Coblechu0797

Predicting the prognosis of mild cognitive impairment (MCI) has outstanding clinical value, and the hippocampal volume is a reliable imaging biomarker of AD diagnosis.

We aimed to longitudinally assess hippocampal sub-regional difference (volume and asymmetry) among progressive MCI (pMCI), stable MCI (sMCI) patients, and normal elderly.

We identified 29 pMCI, 52 sMCI, and 102 normal controls (NC) from the ADNI database. All participants underwent neuropsychological assessment and 3T MRI scans three times. The time interval between consecutive MRI sessions was about 1 year. Volumes of hippocampal subfield were measured by Freesurfer. Based on the analysis of variance, repeated measures analyses, and receiver operating characteristic curves, we compared cross-sectional and longitudinal alteration sub-regional volume and asymmetry index.

Compared to NC, both MCI groups showed significant atrophy in all subfields. At baseline, pMCI have a smaller volume than sMCI in the bilateral subiculum, molecular layer (ML), the molecular and granule cell layers of the dentate gyrus, cornu ammonis 4, and right tail. selleck chemical Furthermore, repeated measures analyses revealed that pMCI patients showed a faster volume loss than sMCI in bilateral subiculum and ML. After controlling for age, gender, and education, most results remained unchanged. However, none of the hippocampal sub-regional volumes performed better than the whole hippocampus in ROC analyses, and no asymmetric difference between pMCI and sMCI was found.

The faster volume loss in subiculum and ML suggest a higher risk of disease progression in MCI patients. The hippocampal asymmetry may have smaller value in predicting the MCI prognosis.

The faster volume loss in subiculum and ML suggest a higher risk of disease progression in MCI patients. The hippocampal asymmetry may have smaller value in predicting the MCI prognosis.

We performed exploratory analyses of retinal thickness data from a clinical trial of the AβPP cleaving enzyme (BACE) inhibitor verubecestat in patients with Alzheimer's disease (AD).

To evaluate 1) possible retinal thickness changes following BACE inhibition; and 2) possible association between retinal thickness and brain atrophy.

Retinal thickness was measured using spectral-domain optical coherence tomography in a 78-week randomized placebo-controlled trial of verubecestat in 1,785 patients with mild-to-moderate AD. Changes from baseline in retinal pigment epithelium, macular grid retinal nerve fiber layer, central subfield retinal thickness, and macular grid volume were evaluated for verubecestat versus placebo. Correlation analyses were performed to investigate the potential association between macular grid retinal nerve fiber layer and central subfield retinal thickness with brain volumetric magnetic resonance imaging (vMRI) data at baseline, as well as correlations for changes from baseline at Week 78 in patients receiving placebo.

Verubecestat did not significantly alter retinal thickness during the trial compared with placebo. At baseline, mean macular grid retinal nerve fiber layer and central subfield retinal thickness were weakly but significantly correlated (Pearson's r values≤0.23, p-values < 0.01) with vMRI of several brain regions including whole brain, hippocampus, and thalamus. At Week 78, correlations between retinal thickness and brain vMRI changes from baseline in the placebo group were small and mostly not statistically significant.

BACE inhibition by verubecestat was not associated with adverse effects on retinal thickness in patients with mild-to-moderate AD. Correlations between retinal thickness and brain volume were observed at baseline.

Clinicaltrials.gov NCT01739348 (registered December 3, 2012; https//clinicaltrials.gov/ct2/show/NCT01739348).

Clinicaltrials.gov NCT01739348 (registered December 3, 2012; https//clinicaltrials.gov/ct2/show/NCT01739348).

Alzheimer's disease (AD) is characterized by accumulation of amyloid-β (Aβ) species and deposition of senile plaques (SPs). Clinical trials with the anti-Aβ antibody aducanumab have been completed recently.

To characterize the proteomic profile of SPs and surrounding tissue in a mouse model of AD in 10-month-old tgAPPPS1-21 mice after chronic treatment with aducanumab for four months with weekly dosing (10 mg/kg).

After observing significant reduction of SP numbers in hippocampi of aducanumab-treated mice, we applied a localized proteomic analysis by combining laser microdissection and liquid chromatography-tandem mass spectrometry (LC-MS/MS) of the remaining SPs in hippocampi. We microdissected three subregions, containing SPs, SP penumbra level 1, and an additional penumbra level 2 to follow the proteomic profile as gradient.

In the aducanumab-treated mice, we identified 17 significantly regulated proteins that were associated with 1) mitochondria and metabolism (ACAT2, ATP5J, ETFA, EXOG, HK1, NDUFA4, NDUFS7, PLCB1, PPP2R4), 2) cytoskeleton and axons (ADD1, CAPZB, DPYSL3, MAG), 3) stress response (HIST1H1C/HIST1H1D, HSPA12A), and 4) AβPP trafficking/processing (CD81, GDI2). These pathways and some of the identified proteins are implicated in AD pathogenesis. Proteins associated with mitochondria and metabolism were mainly upregulated while proteins associated with AβPP trafficking/processing and stress response pathways were mainly downregulated, suggesting that aducanumab could lead to a beneficial proteomic profile around SPs in tgAPPPS1-21 mice.

We identified novel proteomic patterns of SPs and surrounding tissue indicating that chronic treatment with aducanumab could inhibit Aβ toxicity and increase phagocytosis and cell viability.

We identified novel proteomic patterns of SPs and surrounding tissue indicating that chronic treatment with aducanumab could inhibit Aβ toxicity and increase phagocytosis and cell viability.Patients admitted with COVID-19 can develop delirium due to predisposing factors, isolation, and the illness itself. Standard delirium prevention methods focus on interaction and stimulation. It can be challenging to deliver these methods of care in COVID settings where it is necessary to increase patient isolation. This paper presents a typical clinical vignette of representative patients in a tertiary care hospital and how a medical team modified an evidence-based delirium prevention model to deliver high-quality care to COVID-19 patients. The implemented model focuses on four areas of delirium-prevention Mobility, Sleep, Cognitive Stimulation, and Nutrition. Future studies will be needed to track quantitative outcome measures.