Brain Volume Research Articles

Impact of the Novel MRI Contrast Agent Gadopiclenol on Radiotherapy Decision Making in Patients With Brain Metastases.

The aim of this study was to assess the effect of gadopiclenol versus gadobenate dimeglumine contrast-enhanced magnetic resonance imaging (MRI) on decision-making between whole-brain radiotherapy (WBRT) and stereotactic radiosurgery (SRS) for treatment of brain metastases (BMs). Patients with BMs underwent 2 separate MRI examinations in a double-blind crossover phase IIb comparative study between the MRI contrast agents gadopiclenol and gadobenate dimeglumine, both administered at 0.1 mmol/kg. The imaging data of a single site using identical MRI scanners and protocols were included in this post hoc analysis. Patients with 1 or more BMs in any of both MRIs were subjected to target volume delineation for treatment planning. Two radiation oncologists contoured all visible lesions and decided upon SRS or WBRT, according to the number of metastases. For each patient, SRS or WBRT treatment plans were calculated for both MRIs, considering the gross target volume (GTV) as the contrast-enhancing aspects of the tumor. Mean GTVs and volume of healthy brain exposed to 12 Gy (V12), as well as Dice similarity coefficient scores, were obtained. The Spearman rank (ρ) correlation was additionally calculated for assessing linear differences. Three different expert radiation oncologists blindly rated the contrast enhancement for contouring purposes. Thirteen adult patients were included. Gadopiclenol depicted additional BM as compared with gadobenate dimeglumine in 7 patients (54%). Of a total of 63 identified metastatic lesions in both MRI sets, 3 subgroups could be defined: A, 48 (24 pairs) detected equal GTVs visible in both modalities; B, 13 GTVs only visible in the gadopiclenol set (mean ± SD, 0.16 ± 0.37 cm3); and C, 2 GTVs only visible in the gadobenate dimeglumine set (mean ± SD, 0.01 ± 0.01). Treatment indication was changed for 2 (15%) patients, 1 from no treatment to SRS and for 1 from SRS to WBRT. The mean GTVs and brain V12 were comparable between both agents (P = 0.694, P = 0.974). The mean Dice similarity coefficient was 0.70 ± 0.14 (ρ = 0.82). According to the readers, target volume definition was improved in 63.9% of cases (23 of 36 evaluations) with gadopiclenol and 22.2% with gadobenate dimeglumine (8 of 36), whereas equivalence was obtained in 13.9% (5 of 36). Gadopiclenol-enhanced MRI improved BM detection and characterization, with a direct impact on radiotherapy treatment decision between WBRT and SRS. Additionally, a more exact target delineation and planning could be performed with gadopiclenol. A prospective evaluation in a larger cohort of patients is required to confirm these findings.

Application of diceCT to Study the Development of the Zika Virus-Infected Mouse Brain.

Zika virus (ZIKV) impacts the developing brain. Here, a technique was applied to define, in 3D, developmental changes in the brains of ZIKV-infected mice. Postnatal day 1 mice were uninfected or ZIKV-infected, then analysed by iodine staining and micro-CT scanning (diffusible iodine contrast-enhanced micro-CT; diceCT) at 3-, 6-, and 10-days post-infection (dpi). Multiple brain regions were visualised using diceCT: the olfactory bulb, cerebrum, hippocampus, midbrain, interbrain, and cerebellum, along with the lens and retina of the eye. Brain regions were computationally segmented and quantitated, with increased brain volumes and developmental time in uninfected mice. Conversely, in ZIKV-infected mice, no quantitative differences were seen at 3 or 6 dpi when there were no clinical signs, but qualitatively, diverse visual defects were identified at 6-10 dpi. By 10 dpi, ZIKV-infected mice had significantly lower body weight and reduced volume of brain regions compared to 10 dpi-uninfected or 6 dpi ZIKV-infected mice. Nissl and immunofluorescent Iba1 staining on post-diceCT tissue were successful, but RNA extraction was not. Thus, diceCT shows utility for detecting both 3D qualitative and quantitative changes in the developing brain of ZIKV-infected mice, with the benefit, post-diceCT, of retaining the ability to apply traditional histology and immunofluorescent analysis to tissue.

Obesity and brain volumes: mediation by cardiometabolic and inflammatory measures

BackgroundThis study aimed to investigate the relationship between overall obesity, central obesity and brain volumes, as well as to determine the extent to which cardiometabolic and inflammatory measures act as...

More similarity than difference: comparison of within- and between-sex variance in early adolescent brain structure.

Adolescent neuroimaging studies of sex differences in the human brain predominantly examine mean differences between males and females. This focus on between-groups differences without probing relative distributions and similarities may contribute to both conflation and overestimation of sex differences and sexual dimorphism in the developing human brain. We aimed to characterize the variance in brain macro- and micro-structure in early adolescence as it pertains to sex at birth using a large sample of 9-11 year-olds from the Adolescent Brain Cognitive Development (ABCD) Study (N=7,723). Specifically, for global and regional estimates of gray and white matter volume, cortical thickness, and white matter microstructure (i.e., fractional anisotropy and mean diffusivity), we examined: within- and between-sex variance, overlap between male and female distributions, inhomogeneity of variance via the Fligner-Killeen test, and an analysis of similarities (ANOSIM). For completeness, we examined these sex differences using both uncorrected (raw) brain estimates and residualized brain estimates after using mixed-effects modeling to account for age, pubertal development, socioeconomic status, race, ethnicity, MRI scanner manufacturer, and total brain volume, where applicable. The overlap between male and female distributions was universally greater than the difference (overlap coefficient range: 0.585 - 0.985) and the ratio of within-sex and between-sex differences was similar (ANOSIM R range: -0.001 - 0.117). All cortical and subcortical volumes showed significant inhomogeneity of variance, whereas a minority of brain regions showed significant sex differences in variance for cortical thickness, white matter volume, fractional anisotropy, and mean diffusivity. Inhomogeneity of variance was reduced after accounting for other sources of variance. Overlap coefficients were larger and ANOSIM R values were smaller for residualized outcomes, indicating greater within- and smaller between-sex differences once accounting for other covariates. Reported sex differences in early adolescent human brain structure may be driven by disparities in variance, rather than binary, sex-based phenotypes. Contrary to the popular view of the brain as sexually dimorphic, we found more similarity than difference between sexes in all global and regional measurements of brain structure examined. This study builds upon previous findings illustrating the importance of considering variance when examining sex differences in brain structure.

Neuroanatomical and clinical factors predicting future cognitive impairment.

Identifying cognitively normal (CN) older adults who will convert to cognitive impairment (CI) due to Alzheimer's disease is crucial for early intervention. Clinical and neuroimaging measures were acquired from 301 CN adults who converted to CI within 15years of baseline, and 294 who did not. Regional volumes and brain age measures were extracted from T1-weighted magnetic resonance images. Linear discriminant analysis compared non-converters' characteristics against those of short-, mid-, and long-term converters. Conversion was associated with clinical measures such as hearing impairment and self-reported memory decline. Converters' brain volumes were smaller than non-converters' across 48 frontal, temporal, and subcortical structures. Brain age measures of 12 structures were correlated with shorter times to conversion. Conversion prediction accuracy increased from 81.5% to 90.5% as time to conversion decreased. Proximity to CI conversion is foreshadowed by anatomic features of brain aging that enhance the accuracy of predicting conversion.

The allometry of brain size in Euarchontoglires: clade-specific patterns and their impact on encephalization quotients

Abstract The timing and nature of evolutionary shifts in the relative brain size of Primates have been extensively studied. Less is known, however, about the scaling of the brain-to-body size in their closest living relatives, i.e., among other members of Euarchontoglires (Dermoptera, Scandentia, Lagomorpha, Rodentia). Ordinary least squares (OLS), reduced major axis (RMA), and phylogenetic generalized least squares (PGLS) regressions were fitted to the largest euarchontogliran data set of brain and body mass, comprising 715 species. Contrary to previous inferences, lagomorph brain sizes (PGLS slope = 0.465; OLS slope = 0.593) scale relative to body mass similarly to rodents (PGLS = 0.526; OLS = 0.638), and differently than primates (PGLS = 0.607; OLS = 0.794). There is a shift in the pattern of the scaling of the brain in Primates, with Strepsirrhini occupying an intermediate stage similar to Scandentia but different from Rodentia and Lagomorpha, while Haplorhini differ from all other groups in the OLS and RMA analyses. The unique brain–body scaling relationship of Primates among Euarchontoglires illustrates the need for clade-specific metrics for relative brain size (i.e., encephalization quotients; EQs) for more restricted taxonomic entities than Mammalia. We created clade-specific regular and phylogenetically adjusted EQ equations at superordinal, ordinal, and subordinal levels. When using fossils as test cases, our results show that generalized mammalian equations underestimate the encephalization of the stem lagomorph Megalagus turgidus in the context of lagomorphs, overestimate the encephalization of the stem primate Microsyops annectens and the early euprimate Necrolemur antiquus, but provide similar EQ values as our new strepsirrhine-specific EQ when applied to the early euprimate Adapis parisiensis.

Genomic analysis of intracranial and subcortical brain volumes yields polygenic scores accounting for variation across ancestries.

Subcortical brain structures are involved in developmental, psychiatric and neurological disorders. We performed GWAS meta-analyses of intracranial and nine subcortical brain volumes (brainstem, caudate nucleus, putamen, hippocampus, globus pallidus, thalamus, nucleus accumbens, amygdala and, for the first time, the ventral diencephalon) in 74,898 participants of European ancestry. We identified 254 independent loci associated with these brain volumes, explaining up to 35% of phenotypic variance. We observed gene expression in specific neural cell types across differentiation time points, including genes involved in intracellular signalling and brain ageing-related processes. Polygenic scores for brain volumes showed predictive ability when applied to individuals of diverse ancestries. We observed causal genetic effects of brain volumes with Parkinson's disease and ADHD. Findings implicate specific gene expression patterns in brain development and genetic variants in comorbid neuropsychiatric disorders, which could point to a brain substrate and region of action for risk genes implicated in brain diseases.

Association of social and environmental exposures at the neighborhood level with child brain volume and persistent distressing psychotic-like experiences

Association of social and environmental exposures at the neighborhood level with child brain volume and persistent distressing psychotic-like experiences

Alzheimer's disease genetic risk and changes in brain atrophy and white matter hyperintensities in cognitively unimpaired adults.

Reduced brain volumes and more prominent white matter hyperintensities on MRI scans are commonly observed among older adults without cognitive impairment. However, it remains unclear whether rates of change in these measures among cognitively normal adults differ as a function of genetic risk for late-onset Alzheimer's disease, including APOE-ɛ4, APOE-ɛ2 and Alzheimer's disease polygenic risk scores (AD-PRS), and whether these relationships are influenced by other variables. This longitudinal study examined the trajectories of regional brain volumes and white matter hyperintensities in relationship to APOE genotypes (N = 1541) and AD-PRS (N = 1093) in a harmonized dataset of middle-aged and older individuals with normal cognition at baseline (mean baseline age = 66 years, SD = 9.6) and an average of 5.3 years of MRI follow-up (max = 24 years). Atrophy on volumetric MRI scans was quantified in three ways: (i) a composite score of regions vulnerable to Alzheimer's disease (SPARE-AD); (ii) hippocampal volume; and (iii) a composite score of regions indexing advanced non-Alzheimer's disease-related brain aging (SPARE-BA). Global white matter hyperintensity volumes were derived from fluid attenuated inversion recovery (FLAIR) MRI. Using linear mixed effects models, there was an APOE-ɛ4 gene-dose effect on atrophy in the SPARE-AD composite and hippocampus, with greatest atrophy among ɛ4/ɛ4 carriers, followed by ɛ4 heterozygouts, and lowest among ɛ3 homozygouts and ɛ2/ɛ2 and ɛ2/ɛ3 carriers, who did not differ from one another. The negative associations of APOE-ɛ4 with atrophy were reduced among those with higher education (P < 0.04) and younger baseline ages (P < 0.03). Higher AD-PRS were also associated with greater atrophy in SPARE-AD (P = 0.035) and the hippocampus (P = 0.014), independent of APOE-ɛ4 status. APOE-ɛ2 status (ɛ2/ɛ2 and ɛ2/ɛ3 combined) was not related to baseline levels or atrophy in SPARE-AD, SPARE-BA or the hippocampus, but was related to greater increases in white matter hyperintensities (P = 0.014). Additionally, there was an APOE-ɛ4 × AD-PRS interaction in relation to white matter hyperintensities (P = 0.038), with greater increases in white matter hyperintensities among APOE-ɛ4 carriers with higher AD-PRS. APOE and AD-PRS associations with MRI measures did not differ by sex. These results suggest that APOE-ɛ4 and AD-PRS independently and additively influence longitudinal declines in brain volumes sensitive to Alzheimer's disease and synergistically increase white matter hyperintensity accumulation among cognitively normal individuals. Conversely, APOE-ɛ2 primarily influences white matter hyperintensity accumulation, not brain atrophy. Results are consistent with the view that genetic factors for Alzheimer's disease influence atrophy in a regionally specific manner, likely reflecting preclinical neurodegeneration, and that Alzheimer's disease risk genes contribute to white matter hyperintensity formation.

Full-field, frequency-domain comparison of simulated and measured human brain deformation.

We propose a robust framework for quantitatively comparing model-predicted and experimentally measured strain fields in the human brain during harmonic skull motion. Traumatic brain injuries (TBIs) are typically caused by skull impact or acceleration, but how skull motion leads to brain deformation and consequent neural injury remains unclear and comparison of model predictions to experimental data remains limited. Magnetic resonance elastography (MRE) provides high-resolution, full-field measurements of dynamic brain deformation induced by harmonic skull motion. In the proposed framework, full-field strain measurements from human brain MRE in vivo are compared to simulated strain fields from models with similar harmonic loading. To enable comparison, the model geometry and subject anatomy, and subsequently, the predicted and measured strain fields are nonlinearly registered to the same standard brain atlas. Strain field correlations , both global (over the brain volume) and local (over smaller sub-volumes), are then computed from the inner product of the complex-valued strain tensors from model and experiment at each voxel. To demonstrate our approach, we compare strain fields from MRE in six human subjects to predictions from two previously developed models. Notably, global values are higher when comparing strain fields from different subjects ( ) than when comparing strain fields from either of the two models to strain fields in any subject. The proposed framework provides a quantitative method to assess similarity (and to identify discrepancies) between model predictions and experimental measurements of brain deformation, and thus can aid in the development and evaluation of improved models of brain biomechanics.

Frontal brain volume correlates of impaired executive function in schizophrenia

Cognitive impairments affect functional capacity in individuals with schizophrenia (SZH), but their neural basis remains unclear. The Wisconsin Card Sorting Test (WCST), and the Stroop Task (SCWT), are paradigmatic tests which have been used extensively for examining executive function in SZH. However, few studies have explored how deficits on these tasks link to brain volume differences commonly seen in SZH. Here, for the first time, we tested associations between FreeSurfer-derived frontal brain volumes and performance on both WCST and SCWT, in a well-matched sample of 57 SZH and 32 control subjects. We also explored whether these associations were dissociable from links to symptom severity in SZH. Results revealed correlations between volumes and task performance which were unique to SZH. In SZH only, volumes of right middle frontal regions correlated with both WCST and Stroop performance: correlation coefficients were significantly different to those present in the control group, highlighting their specificity to the patient group. In the Stroop task, superior frontal regions also showed associations with Stroop interference scores which were unique to SZH. These findings provide important detail around how deficits on these two paradigmatic executive function tasks link to brain structural differences in SZH. Results align with converging evidence suggesting that neuropathology within right middle frontal regions (BA9 and BA46) might be of particular import in SZH. No volumetric associations with symptom severity were found, supporting the notion that the structural abnormalities underpinning cognitive deficits in SZH differ from those associated with symptomatology.

Mapping brain morphology to cognitive deficits: a study on PD-CRS scores in Parkinson's disease with mild cognitive impairment.

The Parkinson's Disease-Cognitive Rating Scale (PD-CRS) is a widely used tool for detecting mild cognitive impairment (MCI) in Parkinson's Disease (PD) patients, however, the neuroanatomical underpinnings of this test's outcomes require clarification. This study aims to: (a) investigate cortical volume (CVol) and cortical thickness (CTh) disparities between PD patients exhibiting mild cognitive impairment (PD-MCI) and those with preserved cognitive abilities (PD-IC); and (b) identify the structural correlates in magnetic resonance imaging (MRI) of overall PD-CRS performance, including its subtest scores, within a non-demented PD cohort. This study involved 51 PD patients with Hoehn & Yahr stages I-II, categorized into two groups: PD-IC (n = 36) and PD-MCI (n = 15). Cognitive screening evaluations utilized the PD-CRS and the Montreal Cognitive Assessment (MoCA). PD-MCI classification adhered to the Movement Disorder Society Task Force criteria, incorporating extensive neuropsychological assessments. The interrelation between brain morphology and cognitive performance was determined using FreeSurfer. Vertex-wise analysis of the entire brain demonstrated a notable reduction in CVol within a 2,934 mm2 cluster, encompassing parietal and temporal regions, in the PD-MCI group relative to the PD-IC group. Lower PD-CRS total scores correlated with decreased CVol in the middle frontal, superior temporal, inferior parietal, and cingulate cortices. The PD-CRS subtests for Sustained Attention and Clock Drawing were associated with cortical thinning in distinct regions: the Clock Drawing subtest correlated with changes in the parietal lobe, insula, and superior temporal cortex morphology; while the PD-CRS frontal-subcortical scores presented positive correlations with CTh in the transverse temporal, medial orbitofrontal, superior temporal, precuneus, fusiform, and supramarginal regions. Additionally, PD-CRS subtests for Semantic and Alternating verbal fluency were linked to CTh changes in orbitofrontal, temporal, fusiform, insula, and precentral regions. PD-CRS performance mirrors neuroanatomical changes across extensive fronto-temporo-parietal areas, covering both lateral and medial cortical surfaces, in PD patients without dementia. The observed changes in CVol and CTh associated with this cognitive screening tool suggest their potential as surrogate markers for cognitive decline in PD. These findings warrant further exploration and validation in multicenter studies involving independent patient cohorts.

Linkages Between Brain Size and Language Capacity

The organ in the human body that controls all movements and functions, including language, is the brain. The cerebrum, especially the left hemisphere, is crucial for language activities. The human left brain is a domain that functions as a place of concentration and as a regulator and controller of language abilities. The left hemisphere also appears to be involved in sign language processing, similar to how it is involved in non-signers. The right brain is also involved in complex ways but differently for sign language users. Studies on brain and language continue to develop and have shown significant progress. However, findings sometimes appear inconsistent, particularly regarding the involvement of the right brain in language. Many studies suggest that the second language can sometimes be located in the right brain, though this is not always the case. There may be variables that determine the brain's language localization, but these have not yet been fully identified. One factor may be the age at which the second language is learned, as well as the unique growth and development of each individual.

Proteomics identifies potential immunological drivers of postinfection brain atrophy and cognitive decline

Infections have been associated with the incidence of Alzheimer disease and related dementias, but the mechanisms responsible for these associations remain unclear. Using a multicohort approach, we found that influenza, viral, respiratory, and skin and subcutaneous infections were associated with increased long-term dementia risk. These infections were also associated with region-specific brain volume loss, most commonly in the temporal lobe. We identified 260 out of 942 immunologically relevant proteins in plasma that were differentially expressed in individuals with an infection history. Of the infection-related proteins, 35 predicted volumetric changes in brain regions vulnerable to infection-specific atrophy. Several of these proteins, including PIK3CG, PACSIN2, and PRKCB, were related to cognitive decline and plasma biomarkers of dementia (Aβ42/40, GFAP, NfL, pTau-181). Genetic variants that influenced expression of immunologically relevant infection-related proteins, including ITGB6 and TLR5, predicted brain volume loss. Our findings support the role of infections in dementia risk and identify molecular mediators by which infections may contribute to neurodegeneration.

Association of accelerated biological aging with brain volumes: A cross-sectional study

BackgroundMultiple epidemiological studies have observed the connection between aging and brain volumes. The concept of accelerated biological aging (BA) is more powerful for observing the degree of aging of an individual than chronologic age (CA). The objective of this study is to explore the relationship between BA and brain volumes. MethodsBA was measured from clinical traits using two blood-chemistry algorithms, the Klemera-Doubal method (KDM) and the PhenoAge. The two age acceleration biomarkers were calculated by the residuals from regressing CA, termed “KDM-acceleration” and “PhenoAge-acceleration”. Brain volumes were from brain magnetic resonance imaging (MRI) data. After adjustment for confounding factors, general linear regression models were used to examine associations between KDM-acceleration and PhenoAge-acceleration and brain volumes, respectively. Additionally, we stratified participants by sex, age, and the four quartiles of the Townsend Deprivation Index (TDI) for extra subgroup analysis. Results14,725 participants with available information were enrolled. After full adjustment, we observed negative associations between KDM-acceleration and brain volumes, such as gray matter (β = −0.029), white matter (β = −0.021), gray and white matter (β = −0.026), and hippocampus (β = −0.011 for left and β = −0.014 for right). There were also negative associations between PhenoAge-acceleration and brain volumes, such as white matter (β = −0.008), gray and white matter (β = −0.010), thalamus (β = −0.012 for left and β = −0.012 for right). In the subgroup analysis stratified by sex, age, and the four quartiles of TDI, the association between KDM-acceleration and PhenoAge-acceleration and brain volumes still existed. In subgroup analyses, the variation in associations suggests that socioeconomic and biological factors may differentially influence brain aging. ConclusionsOur research indicated that more advanced BA was associated with less brain tissue.

Educational disparities in brain health and dementia across Latin America and the United States.

Education influences brain health and dementia. However, its impact across regions, specifically Latin America (LA) and the United States (US), is unknown. A total of 1412 participants comprising controls, patients with Alzheimer's disease (AD), and frontotemporal lobar degeneration (FTLD) from LA and the US were included. We studied the association of education with brain volume and functional connectivity while controlling for imaging quality and variability, age, sex, total intracranial volume (TIV), and recording type. Education influenced brain measures, explaining 24%-98% of the geographical differences. The educational disparities between LA and the US were associated with gray matter volume and connectivity variations, especially in LA and AD patients. Education emerged as a critical factor in classifying aging and dementia across regions. The results underscore the impact of education on brain structure and function in LA, highlighting the importance of incorporating educational factors into diagnosing, care, and prevention, and emphasizing the need for global diversity in research. Lower education was linked to reduced brain volume and connectivity in healthy controls (HCs), Alzheimer's disease (AD), and frontotemporal lobar degeneration (FTLD). Latin American cohorts have lower educational levels compared to the those in the United States. Educational disparities majorly drive brain health differences between regions. Educational differences were significant in both conditions, but more in AD than FTLD. Education stands as a critical factor in classifying aging and dementia across regions.

Lipases are differentially regulated by hormones to maintain free fatty acid homeostasis for insect brain development

BackgroundFree fatty acids (FFAs) play vital roles as energy sources and substrates in organisms; however, the molecular mechanism regulating the homeostasis of FFA levels in various circumstances, such as feeding and nonfeeding stages, is not fully clarified. Holometabolous insects digest dietary triglycerides (TAGs) during larval feeding stages and degrade stored TAGs in the fat body during metamorphosis after feeding cessation, which presents a suitable model for this study.ResultsThis study reported that two lipases are differentially regulated by hormones to maintain the homeostasis of FFA levels during the feeding and nonfeeding stages using the lepidopteran insect cotton bollworm Helicoverpa armigera as a model. Lipase member H-A-like (Lha-like), related to human pancreatic lipase (PTL), was abundantly expressed in the midgut during the feeding stage, while the monoacylglycerol lipase ABHD12-like (Abhd12-like), related to human monoacylglycerol lipase (MGL), was abundantly expressed in the fat body during the nonfeeding stage. Lha-like was upregulated by juvenile hormone (JH) via the JH intracellular receptor methoprene-tolerant 1 (MET1), and Abhd12-like was upregulated by 20-hydroxyecdysone (20E) via forkhead box O (FOXO) transcription factor. Knockdown of Lha-like decreased FFA levels in the hemolymph and reduced TAG levels in the fat body. Moreover, lipid droplets (LDs) were small, the brain morphology was abnormal, the size of the brain was small, and the larvae showed the phenotype of delayed pupation, small pupae, and delayed tissue remodeling. Knockdown of Abhd12-like decreased FFA levels in the hemolymph; however, TAG levels increased in the fat body, and LDs remained large. The development of the brain was arrested at the larval stage, and the larvae showed a delayed pupation phenotype and delayed tissue remodeling.ConclusionsThe differential regulation of lipases expression by different hormones determines FFAs homeostasis and different TAG levels in the fat body during the feeding larval growth and nonfeeding stages of metamorphosis in the insect. The homeostasis of FFAs supports insect growth, brain development, and metamorphosis.

Predicting Cognitive Decline in Amyloid-Positive Patients With Mild Cognitive Impairment or Mild Dementia.

Cognitive decline rates in Alzheimer disease (AD) vary greatly. Disease-modifying treatments may alter cognitive decline trajectories, rendering their prediction increasingly relevant. We aimed to construct clinically applicable prediction models of cognitive decline in amyloid-positive patients with mild cognitive impairment (MCI) or mild dementia. From the Amsterdam Dementia Cohort, we selected amyloid-positive participants with MCI or mild dementia and at least 2 longitudinal Mini-Mental State Examination (MMSE) measurements. Amyloid positivity was based on CSF AD biomarker concentrations or amyloid PET. We used linear mixed modeling to predict MMSE over time, describing trajectories using a cubic time curve and interactions between linear time and the baseline predictors age, sex, baseline MMSE, APOE ε4 dose, CSF β-amyloid (Aβ) 1-42 and pTau, and MRI total brain and hippocampal volume. Backward selection was used to reduce model complexity. These models can predict MMSE over follow-up or the time to an MMSE value. MCI and mild dementia were modeled separately. Internal 5-fold cross-validation was performed to calculate the explained variance (R2). In total, 961 participants were included (age 65 ± 7 years, 49% female), 310 had MCI (MMSE 26 ± 2) and 651 had mild dementia (MMSE 22 ± 4), with 4 ± 2 measurements over 2 (interquartile range 1-4) years. Cognitive decline rates increased over time for both MCI and mild dementia (model comparisons linear vs squared vs cubic time fit; p < 0.05 favoring a cubic fit). For MCI, backward selection retained age, sex, and CSF Aβ1-42 and pTau concentrations as time-varying effects altering the MMSE trajectory. For mild dementia, retained time-varying effects were Aβ1-42, age, APOE ε4, and baseline MMSE. R2 was 0.15 for the MCI model and 0.26 for mild dementia in internal cross-validation. A hypothetical patient with MCI, baseline MMSE 28, and CSF Aβ1-42 of 925 pg/mL was predicted to reach an MMSE of 20 after 6.0 years (95% CI 5.4-6.7) and after 8.6 years with a hypothetical treatment reducing decline by 30%. We constructed models for MCI and mild dementia that predict MMSE over time. These models could inform patients about their potential cognitive trajectory and the remaining uncertainty and aid in conversations about individualized potential treatment effects.

Cognitive performance and brain volume among survivors of pediatric hematological malignancies: a case-control study.

Cognitive dysfunction may be one of the hazardous late effects among survivors of pediatric hematological malignancies. Our study aimed to explore cognitive performance and assess the global and regional brain volume changes in survivors of hematological malignancies. This case-control study was conducted on 68 survivors of hematological malignancies, with a median follow-up period of 2years (ranging from 1 to 6.2years). Stanford-Binet Testwas used for cognitive assessment. A quantitative volumetric assessment of the brain was done using the NeuroQuant Brain Magnetic Resonance. Age and sex-matched 68 children were selected as a comparison group. Cancer survivors showed significantly lower levels of IQ and their subtests than the control group. Global brain atrophy was observed in the majority of the survivors. Many risk factors significantly affected different IQ subtests, such as radiotherapy (RTH), high cumulative doses of methotrexate (MTX), and prednisone. At the same time, low white matter volume (WMV) was observed with higher cumulative doses of MTX and anthracyclines. Hematological malignancies have a negative impact on cognition. Neurocognitive impairment and related brain changes were evident in those who received RTH, HDMTX, or high cumulative doses of steroids.

Anti-Inflammatory Diet and Dementia in Older Adults With Cardiometabolic Diseases

Inflammation has been proposed as a mechanism linking cardiometabolic diseases (CMDs) to increased risk of dementia. However, whether an anti-inflammatory diet can support brain and cognitive health among people with CMDs is unclear. To examine CMD status and dietary inflammatory potential in association with dementia risk and brain magnetic resonance imaging (MRI) measures using joint effect analysis. The UK Biobank is an ongoing community-based cohort study with baseline assessments conducted between March 13, 2006, and October 1, 2010. The present study included 84 342 dementia-free older adults (≥60 years), who were followed up until January 20, 2022 (maximum, 15 years). A subsample (n = 8917) underwent brain MRI scans between May 2, 2014, and March 13, 2020. Baseline CMDs (including type 2 diabetes, heart disease, and stroke) were ascertained from medical records. Dietary Inflammatory Index scores (anti-inflammatory [≤-1.5 points], neutral [>-1.5 to <0.5 points], or proinflammatory [≥0.5 points]) were calculated from participants' average intake of 31 nutrients, assessed up to 5 times using the Oxford WebQ, a web-based, 24-hour dietary assessment. Incident dementia was identified through linkage to medical records. Regional brain volumes were collected from brain MRI scans. The study included 84 342 participants (mean [SD] age, 64.1 [2.9] years; 43 220 [51.2%] female). At baseline, 14 079 (16.7%) had at least 1 CMD. Over a median follow-up of 12.4 (IQR, 11.8-13.1) years, 1559 individuals (1.9%) developed dementia. With the use of joint effect analysis, the hazard ratio of dementia was 2.38 (95% CI, 1.93-2.93) for people with CMDs and a proinflammatory diet and 1.65 (95% CI, 1.36-2.00) for those with CMDs and an anti-inflammatory diet (reference: CMD-free, anti-inflammatory diet). Dementia risk was 31% lower (hazard ratio, 0.69; 95% CI, 0.55-0.88; P = .003) among people with CMDs and an anti-inflammatory diet. On brain MRI, participants with CMDs and an anti-inflammatory diet compared with a proinflammatory diet additionally had significantly larger gray matter volume (β = -0.15; 95% CI, -0.24 to -0.06 vs β = -0.27; 95% CI, -0.38 to -0.16) and smaller white matter hyperintensity volume (β = 0.05; 95% CI, -0.04 to 0.14 vs β = 0.16; 95% CI, 0.05-0.27). In this cohort study, people with CMDs and an anti-inflammatory compared with proinflammatory diet had a significantly lower hazard ratio of dementia, larger gray matter volume, and smaller white matter hyperintensity volume.