Publications

Deficits in cholinergic function have been postulated to cause delirium and cognitive decline. This review examines current understanding of the cholinergic deficiency hypothesis in delirium by synthesizing evidence on potential pathophysiological pathways. Acetylcholine synthesis involves various precursors, enzymes, and receptors, and dysfunction in these components can lead to delirium. Insults to the brain, like ischemia and immunological stressors, can precipitously alter acetylcholine levels. Imbalances between cholinergic and other neurotransmitter pathways may result in delirium. Furthermore, genetic, enzymatic, and immunological overlaps exist between delirium and dementia related to the cholinergic pathway. Important areas for future research include identifying biomarkers, determining genetic contributions, and evaluating response to cholinergic drugs in delirium. Understanding how the cholinergic pathway relates to delirium may yield innovative approaches in the diagnosis, prevention, and treatment of this common, costly, and morbid condition.

BACKGROUND: Experts recommend that clinicians target mammography and colon cancer screening to individuals with at least 5 years life expectancy. Generally, immunizations and exercise counseling are recommended for all women aged > or =65 years, while Pap smears are generally not encouraged for these women.

METHODS: We used the 2005 National Health Interview Survey to examine receipt of several preventive health measures simultaneously among community dwelling US women aged > or =65 years by age and health status. We used functional status, significant diseases, and perceived health to categorize women into those most likely to be in above-average, average, or below-average health status. We used age and health status to estimate life expectancy.

RESULTS: Of 4683 participants, 25.8% were > or =80 years; 81.8% were non-Hispanic white; 21% were in above-average and 20% were in below-average health status. Receipt of mammography and colon cancer screening decreased with age and was not associated with health status for women aged > or =80 years. Nearly half (49%) of women aged > or =80 years in below-average health received mammography screening, while 19% of women aged 65-79 years in above-average health did not report receiving mammography. Nearly half of women aged 65-79 years (49%) in above-average health did not report receiving colon cancer screening. Pap smear screening was common among older women. Few (34%) reported receiving exercise counseling. Many did not report receiving pneumococcal (43%) or flu vaccinations (40%).

CONCLUSIONS: In our comprehensive review of preventive health measures for older women, we found evidence to suggest a need to improve delivery and targeting of preventive health services.

Older adults continue to be underrepresented in clinical research despite their burgeoning population in the United States and worldwide. Physicians often propose treatment plans for older adults based on data from studies involving primarily younger, more-functional, healthier participants. Major barriers to recruitment of older adults in aging research relate to their substantial health problems, social and cultural barriers, and potentially impaired capacity to provide informed consent. Institutionalized older adults offer another layer of complexity that requires cooperation from the institutions to participate in research activities. This paper provides study recruitment and retention techniques and strategies to address concerns and overcome barriers to older adult participation in clinical research. Key approaches include early in-depth planning; minimizing exclusion criteria; securing cooperation from all interested parties; using advisory boards, timely screening, identification, and approach of eligible patients; carefully reviewing the benefit:risk ratio to be sure it is appropriate; and employing strategies to ensure successful retention across the continuum of care. Targeting specific strategies to the condition, site, and population of interest and anticipating potential problems and promptly employing predeveloped contingency plans are keys to effective recruitment and retention.

BACKGROUND: Persistent delirium at the time of hospital discharge is associated with poor outcomes. The objectives of this study were to develop and validate a predictive model for persistent delirium at hospital discharge.

METHODS: This study followed a prospective validation design. For the development cohort, 491 consecutive patients 70 years or older admitted to the hospital without delirium and surviving to discharge were enrolled from the general medical units of an academic teaching hospital. For the validation cohort, 461 comparable subjects were enrolled. Twenty-two candidate risk factors were examined, including 12 baseline factors (present on admission) and 10 precipitating factors (hospital related). The primary outcome was delirium at hospital discharge, measured by the Confusion Assessment Method.

RESULTS: Delirium at discharge was present in 58 patients (11.8%) in the development cohort. Five independent risk factors for delirium at discharge were identified: dementia (odds ratio [OR], 2.3; 95% confidence interval [CI], 1.4-3.7); vision impairment (OR, 2.1; 95% CI, 1.3-3.2); functional impairment (OR, 1.7; 95% CI, 1.2-3.0); high comorbidity (OR, 1.7; 95% CI, 1.1-2.6); and use of physical restraints during delirium (OR, 3.2; 95% CI, 1.9-5.2). A risk stratification system was created by adding 1 point for each factor present. Rates of delirium for the low-risk (0-1 factors), intermediate-risk (2-3 factors), and high-risk (4-5 factors) groups were 4%, 18%, and 63%, respectively (P < .001). The corresponding rates in the validation cohort, where 28 patients (6.1%) had delirium at discharge, were 3%, 14%, and 27% (P < .001).

CONCLUSIONS: A predictive model based on 5 risk factors has been successfully validated for prediction of delirium at discharge in hospitalized older patients. At least 4 of these risk factors are amenable to intervention strategies.

BACKGROUND: Delirium is common among hospitalized elders and may persist for months. Therefore, the adverse impact of delirium on independence often occurs in the post acute care (PAC) setting. The effect of psychomotor subtypes on delirium remains uncertain. The purpose of this study is to examine the association between psychomotor activity delirium subtypes and 1-year mortality among 457 newly admitted delirious PAC patients.

METHODS: Patients were screened for delirium on admission to PAC facilities after an acute hospitalization, and patients with "Confusion Assessment Method"-defined delirium were enrolled. Psychomotor activity was assessed using the Memorial Delirium Assessment Scale, and patients were classified as to their delirium subtype (hyperactive, hypoactive, mixed, or normal). One-year mortality data were obtained from the National Death Index. A Kaplan-Meier survival analysis and a proportional hazards analysis using indicator (dummy) variables with normal psychomotor activity as the referent were performed.

RESULTS: The normal psychomotor activity group had the lowest 1-year mortality rate, followed by the hyperactive, mixed, then hypoactive groups in increasing order. Independent of age, gender, comorbidity, dementia, and delirium severity, hypoactive patients were 1.60 (95% confidence interval [CI], 1.09-2.35) times more likely to die during the 1-year follow-up period than were patients with normal psychomotor activity. The hyperactive (hazard ratio = 1.30; 95% CI, 0.73-2.31) and mixed (hazard ratio = 1.25; 95% CI, 0.72-2.17) psychomotor groups had nonsignificant elevated risks relative to the normal psychomotor behavior group.

CONCLUSIONS: All three psychomotor disturbance subtypes had an elevated risk of dying during the 1-year follow-up relative to the normal psychomotor group, though the hypoactive group had the highest mortality risk and was the only group with a statistically significantly elevated risk relative to the normal group.

BACKGROUND: Delirium is a common, morbid, and costly syndrome that occurs frequently after surgery for atherosclerosis. We hypothesized that vascular risk factors and mildly impaired cognitive performance would independently predispose nondemented patients to develop delirium after noncardiac surgery.

METHODS: The International Study of Postoperative Cognitive Dysfunction recruited patients undergoing noncardiac surgery from 8 countries. Subjects provided detailed medical history and underwent preoperative testing of multiple cognitive domains with a neuropsychologic battery. Postoperatively, subjects (n=1161) were assessed daily for delirium.

RESULTS: Ninety-nine subjects (8%) developed delirium. In bivariable analysis, several vascular risk factors were significantly associated with the likelihood of delirium, including male sex, exposure to tobacco, previous myocardial infarction, and vascular surgery. After adjustment for age, tobacco exposure and vascular surgery were independent vascular risk factors for delirium (adjusted relative risk [RR] 3.2, 95% confidence interval [CI], 2.1-4.9). In addition, mildly impaired cognitive performance, defined as performance 1.5 standard deviation below the mean on either of 2 neuropsychologic tests, was independently associated with delirium (adjusted RR 2.2, 95% CI, 1.4-3.6). Subjects with both vascular risk factors and mildly impaired cognitive performance were at double the risk of delirium (RR 2.2, 95% CI, 1.2-4.2) compared with those with either of these risk factors alone.

CONCLUSIONS: Vascular risk and mildly impaired cognitive performance independently predispose patients to delirium after noncardiac surgery. These factors will help to identify high-risk patients for delirium and to design and target future intervention strategies.

OBJECTIVES: Neurologic injury after cardiac surgery, often manifested as neurocognitive decline, is a common postoperative complication without clear cause. We studied acute variations in gene-expression profiles of patients with neurocognitive decline (NCD group) compared with those without neurocognitive decline (NORM group) after cardiopulmonary bypass.

METHODS: Forty-two patients undergoing coronary artery bypass grafting, valve procedures, or both by using cardiopulmonary bypass were administered a validated neurocognitive battery preoperatively and postoperatively at day 4. Neurocognitive decline was defined as 1 standard deviation from baseline on 25% or greater of tasks. Whole-blood mRNA was isolated preoperatively and at 6 hours after surgical intervention for fold-change calculation. Relative gene expression in the NCD versus the NORM group was assessed by using Affymetrix GeneChip U133 Plus 2.0 (>40,000 genes) from mRNA samples collected. Differential expression, clustering, gene ontology, and canonical pathway analysis were performed. Validation of microarray gene expression was performed with SYBR Green real-time polymerase chain reaction.

RESULTS: Patients with neurocognitive decline (17/42 [40.5%] patients) were associated with a significantly different gene-expression response compared with that of healthy patients. Compared with preoperative samples, 6-hour samples had 531 upregulated and 670 downregulated genes uniquely in the NCD group compared with 2214 upregulated and 558 downregulated genes uniquely in the NORM group (P < .001; lower confidence bound, > or =1.2). Compared with patients in the NORM group, patients with neurocognitive decline had significantly different gene-expression pathways involving inflammation (including FAS, IL2RB, and CD59), antigen presentation (including HLA-DQ1, TAP1, and TAP2), and cellular adhesion (including ICAM2, ICAM3, and CAD7) among others.

CONCLUSIONS: Patients with neurocognitive decline have inherently different genetic responses to cardiopulmonary bypass compared with those of patients without neurocognitive decline Genetic variations in inflammatory, cell adhesion, and apoptotic pathways might be important contributors to the pathophysiology of neurologic injury after cardiopulmonary bypass and could become a target for prevention and risk stratification.

OBJECTIVE: Language barriers have been shown to negatively impact health care for immigrants. We evaluated the association between language use and the diagnosis of hypertension among elderly Mexican Americans.

STUDY POPULATION: We studied subjects from the Hispanic Established Populations for Epidemiologic Studies of the Elderly, a cohort of 3050 Mexican American subjects age > or =65.

PREDICTORS: Measures of language included Spanish and/or English language read/spoken, language used in social situations, and language of mass media use.

OUTCOME MEASURE: Undiagnosed hypertension on physical exam was defined as systolic blood pressure > or =140 mm Hg and/or diastolic blood pressure > or =90 mm Hg in persons who did not report previous hypertension diagnosis or were not current users of anti-hypertensive medications.

RESULTS: The age- and sex-adjusted prevalence of diagnosed hypertension and undiagnosed hypertension were 50.5% and 19.3%, respectively. Among 1347 older adults without previous diagnosis of hypertension that were included in the primary analysis, the mean age was 72 years and 43% were immigrants. After adjusting for age, gender, and education, Spanish use more often than English use in mass media was significantly associated with undiagnosed hypertension (adjusted OR 2.2 [1.3-3.6]). Other measures of acculturation were not independently associated with undiagnosed hypertension. In analyses restricted to persons with hypertension, similar language factors distinguished those who had been diagnosed from those whose hypertension was undiagnosed.

CONCLUSIONS: Mexican American elders who reported using Spanish more often than English use in mass media were more likely to have undiagnosed hypertension compared to those using English language in mass media. Further studies are needed to elucidate the role of mass media language in hypertension awareness and management among Hispanic elders.

BACKGROUND: Although guidelines recommend that clinicians consider life expectancy before screening older women for breast cancer, many older women with limited life expectancies are screened. We aimed to identify factors important to mammography screening decisions among women aged 80 and older compared to women aged 65-79.

METHODS: Telephone surveys of 107 women aged 80+ and 93 women aged 65-79 randomly selected from one academic primary care practice who were able to communicate in English (60% response rate). The survey addressed the following factors in regards to older women's mammography screening decisions: perceived importance of a history of breast disease, family history of breast cancer, doctor's recommendations, habit, reassurance, previous experience, mailed reminder cards, family/friend's recommendations or experience with breast cancer, age, health, and media. The survey also assessed older women's preferred role in decision making around mammography screening.

RESULTS: Of the 200 women, 65.5% were non-Hispanic white and 82.8% were in good to excellent health. Most (81.3%) had undergone mammography in the past 2 years. Regardless of age, older women ranked doctor's recommendations as the most important factor influencing their decision to get screened. Habit and reassurance were the next two highly ranked factors influencing older women to get screened. Among women who did not get screened, women aged 80 and older ranked age and doctor's counseling as the most influential factors and women aged 65-79 ranked a previous negative experience with mammography as the most important factor. There were no significant differences in preferred role in decision-making around mammography screening by age, however, most women in both age groups preferred to make the final decision on their own (46.6% of women aged 80+ and 50.5% of women aged 65-79).

CONCLUSION: While a doctor's recommendation is the most important factor influencing elderly women's mammography screening decisions, habit and reassurance also strongly influence decision-making. Interventions aimed at improving clinician counseling about mammography, which include discussions around habit and reassurance, may result in better decision-making.