Severe dysosmia is specifically associated with Alzheimer-like memory deficits in nondemented elderly retirees.

OBJECTIVES: To determine whether or not (1) impaired olfactory function is associated with impaired memory on neuropsychological testing in healthy retirees, and if so then (2) whether memory impairment is most consistent with a mesiotemporal rather than frontal system disorder. METHODS: 173 independent residents of a continuing care retirement community were studied. Subjects completed the University of Pennsylvania Smell Identification Test (UPSIT) and a battery of both general and specific cognitive measures that included the Mini-Mental State Examination (MMSE) and the Executive Interview (EXIT25). Subjects were examined twice over 3 years. RESULTS: UPSIT performance was normal in 21% and in the 'anosmic' range in 25% of subjects. Anosmic UPSIT performance was associated with significantly worse performance on all cognitive tests. However, only short-term verbal memory was independently associated with UPSIT-defined anosmia. This association remained significant after adjusting for the other cognitive and sociodemographic variables. The memory deficits of anosmic subjects were qualitatively consistent with a cortical type (type 1) dementing illness such as Alzheimer's disease (AD). Over time, UPSIT-defined 'anosmic' cases suffered significantly greater declines on both the MMSE and the EXIT25, independently of baseline age, gender and MMSE score. CONCLUSIONS: Impaired odor identification in individuals without overt dementia is associated with an AD-like memory impairment and an increased rate of cognitive decline. The comorbid association of these deficits is consistent with the known hierarchical spread of preclinical AD pathology and may be a specific indicator of future clinical AD dementia.

Correlates of disability among elderly retirees with "subclinical" cognitive impairment.

BACKGROUND: We assessed the effects of impaired Executive Control Function (ECF) on Instrumental Activities of Daily Living (IADL) and level of care among noninstitutionalized elderly retirees with "subclinical" cognitive impairment. METHODS: Subjects (N = 561; age 78.2 +/- 5.0 years) were residents of a single, 1,500 bed, continuing care retirement community. Subjects were examined for cognitive impairment using the Executive Interview (EXIT25), Mini-Mental State Examination (MMSE), and an executive clock-drawing task (CLOX). The CLOX is divided into executively sensitive (CLOX 1) and simple constructional (CLOX2) subtests. RESULTS: Residents in congregate high-rises (n = 301) differed significantly from those in independent-living apartments (n = 260) with respect to age, gender, percent living alone, EXIT25, CLOX1, MMSE, and CLOX2 scores (all p < .03). Only differences in ECF measures persisted after adjusting for age and living alone (p < .004). The EXIT25 (p < .006) and CLOX2 (p = .02) were associated with the use of prostheses. The differences in EXIT25 scores persisted after adjusting for level and living alone (p = .01). All instruments distinguished residents with impairment in IADLs. However, only CLOX2 (p < .001), EXIT25 (p < .001), and age (p < .001) made significant independent contributions. CONCLUSIONS: ECF has statistically significant effects on level of care and IADL impairment, even among noninstitutionalized retirees. This emergent disability is not well detected by traditional global cognitive measures. Evaluation and treatment may be delayed unless ECF measures are employed.

Clock drawing is sensitive to executive control: a comparison of six methods.

We examined six clock-drawing task (CDT) scoring systems relative to the Executive Interview (EXIT25, a measure of Executive Control Function [ECF]) and the Mini-Mental State Exam (MMSE). Subjects included n = 33 National Institute of Neurological, Communicative Disorders, and Stroke "probable" Alzheimer's disease (AD) cases and n = 52 independent living controls. AD cases and controls differed on the EXIT25, MMSE, and all CDTs. All CDTs were significantly correlated with the EXIT25 (ranging from r = .56 to r = .78). These associations generally persisted after adjusting for Age, Education, and MMSE scores. In backwards stepwise linear multivariate regression models, only CLOX: An Executive Clock-Drawing Task scores contribute significantly to EXIT25 scores (R2 = .68) and MMSE scores (R2 = .72). Clock drawing draws upon both executive and general cognitive resources. CLOX explains incrementally more variance in ECF than other CDTs.

Function and medical comorbidity in south Texas nursing home residents: variations by ethnic group.

OBJECTIVE: To evaluate differences in functional status and burdens of medical conditions in Mexican American and non-Hispanic white nursing home residents. DESIGN AND SETTING: Cross-sectional survey of 17 nursing homes in south Texas. PARTICIPANTS: A total of 617 older nursing home residents, of whom 366 were Mexican American and 251 were non-Hispanic white. MEASURES: Activities of Daily Living (ADL) status abstracted from standard nurses notes and Burden of Disease abstracted from medical records. RESULTS: Mexican American residents had greater numbers of ADL dependencies and poorer overall ADL scores than non-Hispanic white residents. This poor functioning was not explained by age, gender, or marital or educational status. The average number of medical conditions was greater, and specific conditions, such as cerebrovascular disease, recent acute infections, diabetes, hypertension, and anemia, were more common in Mexican American residents compared with non-Hispanic white residents. In models relating function with medical conditions and ethnic group, ADL scores and dependencies were significantly related to bowel and bladder incontinence, cerebrovascular disease, dementia, recent infections, and skin decubiti, but not to ethnic group. CONCLUSION: Mexican American nursing home residents are more functionally dependent than non-Hispanic white residents. The difference in function is explained by a greater burden of medical conditions in the Mexican American residents.

Discovery of a brain promoter from the human transferrin gene and its utilization for development of transgenic mice that express human apolipoprotein E alleles.

Transgenic mice carrying heterologous genes directed by a 670-bp segment of the regulatory sequence from the human transferrin (TF) gene demonstrated high expression in brain. Mice carrying the chimeric 0.67kbTF-CAT gene expressed TF-CAT in neurons and glial cells of the nucleus basalis, the cerebrum, corpus callosum, cerebellum, and hippocampus. In brains from two independent TF-CAT transgenic founder lines, copy number of TF-CAT mRNA exceeded the number of mRNA transcripts encoding either mouse endogenous transferrin or mouse endogenous amyloid precursor protein. In two transgenic founder lines, the chloramphenicol acetyltransferase (CAT) protein synthesized from the TF-CAT mRNA was estimated to be 0.10-0.15% of the total soluble proteins of the brain. High expression observed in brain indicates that the 0.67kbTF promoter is a promising director of brain expression of heterologous genes. Therefore, the promoter has been used to express the three common human apolipoprotein E (apoE) alleles in transgenic mouse brains. The apoE alleles have been implicated in the expression of Alzheimer disease, and the human apoE isoforms are reported to interact with different affinities to the brain beta-amyloid and tau protein in vitro. Results of this study demonstrate high expression and production of human apoE proteins in transgenic mouse brains. The model may be used to characterize the interaction of human apoE isoforms with other brain proteins and provide information helpful in designing therapeutic strategies for Alzheimer disease.

Performance of case-finding tools for depression in the nursing home: influence of clinical and functional characteristics and selection of optimal threshold scores.

OBJECTIVE: To compare case-finding tools for depression in the nursing home setting and to evaluate effects of subject function, cognition, and disease number on test performance. DESIGN: Cross-sectional survey. SETTING: One academic and four community homes. SUBJECTS: One hundred thirty-four randomly selected, mildly cognitively impaired, functionally dependent residents. METHODS AND MEASURES: The Geriatric Depression Scale (GDS), Short Geriatric Depression Scale (SGDS), Center for Epidemiologic Studies Depression Scale (CES-D), and Brief Carrol Depression Rating Scale (BCDRS) were administered. The Structured Clinical Interview for DSM-III-R diagnoses was administered independently,. Operating characteristics and the effects of subject characteristics on test performance were evaluated using McNemar's test and logistic regression. Selection of "optimal" threshold scores was guided by Kraemer's quality indices and clinical judgment. RESULTS: Thirty-five subjects (26%) had major depression. No differences were found among the instruments in sensitivity (range 0.74-0.89), specificity (range 0.62-0.77), or area under the receiver operating curve (ROC) (range 0.85-0.91). Resident characteristics did not affect test performance. Quality indices showed the GDS and BCDRS met criteria for moderate to substantial agreement with the criterion standard, whereas the SGDS and the CES-D achieved only fair agreement. No change in threshold scores was warranted. CONCLUSIONS: The GDS and BCDRS performed well in the nursing home. As the GDS can serve as a both a case-finding and severity instrument, it is preferred. Use of brief, interviewer-administered tools may improve detection of depression in the nursing home.

Functional status of Mexican American nursing home residents.

OBJECTIVE: To compare sociodemographic characteristics, physical function, and cognition of Mexican American and non-Hispanic white nursing home residents. DESIGN AND SETTING: Cross-sectional survey of residents in eight proprietary nursing homes and one Veterans Affairs nursing home in San Antonio, Texas. SUBJECTS: Residents with lengths of stay greater than or equal to 90 days. MEASUREMENTS: Sociodemographic characteristics, residence prior to admission, and dependency in activities of daily living (ADL) were abstracted from the medical record. The Folstein Mini-Mental State Examination (MMSE) was administered in the resident's self-selected language to a subset of residents. MAIN RESULTS: There were 1160 participants, 261 Mexican American (23%) and 899 non-Hispanic white residents (77%). Mexican Americans were younger (77.1 vs 80.7 years), more often men (44% vs 30%), less educated (6.2 vs 10.8 years), and more often dependent on Medicaid funding (66% vs 40%) than non-Hispanic whites. Mexican Americans were less independent in feeding (34% vs 49%), transfers (18% vs 30%), toileting (19% vs 29%), and dressing (12% vs 19%). Mean MMSE scores were different in Mexican Americans and non-Hispanic whites (8.93 vs 11.85), and this difference remained significant after adjustment for age and education (P = 0.04). ADL function was strongly associated with MMSE (P = 0.0001) and less strongly associated with ethnicity (P = 0.056) in multiple regression analysis. CONCLUSIONS: This study provides the strongest evidence to date that Mexican American nursing home residents are more cognitively and functionally impaired than non-Hispanic white residents. Further studies should explore whether medical conditions, selection and referral patterns or cultural factors explain functional differences between Mexican American and non-Hispanic white nursing home residents.

Medical treatment preferences of nursing home residents: relationship to function and concordance with surrogate decision-makers.

OBJECTIVE: To describe treatment preferences of nursing home residents, concordance with decisions by self-selected proxies and to establish the relationship of sociodemographic and functional measures to decisions. SETTING AND SUBJECTS: 52 patient-proxy pairs at a Veterans Affairs nursing home. METHODS: Treatment preferences were elicited from residents and proxies regarding cardiopulmonary resuscitation, mechanical ventilation, and intensive care unit care. Hospitalization, intravenous antibiotics, intravenous fluid administration, and tube feeding were presented in three separate health scenarios. Concordance was determined for the entire interview and separately for each scenario. Treatment-seeking intensity and decision-making consistency were scored and used to explore associations with sociodemographic variables and function. RESULTS: Subjects were predominantly male (97%) and non-Hispanic white (74%); average age was 70 +/- 12 years, with 4 +/- 2.9 diagnoses. Residents accepted 70% of all treatments. The proportion of subjects accepting interventions declined parallel to health status in each scenario. Only 7/52 (13%) subjects made inconsistent decisions. Resident treatment acceptance was inversely associated with GDS scores but not associated with any other sociodemographic or functional measure. Concordance with proxies was no greater than chance. Proxies' decisions were not systematically biased against resident preferences or influenced by patient characteristics. CONCLUSIONS: Veterans desired most treatments, but adjusted preferences according to health status and were not inconsistent. Depressive symptoms should be addressed prior to advance directive selection. The patient remains the best source of information, but proxies' decisions exhibit no bias and are not affected by patient status.

The impact of physical therapy on nursing home patient outcomes.

The objective of this retrospective study was to assess the intensity and outcome of individual components of interdisciplinary care, including physical therapy, in a teaching nursing home. Two independent reviewers abstracted records from 90 consecutive patients admitted to the nursing home. They rated intensity and outcome of each program component using a structured, standardized data-abstraction form. Program components were physical therapy, speech therapy, psychosocial therapy, medication adjustment, and other medical and nursing care. Physical therapy and medication adjustment were the most frequently received therapies. Eighty-eight percent of the patients receiving high-intensity physical therapy and 33% of the patients receiving moderate-intensity physical therapy improved. For medication adjustment, 93% and 72% of the high- and moderate-intensity groups, respectively, improved. In univariate analyses, physical therapy intensity and age were associated with improvement. Baseline function in activities of daily living and cognitive function were not associated with physical therapy outcome. A stepwise multiple logistic regression analysis revealed that only therapy intensity was associated with improved outcome. We conclude that physical therapy was efficacious for patients receiving high-intensity treatment. Advanced age, activities-of-daily-living status, and cognitive impairment were not associated with poor physical therapy outcome.