Development of an accelerated cellular model for early changes in Alzheimer's disease.

Alzheimer's Disease (AD) is a leading cause of dementia characterized by amyloid plaques and neurofibrillary tangles, and its pathogenesis remains unclear. Current cellular models for AD often require several months to exhibit phenotypic features due to the lack of an aging environment in vitro. Lamin A is a key component of the nuclear lamina. Progerin, a truncated protein resulting from specific lamin A mutations, causes Hutchinson-Gilford Progeria Syndrome (HGPS), a disease that prematurely ages individuals. Studies have reported that lamin A expression is induced in the brains of AD patients, and overlapping cellular phenotypes have been observed between HGPS and AD cells. In this study, we investigated the effects of exogenous progerin expression on neural progenitor cells carrying familial AD mutations (FAD). Within three to four weeks of differentiation, these cells exhibited robust AD phenotypes, including increased tau phosphorylation, amyloid plaque accumulation, and an elevated Aß42 to Aß40 ratio. Additionally, progerin expression significantly increased AD cellular phenotypes such as cell death and cell cycle re-entry. Our results suggest that progerin expression could be used to create an accelerated model for AD development and drug screening.

Quantifying the Cost of Disability Transitions in Medicare.

OBJECTIVE: To investigate the impact of disability transitions on annual Medicare Part A and B cost. METHOD: We analyzed 6,385 community-dwelling beneficiaries who were continuously enrolled in fee-for-service Medicare Part A and B from 2008 to 2009. We estimated adjusted effects of disability transitions on Medicare cost using a generalized linear model. RESULTS: Transitions to more severe disability states were associated with significantly higher average annual Medicare cost ranging from US$2,639 to US$5,405. Lower spending levels were observed for beneficiaries with improvements in functioning. Beneficiaries who transitioned from severe to moderate activities of daily living (ADLs) disability cost significantly less (-US$6,045) than those who remained severely disabled. DISCUSSION: Interventions aimed at preventing disability progression and efforts to restore functional capacity are promising strategies for containing costs and generating savings for Medicare. Future research is needed to assess the longer term impact of disability in association with the progression of chronic conditions.

Stability of postoperative delirium psychomotor subtypes in individuals with hip fracture.

OBJECTIVES: To determine the stability of psychomotor subtypes of delirium over time and identify characteristics associated with delirium psychomotor subtypes in individuals undergoing surgical repair of hip fracture. DESIGN: Prospective cohort study. SETTING: The Transfusion Trigger Trial for Functional Outcomes in Cardiovascular Patients Undergoing Surgical Hip Fracture Repair Cognitive Ancillary Study was conducted at 13 participating sites from 2008 to 2009. PARTICIPANTS: Individuals who had undergone surgical repair of hip fracture (N=139). MEASUREMENTS: Delirium was assessed up to four times postoperatively using the Confusion Assessment Method (CAM) and the Memorial Delirium Assessment Scale. Psychomotor subtypes of delirium were categorized as hypoactive, hyperactive, mixed, and normal psychomotor activity. RESULTS: Incidence of postoperative delirium was 41% (n=57). Of 90 CAM-positive (CAM+) observations, 56% were hypoactive, 10% were hyperactive, 21% were mixed, and 14% had normal psychomotor symptoms. Of 26 participants with more than one CAM+ assessment, 50% maintained subtype stability over time. Participants with hypoactive or normal psychomotor symptoms (n=31) were less likely to have chart documentation of delirium than participants with any hyperactive symptoms (n=19) (22% vs 58%, P=.009). CONCLUSION: Psychomotor subtypes of delirium often fluctuate from assessment to assessment, rather than representing fixed categories of delirium. Hypoactive delirium is the most common presentation of delirium but is the least likely to be documented by healthcare providers.