Association between household size and risk of incident dementia in the UK Biobank study.

Currently, the relationship between household size and incident dementia, along with the underlying neurobiological mechanisms, remains unclear. This prospective cohort study was based on UK Biobank participants aged ≥ 50 years without a history of dementia. The linear and non-linear longitudinal association was assessed using Cox proportional hazards regression and restricted cubic spline models. Additionally, the potential mechanisms driven by brain structures were investigated by linear regression models. We included 275,629 participants (mean age at baseline 60.45 years [SD 5.39]). Over a mean follow-up of 9.5 years, 6031 individuals developed all-cause dementia. Multivariable analyses revealed that smaller household size was associated with an increased risk of all-cause dementia (HR, 1.06; 95% CI 1.02-1.09), vascular dementia (HR, 1.08; 95% CI 1.01-1.15), and non-Alzheimer's disease non-vascular dementia (HR, 1.09; 95% CI 1.03-1.14). No significant association was observed for Alzheimer's disease. Restricted cubic splines demonstrated a reversed J-shaped relationship between household size and all-cause and cause-specific dementia. Additionally, substantial associations existed between household size and brain structures. Our findings suggest that small household size is a risk factor for dementia. Additionally, brain structural differences related to household size support these associations. Household size may thus be a potential modifiable risk factor for dementia.

An NIR-IIb emissive transmembrane voltage nano-indicator for the optical monitoring of electrophysiological activities in vivo.

In vivo transmembrane-voltage detection reflected the electrophysiological activities of the biological system, which is crucial for the diagnosis of neuronal disease. Traditional implanted electrodes can only monitor limited regions and induce relatively large tissue damage. Despite emerging monitoring methods based on optical imaging have access to signal recording in a larger area, the recording wavelength of less than 1000 nm seriously weakens the detection depth and resolution in vivo. Herein, a Förster resonance energy transfer (FRET)-based nano-indicator, NaYbF4:Er@NaYF4@Cy7.5@DPPC (Cy7.5-ErNP) with emission in the near-infrared IIb biological window (NIR-IIb, 1500-1700 nm) is developed for transmembrane-voltage detection. Cy7.5 dye is found to be voltage-sensitive and is employed as the energy donor for the energy transfer to the lanthanide nanoparticle, NaYbF4:Er@NaYF4 (ErNP), which works as the acceptor to achieve electrophysiological signal responsive NIR-IIb luminescence. Benefiting from the high penetration and low scattering of NIR-IIb luminescence, the Cy7.5-ErNP enables both the visualization of action potential in vitro and monitoring of Mesial Temporal lobe epilepsy (mTLE) disease in vivo. This work presents a concept for leveraging the lanthanide luminescent nanoprobes to visualize electrophysiological activity in vivo, which facilitates the development of an optical nano-indicator for the diagnosis of neurological disorders.

Altered neurovascular coupling in migraine without aura.

Neurovascular coupling (NVC) provides new insights into migraine, a neurological disorder impacting over one billion people worldwide. This study compared NVC and cerebral blood flow (CBF) in patients with migraine without aura (MwoA) and healthy controls. About 55 MwoA patients in the interictal phase and 40 age- and sex-matched healthy controls underwent resting-state functional magnetic resonance imaging and arterial spin-labeling perfusion imaging scans. The CBF and resting-state neuronal activity indicators, including the amplitudes of low-frequency fluctuation (ALFF), regional homogeneity (ReHo), and degree centrality (DC), were calculated for each participant. The global and regional NVCs were assessed using cross-voxel CBF-neuronal activity correlations and CBF/neuronal activity ratios. Patients with MwoA showed increased CBF/ALFF ratios in the left media, superior and inferior frontal gyri, and anterior cingulate gyrus, increased CBF/DC ratios in the left middle and inferior frontal gyri, and increased CBF/ReHo ratios in the right corpus callosum and right posterior cingulate gyrus. Lower CBF/ALFF ratios in the right rectal gyrus, the left orbital gyrus, the right inferior frontal gyrus, and the right superior temporal gyrus were also found in the MwoA patients. Furthermore, the CBF/ALFF ratios in the inferior frontal and superior temporal gyri were positively correlated with the Headache Impact Test scores and Hamilton anxiety scale scores in the MwoA patients. These findings provide evidence for the theory that abnormal NVC contributes to MwoA.

Simultaneous ischemic regions targeting and BBB crossing strategy to harness extracellular vesicles for therapeutic delivery in ischemic stroke.

Extracellular vesicles (EVs) derived from adipose-derived stem cells (ADSC-EVs) hold great promise for ischemic stroke treatment, but their therapeutic efficacy is greatly limited due to insufficient targeting ability. Previous reports focused on single ischemic targeting or blood-brain barrier (BBB) penetration, precise delivery to the brain parenchyma has not been fully considered. This study leveraged the targeting ability of RGD peptide and the cell penetrating ability of Angiopep-2 peptide to deliver ADSC-EVs precisely to the impaired brain parenchyma. We found that dual-modified EVs (RA-EVs) significantly enhanced the transcellular permeability across BBB in vitro, and not only targeted ischemic blood vessels but also achieved rapid accumulation in the ischemic lesion area after intravenous administration in vivo. RA-EVs further decreased the infarct volume, apoptosis, BBB disruption, and neurobehavioral deficits. RNA sequencing revealed the molecular regulation mechanism after administration. These findings demonstrate that dual-modification optimizes brain parenchymal targeting and highlights the significance of recruitment and penetration as a previously unidentified strategy for harnessing EVs for therapeutic delivery in ischemic stroke.