BACKGROUND: Multiple 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.
METHODS: BA 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.
RESULTS: 14,725 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.
CONCLUSIONS: Our research indicated that more advanced BA was associated with less brain tissue.

OBJECTIVE: To examine the associaiton between environmental measures and brain volumes and its potential mediators.
METHODS: This was a prospective study.
METHODS: Our analysis included 34,454 participants (53.4% females) aged 40-73 years at baseline (between 2006 and 2010) from the UK Biobank. Brain volumes were measured using magnetic resonance imaging between 2014 and 2019.
RESULTS: Greater proximity to greenspace buffered at 1000 m at baseline was associated with larger volumes of total brain measured 8.8 years after baseline assessment (standardized β (95% CI) for each 10% increment in coverage: 0.013(0.005,0.020)), grey matter (0.013(0.006,0.020)), and white matter (0.011(0.004,0.017)) after adjustment for covariates and air pollution. The corresponding numbers for natural environment buffered at 1000 m were 0.010 (0.004,0.017), 0.009 (0.004,0.015), and 0.010 (0.004,0.016), respectively. Similar results were observed for greenspace and natural environment buffered at 300 m. The strongest mediator for the association between greenspace buffered at 1000 m and total brain volume was smoking (percentage (95% CI) of total variance explained: 7.9% (5.5-11.4%)) followed by mean sphered cell volume (3.3% (1.8-5.8%)), vitamin D (2.9% (1.6-5.1%)), and creatinine in blood (2.7% (1.6-4.7%)). Significant mediators combined explained 18.5% (13.2-25.3%) of the association with total brain volume and 32.9% (95% CI: 22.3-45.7%) of the association with grey matter volume. The percentage (95% CI) of the association between natural environment and total brain volume explained by significant mediators combined was 20.6% (14.7-28.1%)).
CONCLUSIONS: Higher coverage percentage of greenspace and environment may benefit brain health by promoting healthy lifestyle and improving biomarkers including vitamin D and red blood cell indices.

UNASSIGNED: Sensorineural hearing loss (SNHL) can arise from a diverse range of congenital and acquired factors. Detecting it early is pivotal for nurturing speech, language, and cognitive development in children with SNHL. In our study, we utilized synthetic magnetic resonance imaging (SyMRI) to assess alterations in both gray and white matter within the brains of children affected by SNHL.
UNASSIGNED: The study encompassed both children diagnosed with SNHL and a control group of children with normal hearing {1.5-month-olds (n = 52) and 3-month-olds (n = 78)}. Participants were categorized based on their auditory brainstem response (ABR) threshold, delineated into normal, mild, moderate, and severe subgroups.Clinical parameters were included and assessed the correlation with SNHL. Quantitative analysis of brain morphology was conducted using SyMRI scans, yielding data on brain segmentation and relaxation time.Through both univariate and multivariate analyses, independent factors predictive of SNHL were identified. The efficacy of the prediction model was evaluated using receiver operating characteristic (ROC) curves, with visualization facilitated through the utilization of a nomogram. It\'s important to note that due to the constraints of our research, we worked with a relatively small sample size.
UNASSIGNED: Neonatal hyperbilirubinemia (NH) and children with inner ear malformation (IEM) were associated with the onset of SNHL both at 1.5 and 3-month groups. At 3-month group, the moderate and severe subgroups exhibited elevated quantitative T1 values in the inferior colliculus (IC), lateral lemniscus (LL), and middle cerebellar peduncle (MCP) compared to the normal group. Additionally, WMV, WMF, MYF, and MYV were significantly reduced relative to the normal group. Additionally, SNHL-children with IEM had high T1 values in IC, and LL and reduced WMV, WMF, MYV and MYF values as compared with SNHL-children without IEM at 3-month group. LL-T1 and WMF were independent risk factors associated with SNHL. Consequently, a prediction model was devised based on LL-T1 and WMF. ROC for training set, validation set and external set were 0.865, 0.806, and 0.736, respectively.
UNASSIGNED: The integration of T1 quantitative values and brain volume segmentation offers a valuable tool for tracking brain development in children affected by SNHL and assessing the progression of the condition\'s severity.

This study aimed to investigate the cross-sectional associations between regional Alzheimer\'s disease (AD) biomarkers, including tau, β-amyloid (Aβ), and brain volume, within the Papez circuit, and neuropsychological functioning across the preclinical and clinical spectrum of AD. We utilized data from the Alzheimer\'s Disease Neuroimaging Initiative (ADNI) database, including 251 Aβ-positive participants. Participants were categorized into three groups based on the Clinical Dementia Rating (CDR): 73 individuals with preclinical AD (CDR = 0), 114 with prodromal AD (CDR = 0.5), and 64 with clinical AD dementia (CDR ≥ 1). Linear regression analyses, adjusted for age, gender, and education years, were employed to evaluate the associations between five regions of interest (the hippocampus, para-hippocampus, entorhinal cortex, posterior cingulate cortex, and thalamus) and five neuropsychological tests across the three imaging modalities. In the preclinical stage of AD, flortaucipir PET was associated with impaired global cognition and episodic memory (range standardized β = 0.255-0.498, p < 0.05 corrected for multiple comparisons), while florbetapir PET and brain volume were marginally related to global cognition (range standardized β = 0.221-0.231, p < 0.05). In the clinical stages of AD (prodromal and dementia), both increased flortaucipir uptake and decreased brain volume were significantly associated with poorer global neuropsychological and episodic memory performance (range standardized β = 0.222-0.621, p < 0.05, most regions of interest survived correction for multiple comparisions). However, a slight relationship was observed between florbetapir uptake and poorer global cognitive function. The regions most affected by flortaucipir PET were the hippocampus, para-hippocampus, and posterior cingulate cortex. During the clinical stages, the hippocampus and entorhinal cortex exhibited the most significant volumetric changes. Tau PET and brain volume measurements within the Papez circuit are more sensitive indicators of early cognitive deficits in AD than Aβ PET. Furthermore, during the clinical stages of AD, both flortaucipir PET and brain volume of the Papez circuit are closely correlated with cognitive decline. These findings underscore the importance of integrating multiple biomarkers for the comprehensive evaluation of AD pathology and its impact on cognition.

UNASSIGNED: Amphetamine-type stimulants (ATS) have become a critical public health issue. Animal models have indicated a clear neurotoxic potential of ATSs. In humans, chronic use has been associated with cognitive deficits and structural brain abnormalities. However, cross-sectional retrospective designs in chronic users cannot truly determine the causal direction of the effects.
UNASSIGNED: To prospectively determine effects of occasional ATS use on cognitive functioning and brain structure.
UNASSIGNED: In a prospective longitudinal study design, cognitive functioning and brain structure were assessed at baseline and at 12-month follow-up in occasional ATS users (cumulative lifetime use <10 units at baseline).
UNASSIGNED: Examination of change scores between the initial examination and follow-up revealed declined verbal memory performance and putamen volume in users with high relative to low interim ATS exposure. In the entire sample, interim ATS use, memory decline, and putamen volume reductions were strongly associated.
UNASSIGNED: The present findings support the hypothesis that ATS use is associated with deficient dorsal striatal morphology that might reflect alterations in dopaminergic pathways. More importantly, these findings strongly suggest that even occasional, low-dose ATS use disrupts striatal integrity and cognitive functioning.

BACKGROUND: Growing evidence indicates that dynamic changes in gut microbiome can affect intelligence; however, whether these relationships are causal remains elusive. We aimed to disentangle the poorly understood causal relationship between gut microbiota and intelligence.
METHODS: We performed a 2-sample Mendelian randomization (MR) analysis using genetic variants from the largest available genome-wide association studies of gut microbiota (N = 18,340) and intelligence (N = 269,867). The inverse-variance weighted method was used to conduct the MR analyses complemented by a range of sensitivity analyses to validate the robustness of the results. Considering the close relationship between brain volume and intelligence, we applied 2-step MR to evaluate whether the identified effect was mediated by regulating brain volume (N = 47,316).
RESULTS: We found a risk effect of the genus Oxalobacter on intelligence (odds ratio = 0.968 change in intelligence per standard deviation increase in taxa; 95% CI, 0.952-0.985; p = 1.88 × 10-4) and a protective effect of the genus Fusicatenibacter on intelligence (odds ratio = 1.053; 95% CI, 1.024-1.082; p = 3.03 × 10-4). The 2-step MR analysis further showed that the effect of genus Fusicatenibacter on intelligence was partially mediated by regulating brain volume, with a mediated proportion of 33.6% (95% CI, 6.8%-60.4%; p = .014).
CONCLUSIONS: Our results provide causal evidence indicating the role of the microbiome in intelligence. Our findings may help reshape our understanding of the microbiota-gut-brain axis and development of novel intervention approaches for preventing cognitive impairment.

BACKGROUND: Hearing loss and tinnitus have been proposed as potential indicators of impaired mental health and brain morphological changes.
OBJECTIVE: To assess the associations of hearing loss and tinnitus with the risk of depression and anxiety and with brain volume.
METHODS: We conducted a community-based cohort study including 129 610 participants aged 40-69 years at recruitment to the UK Biobank with a follow-up period during 2006-2021 to estimate the risk of depression and anxiety after detection of hearing loss and reported tinnitus. We also assessed the associations of hearing loss and tinnitus with brain volume in a subsample with available brain magnetic resonance imaging data (N = 5222).
RESULTS: We observed an increased risk of depression among individuals with hearing loss (hazard ratio [HR] 1.14, 95% CI 1.03-1.26), tinnitus (HR 1.30, 95% CI 1.21-1.41) or both (HR 1.32, 95% CI 1.15-1.52), compared with individuals with neither hearing loss nor tinnitus. Similar results were noted for anxiety (HR 1.18, 95% CI 1.07-1.30 for hearing loss; HR 1.32, 95% CI 1.22-1.43 for tinnitus; and HR 1.48, 95% CI 1.30-1.68 for both). Hearing loss was associated with decreased overall brain volume as well as decreased volume of different brain regions. The latter associations disappeared after adjustment for whole intracranial volume. Tinnitus was associated with greater left accumbens and right occipital pole volume after adjustment for the whole intracranial volume.
CONCLUSIONS: Individuals with tinnitus are at increased risk of depression and anxiety. Hearing loss, on the other hand, is associated with both mood disorders and altered brain morphology.

The rise of new media has greatly changed the lifestyles, leading to increased time on these platforms and less time spent reading. This shift has particularly profound impacts on early adolescents, who are in a critical stage of brain development. Previous studies have found associations between screen use and mental health, but it remains unclear whether screen use is the direct cause of the outcomes. Here, the Adolescent Brain Cognitive Development (ABCD) dataset is utlized to examine the causal relationships between screen use and brain development. The results revealed adverse causal effects of screen use on language ability and specific behaviors in early adolescents, while reading has positive causal effects on their language ability and brain volume in the frontal and temporal regions. Interestingly, increased screen use is identified as a result, rather than a cause, of certain behaviors such as rule-breaking and aggressive behaviors. Furthermore, the analysis uncovered an indirect influence of screen use, mediated by changes in reading habits, on brain development. These findings provide new evidence for the causal influences of screen use on brain development and highlight the importance of monitoring media use and related habit change in children.

BACKGROUND: The co-occurrence of cardiometabolic diseases (CMDs) is increasingly prevalent and has been associated with an additive risk of dementia in older adults, but the extent to which this risk can be offset by a healthy lifestyle is unknown. We aimed to examine the associations of cardiometabolic multimorbidity and lifestyle with incident dementia and related brain structural changes.
METHODS: This prospective study extracted health and lifestyle data from 171 538 UK Biobank participants aged 60 years or older without dementia at baseline between 2006 and 2010 and followed up until July 2021, as well as brain structural data in a nested imaging subsample of 11 972 participants. Cardiometabolic multimorbidity was defined as the presence of two or more CMDs among type 2 diabetes, coronary heart disease, stroke, and hypertension. Lifestyle patterns were determined based on 7 modifiable lifestyle factors including smoking, alcohol consumption, physical activity, diet, sleep duration, sedentary behavior, and social contact.
RESULTS: Over a median follow-up of 12.3 years, 4479 (2.6%) participants developed dementia. The presence of CMDs was dose-dependently associated with an increased risk of dementia. Compared with participants with no CMDs and a favourable lifestyle, those with ≥ 3 CMDs and an unfavourable lifestyle had a five times greater risk of developing dementia (HR 5.33, 95% CI 4.26-6.66). A significant interaction was found between CMD status and lifestyle (Pinteraction=0.001). The absolute difference in incidence rates of dementia per 1000 person years comparing favourable versus unfavourable lifestyle was - 0.65 (95% CI - 1.02 to - 0.27) among participants with no CMDs and - 5.64 (- 8.11 to - 3.17) among participants with ≥ 3 CMDs, corresponding to a HR of 0.71 (0.58-0.88) and 0.42 (0.28-0.63), respectively. In the imaging subsample, a favourable lifestyle was associated with larger total brain, grey matter, and hippocampus volumes across CMD status.
CONCLUSIONS: Our findings suggest that adherence to a healthy lifestyle might substantially attenuate dementia risk and adverse brain structural changes associated with cardiometabolic multimorbidity.

To investigate the association between kidney function with the risk of dementia and brain volumes.
A total of 452,996 UK Biobank participants with calculated glomerular filtration rate (eGFR) and albumin-to-creatinine ratio (ACR) were included. We utilized Cox proportional hazards regression models and restricted cubic spline analyses to examine the relationships between kidney function and the risk of all-cause dementia (ACD), Alzheimer\'s disease (AD), and vascular dementia (VD). Additionally, we explored the correlations between kidney function and brain magnetic resonance indicators among 40,380 participants.
During a median follow-up of 12 years, 5,258 incident ACD cases were identified. The deterioration of kidney function was associated with an increased risk of ACD. When compared to eGFR ≥ 90 ml/min/1.73 m², the highest risk increase was evident for eGFRcre < 30 ml/min/1.73 m² (adjusted HR = 2.372, 95% CI: 1.444-3.897, P < 0.001), with eGFRcys showing greater significance (adjusted HR = 3.045, 95% CI: 2.212-4.191, P < 0.001), especially in relation to AD. Compared to the ACR level in the range of 3-30 mg/mmol, the category of > 30 mg/mmol was associated with an increased risk of ACD (adjusted HR = 1.720, 95% CI: 1.350-2.190, P < 0.001). Moreover, the decline in kidney function was associated with the total brain volume atrophy and reduction in certain subcortical areas.
Our study indicates that diminished kidney function, as evidenced by a drop in eGFR and aggravated proteinuria, elevates dementia risk. Associated brain structural changes further underpin this connection from a neuro-pathophysiological perspective.