Publications

Current pharmacological therapy for Alzheimer's disease (AD) includes the cholinesterase inhibitors (ChEIs) donepezil, rivastigmine, and galantamine and the N-methyl D-aspartate receptor antagonist memantine. Based on the results of randomized controlled trials and several meta-analyses, ChEIs appear to show modest but statistically significant improvements on several measures, including cognition and global functioning. Given their modest effects, there is a lack of consensus among clinicians regarding issues related to initiation, optimal duration, and discontinuation of ChEI therapy across the spectrum of AD. There is evidence from long-term observational controlled studies that early initiation and persistent exposure to AD therapy lead to delays in nursing home admission and significantly slower rates of cognitive and functional impairment. In the moderate to severe stages of AD, therapeutic trials of higher dose ChEIs and the addition of memantine are recommended for patients who are no longer responding to lower doses. While side effects are generally mild and gastrointestinal in nature, these events can lead to significant morbidity in more susceptible patients with advanced disease. Patients should thus be regularly monitored for any potential serious side effects of ChEI therapy, which also may include syncope and bradycardia. At the terminal stages of AD, such as when patients become hospice eligible, attempts to cautiously discontinue all medications not necessary for quality of life, including AD drugs, should be made.

BACKGROUND

Anemia is very common in patients with human immunodeficiency virus (HIV)-associated tuberculosis, and hepcidin may be key in mediating this. We explored the relationship between blood hepcidin concentrations and anemia severity, mycobacterial burden and mortality in patients with HIV-associated tuberculosis.

METHODS

Consecutive unselected HIV-infected adults in South Africa were systematically investigated for tuberculosis. Three groups were studied: 116 hospitalized inpatients with HIV infection and tuberculosis (hereafter, "hospitalized patients"), 58 ambulatory outpatients with HIV infection and newly diagnosed tuberculosis (hereafter, "ambulatory patients with tuberculosis"), and 58 ambulatory outpatients with HIV infection and without tuberculosis (hereafter, "ambulatory patients without tuberculosis"). Blood hepcidin concentrations were determined for all patients. Vital status at 3 months was determined, and independent predictors of mortality were identified.

RESULTS

Median hepcidin concentrations were 38.8 ng/mL among hospitalized patients, 19.1 ng/mL among ambulatory patients with tuberculosis, and 5.9 ng/mL among ambulatory patients without tuberculosis (P < .001). In both groups with HIV-associated tuberculosis, hepcidin concentrations were strongly associated with greater anemia severity. Additionally, strong, graded associations were observed between hepcidin and composite indices of mycobacterial burden and dissemination. Patients dying within 3 months had significantly higher hepcidin concentrations, which independently predicted mortality.

CONCLUSIONS

High hepcidin concentrations were strongly associated with disseminated disease, anemia, and poor prognosis in patients with HIV-associated tuberculosis. Hepcidin may be a mechanistically important mediator underlying the high prevalence of severe anemia in these patients.