy—and its relationship to motor performance. Here investigate this relationship using standardized motor function assessment tools.MethodParticipants along a control‐to‐impaired continuum were enrolled in the Alzheimer’s Disease Connectome Project and underwent T1‐weighted MRI (N=206), with a subset undergoing [C‐11]PiB (N=61) and [F‐18 ]Flortaucipir PET (N=58) (Table 1) imaging for amyloid and tau pathology, respectively. T1‐weighted scans were processed using Freesurfer to estimate regional cortical thickness. [C‐11]PiB distribution volume ratios (DVR; cerebellar GM reference region) and [F‐18] Flortaucipir standardized uptake value ratios (SUVr; inferior cerebellar GM reference region) were assessed. Regions of interest (ROI) for analysis included the parahippocampal, entorhinal, motor, and frontal regions. Motor function was assessed utilizing NIH toolbox tests including the 2‐minute walking, 9‐hole pegboard dexterity, and dynamometer grip strength assessments. Motor performance was analyzed using participants uncorrected standardized scores. Scores were collected from participant‐reported dominant hand assessments. Multiple linear regression models tested relationships between AD biomarker burden and motor performance while controlling for age and sex of participants.ResultIncreased amyloid‐β (β‐0.42, p‐value: &lt;0.05) and tau (β: ‐0.53, p‐value: &lt;0.05) burden in primary motor cortices were associated with worse dexterity scores independent of age and sex. Grip strength did not show a significant correlation to cortical amyloid‐β (β: ‐0.14, p‐value 0.33) or tau burden (β: 0.23, p‐value: 0.36). Higher cortical thickness in primary motor regions were associated with higher dexterity (β: 0.21, p‐value &lt;0.0001) and 2‐minute walking scores (β: 0.24, p‐value &lt;0.001). When controlling for age and sex, grip strength predicted decreasing cortical thickness (β: 0.01, p‐value: &lt;0.001) (Table 2).ConclusionLower dexterity performance may be driven by elevated AD pathological burden and cortical thinning in cortical motor regions. Further research into motor performance and clinical disease manifestation is needed to determine the diagnostic utility of fine motor assessment as a predictor of motor decline in individuals with Alzheimer’s disease pathology.

Neuroanatomical alterations in middle frontal gyrus and the precuneus related to tinnitus and tinnitus distress

Tinnitus is the phantom perception of sound when there is no external auditory input. This sound is mostly perceived as a ringing, whistling or buzzing in the ear. There is evidence of neural changes in both central auditory regions as well as other brain areas like the prefrontal cortex and the limbic system. However, brain morphological studies assessing gray matter volume and cortical thickness have shown inconsistent results. We here investigated neuroanatomical alterations in tinnitus related to the tinnitus perception along with tinnitus distress and cognitive abilities. Twenty tinnitus patients and 20 control participants matched in age, sex and hearing loss participated in the study. They underwent magnetic resonance imaging and audiometric as well as cognitive assessments. Our results demonstrate increased gray matter volume in the middle frontal gyrus and frontal pole in tinnitus compared to control participants. Moreover, we found increased cortical thickness in the precuneus associated with tinnitus distress as well as an interaction between group and cognitive assessment scores in cortical thickness of the middle frontal gyrus, indicating higher cortical thickness with better scores in controls and lower scores in tinnitus patients. These findings indicate that increased tinnitus awareness and annoyance is reflected in increased brain structural changes in the precuneus, frontal pole and middle frontal gyrus that may also have implications on general cognitive abilities.

Imaging and genetics in Parkinson's disease: assessment of the GBA1 mutation.

Several genetic variants are associated with an increased risk for developing Parkinson's Disease (PD) and limited genotype/phenotype correlation. Specifically, mutations in GBA1, the gene coding for the lysosomal enzyme glucocerebrosidase, are associated with an earlier age of onset and faster disease progression. Given these phenotypic differences associated with GBA1 variants, we explored whether cortical thickness and other biomarkers of neurodegeneration differed in healthy controls and PD patients with and without GBA1 variants. To understand how different GBA1 variants influence PD phenotype early in the disease, we retrieved neuroimaging and biospecimen data from the Parkinson's Progression Markers Initiative database. Using FreeSurfer, we compared T1-weighted MRI images from healthy controls (N = 47) to PD patients with heterozygous N370S (N = 21), heterozygous E326K (N = 18) or heterozygous T369M (N = 8) variants, and GBA1 non-mutation carriers (N = 47). Cortical thickness in PD patients differed from controls in the parietal cortex, with E365K, T369M variants, and GBA1 non-mutation carriers showing more cortical thinning than N370S variants. Patients with N370S variants had significantly higher serum neurofilament light levels among all groups. Our results demonstrate significant cortical thinning in PD patients independent of genotype in superior parietal and postcentral regions when compared to the controls. They highlight the impact of GBA1 variants on cortical thickness in the parietal cortex. Finally, they suggest that recently diagnosed PD patients with N370S variants have a higher cortical thickness and increased active neurodegeneration when compared to PD patients without GBA1 mutations and PD patients with E326K or T369M variants.

Brain Structure and Function Predict Adherence to an Exercise Intervention in Older Adults.

Individual differences in brain structure and function in older adults are potential proxies of brain reserve or maintenance and may provide mechanistic predictions of adherence to exercise. We hypothesized that multimodal neuroimaging features would predict adherence to a 6-month randomized controlled trial of exercise in 131 older adults (age, 65.79 ± 4.65 yr, 63% female), alone and in combination with psychosocial, cognitive, and health measures. Regularized elastic net regression within a nested cross-validation framework was applied to predict adherence to the intervention in three separate models (brain structure and function only; psychosocial, health, and demographic data only; and a multimodal model). Higher cortical thickness in somatosensory and inferior frontal regions and less surface area in primary visual and inferior frontal regions predicted adherence. Higher nodal functional connectivity (degree count) in default, frontoparietal, and attentional networks and less nodal strength in primary visual and temporoparietal networks predicted exercise adherence ( r = 0.24, P = 0.004). Survey and clinical measures of gait and walking self-efficacy, biological sex, and perceived stress also predicted adherence ( r = 0.17, P = 0.056); however, this prediction was not significant when tested against a null test statistic. A combined multimodal model achieved the highest predictive strength ( r = 0.28, P = 0.001). Our results suggest that there is a substantial utility of using brain-based measures in future research into precision and individualized exercise interventions older adults.

Lower cognitive resilience against brain atrophy in cognitively unimpaired elderly is partly explained by Alzheimer's disease pathology

AbstractBackgroundCognitive resilience refers to processes involved in coping with effects of brain pathology on cognition. Factors contributing to cognitive resilience against brain atrophy are unclear, as there have been few longitudinal studies investigating this. Therefore we aimed to identify factors explaining the discrepancy between brain atrophy and longitudinal cognitive decline. One proposed method of investigating cognitive resilience is a residual approach, which suggests using the variance in cognition not explained by a specified predictor as a measure of resilience.MethodCognitively unimpaired subjects (n=406) from The Swedish BioFINDER Study with magnetic resonance imaging (MRI) and cognitive test results from at least two time points were included. Using FreeSurfer, global cortical thickness was calculated. A cognitive composite score was calculated from Mini Mental State Examination, Alzheimer´s Disease Assessment Scale – Cognitive Subscale delayed word recall, Trail Making Test B, and Animal fluency. For each subject, the beta coefficients for change in cortical thickness and change in cognition over time were calculated. Linear regression was performed between the two beta coefficients, and the residuals were used as a measure of cognitive resilience. Associations were calculated between this resilience measure and baseline demographics, biomarkers of amyloid (cerebrospinal fluid (CSF) β‐amyloid (Aβ) 42/40 ratio), tau (CSF phosphorylated tau (p‐tau)), and vascular (MRI white matter lesion (WML) volume) pathology as well as neurodegeneration (CSF neurofilament light (NfL)). For dichotomous variables (sex and pathologic Aβ42/40 ratio) independent samples t‐tests, and for continuous variables (all other variables) Pearson correlations, were performed.ResultIn univariate models, lower age at baseline, female sex, higher cortical thickness and better cognitive results at baseline were associated with higher cognitive resilience against cortical atrophy, while education was not. Further, pathological Aβ42/40 ratio and higher levels of p‐tau, NfL, and WMLs at baseline were negatively associated with cognitive resilience in univariate analyses. In a multivariable linear regression model, lower baseline cortical thickness, a pathological Aβ42/40 ratio, and higher NfL were significantly associated with worse cognitive resilience (Figure 1, Table 1).ConclusionMarkers of Alzheimer´s disease pathology and neurodegeneration are associated with worse than expected cognitive decline at a given rate of brain atrophy.

The Bone Microarchitecture Deficit in Patients with Hemophilia Is Influenced by Arthropathy, Hepatitis C Infection, and Physical Activity.

Low bone mineral density (BMD) is common in patients with hemophilia (PWHs). The aim of the present study was to describe BMD and microarchitecture in PWHs in Northern Germany and to determine factors contributing to possible skeletal alterations. Demographic characteristics, BMD and microarchitecture, bone metabolism markers, and orthopaedic joint score (OJS) were assessed during routine check-ups. Areal BMD was assessed by dual-energy X-ray absorptiometry (DXA) at the hip and lumbar spine. Volumetric BMD and microarchitecture were quantified by high-resolution peripheral quantitative computed tomography at the distal radius and tibia. Eighty male PWHs (median age, 33 years; range, 18-77) were retrospectively analyzed, of whom 67 (84.0%) and 13 (16.0%) had hemophilia A and B, respectively. Fifty-four (68.0%), six (7.0%), and 20 (25.0%) patients had severe, moderate, or mild hemophilia, and 35 (44.0%) were hepatitis C virus (HCV) positive. DXA analysis revealed low BMD (Z-score ≤ - 2.0) in 27.5% of PWHs, and higher bone turnover values were associated with lower BMD. Bone microarchitecture was dominated by cortical deficits at the radius and trabecular deficits at the tibia. Cortical deficits at the radius were influenced by lower body mass index, low-grade inflammation, and treatment regimen (higher cortical thickness on primary prophylaxis). Trabecular alterations at the tibia were mainly associated with OJS and HCV status. A positive effect of self-reported sportive activity on BMD could be shown. In conclusion, our findings demonstrate that the site-specific microarchitectural deficit observed in PWHs is primarily negatively influenced by poor joint status, inflammation, HCV infection, and high bone turnover.