Assessing financial capacity in patients with Alzheimer disease: A conceptual model and prototype instrument.

OBJECTIVE: To investigate financial capacity in patients with Alzheimer disease (AD) using a new theoretical model and prototype psychometric instrument. DESIGN: Cross-sectional comparisons of older control subjects (n=23) and patients with mild (n=30) and moderate AD (n=20). MAIN OUTCOME MEASURES: Financial capacity was measured using the Financial Capacity Instrument, a prototype psychometric instrument that tests financial capacity using 14 tasks of financial ability comprising 6 clinically relevant domains of financial activity: basic monetary skills, financial conceptual knowledge, cash transactions, checkbook management, bank statement management, and financial judgment. RESULTS: The Financial Capacity Instrument tasks and domains showed adequate to excellent internal, interrater, and test-retest reliabilities. At the task level, patients with mild AD performed equivalently with controls on simple tasks such as counting coins/currency and conducting a 1-item grocery purchase, but significantly below controls on more complex tasks such as using a checkbook/register and understanding and using a bank statement. At the domain level, patients with mild AD performed significantly below controls on all domains except basic monetary skills. Patients with moderate AD performed significantly below controls and patients with mild AD on all tasks and domains. Regarding capacity status outcomes (capable, marginally capable, incapable) on domains, patients with mild AD had high proportions of marginally capable or incapable outcomes (range, 47%-87%), particularly on difficult domains like bank statement management (domain 5) and financial judgment (domain 6), but variability in individual outcomes. Patients with moderate AD had almost exclusively incapable outcomes across the 6 domains (range, 90%-100%). CONCLUSIONS: Financial capacity is already significantly impaired in mild AD. Patients with mild AD demonstrate deficits in more complex financial abilities and impairment in most financial activities. Patients with moderate AD demonstrate severe impairment of all financial abilities and activities. The Financial Capacity Instrument has promise as an instrument for assessing domain-level financial activities and task-specific financial abilities in patients with dementia. Arch Neurol. 2000.

Cannabinoids inhibit LPS-inducible cytokine mRNA expression in rat microglial cells.

The effect of cannabinoids on the induction of cytokine mRNA by rat microglial cells was examined. Exposure of neonatal rat cortical microglial cells to the exogenous cannabinoid delta(9)-tetrahydrocannabinol (THC) resulted in reduced amounts of lipopolysaccharide (LPS)-induced mRNAs for IL-1alpha, IL-1beta, IL-6, and TNF-alpha. Of these cytokine mRNAs, the response of that for IL-6 was exquisitely sensitive to THC. Similarly, exposure of microglial cells to the putative endogenous cannabinoid anandamide before LPS treatment resulted in a decrease in cytokine mRNA levels, but not to the same extent as that caused by THC; however, when methanandamide, the non-hydrolyzable analog of anandamide was tested, its ability to inhibit cytokine mRNA expression was comparable to that of THC. Exposure of microglial cells to either of the paired enantiomers CP55,940 or CP56,667 resulted in similar inhibition of LPS-induced cytokine mRNA expression. A comparable inhibitory outcome was obtained when the paired enantiomers levonantradol and dextronantradol were employed. Neither the CB(1)-selective antagonist SR141716A nor the CB(2)-selective antagonist SR144528 was able to reverse the inhibition of cytokine mRNA expression by levonantradol. The CB(2) antagonist, however, when administered alone augmented the production of cytokine mRNAs. Collectively, these studies demonstrate that cannabinoids can modulate levels of cytokine mRNA in rat microglial cells; however, the inhibition of cytokine mRNA expression is apparently not mediated through either the CB(1) or CB(2) cannabinoid receptors.

A method for assessing clinically relevant individual cognitive change in older adult populations.

The evaluation of individual cognitive change has relied heavily upon the raw change score, defined simply as the difference between follow-up and baseline scores. However, raw changes scores are susceptible to the confounding effects of both regression-to-the-mean and practice effect. The clinical relevance of raw change scores for the older adult is also obscured by normal, age-related cognitive change. The present study illustrates the use of a standardized regression-based (SRB) methodology to generate an alternative to the raw change score; the SRB change score. SRB change scores provide a standardized alternative to the raw change score, allowing the clinician to evaluate the magnitude of change on one or more variables along a common metric that controls for practice effect, regression-to-the-mean, and normal cognitive decline. Case data illustrate how SRB change scores can identify clinically relevant cognitive change in the individual older adult patient.

Comparison of olestra absorption in guinea pigs with normal and compromised gastrointestinal tracts.

Female guinea pigs (12/group) were given a single dose of [14C]olestra by gavage after consuming either 3% poligeenan in tap water (Compromised group) or just tap water (Normal group) for 5 weeks. A Sentinel group (N = 2) was given 3% poligeenan for 5 weeks. Ten sentinel animals were killed 1 day before and 10 1 day after the other animals were dosed with [14C]olestra and their gastrointestinal tracts were examined by histology. The Compromised and Normal animals were endoscoped just before dosing with [14C]olestra. Urine and feces were collected continuously and CO2 was collected for 7 days after dosing. The samples were analyzed for 14C and urine was also analyzed for [14C]sucrose. Animals (3/group) were killed 1, 3, 7, and 21 days after dosing, and tissues were collected and assayed for 14C. Tissue lipids were extracted, fractionated by high-pressure liquid chromatography, and analyzed for [14C]olestra by liquid scintillation. Animals fed poligeenan showed mucosal edema, congestion, ulceration, and fibrin deposition within the distal colon and rectum. Histology revealed inflammation, epithelial degeneration, and multifocal ulceration of the cecum, distal colon, and rectum. The gastrointestinal mucosae of nonpoligeenan fed animals were normal. No [14C]olestra was detected in liver lipids and no [14C]sucrose was found in the urine for any animal in the Normal or Compromised groups, indicating that intact olestra was not absorbed. The amount, distribution, and elimination of absorbed 14C did not differ between guinea pigs with normal and compromised gastrointestinal tracts. The poligeenan-treated animals displayed mucosal damage similar to that seen in human inflammatory bowel diseases; therefore, these results suggest that patients with inflammatory bowel conditions will not absorb olestra to any greater extent than normal healthy people.

Health beliefs and practices of rural elders.

Understanding the rural elderly is essential to developing effective programs to prevent disease and promote health.

An interactive perspective on the health beliefs & practices of rural elders.

1. In this study, major themes involving health were closely tied to an affective response of "feeling good" and cognitive appraisal of health status as "being able to function." 2. Rural elderly who participated in the study reported engaging in at least one activity to maintain their health and tended to rely on their own appraisal and resources to manage health problems. 3. Half of the participants indicated a need for services such as blood pressure and diabetic screening, health education classes on diet, cholesterol reduction, hypertension and diabetes management, new therapies in health care, and life management counseling.

Age-dependent responses to 2-acetylaminofluorene in BALB/c female mice.

In order to evaluate the influence of age on 2-acetylaminofluorene (2-AAF) carcinogenesis, female BALB/c mice were fed diets containing 500 ppm 2-AAF for 6 mo, starting at 1, 7, or 13 mo of age. Groups of mice were killed immediately, 3 or 6 mo after termination of treatment, or were allowed to complete their life span. Mice corresponding to the age of each sacrifice group of the 2-AAF-treated mice and a life-span group were also included as controls. The study was moved to a different animal room area after 25 wk into the study. Thus, certain treatment groups were replicated to evaluate the impact of the change in environment. Controls and the young 2-AAF-treatment group killed at 7 mo of age were replicated twice in the new animal room at 6-mo intervals. Similarly, controls and the mid-aged treatment group killed at 13 mo of age were repeated once in the new animal room. This resulted in mice of each age/treatment group being treated simultaneously in the same room and killed as soon as treatment was stopped. The main histopathologic responses to 2-AAF were observed in the urinary bladder, liver, and mammary glands. In all three replicates urinary bladder hyperplasia was less severe when young mice were treated than when mid-aged or old mice were treated. In contrast, there was no clear influence of age on bladder tumorigenesis, although replicate variation in this response was very great. Tentatively one also may conclude that (1) sensitivity to the induction of mammary tumorigenesis by 2-AAF increased with the age of mice at the time of treatment, and (2) old mice were sensitive to induction of liver karyomegaly and cytoplasmic and nuclear inclusions, while young and mid-aged mice were resistant to this influence. Perhaps the most important conclusion to be made from this study is that replicate variation, probably due to environmental factors, may result in false conclusions concerning age sensitivity to a carcinogen if differing age groups are not treated simultaneously and/or key parts of an experiment are not replicated to eliminate the possibility of an influence of environmental factors or nonrandom assignment of animals to age groups.

A lysosomal storage disorder in the BALB/c mouse: bone marrow transplantation.

The morphological and biochemical consequences of transplanting affected bone marrow from donor BALB/c mice with a lysosomal storage disorder (BALB/c LSD) into normal recipient mice were studied. Bone marrow was removed from normal BALB/c and BALB/c LSD mice and transfused into normal BALB/c recipient mice four hours after the mice received 850 rads of irradiation. Tissues of the recipient mice were examined 240 days later. This study revealed that the defective cells that constituted the visceral lesions of BALB/c LSD could be transplanted to normal BALB/c mice by the use of bone marrow from affected BALB/c LSD homozygote; that the defective cells of BALB/c LSD proliferated and disseminated throughout the mononuclear phagocytic system of the recipient; that there were increases in cholesterol, sphingolipids, and cystine with decreases in sphingomyelinase and glucocerebrosidase activity in tissues of the recipients; and that the recipients survived substantially longer than BALB/c LSD homozygotes and their lifespan was compromised mainly by the secondary effects of irradiation. These lesions, although not as extensive as in homozygous BALB/c LSD, paralleled the lesions which develop in BALB/c LSD. Since the recipient mice were not compromised by the short life span (70 days) of the BALB/c LSD mice, they may be used to study the long-term chronic effects of these metabolic lesions.

A genetic storage disorder in BALB/C mice with a metabolic block in esterification of exogenous cholesterol.

Cholesterol metabolism has been investigated in a strain of BALB/C mice that carry an autosomal recessive mutation associated with decreased sphingomyelinase and glucocerebrosidase activity and storage of sphingomyelin and glucocerebroside as well as cholesterol in lysosomes (Pentchev, P. G., Gal, A. E., Boothe, A. D., Omodeo-Sale, F., Fouks, J., Neumeyer, B. A., Quirk, J. M., Dawson, G., and Brady, R. O. (1980) Biochim. Biophys. Acta 619, 669-679). When affected animals are placed on a diet high in cholesterol, they develop hepatomegaly associated with an extensive accumulation of unesterified cholesterol in the liver. Cultured skin fibroblasts derived from these mice also manifest a defect in cholesterol esterification although the uptake and intracellular location of exogenous cholesterol is comparable to that of controls. Microsomal fatty acyl-CoA:cholesterol acyltransferase activity was normal or elevated in extracts of tissues from the affected animals. Furthermore, the subcellular distribution and membrane orientation of acyl-CoA:cholesterol acyltransferase appeared normal in microsomal preparations isolated from affected mice. The blockage of esterification of exogenous cholesterol in the presence of normal transferase activity is suggestive of a defect in a component involved in the intracellular disposition of this sterol. The attenuation in tissue levels of sphingomyelinase and glucocerebrosidase and the accumulation of sphingolipids may reflect alterations in lysosomal function resulting from an imbalance of unesterified cholesterol in these organelles.

Correlations between gross and microscopic lesions in carcinogenic studies in mice.

Microscopic diagnoses of a number of spontaneous and induced neoplasms in mice were correlated with the gross findings of the ED01 and a number of other carcinogenic studies conducted at NCTR to determine the value of detailed histopathologic examinations in bioassay testing. The results indicated that for organs such as thymus, lung, adrenal, Harderian gland and urinary bladder 50% or more of the neoplastic lesions would be missed if at least one histological section were not examined from each organ. For organs such as the liver and mammary gland, a single tissue section did not greatly improve the ability to detect neoplastic lesions beyond that afforded by a thorough necropsy examination.

A lysosomal storage disorder in mice characterized by the accumulation of several sphingolipids.

A strain of BALB/c mice with an autosomal recessive neurologic disorder has been reported previously [1, 2]. The tissues of affected animals have been further examined and the activities of varius lysosomal hydrolases and levels of sphingolipids were compared to those in control mice. There was a substantial diminution of sphingomyelinase and glucocerebrosidase activities in liver, spleen, lung, thymus, and kidney of affected mice. There was a corresponding accumulation of sphingomyelin and glucocerebroside in these tissues. The activity of several other lysosomal hydrolases was elevated. Heterozygotes did not show any of the enzymatic alterations. The brain of affected animals showed substantial accumulation of the gangliosides GM3 and GM2.

Experimental toxoplasmosis in calves and pregnant cows.

Experimental Toxoplasma gondii infections were studied in pregnant cows and in calves. In tests to compare their virulence, three strains of the toxoplasmal parasite were red to cats; then fecal oocysts were collected and given per os to calves. In tests to determine their effects, virulent tachyzoites or oocysts were given to 10 calves and to 22 pregnant cows by the oral, IV, or intraamniotic routes. Clinical signs were fever and inappetence. One cow in early gestation aborted 24 days after IV administration of tachyzoites. Gross and microscopic changes were slight and nonspecific. Toxoplasmas were isolaated from brain or liver of 4 cows, placenta of 2 cows, gastric contents of 2 near-term fetuses, and blood and tissues of calves. Toxoplasmas were not isolated from control cows.

Ultrastructural studies of a visna-like syncytia-producing virus from cattle with lymphocytosis.

A virus structurally similar to viruses associated with maedi, progressive pneumonia, and visna of sheep has been isolated from buffy coat cells of cattle with chronic lymphocytosis. Electron microscope studies revealed three variants of the virion: (i) an intracytoplasmic form 98 to 116 nm in diameter when occurring in a nonlaminated form, (ii) a budding form 120 to 130 nm in diameter, and (iii) an extracellular form 80 to 130 nm in diameter and containing a 30 to 43 nm eccentrically located electron-dense core.