An ecological systems examination of elder abuse: a week in the life of adult protective services.

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.

Pittsburgh compound B and the postmortem diagnosis of Alzheimer disease.

OBJECTIVE: Deposition of the amyloid-ß (Aß) 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 Aß and other common indices of AD pathology. We hypothesized that recent advances in our ability to accurately measure Aß postmortem (for example, using PiB), could form the basis of a simple means to deliver an accurate AD diagnosis. METHODS: We conducted a comprehensive analysis of the amount of Aß40 and Aß42 in increasingly insoluble fractions, oligomeric Aß, and fibrillar Aß (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. RESULTS: Both PiB binding and the amount of sodium dodecyl sulfate (SDS)-soluble Aß were able to predict disease status; however, SDS-soluble Aß was a better measure. Oligomeric Aß 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. INTERPRETATION: Although postmortem PiB binding was somewhat useful in distinguishing AD from control cases, SDS-soluble Aß measured by standard immunoassay was substantially better. These findings have important implications for the development of imaging-based biomarkers of AD.

Improving dementia care: the role of screening and detection of cognitive impairment.

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.

The ALS Nutrition/NIPPV Study: design, feasibility, and initial results.

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.

Acetylcholinesterase inhibitor treatment is associated with relatively slow cognitive decline in patients with Alzheimer's disease and AD + DLB.

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.

Victim, Allegation, and Investigation Characteristics Associated With Substantiated Reports of Sexual Abuse of Adults in Residential Care Settings.

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.

Lack of valproic acid-associated weight gain in prepubertal children.

We evaluated whether prepubertal children treated with valproic acid did not gain excessive weight. This retrospective study of children with epilepsy, aged <12 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.

Clinicopathologic correlations in a large Alzheimer disease center autopsy cohort: neuritic plaques and neurofibrillary tangles "do count" when staging disease severity.

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.

Alzheimer's disease and head circumference.

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.

Relationship of creatine kinase to body composition, disease state, and longevity in ALS.

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.

Designing a Brief Alzheimer Screen (BAS).

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 PARTICIPANTS: A 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 MEASURE: Logistic 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.

Estimating daily energy expenditure in individuals with amyotrophic lateral sclerosis.

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.

Autonomic nervous system function following prenatal opiate exposure.

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 < 0.01), greater mean SDDRR during nutritive sucking (p = 0.02), and higher powers in the low and high frequency bands during nutritive feedings. Our findings suggest that prenatal opiate exposure may be associated with changes in autonomic nervous system (ANS) functioning involving both sympathetic and parasympathetic branches. Future studies are needed to examine the effects of prenatal opiate exposure on ANS function.

Practice effects in a longitudinal, multi-center Alzheimer's disease prevention clinical trial.

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.

Preclinical AD Workgroup staging: pathological correlates and potential challenges.

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.

Mild cognitive impairment: statistical models of transition using longitudinal clinical data.

Mild cognitive impairment (MCI) refers to the clinical state between normal cognition and probable Alzheimer's disease (AD), but persons diagnosed with MCI may progress to non-AD forms of dementia, remain MCI until death, or recover to normal cognition. Risk factors for these various clinical changes, which we term "transitions," may provide targets for therapeutic interventions. Therefore, it is useful to develop new approaches to assess risk factors for these transitions. Markov models have been used to investigate the transient nature of MCI represented by amnestic single-domain and mixed MCI states, where mixed MCI comprised all other MCI subtypes based on cognitive assessments. The purpose of this study is to expand this risk model by including a clinically determined MCI state as an outcome. Analyses show that several common risk factors play different roles in affecting transitions to MCI and dementia. Notably, APOE-4 increases the risk of transition to clinical MCI but does not affect the risk for a final transition to dementia, and baseline hypertension decreases the risk of transition to dementia from clinical MCI.

Vitamin E and all-cause mortality: a meta-analysis.

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 range from 28 to 39,876 (median = 423), yielding 246,371 subjects and 29,295 all-cause deaths. Duration of supplementation for the 57 trials range from one to 10.1 years (median = 2.6 years). A random effects meta-analysis produce 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.

Occupational status, work-site cessation programs and policies and menthol smoking on quitting behaviors of US smokers.

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.

Health profile differences for menthol and non-menthol smokers: findings from the National Health Interview Survey.

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 that former menthol smokers had higher body mass indices (BMIs) (OR: 1.01; 95% CI: 1.00, 1.02) and were more likely 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.