Dementia and disability: impact on mortality. The Italian Longitudinal Study on Aging.

Dementia is known to be associated with excess mortality. Physical disability, as a marker of dementia severity, is often considered the last step on the way from disease to death. The objective of this study was to investigate the direct effect of dementia on mortality in a population-based study, carried out in Italy, with a sample of 5,632 individuals aged 65-84 years. At 4-year follow-up, 998 participants had died. The independent predictors of death were: age (75-84 years; HR 2.63, CI = 2.11-3.27), male sex (HR 1.45, CI = 1.22-1.74), coronary heart disease (HR 1.61, CI = 1.34-1.94), moderate and severe instrumental activities of daily living disability (HR 1.98, CI = 1.30-3.03 and HR 3.26, CI = 2.09-5.09, respectively), diabetes in subjects with a survival time greater than 23 months (HR 0.68, CI = 0.43-1.08) and dementia (HR 2.07, CI = 1.62-2.66). These data provide evidence that dementia per se, independently from physical disability, is a strong predictor of death in the elderly.

Inhibition of fasL sustains phagocytic cells and delays myogenesis in regenerating muscle fibers.

Macrophage-muscle cell interactions are complex, and the majority is unknown. The persistence of inflammatory cells in skeletal muscle could be critical for myofiber viability. In the present paper, we show that FasL plays a role in the resolution of muscle inflammation. We analyzed inflamed muscles of normal mice treated from day 3 to day 8 with a FasL inhibitor (Fas-Ig) or with control Ig. Treated muscles were collected at 3, 5, and 10 days. The treatment with recombinant Fas-Ig protein induced a severe persistence of inflammatory cells at 5 days (115,000+/-27,838 vs. 41,661+/-6848, p<0.01) and 10 days from injury (145,500+/-40,850 vs. 5000+/-1000, p<0.001). Myofiber regeneration was highly impaired (37+/-14 vs. 252+/-28, p<0.01). Apoptosis of phagocytic cells was absent during Fas-Ig treatment (0.9+/-0.6 vs. 1300+/-150, p<0.0001), but apoptotic, mononucleated cells appeared at day 10, 2 days after the suspension of Fas-Ig administration. The time course of FasL expression during muscle inflammation, at mRNA and protein level, reveals a peak during myoblast proliferation. The peak of FasL expression coincides with the peak of apoptosis of phagocytic cells. In situ hybridization shows the co-expression of FasL and MyoD mRNA in mononucleated cells, i.e., myoblasts. Experiments on the myoblast cell culture confirmed the expression of FasL in myoblasts. The findings shown here indicate one of the pathways to control myoblast-macrophage interaction and might be relevant for the control of inflammatory cells in muscle tissue. Perhaps altering FasL expression with recombinant proteins could ameliorate inflammation in degenerative myopathies and up-regulate muscle regeneration.

Long-term persistence of low bone density in orthotopic liver transplantation.

We determined bone density and metabolism in 46 patients (35 males, 11 females) who had undergone liver transplantation 1-48 months previously. Twenty-one patients were then followed for the next 24 months. At each visit, blood and urine samples for bone and liver metabolism parameters, as well as spinal and femoral dual-energy X-ray absorptiometry (DXA) scans, were obtained. Basal spinal and femoral density was low (p < 0.001). Patients with pre-transplant cholestatic diseases had lower spinal density than all the other subjects (p <0.05) and the cumulative methylprednisolone intake was an independent negative predictor of total hip density (p < 0.02). At baseline, urinary hydroxyproline and N-telopeptide were at the upper normal level and decreased only after 24 months of follow-up (p < 0.05). During the first year of follow-up, femoral density decreased (p < 0.05) and a partial recovery was observed for both spine and femur after 24 months. After 12 months, femoral bone density was negatively associated with serum cyclosporin A levels (p < 0.005) and cumulative methylprednisolone intake (p < 0.05), while the percent decrease in spinal density after the first 12 months was negatively predicted by mean daily methylprednisolone intake (p < 0.05). In patients with pre-transplant cholestatic diseases, femoral and spinal density increased after the first (p < 0.05) and second year (p < 0.05), respectively. In patients with previous post-necrotic cirrhosis, femoral density decreased after 12 months (p<0.05) and was still lower than baseline after 24 months (p < 0.05). However, at the end of the study the cumulative percentage of femoral neck osteoporosis was 43%. In conclusion, an elevated prevalence of spinal and femoral osteoporosis is present even many years after liver transplantation, with immunosuppressive treatment and pre-transplant liver disease being the most important pathogenetic factors.

The effect of recurrence of HCV infection of life after liver transplantation.

The present study evaluated the quality of life (QOL) of adult cirrhotic patients before orthotopic liver transplantation (OLT), the effect of OLT on QOL in the long-term and the effect of HCV recurrence within medical complications on QOL. Three groups of patients were studied: 19 pre-OLT, 33 during the first year post-OLT and 41 1 to 5 years post-OLT. The patients completed questionnaires on QOL and underwent liver function tests, immunosuppressive drug blood level determinations and medical complications evaluation. Somatization and depression and anxiety scores improved significantly during the first year post-OLT compared with pre-OLT, but they worsened again during the 1-5-year period post-OLT. Physical functioning and life satisfaction scores improved significantly during the first year post-OLT completed with pre-OLT and the improvement persisted 1-5-year during the period post-OLT. Patients with HCV recurrence compared with patients without HCV recurrence during the first year post-OLT showed a significant worsening of most of the domains of QOL. In conclusion, OLT improved most of the domains of QOL by the end of the first post-transplant year, though the improvements did not all persist in the long-term. Recurrence of HCV infection plays a major role in the impairment of QOL after OLT.