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The purpose of this study was to identify characteristics of investigations of sexual abuse concerning vulnerable adults residing in facility settings that were associated with case substantiation. Data on 410 reports of sexual abuse were collected prospectively from Adult Protective Services (APS) and state licensure agency staff in New Hampshire, Oregon, Tennessee, Texas, and Wisconsin over a six-month period. Specifically, we examined differences between reports that were substantiated and those that were not by comparing characteristics of alleged victims, alleged perpetrators, and aspects of investigation using logistic regression. We found that a relatively low proportion of cases (18%) were substantiated overall. Compared to cases that were not substantiated, cases that were substantiated were more likely to feature nursing home residents, older victims, female victims, and allegations of physical contact between the alleged perpetrator and victim. Despite the high proportion of alleged perpetrators who were facility staff (51%) compared to resident perpetrators (25%), cases with resident-to-resident allegations of abuse were much more likely to be substantiated, accounting for 63% of substantiated cases. In light of these findings, we believe it is important that investigators are trained to handle sexual abuse cases appropriately and that they are able to investigate the case thoroughly, promptly, and with as much information as possible. It is also critical that investigators make substantiation decisions using the appropriate standard for confirmation (e.g., preponderance of the evidence, beyond a reasonable doubt, clear and convincing evidence) as state law dictates.

Using Bronfenbrenner's ecological systems model, this study examined allegations of elder abuse made to Kentucky Adult Protective Services (APS) and the investigation that followed, in order to understand how APS addressed the needs of abused elders. Elder abuse allegations made to APS during the study week were collected using 3 study tools. Allegations and resulting investigations were analyzed. During the study week, APS received 1,002 calls alleging elder abuse. Of these, 483 were categorized as reports needing protective services, with 177 reports screened in for investigation and 167 actually investigated. Results describe characteristics of abuse calls, investigations, victims, perpetrators, and total investigation times. Substantiation ratio, recidivism, and whether investigation increased or decreased the risk of abuse were also assessed. An examination of APS casework through the lens of nested systems frames the study findings and discussion. Such an examination has the potential to improve the quality of services provided to older adults.

The value of screening for cognitive impairment, including dementia and Alzheimer's disease, has been debated for decades. Recent research on causes of and treatments for cognitive impairment has converged to challenge previous thinking about screening for cognitive impairment. Consequently, changes have occurred in health care policies and priorities, including the establishment of the annual wellness visit, which requires detection of any cognitive impairment for Medicare enrollees. In response to these changes, the Alzheimer's Foundation of America and the Alzheimer's Drug Discovery Foundation convened a workgroup to review evidence for screening implementation and to evaluate the implications of routine dementia detection for health care redesign. The primary domains reviewed were consideration of the benefits, harms, and impact of cognitive screening on health care quality. In conference, the workgroup developed 10 recommendations for realizing the national policy goals of early detection as the first step in improving clinical care and ensuring proactive, patient-centered management of dementia.

Cognitively intact elderly research volunteers at the University of Kentucky have been recruited, followed longitudinally, and autopsied with extensive neuropathological evaluations since 1989. To date, the cohort has recruited 1,030 individuals with 552 participants being actively followed, 363 deceased, and 273 autopsied. An extensive database has been constructed with continuous updates that include textured clinical, neuropsychological, neuroimaging, and pathological information. The history, demographics, clinical observations, and pathological features of this research cohort are described. We also explain some of the evolving methodologies and the academic contributions that have been made due to this motivated group of older Kentuckians.

The current analysis reexamines the relationship between supplemental vitamin E and all-cause mortality. All randomized, controlled trials testing the treatment effect of vitamin E supplementation in adults for at least one year were sought. MEDLINE, the Cochrane Library, and Biological Abstracts databases were searched using the terms “vitamin E,” “alpha-tocopherol,” “antioxidants,” “clinical trial,” and “controlled trial” for studies published through April 2010; results were limited to English, German, or Spanish language articles. Studies were also obtained through reference mining. All randomized controlled trials using vitamin E, with a supplementation period of at least one year, to prevent or treat disease in adults were identified and abstracted independently by two raters. Mortality data from trials with a supplementation period of at least one year were pooled. The selected trials (n = 57) were published between 1988 and 2009. Sample sizes ranged from 28 to 39,876 (median = 423), yielding 246,371 subjects and 29,295 all-cause deaths. Duration of supplementation for the 57 trials ranged from one to 10.1 years (median = 2.6 years). A random effects meta-analysis produced an overall risk ratio of 1.00 (95% confidence interval: 0.98, 1.02); additional analyses suggest no relationship between dose and risk of mortality. Based on the present meta-analysis, supplementation with vitamin E appears to have no effect on all-cause mortality at doses up to 5,500 IU/d.

Our objective was to investigate the nutritional requirements in ALS and to determine the feasibility of early intervention with NIPPV. Subjects were enrolled into one of two arms. In the nutrition arm, total daily energy expenditure (TDEE) was determined longitudinally over 48 weeks using the Doubly Labeled Water method. In the NIPPV arm, NIPPV was offered at 80% vs. 50% FVC. Additional measurements were obtained in both arms to ultimately formulate equations to predict TDEE and to estimate sample size for a phase III study of early NIPPV. Eighty subjects were enrolled in the nutrition arm and 73 in the NIPPV arm. Baseline characteristics of the participants are described. TDEE was available for 80 subjects in 249 independent determinations during disease progression. Other variables were measured simultaneously for future modeling of ALS-specific equations to predict TDEE. In the NIPPV arm, rates of progression to the criteria for NIPPV intervention (80% or 50% predicted FVC) were computed. Additional factors were obtained longitudinally to develop indices of early ventilatory insufficiency. The results of this study will allow us to model equations to predict the energy requirements in ALS and to plan a study of early intervention with NIPPV.

Aims Although the adverse effects of smoking are well known, limited information exists about the overall health profiles of menthol smokers when compared to their non-menthol smoking counterparts. Using a well-known nationally representative survey, this study examines differences between self-reported health characteristics for menthol and non-menthol smokers. Design Cross-sectional data from the 2005 National Health Interview Survey and its cancer control supplement were used to analyze responses for current and former smokers (n = 12 004) independently. All analyses were conducted using SAS version 9.2 and SAS callable SUDAAN version 9.0.3. Multiple logistic regression analysis was used to model menthol smoking. Findings After controlling for sex, age and race, we found that in current smokers the mean number of cigarettes smoked per day is significantly lower for menthol smokers when compared to non-menthol smokers [odds ratio (OR): 0.99; 95% confidence interval (CI): 0.98, 1.00]. Also, we found thatformermentholsmokershadhigherbodymassindices(BMIs)(OR:1.01;95%CI:1.00,1.02)andweremorelikely to have visited the emergency room due to asthma (OR: 2.30, 95% CI: 1.04, 5.09). Conclusions Overall, current menthol and non-menthol smokers have similar health profiles. However, menthol smokers reported smoking fewer cigarettes per day than their non-menthol counterparts. While these findings are supportive of other published data, future studies may need to tease out the health-related significance of smoking fewer menthol cigarettes per day but having similar health outcomes to those who smoke more non-menthol cigarettes per day. Additionally, our findings suggest that there may be some differences between the former menthol and non-menthol smoker.

Aim This exploratory study sought to examine the relationships among occupational status, menthol smoking preference and employer-sponsored smoking cessation programs and policies on quitting behaviors. Design Data for this cross-sectional study were obtained from the 2006 Tobacco Use Supplement to the Current Population Survey (TUS CPS), a large national survey representative of the civilian population, containing approximately 240 000 respondents. The total sample for the current study was 30 176. Measurements The TUS CPS regularly collects data on cigarette prevalence, quitting behaviors, smoking history and consumption patterns. We performed a logistic regression with ‘life-time quitting smoking for 1 day or longer because they were trying to quit’ as outcome variable. Independent variables included type of occupation, employer-sponsored cessation programs and policies and menthol status. Findings When controlling for occupational status and work-place policies, there were no differences for menthol versus non-menthol smokers on quitting behaviors [odds ratio (OR) = 0.98; 95% confidence interval (CI) = 0.83, 1.15]. Service workers were less likely to quit compared with white-collar workers (OR = 0.80; 95% CI = 0.69, 0.94), and those with no employer-sponsored cessation program were less likely to quit (OR = 0.70; 95% CI = 0.60, 0.83). White-collar workers, compared with blue-collar and service workers, were more likely to have a smoking policy in the work area (93% versus 86% versus 88%, respectively). Conclusions When occupational status and work-place smoking policies are controlled for, smokers of menthol cigarettes in the United States appear to have similar self-reported life-time rates of attempts to stop smoking to non-menthol smokers.

We evaluated the association between mini-mental status examination (MMSE) scores proximal to death and the values of 43 different clinical and pathological parameters. Studies were performed using data from 334 elderly, longitudinally evaluated research subjects who had undergone autopsy and satisfied inclusion criteria from an initial study group of 501. Interindividual variance in MMSE scores was used as a surrogate for the severity of cognitive impairment linked to aging (CILA). A statistical linear regression-based model provided a framework for assessing the parameters with significant, direct impact on CILA severity. Strong association between CILA and Alzheimer's disease (AD) pathology, especially isocortical neurofibrillary tangles, was evident. The pattern of association between AD lesion densities with cognitive impairment severity was biologically informative, with neuritic plaques having more impact in relatively high-functioning individuals. Abundant isocortical Lewy bodies tended to be an additive pathology correlating with final MMSE scores approximately 10 points lower. In a subset of cases we found evidence for association between TDP-43-related pathology and CILA severity, independent of AD or hippocampal sclerosis. There was no support for independent association between CILA severity and most evaluated indices including diffuse plaques, argyrophilic grains, heart disease, education level, apolipoprotein E alleles or diabetes.

Dementia can be caused by different diseases including Alzheimer's disease (AD), dementia with Lewy bodies (DLB), or both (AD + DLB). University of Kentucky AD Center pathologically-diagnosed AD and AD + DLB cases were evaluated who had three or more longitudinal antemortem mental status examinations (n = 156). Patients with important concomitant pathology (n = 5) or patients that were profoundly demented at recruitment (intake MMSE < 20; n = 86) were excluded to strengthen our ability to test the association of specific clinical and pathological indices. Patients with pathologically-diagnosed AD + DLB (n = 25) lost cognitive capacity faster than patients with AD alone (n = 40). In both diseases, treatment with acetylcholinesterase inhibitors was associated with a slower rate of cognitive decline.

This article reports research findings concerning 119 alleged sexual perpetrators who were reported to state authorities for abusing elderly individuals residing in care facilities. The largest group of accused was employees of the facilities, followed by facility residents. Family members of the alleged victims and visitors to the facilities also were among those reported as sexually abusive. Investigation of the allegations by Adult Protective Services and regulatory staff resulted in 32 of these individuals being confirmed as sexual perpetrators against vulnerable elders. Male and female alleged and confirmed sexual perpetrators were identified as well as both male and female elderly sexual abuse victims. Perpetrator characteristics, victim vulnerabilities, abuse acts, locations of assaults, and available case outcomes are presented. Implications of the findings are discussed.

Previous research on the sexual abuse of older adults has revealed few cases of the sexual abuse of older men. The first national study of the sexual abuse of vulnerable adults in facilities, reported in this article, collected data on alleged, investigated, and substantiated cases of sexual abuse. This study revealed 26 cases reported and screened in for investigation concerning the alleged sexual abuse of older men (aged 50 and older) residing in nursing homes. Cases occurred in five states within a six month time period. Of these cases, six were confirmed upon investigation by Adult Protective Services or other regulatory agencies. Victims tended to be predominantly white males with cognitive and physical deficits that limited their ability for self care. The most typical sexual abuse alleged and substantiated was fondling. Residents were more often substantiated as the abuser than other perpetrators. Sexual abuse of older men in nursing homes crosses traditional gender, cultural, and role boundaries for both victims and perpetrators.

This article explores the issue of sexual abuse of vulnerable younger and older adults living in long-term care facilities. Clinical findings regarding the sexual abuse of adults who are elderly or have disabilities are presented, and practice implications for psychiatric nurses are discussed. A review of relevant existing literature and previous research is provided. A research study presently under way is then described. This is the first national study of sexual abuse in long-term care. This study seeks to fill current knowledge gaps and inform the practice of nursing and other professionals who are responsible for the care of vulnerable adults.

Objectives To report experience with a large, nation-wide public memory screening program. Design Descriptive study of community-dwelling elderly adults. Setting Local community sites (48 sites agreed to provide data) throughout the United States participating in National Memory Screening Day in November 2010. Participants Of 4,369 reported participants, 3,064 had complete data records and are included in this report. Measurements Participants completed a questionnaire that included basic demographic information and a question about subjective memory concerns. Each site selected one of seven validated cognitive screening tests: Mini-Cog, General Practitioner assessment of Cognition, Memory Impairment Screen, Kokmen Short Test of Mental Status, Mini-Mental State Examination, Montreal Cognitive Assessment, Saint Louis University Mental Status Examination. Results Overall, 11.7% failed one of the seven screening tests. As expected, failure rates were higher in older and less-educated participants (P's

Our objective was to explore if creatine kinase (CK) levels correlate with survival in amyotrophic lateral sclerosis (ALS), and whether a correlation is independent of other well-studied predictors such as location of onset, gender, age, fat free mass, spasticity, cramps, and fasciculations. We analyzed data from 80 ALS patients from a 48-week non-interventional longitudinal multicenter nutrition study with long term follow-up. The overall mean CK was 214 ± 191.8 U/l (range 22–1992 U/l). Forty-five percent of patients had at least one high CK value (> 200 U/l), and about half maintained a high CK value, but there was no trend over the study period. Male gender and extremity onset were significantly associated with high CK. In univariate analysis, age, bioelectric impedance spectroscopy (BIS) fat free mass, spasticity, and fasciculations were not associated with CK level. There was an association between CK and muscle cramps (p < 0.001). In survival analysis, low CK (≤ 200 U/l) was associated with a longer overall survival (p = 0.02), when adjusting for location of onset, age, race, gender, BIS fat free mass, and study site. In conclusion, CK may be a useful marker for ALS survival, which has implications for clinical care and the design of future clinical trials.

As the U.S. population of individuals older than age 65 increases, so does the number of employees providing informal care to aging family members and friends. Yet few studies have investigated the types of elder care issues that employees encounter and the strategies used to care for their elder loved one. Using quantitative data, the authors describe the types of elder care situations experienced by individuals employed at one large organization. The authors present demographic information about employee caregivers and the people for whom they are seeking services, the reasons employees seek elder care consultation and services, and the types of services offered by the elder care program. Employees’ perceived benefits of utilizing elder care resources programs are also examined. Implications for practice, policy, and further research are discussed.

Using a unique measure of unmet need that taps into several dimensions of informal long-term care, the present study included data from 694 informal caregivers of persons suffering from dementia at different times in the caregiving career (e.g., at home, following institutionalization, following the death of the care recipient). Multivariate regression models found that unmet need for either confidante or formal support had key implications for caregivers’ emotional distress in each of the care situations. The findings suggest that conceptual models should incorporate unmet need as a viable predictor of caregiving outcomes and that assessment of unmet need may provide guidance in the development of more refined psychosocial and community-based intervention protocols.

Background: Patients with amyotrophic lateral sclerosis (ALS) experience progressive limb weakness, muscle atrophy, and dysphagia, making them vulnerable to insufficient energy intake. Methods to estimate energy requirements have not been devised for this patient group. Objective: The goal was to develop equations to estimate energy requirements of ALS patients. Design: We enrolled 80 ALS participants at varying stages of their illness and studied them every 16 wk over 48 wk. At each time, we determined total daily energy expenditure (TDEE) in the home setting over a 10-d period by using the doubly labeled water method. We then developed statistical models to estimate TDEE by using factors easily obtained during a routine clinical visit. Results: The most practical TDEE models used the Harris-Benedict, Mifflin-St Jeor, or Owen equations to estimate resting metabolic rate (RMR) and 6 questions from the revised ALS Functional Rating Scale (ALSFRS-R) that relate to physical activity. We developed a Web-based calculator to facilitate its use. In the research setting, measuring body composition with bioelectrical impedance spectroscopy enabled the estimation of RMR with the Rosenbaum equation and the same 6 questions from the ALSFRS-R to estimate TDEE. By using these models, the estimate of TDEE for nutritional maintenance was ±500 kcal/d across the spectrum of ALS progression. Conclusions: Our results emphasize the importance of physical function and body composition in estimating TDEE. Our predictive equations can serve as a basis for recommending placement of a feeding gastrostomy in ALS patients who fail to meet their energy requirements by oral intake. This trial was registered at clinicaltrials.gov as {"type":"clinical-trial","attrs":{"text":"NCT00116558","term_id":"NCT00116558"}}NCT00116558.

The Mini Mental State Examination (MMSE) is widely used to measure dementia severity in Alzheimer's disease patients. While changes over time in the MMSE due to dementia have been studied, the relationship between MMSE scores and the duration of disease course is less well understood. Using the Consortium to Establish a Registry for Alzheimer's Disease (CERAD) data, we modelled change in MMSE as a function of time for this population. For this purpose we used the interval between consecutive MMSE assessments as the time factor. We also investigated the impact of sex, education and age at testing on the resulting model. Analyses showed that Alzheimer's disease progression over time (ADP) can be modelled using a cubic or a logarithmic function of MMSE score. From these curves ADP can be obtained as a function of MMSE. These models demonstrate that there are different rates of change for various ranges of the MMSE. Additional analyses suggest that patient factors affect rates of ADP, younger patients and more educated patients progress more rapidly, while sex has little impact on ADP. Such estimations of disease course are useful when comparing different populations for both clinical and research purposes.

We study a general approximation scheme for infinite-dimensional linear programming (LP) problems which arise naturally in stochastic control. We prove that the optimal value of the approximating problems converges to the value of the original LP problem. For the controls, we show that if the approximating optimal controls converge, the limiting control is an optimal control for the original LP problem. As an application of this theory, we present numerical approximations to the LP formulation of stochastic control problems in continuous time. We study long-term average and discounted control problems. For the example for which the theoretical solution is known, our approximation results are very accurate.

In utero exposure to opiates may affect autonomic functioning of the fetus and newborn. We investigated heart rate variability (HRV) as a measure of autonomic stability in prenatal opiate-exposed neonates (n = 14) and in control term infants (n = 10). Electrocardiographic data during both non-nutritive and nutritive sucking were evaluated for RR intervals, heart rate (HR), standard deviation of the consecutive RR intervals (SDRR), standard deviation of the differences of consecutive RR intervals (SDDRR), and the power spectral densities in low and high frequency bands. In controls, mean HR increased significantly, 143–161 per min (p = 0.002), with a trend toward a decrease in RR intervals from non-nutritive to nutritive sucking; these measures did not change significantly among exposed infants. Compared to controls, exposed infants demonstrated significantly greater HRV or greater mean SDRR and SDDRR during non-nutritive period (p

Deposition of the amyloid-β (Aβ) peptide in neuritic plaques is a requirement for the diagnosis of Alzheimer disease (AD). Although the continued development of in vivo imaging agents such as Pittsburgh compound B (PiB) is promising, the diagnosis of AD is still challenging. This can be partially attributed to our lack of a detailed understanding of the interrelationship between the various pools and species of Aβ and other common indices of AD pathology. We hypothesized that recent advances in our ability to accurately measure Aβ postmortem (for example, using PiB), could form the basis of a simple means to deliver an accurate AD diagnosis.We conducted a comprehensive analysis of the amount of Aβ40 and Aβ42 in increasingly insoluble fractions, oligomeric Aβ, and fibrillar Aβ (as defined by PiB binding), as well as plaques (diffuse and neuritic), and neurofibrillary tangles in autopsy specimens from age-matched, cognitively normal controls (n = 23) and AD (n = 22) cases, across multiple brain regions.Both PiB binding and the amount of sodium dodecyl sulfate (SDS)-soluble Aβ were able to predict disease status; however, SDS-soluble Aβ was a better measure. Oligomeric Aβ was not a predictor of disease status. PiB binding was strongly related to plaque count, although diffuse plaques were a stronger correlate than neuritic plaques.Although postmortem PiB binding was somewhat useful in distinguishing AD from control cases, SDS-soluble Aβ measured by standard immunoassay was substantially better. These findings have important implications for the development of imaging-based biomarkers of AD.

*adjusted for: weight at 43 years, socio-economic position, educational attainment, physical activity level at 43 and 53 years, smoking status at 43 and 53 years, overall health at 53 years, self-reported recent bad health at 53 years and for cognitive ability in childhood (composite measure of: vocabulary, sentence completion, pronunciation and picture intelligence), and cognitive reserve in midlife (measured by the national adult reading test, NART). Figure 1. Cumulative MCI and dementia cases (N 1⁄4 201). Poster Presentations: P1 P144

This exploratory study sought to examine the relationships among occupational status, menthol smoking preference and employer-sponsored smoking cessation programs and policies on quitting behaviors.Data for this cross-sectional study were obtained from the 2006 Tobacco Use Supplement to the Current Population Survey (TUS CPS), a large national survey representative of the civilian population, containing approximately 240,000 respondents. The total sample for the current study was 30,176.The TUS CPS regularly collects data on cigarette prevalence, quitting behaviors, smoking history and consumption patterns. We performed a logistic regression with 'life-time quitting smoking for 1 day or longer because they were trying to quit' as outcome variable. Independent variables included type of occupation, employer-sponsored cessation programs and policies and menthol status.When controlling for occupational status and work-place policies, there were no differences for menthol versus non-menthol smokers on quitting behaviors [odds ratio (OR) = 0.98; 95% confidence interval (CI) = 0.83, 1.15]. Service workers were less likely to quit compared with white-collar workers (OR = 0.80; 95% CI = 0.69, 0.94), and those with no employer-sponsored cessation program were less likely to quit (OR = 0.70; 95% CI = 0.60, 0.83). White-collar workers, compared with blue-collar and service workers, were more likely to have a smoking policy in the work area (93% versus 86% versus 88%, respectively).When occupational status and work-place smoking policies are controlled for, smokers of menthol cigarettes in the United States appear to have similar self-reported life-time rates of attempts to stop smoking to non-menthol smokers.

There is uncertainty regarding the association of cognitive decline in Alzheimer disease (AD) with classic histopathologic features- neurofibrillary tangles (NFTs) and "neuritic" amyloid plaques (NPs). This uncertainty fuels doubts about the diagnostic importance of NFTs and NPs and leads to confusion regarding hypotheses of AD pathogenesis. Three hundred ninety subjects who underwent longitudinal premortem clinical workup and postmortem quantitative neuropathologic assessment served as the group to address this issue. Subjects with concomitant brain disease(s) were analyzed independently to more accurately assess the contribution of distinct pathologies to cognitive decline. More than 60% of patients of all age groups had important non-AD brain pathologies. However, subjects without superimposed brain diseases showed strong correlations between AD-type pathology counts (NFTs > NPs) and premortem Mini-Mental State Examination scores. The observed correlation was stronger in isocortex than in allocortex and was maintained across age groups including patients older than 90 years. A theoretical model is proposed in which our results are interpreted to support the "amyloid cascade hypothesis" of AD pathogenesis. Our data show that there are many important contributory causes to cognitive decline in older persons. However, NFTs and NPs should not be dismissed as irrelevant in AD based on clinicopathologic correlation.

We evaluated whether prepubertal children treated with valproic acid did not gain excessive weight. This retrospective study of children with epilepsy, aged12 years at enrollment, examined weight gain associated with valproic acid or carbamazepine monotherapy. There was no significant difference between the valproic acid (n = 31) and carbamazepine (n = 49) treated groups in average duration of therapy or mean age. Body mass index scores at the beginning and end of the study were used to evaluate weight gain, while compensating for gains in height. For valproic acid, the linear mixed model detected no gain in body mass index z-scores over time (T = 0.25, DF = 17.3, P = 0.80), though it detected a significant gain in body mass index z-scores for carbamazepine (T = 2.32, DF = 36.7, P = 0.02). Results for McNemar chi-square tests were similar. No significant proportion change occurred among children on valproic acid (chi(2) = 2.0, P = 0.15), whereas a significant increase in the proportion of overweight children occurred on carbamazepine (chi(2) = 4.5, P = 0.03). We detected no excessive weight gain for children on valproic acid, whereas this was demonstrated for a similar socioeconomic group on carbamazepine.

The potential of early interventions for dementia has increased interest in cognitive impairments less severe than dementia. However, predictors of the trajectory from intact cognition to dementia have not yet been clearly identified. The purpose of this study was to determine whether known risk factors for dementia increased the risk of mild cognitive impairments or progression from mild cognitive impairments to dementia. A polytomous logistic regression model was used, with parameters governing transitions within transient states (intact cognition, mild cognitive impairments, global impairment) estimated separately from parameters governing the transition from transient to absorbing state (dementia or death). Analyses were based on seven annual examinations (1991-2002) of 470 Nun Study participants aged > or = 75 years at baseline and living in the United States. Odds of developing dementia increased with age primarily for those with low educational levels. In these women, presence of an apolipoprotein E gene *E4 allele increased the odds more than fourfold by age 95 years. Age, education, and the apolipoprotein E gene were all significantly associated with mild cognitive impairments. Only age, however, was associated with progression to dementia. Thus, risk factors for dementia may operate primarily by predisposing individuals to develop mild cognitive impairments; subsequent progression to dementia then depends on only time and competing mortality.

Objective The objective of this study was to determine whether chronic use of medications with anticholinergic (AC) properties impact older adults' cognitive functioning. Methods Six years of cognitive test data from two groups of older adults (AC and control) were examined retrospectively (N = 592). Results Declines over time were found for the AC group on parts A and B of the Trail Making Test. Conclusion Physicians prescribing ACs to older adult patients should be aware of their potential effects on psychomotor speed and executive functioning. These cognitive effects may lead to impairments in daily functioning resulting in the need to reevaluate patient medications.

Objective: Larger brains may contain more neurons and synaptic connections, providing a greater reserve against cognitive decline in Alzheimer's disease (AD). Larger head circumference (HC) may therefore be associated with later detection and diagnosis of AD. We investigated HC in nondemented individuals and AD patients using cross-sectional and prospective analyses. Methods: The cross sectional analysis compared mean HC between 592 AD patients and 459 nondemented controls. Prospective analysis was based on the same initially normal controls who were followed longitudinally for conversion to dementia. Diagnosis of AD was made by neurologists using NINDS-ADRDA criteria. Results: When compared to AD patients, controls had a significantly larger mean HC by 0.58 cm in men and by 0.31 cm in women, but these differences were no longer significant after adjustment for age and years of education. HC varied inversely with age and directly with years of education but did not vary with presence/absence of dementia in first-degree relatives or with apolipoprotein-E (ApoE) genotype. In the prospective analysis, the hazard ratio for time to conversion to AD was not significant for HC when adjusted for age at entry, ApoE allele status, family history of dementia, gender, and years of education. ApoE allele status, first degree relative with dementia, and baseline age conferred an increased risk for conversion to AD, consistent with other studies. Conclusions: We observed a smaller HC in AD patients compared to nondemented individuals, but AD per se accounted for little of this difference. HC was not a statistically significant predictor for conversion to AD in our longitudinal group.

Objective: To identify risk factors associated with transitions from cognitively normal to various forms of mild cognitive impairment (MCI) and then from MCI into early dementia with death as a competing state. Methods: Cognitive assessments from 554 subjects participating in a longitudinal study at the University of Kentucky AD Center were used to classify individuals into one of three transient states at any visit: cognitively normal, amnestic MCI, or mixed MCI. Between visits subjects could die or become demented. A series of polytomous logistic models were used to model transitions among these states over time and to determine how the log odds of these transitions vary with age, education, sex, family history of dementia, and APOE status. Results: Age affects all transitions among transient states as well as those to dementia or death. Presence of at least one apolipoprotein 4 allele affects transitions from cognitively normal into amnestic MCI or into dementia. At most 12 years of education affects transitions into mixed MCI. Transitions do not vary with sex or family history. Conclusion: Aside from age, the usual risk factors associated with conversion from cognitively normal into dementia are likely risk factors for transitions into mild cognitive impairment.

We tested the hypothesis that the ALSFRS‐R can be accurately administered exclusively to the spouse/caregiver over the telephone (phone) in 31 patients with clinically possible, probable, or definite ALS (El Escorial criteria) by comparing the phone response to the consensus assessment during a clinic visit using a standardized script. We also compared the responses of the spouse/caregiver, during a private assessment, to the consensus assessment. Both the phone and private assessments were highly correlated with the consensus assessment, even considering that the evaluations were performed by multiple phone assessors and, in three instances, multiple home assessors. These results suggest the possibility of using this approach to conduct research in ALS.

The low density lipoprotein receptor (LDLR) is an attractive candidate gene for genetic association with Alzheimer's disease (AD) because: (i) the LDLR is an apolipoprotein E (apoE) receptor, alleles of which have been associated with AD, (ii) LDLR resides at chromosome 19p13.3 within a region linked to AD, and (iii) LDLR modulates the homeostasis of cholesterol, which itself appears associated with AD. Therefore, we evaluated whether LDLR haplotypes alter the odds of AD by performing an association study examining three LDLR single nucleotide polymorphisms (SNPs) in 118 AD patients and 133 non-AD subjects. LDLR genotypes were obtained by TaqMan allelic discrimination assays. Although individual LDLR SNPs were not associated with AD, analyses of unambiguous haplotypes suggested the hypothesis that the 211 LDLR haplotype was associated with reduced odds of AD. We then evaluated this hypothesis in a second study cohort, i.e., the Religious Orders Study. These results supported the hypothesis that the 211 LDLR haplotype is associated with reduced odds of AD. Moreover, these data suggested further associations between LDLR variants and AD. Thus, LDLR variants appear significantly associated with AD and merit additional study.

Recent research in Alzheimer's disease (AD) is centred about the early detection and prevention of this disease. Several recent moderate size clinical trials targeted at high risk cohorts have been designed along this theme. There have been few attempts to design a large trial to prevent this disease in elderly individuals at low risk for the disease. The purpose of this paper is to suggest a framework for designing a simple, large AD prevention trial. This framework uses a discrete time hazard model for decreasing the incidence of AD when participants are randomly assigned to one or more active prevention agents or placebo. This design allows for differential incidence among participants due to age, family history, genetic disposition, and ethnicity. It takes into account the length of the follow-up period, participant mortality, drop-outs, drop-ins, and loss to follow-up. This framework is illustrated by PREADVISE, a recently initiated large add-on prevention trial investigating the use of anti-oxidants for preventing AD among men enrolled in a even larger prostate cancer prevention study, SELECT.

Context With advances in the treatment of Alzheimer's disease (AD), clinical focus has shifted to early patient identification. Memory recall tests and category fluency distinguish normal individuals from early AD patients. Objective Develop a brief test for general practitioners to screen for AD. Design Examination of items from the MMSE and category fluency. Setting and ParticipantsA Brief Alzheimer Screen (BAS) was developed from cognitive assessments on 406 normal subjects and 342 mild AD patients in the CERAD (Consortium to Establish a Registry for AD) dataset. The derived measure was then applied to a second validation sample. Main Outcome MeasureLogistic regression was used to derive a predictive equation, which was then applied to two validation samples to estimate sensitivity and specificity. Results The resulting logistic model for discriminating between mild AD and controls included: recall of 3 words, number of animals named in 30 seconds, date, and spelling of WORLD backwards, ( p< 0.001 for each) accounting for 77% of the variance. When applied to the validation samples, sensitivity and specificity were over 99% and 87%, respectively. Conclusions These data support the use of the BAS as a potential screen of patients over 60 years of age.

The purpose of this study was to ascertain variations between primary and “secondary” caregivers (those who play a more supplemental role in the care of a relative). Survey data were collected from a sample of dementia caregivers recruited from the University of Kentucky Alzheimer's Disease Research Center (N = 1,016). Bivariate analyses found that primary and secondary caregivers varied on a number of background characteristics, and regression models indicated that primary caregivers provided a wider range of assistance with instrumental activities of daily living (IADLs), but not help with activities of daily living (ADLs). Primary and secondary caregivers did not differ significantly in reports of subjective health. The findings suggest that future research and interventions should be inclusive of primary and secondary caregivers.

This study examined the characteristics of entry into the caregiving role for family and friends of older adults suffering from dementia. Using data from a large community survey of informal caregivers of patients who visited the University of Kentucky's Alzheimer's Disease Research Center (n = 1055), respondents were classified into one of four onset sequences: recognition-diagnosis, care provision, recognition-care, and diagnosis dependent. A multinomial logistic regression identified several characteristics (i.e., caregiver income, time since onset, care recipient gender, care recipient living status, and primary caregiver identification) that were significantly associated with various caregiving onset patterns. The findings describe the complexity of the entry process and its potential association with health-related transitions in the caregiving career.

This paper provides a tractable numerical method for long-term average stochastic control problems in which the cost includes a term based on the local time process of a diffusion. The control problem is reformulated as a linear program over the set of invariant distributions for the process. In particular, the long-term average local time cost is expressed in terms of the invariant distribution. Markov chain approximations are used to reduce the infinite-dimensional linear programs to finite-dimensional linear programs and conditions for the convergence of the optimal values are given.

Background Practice effects are a known threat to reliability and validity in clinical trials. Few studies have investigated the potential influence of practice on repeated screening measures in longitudinal clinical trials with a focus on dementia prevention. The current study investigates whether practice effects exist on a screening measure commonly used in aging research, the Memory Impairment Screen (MIS). Methods The PREADViSE trial is a clinical intervention study evaluating the efficacy of vitamin E and selenium for Alzheimer’s disease prevention. Participants are screened annually for incident dementia with the MIS. Participants with baseline and three consecutive follow-ups who made less than a perfect score at one or more assessments were included in the current analyses (N=1,803). An additional subset of participants with four consecutive assessments but who received the same version of the MIS at baseline and first follow-up (N=301) was also assessed to determine the effects of alternate forms on mitigating practice. We hypothesized that despite efforts to mitigate practice effects with alternate versions, MIS scores would improve with repeated screening. Linear mixed models were used to estimate mean MIS scores over time. Results Among men with four visits and alternating MIS versions, although there is little evidence of a significant practice effect at the first follow-up, mean scores clearly improve at the second and third follow-ups for all but the oldest participants. Unlike those who received alternate versions, men given the same version at first follow-up show significant practice effects. Conclusion While increases in the overall means were small, they represent a significant number of men whose scores improved with repeated testing. Such improvements could bias case ascertainment if not taken into account.

The National Institute on Aging Preclinical Alzheimer’s disease Workgroup (PADW) has issued a preliminary report with recommendations for classifying preclinical Alzheimer’s disease (pAD) according to 3 early disease stages. Here we examine the PADW recommendations in relation to neuropathological features in a large, consecutive series of cognitively intact elderly persons, autopsied within a year after cognitive testing (n = 126 cognitively intact patients with mean age 83.7 years at death). Subjects were grouped based on a hypothetical construct correlating pathological features with PADW stages. Many cognitively intact individuals were classifiable as pAD (53/126 or 43%), as expected based on epidemiological and biomarker studies. Of these, most (48%) were in “stage 3”, which corresponds to amyloid pathology with early neurodegeneration. As with prior studies, our data indicate that the development of neocortical neurofibrillary tangles is the key pathological event that is not observed in pAD cases: Braak stages III or IV pathology are hence not truly a substrate for “intermediate likelihood” that cognitive impairment is due to Alzheimer’s disease (AD). We also stress the importance of comorbid non-Alzheimer’s disease brain pathologies (hippocampal sclerosis, neocortical alpha-synucleinopathy, cerebrovascular disease, and brains with hippocampal neurofibrillary tangles but no cortical amyloid plaques) that can contribute to the development of cognitive impairment, or which may serve as confounds in the application of the PADW recommendations. While the final recommendations from the PADW working group have not yet been released, this preliminary analysis provides a perspective on those recommendations from a neuropathological point of view.