Objective: To estimate age-specific incidence rates of AD in the Baltimore Longitudinal Study of Aging (BLSA). Background: The BLSA is a volunteer cohort of normal subjects followed longitudinally with biennial evaluations at the Gerontology Research Center of the National Institute on Aging. Methods: Subjects are 1236 participants (802 men, 434 women) in the BLSA with longitudinal follow-up between January 1985 and May 1998. The average length of follow-up was 7.5 years, with participants evaluated every 2 years by physical, neurologic, and neuropsychological examinations. Using Diagnostic and Statistical Manual of Mental Disorders, 3rd ed., revised and National Institute of Neurological and Communicative Disorders and Stroke–Alzheimer’s Disease and Related Disorders Association criteria, the authors diagnosed dementia and AD. Results: The authors diagnosed 155 cases of dementia, of which 114 (74%) were AD. Incidence rates of AD increased with age from an estimated 0.08% per year (95% CI 0.00 to 0.43) in the 60 to 65 age group to an estimated 6.48% per year (95% CI 5.01 to 8.38) in the 85+ age group for men and women combined. The doubling time of incidence rates was estimated to be approximately 4.4 years and the median time of conversion from mild cognitive impairment to diagnosis of AD was estimated to be 4.4 years. There was a trend for women to have higher incidence rates than men and for fewer years of education to be associated with higher incidence rates; however, these effects were not significant. Conclusion: Incidence rates for AD in the BLSA are consistent with published rates in other studies. The longitudinally followed subjects of the BLSA offer a unique opportunity to prospectively investigate the antecedents of AD.

Intracellular calcium signaling cascade induced by adenosine A3 receptor activation was studied in this work. It was found that adenosine A3 receptor activation (and not A1 or A2A adenosine receptors activation) leads to an increase in cytosolic calcium and its further extrusion. A selective A3 agonist Cl-IB-MECA (2-chloro-N6-(3-iodobenzyl)adenosine-5′-N-methyluronamide) induced an increase in cytoplasmic calcium in a dose-dependent manner, and was independent on extracellular calcium. The Ca2+ signal in newborn cardiomyocytes, induced by A3 receptor activation, is dependent on a pertussis toxin-sensitive G-protein. The action of Cl-IB-MECA was not inhibited by an inhibitor of phospholipase C (PLC), and by antagonists to inositol 1,4,5-trisphosphate (IP3) receptor. In contrast, inhibition of ryanodine receptor prevented calcium elevation induced by this agonist. It was shown that extrusion of the elevated cytosolic Ca2+ was achieved via activation of sarcoplasmic reticulum (SR) Ca2+-reuptake and of sarcolemmal Na+/Ca2+ exchanger (NCX). The increase in the SR Ca2+-uptake and NCX Ca2+ efflux were sufficient not only for compensation of Ca2+ release from SR after A3 receptor activation, but also for an effective prevention of extensive increase in intracellular Ca2+ and may provide mechanism against cellular Ca2+ overload. In cells with elevated [Ca2+]i (due to increase of [Ca2+]o), adenosine or Cl-IB-MECA decreased the [Ca2+]i toward diastolic control level, whereas agonist of A1 receptor was ineffective. The protective effect of A3 receptor agonist was abolished in the presence of selective A3 receptor antagonist MRS1523.

A procedure is described for the measurement of DL-alpha-difluoromethylornithine (DFMO), a selective irreversible inhibitor of ornithine decarboxylase, in biological specimens. The drug is separated from other amino acids with a commerical amino-acid analyser and detected by formation of its alkylthio-isoindole derivative with o-phthalaldehyde. DFMO concentrations of 0.1 nmol can be determined in a sample volume of 100 microliter. The assay has been used to determine the half-life of DFMO in serum of several species and the relationships between serum and tissue concentrations.