Prevalence of dementia in the United States: the aging, demographics, and memory study.

AIM: To estimate the prevalence of Alzheimer's disease (AD) and other dementias in the USA using a nationally representative sample. METHODS: The Aging, Demographics, and Memory Study sample was composed of 856 individuals aged 71 years and older from the nationally representative Health and Retirement Study (HRS) who were evaluated for dementia using a comprehensive in-home assessment. An expert consensus panel used this information to assign a diagnosis of normal cognition, cognitive impairment but not demented, or dementia (and dementia subtype). Using sampling weights derived from the HRS, we estimated the national prevalence of dementia, AD and vascular dementia by age and gender. RESULTS: The prevalence of dementia among individuals aged 71 and older was 13.9%, comprising about 3.4 million individuals in the USA in 2002. The corresponding values for AD were 9.7% and 2.4 million individuals. Dementia prevalence increased with age, from 5.0% of those aged 71-79 years to 37.4% of those aged 90 and older. CONCLUSIONS: Dementia prevalence estimates from this first nationally representative population-based study of dementia in the USA to include subjects from all regions of the country can provide essential information for effective planning for the impending healthcare needs of the large and increasing number of individuals at risk for dementia as our population ages.

Cryptosporidium parvum-specific antibody responses among children residing in Milwaukee during the 1993 waterborne outbreak.

A major gastroenteritis outbreak among >400,000 residents of Milwaukee, Wisconsin, in April 1993 was attributed to Cryptosporidium parvum oocysts in drinking water. Plasma specimens obtained from children (6 months to 12 years old) for routine blood lead level surveillance March-May 1993 were assayed by ELISA for levels of IgG antibody against the immunodominant Triton-17 and 27-kDa C. parvum antigens. Over a 5-week period, the seroprevalence for antibodies to the 2 antigens increased from 15% to 82% and from 17% to 87%, respectively, in samples from children living in southern ZIP code areas (n=218), whereas smaller increases (20% to 43% and 22% to 46%, respectively) were noted among samples from children living in northern ZIP code areas (n=335; P<.0001). The results demonstrate that C. parvum infection was much more widespread than previously appreciated and confirm that infection was associated with residence in the area served by the southern water treatment plant.

Circadian rhythmicity in the locomotor activity of larval zebrafish.

The zebrafish (Danio rerio) may be useful for mutational analyses of vertebrate circadian clock mechanisms if efficient assays of circadian rhythmicity are available. Using an automated video image analysis system, we found robust circadian rhythms in the locomotor activity of larval (10- to 15-day-old) zebrafish maintained in constant conditions. Activity was rhythmic in > 95% of the animals tested. The timing of peak activity in constant conditions was determined by the prior light:dark cycle, with highest activity during the subjective day. The mean freerunning period of the activity rhythms was 25.6 h, and the within-experiment standard deviation of freerunning period ranged from 0.5 to 1.0 h. Therefore, it should be possible to detect mutations that lengthen or shorten the freerunning circadian period of zebrafish activity rhythms by 1-2 h.

The significance of circadian organization for longevity in the golden hamster.

While functional roles for biological clocks have been demonstrated in organisms throughout phylogeny, the adaptive advantages of circadian organization per se are largely matters of conjecture. It is generally accepted, though without direct experimental evidence, that organisms derive primary benefits from the temporal organization of their physiology and behavior, as well as from the anticipation of daily changes in their environment and their own fluctuating physiological requirements. However, the consequences of circadian dysfunction that might demonstrate a primary adaptive advantage and explain the natural origins and apparent ubiquity of circadian systems have not been documented. The authors report that longevity in hamsters is decreased with a noninvasive disruption of rhythmicity and is increased in older animals given suprachiasmatic implants that restore higher amplitude rhythms. The results substantiate the importance of the temporal organization of physiology and behavior provided by the circadian clock to the health and longevity of an organism.

Circadian rhythms of locomotor activity in zebrafish.

As part of an effort to characterize the circadian system of the zebrafish, we examined the circadian regulation of locomotor activity in adult males and females. Gross locomotor activity was measured using infrared movement detectors. The effects of light, dark, and temperature on the amplitude, phase, and free-running periods of locomotor rhythms were determined. When zebrafish were maintained in a 12-h light:12 h dark cycle at 25 degrees C, 86% of the fish were most active during the light phase of the cycle. The phases of free-running rhythms measured after transfer of fish from light cycles to constant conditions indicate that this diurnal activity profile reflects entrained circadian rhythmicity. When animals were maintained in constant conditions, the proportion that expressed significant circadian rhythmicity depended on ambient temperature. At 21 degrees C, 73% of the animals were rhythmic in constant darkness, and 65% were rhythmic in constant light. Fewer (28-59%) were rhythmic at 18 degrees, 25 degrees, and 28.5 degrees C. The free-running period of rhythmic animals was not affected by temperature within this range. The average period was shorter in constant light (LL; 12 lx) than in constant darkness (DD) in all but one experiment, and the difference was statistically significant for animals held at 21 degrees C. These data indicate that zebrafish locomotor activity is regulated by a circadian clock that is temperature compensated. Because rhythmicity is most robust at 21 degrees C, this would be the optimal temperature for future studies of the physiological basis of zebrafish behavioral rhythms.

Asset and Health Dynamics Among the Oldest Old: an overview of the AHEAD Study.

This chapter provides background information for the study of Asset and Health Dynamics Among the Oldest Old (AHEAD), a prospective panel survey of persons born in 1923 or earlier who were residing in the community at the time of the 1993 baseline. Interviews were sought with both spouses in married households, and an overall total of 8,222 were completed. We review the interdisciplinary scientific issues that motivated the study, describe the fundamental design decisions that structured AHEAD, and summarize the content in the core and experimental modules. The study provides unusually detailed data on cognition, family structure and transfers, and assets. Data are presented on sample selections, response rates, and oversamples of minority groups. Basic descriptive data on the demographic, health, and socioeconomic attributes of respondents also are presented. Plans for future waves of AHEAD are described, including a next-of-kin interview for decreased respondents.

Inactivation of Cryptosporidium parvum oocysts and Clostridium perfringens spores by a mixed-oxidant disinfectant and by free chlorine.

Cryptosporidium parvum oocysts and Clostridium perfringens spores are very resistant to chlorine and other drinking-water disinfectants. Clostridium perfringens spores have been suggested as a surrogate indicator of disinfectant activity against Cryptosporidium parvum and other hardy pathogens in water. In this study, an alternative disinfectant system consisting of an electrochemically produced mixed-oxidant solution (MIOX; LATA Inc.) was evaluated for inactivation of both Cryptosporidium parvum oocysts and Clostridium perfringens spores. The disinfection efficacy of the mixed-oxidant solution was compared to that of free chlorine on the basis of equal weight per volume concentrations of total oxidants. Batch inactivation experiments were done on purified oocysts and spores in buffered, oxidant demand-free water at pH 7 an 25 degrees C by using a disinfectant dose of 5 mg/liter and contact times of up to 24 h. The mixed-oxidant solution was considerably more effective than free chlorine in activating both microorganisms. A 5-mg/liter dose of mixed oxidants produced a > 3-log10-unit (> 99.9%) inactivation of Cryptosporidium parvum oocysts and Clostridium perfringens spores in 4 h. Free chlorine produce no measurable inactivation of Cryptosporidium parvum oocysts by 4 or 24 h, although Clostridium perfringens spores were inactivated by 1.4 log10 units after 4 h. The on-site generation of mixed oxidants may be a practical and cost-effective system of drinking water disinfection protecting against even the most resistant pathogens, including Cryptosporidium oocysts.

Medical insurance and the use of health care services by the elderly.

The objective of this paper is to find how health insurance influences the use of health care services by the elderly. On the basis of the first wave of the Asset and Health Dynamics Survey, we find that those who are the most heavily insured use the most health care services. Because our data show little relationship between observable health measures and either the propensity to hold or to purchase private insurance, we interpret this as an effect of the incentives embodied in the insurance, rather than as the result of adverse selection in the purchase of insurance.

Inactivation of Cryptosporidium parvum Oocysts and Clostridium perfringens Spores by a Mixed-Oxidant Disinfectant and by Free Chlorine.

Volume 63, no. 4, p. 1600: The caption to Table 2 should read as follows: "Inactivation of Clostridium perfringens spores by 5-mg/liter doses of mixed oxidants or free chlorine in buffer at pH 7 at 25(deg)C." [This corrects the article on p. 1598 in vol. 63.].

Pacemaker interactions in the mammalian circadian system.

Circadian rhythms in mammals are generated by pacemaker cells located in the suprachiasmatic nucleus (SCN) of the anterior hypothalamus. The identity of these cells, however, is not known, and little information exists regarding the mechanisms by which they communicate with each other and with the organism. Nonetheless, pacemaker interactions must occur to produce single, coherent rhythms of behavior and physiology. Recently it has become possible to observe the result of these interactions using circadian chimeras, animals with two clocks with distinct periods, that have been produced by SCN transplantation. Using the tau mutation in golden hamsters, chimeras expressing two circadian rhythms of behavior simultaneously were created. The two rhythms exhibited complex interactions including cases of relative coordination. This basic result indicates that pacemaker interactions are rhythmic and phase dependent. Further analysis should help to elucidate the nature of the coupling signal and the identity of the pacemaker cells.

Pacemaker interactions in the mammalian circadian system

Circadian rhythms in mammals are generated by pacemaker cells located in the suprachiasmatic nucleus (SCN) of the anterior hypothalamus. The identity of these cells, however, is not known, and little information exists regarding the mechanisms by which they communicate with each other and with the organism. Nonetheless, pacemaker interactions must occur to produce single, coherent rhythms of behavior and physiology. Recently it has become possible to observe the result of these interactions using circadian chimeras, animals with two clocks with distinct periods, that have been produced by SCN transplantation. Using the tau mutation in golden hamsters, chimeras expressing two circadian rhythms of behavior simultaneously were created. The two rhythms exhibited complex interactions including cases of relative coordination. This basic result indicates that pacemaker interactions are rhythmic and phase dependent. Further analysis should help to elucidate the nature of the coupling signal and the identity of the pacemaker cells.

Circadian locomotor rhythms in aged hamsters following suprachiasmatic transplant.

Circadian activity rhythms that have been eliminated by lesions of the suprachiasmatic nucleus (SCN) can be restored by fetal SCN grafts. Partial lesions of the host allow simultaneous expression of both donor and host rhythms. Because partial SCN ablation produces characteristic changes in activity rhythms that are similar to those that occur with age, including shortened period, reduced amplitude, and fragmentation, we investigated the extent to which fetal SCN grafts may be expressed by an animal whose activity rhythm exhibits these age-dependent changes. The results indicate that expression of a transplanted clock is possible in an unlesioned aged host. Grafts of fetal SCN into young hosts and cortical tissue grafts into intact aged hosts have no effect. In those aged animals that received SCN grafts, three patterns of expression emerged in the subsequent locomotor activity record: complete dominance of locomotor rhythmicity by the donor; relative coordination between donor and host rhythms; and spontaneous switching between host and donor phenotypes. The results suggest that the expression of rhythmicity by the grafted SCN may depend on the relative amplitude or strength of signals produced by the host and donor SCN.

A new method for evaluating experimental cryptosporidial parasite loads using immunofluorescent flow cytometry.

A flow cytometric method for the quantification of Cryptosporidium parvum oocysts in stool specimens was developed to replace conventional microscopic immunofluorescent assays. Fecal pellets were collected from control (uninfected) severe combined immune-deficient mice, suspended in 2.5% potassium dichromate at a ratio of 400 microliter per pellet, and homogenized by vortexing. Purified oocytes were added to the samples (10(5), 10(4), 10(3), and 10(2)/ml). Aliquots (200 microliters) of the vortexed samples were centrifuged over microscale discontinuous sucrose gradients. The oocyst-containing fractions were collected, washed, and incubated with an oocyst-specific monoclonal antibody (labeled with fluorescein isothiocyanate) for 30 min at 37 degrees C. Sample volumes were adjusted to 600 microliters with phosphate-buffered saline and assayed by using logical gating of forward/side scatter and fluorescence signal on a flow cytometer. Seeded samples showed a linear correlation with the number of oocysts recovered from the gradients. Analyses of stool samples from chronically infected mice demonstrated that the flow cytometry method was approximately 10 times more sensitive than conventional immunofluorescent assays.

Split tolerance in spleen chimeras.

Transferring small doses of T cells to heavily irradiated F1 mice expressing isolated MHC class I or class II differences invariably leads to rapid death from graft-vs-host disease (GVHD). Paradoxically, GVHD is mild or absent when irradiated F1 mice are reconstituted with large doses of unseparated parental strain spleen cells. This applies when bulk populations of B6 spleen cells are transferred to irradiated class II-different (B6 x bm12)F1 mice or class I-different (B6 x bm1)F1 mice. In this study, we examined whether the donor T cells in long-term spleen chimeras become tolerant to host MHC Ags. On the basis of skin-allograft rejection and induction of GVHD on adoptive transfer, the results show that the donor T cells display strong tolerance to host antigens; this applies to CD4+ cells in class II-different chimeras and to CD8+ cells in class I-different chimeras. In marked contrast to the profound tolerance seen by these in vivo parameters, little or no tolerance is observed in standard in vitro assays. The results illustrate that typical in vitro tests for alloreactivity are an imprecise guide to physiologic tolerance of T cells in vivo.

Circadian pacemakers in vertebrates.

The identification and isolation of circadian pacemaker cells is of critical importance to studies of circadian clocks at all phylogenetic levels. In the vertebrate classes, a few structures of diencephalic origin have been implicated as potential sites but for only two, the avian pineal and the mammalian suprachiasmatic nucleus (SCN), has a pacemaker role in addition to oscillatory behaviour been demonstrated by the transfer of pacemaker properties from one organism to another. Studies of the mammalian system in particular have benefited from the ability to restore circadian function using transplantation of tissue from the SCN and from the availability of a hamster period mutant, tau, that allows donor-derived and host-derived rhythms to be distinguished easily. Initial cross-genotype transplantation studies and the subsequent creation of circadian chimeras expressing two phenotypes simultaneously demonstrated the pacemaker capability of the SCN, and demonstrated the relative autonomy of this nucleus as a pacemaking structure. Despite an abundance of information regarding the anatomy, physiology and pharmacology of these nuclei, the identity of the pacemaker cells and their methods of communication with each other and the organism remain obscure. None the less, it is possible under certain conditions to create chimeras with two clocks that interact. The behaviour of these animals provides a unique opportunity to study the nature and timing of pacemaker communication.