Participation in Clinical Trials and Long-Term Outcomes in Alzheimer's Disease

The objective of this study was to determine whether participation in clinical trials affects long-term outcomes in Alzheimer's disease (AD). Participation in clinical trials for persons with dementia is often justified on the grounds that patients benefit from the medical oversight typical of trials, even when experimental agents do not demonstrate short-term benefits. This claim has not been rigorously assessed. Of 215 community-resident subjects enrolled in a prospective study of outcomes in AD, 101 participated in randomized clinical trials (RCTs) during the first 2 years of follow-up. These subjects were compared with subjects who met eligibility requirements for RCTs but did not participate (N = 57) and with subjects who were ineligible (N = 57), over a total of 3.5 years of follow-up. Survival analyses assessed risk of death, nursing home placement, and incident functional deficit end points, adjusting for baseline differences. Subjects who participated in RCTs were younger and more highly educated. Mortality, risk of hospitalization, number of medical examinations conducted by study physicians, and onset of severe functional deficit did not differ between the groups, but risk of nursing home admission was significantly lower among RCT participants compared with eligible nonparticipants and ineligible subjects (16.8% versus 36.8% and 31.6%, respectively [p = 0.01]). The difference in risk of nursing home placement may represent a long-term, drug-related benefit to patients, a selection effect (caregivers of patients who participate in RCTs differ from caregivers of patients who do not), or a positive effect on caregivers (greater contact with a medical service may be associated with better care-giving outcomes). Further research is required to assess these effects

The Relation of Patient Dependence to Home Health Aide Use in Alzheimer's Disease

BACKGROUND: Although there has been much research devoted to understanding the predictors of nursing home placement (NHP) in Alzheimer's disease (AD) patients, there is currently a lack of research concerning the predictors of home health care. The objective of this study was to examine whether the Dependence Scale can predict home health aide (HHA) use. METHODS: The sample is drawn from the Predictors Study, a large, multicenter cohort of patients with probable AD, prospectively followed annually for up to 7 years in three university-based AD centers in the United States. Markov analyses (n=75) were used to calculate annual transition probabilities for the "new onset" of HHA use (instances where an HHA was absent at the previous visit, but present at the next visit) as a function of HHA presence at the preceding year's visit and dependence level at that preceding year's visit. RESULTS: The dependence level at the previous year's visit was a significant predictor of HHA use at the next year's visit. Three specific items of the Dependence Scale (needing household chores done for oneself, needing to be watched or kept company when awake, and needing to be escorted when outside) were significant predictors of the presence of an HHA. CONCLUSION: The Dependence Scale is a valuable tool for predicting HHA use in AD patients. Obtaining a better understanding of home health care in AD patients may help delay NHP and have a positive impact on the health and well-being of both the caregiver and the patient

Assessing Patient Dependence in Alzheimer's Disease

Background. While cognitive and functional deficits are the hallmark of Alzheimer's disease (AD), loss of social function (and the dependence this implies) is also critical, especially in early stages of disease. Little attention has been directed to this facet of dementing disease. We describe a scale for assessing dependency in AD and present a baseline profile of dependency in a cohort of AD patients. Methods. In a study of the predictors of the course of AD, 233 patients in early stages of disease (modified MMS ≥ 30) were assessed. Psychometric properties of the dependence scale were established. To validate the scale, dependence scores at baseline were correlated with a series of measures assessing cognition and function. The course of dependency over 18 months of follow-up was also analyzed. Results. The scale shows adequate reliability (test-retest, intraclass correlation). Dependence stage was related to other measures of disease severity. Scalogram analysis shows that the dependence scale is consistent with the course of functional loss established for dementing disease. Prospective data indicate sensitivity of the scale to disease progression. Conclusion. Dependency is a distinct, measurable component of dementing disease and should be considered an important outcome in studies of AD

Neuropsychological Predictors of Dependency in Patients with Alzheimer Disease

OBJECTIVE: To determine whether specific cognitive deficits can predict the progression of Alzheimer disease (AD). METHODS: Two hundred fifty-two patients with AD enrolled in the Predictors Study were followed at 6-month intervals for up to 4.5 years with neurologic, cognitive, and psychiatric examinations. Neuropsychological functions were assessed by the Modified Mini-Mental State Examination (mMMSE). Items of mMMSE were divided into five cognitive domains: temporospatial orientation, short-term memory, long-term memory, language, and visuoconstructive functions. Loss of autonomy was assessed by both the Dependency Scale (DS) and the Equivalent Institutional Care (EIC) rating. Cox proportional hazards models, adjusted for age, sex, estimated duration of illness at entry into the study, and presence of extrapyramidal signs and behavioral disturbances, were used to determine the predictive value of each neuropsychological domain on dependency outcomes. RESULTS: Global mMMSE, temporospatial orientation, and short-term memory scores were associated with a greater relative risk of moderate or severe dependency. The visuoconstructive score predicted the development of severe dependency. Long-term memory and language scores were not predictive of the EIC or DS endpoints. CONCLUSIONS: The presence of certain neuropsychological deficits at a patient's initial visit, such as short-term memory, temporospatial orientation, and constructive apraxia, predict more rapid dependency in patients with Alzheimer disease. Neuropsychological items have different weights in term of predictive power, and these effects are independent of the influence of age and disease duration at baseline

Longitudinal Study of Quality of Life in People with Advanced Alzheimer's Disease

The authors examined three indicators of health-related quality of life in people with advanced Alzheimer's disease ([AD]; N = 150): confinement to home, null activity, and null positive affect, as reported by patient proxies. Dementia severity predicted time-to-onset for all three disease milestones in models that controlled for sociodemographic indicators, nursing home status, and death in the follow-up period. Patients whose dementia worsened over follow-up were more likely to reach each milestone. These outcomes represent key milestones in the care of patients; they are sensitive to disease progression, and they are likely to be useful for studying treatment in advanced AD

Dissociating Confidence and Accuracy: Functional Magnetic Resonance Imaging Shows Origins of the Subjective Memory Experience

Successful memory typically implies both objective accuracy and subjective confidence, but there are instances when confidence and accuracy diverge. This dissociation suggests that there may be distinct neural patterns of activation related to confidence and accuracy. We used event-related functional magnetic resonance imaging to study the encoding of novel face–name associations, assessed with a postscan memory test that included objective measures of accuracy and subjective measures of confidence. We showed specific neural activity in the left inferior prefrontal cortex associated with trials when subjects expressed high confidence that they had chosen the correct name for the face and made a correct identification. Moreover, we found that this region was also associated with imparting high confidence when subjects chose the incorrect name. However, medial temporal lobe regions showed activity only for high-confidence correct trials. Many functional magnetic resonance imaging studies have shown that the medial temporal lobe and left prefrontal regions are particularly important for the successful formation of memories by using a combination of subjective and objective measures. Our findings suggest that these regions may be differentially involved in the objective and subjective components of memory and that the origins of confidence–accuracy dissociations may be related to incomplete activation of the neural pattern seen in successful encoding. These findings may also aid understanding of eyewitness misidentifications and memory distortions.Psycholog

Phosphotyrosine profiling of human cerebrospinal fluid

Additional file 3: Figure S1. A relative abundance of the tyrosine phosphorylated peptides in the CSF samples

Change in Body Mass Index before and after Alzheimer's Disease Onset

OBJECTIVES: A high body mass index (BMI) in middle-age or a decrease in BMI at late-age has been considered a predictor for the development of Alzheimer's disease (AD). However, little is known about the BMI change close to or after AD onset. METHODS: BMI of participants from three cohorts, the Washington Heights and Inwood Columbia Aging Project (WHICAP; population-based) and the Predictors Study (clinic-based), and National Alzheimer's Coordinating Center (NACC; clinic-based) were analyzed longitudinally. We used generalized estimating equations to test whether there were significant changes of BMI over time, adjusting for age, sex, education, race, and research center. Stratification analyses were run to determine whether BMI changes depended on baseline BMI status. RESULTS: BMI declined over time up to AD clinical onset, with an annual decrease of 0.21 (p=0.02) in WHICAP and 0.18 (p=0.04) kg/m2 in NACC. After clinical onset of AD, there was no significant decrease of BMI. BMI even increased (b=0.11, p=0.004) among prevalent AD participants in NACC. During the prodromal period, BMI decreased over time in overweight (BMI>/=25 and /=30) NACC participants. After AD onset, BMI tended to increase in underweight/normal weight (BMI<25) patients and decrease in obese patients in all three cohorts, although the results were significant in NACC study only. CONCLUSIONS: Our study suggests that while BMI declines before the clinical AD onset, it levels off after clinical AD onset, and might even increase in prevalent AD. The pattern of BMI change may also depend on the initial BMI

Psychopathological Features in Alzheimer's Disease: Course and Relationship with Cognitive Status

OBJECTIVES: To examine the course, clinical correlates, and relationship between cognitive status and psychopathological features in patients with probable Alzheimer's disease (AD) followed over a 5-year period. DESIGN: Cohort study with follow-up of 5 years. SETTING: Patients were recruited at three sites: 91 patients at Columbia Medical Center, 84 at Johns Hopkins School of Medicine, and 61 at Massachusetts General Hospital. PARTICIPANTS: Patients diagnosed with probable AD (n = 236) enrolled in a longitudinal study (Predictors study). MEASUREMENTS: Wandering/agitation, physical aggression, hallucinations, and delusions were evaluated at 6-month intervals using the Columbia Scale for Psychopathology in Alzheimer's Disease. Descriptive analyses were used to provide estimates of prevalence and course of psychopathological features. General estimating equations determined the odds of having any of the four psychopathological behaviors as a function of cognitive status. Markov analyses provided 6-month transition probabilities for psychopathological behaviors given patients' cognitive status and the presence or absence of such behaviors in the previous evaluation. RESULTS: For wandering/agitation, prevalence (39-57%) and persistence increased as a function of time and decrement in cognitive status. Physical aggression was less prevalent (6-22%) and increased as a function of cognitive decline but tended to persist only in the more severely impaired patients. Delusions (34-49%) reached a peak at the second year and then declined. The odds of delusions were maximal with intermediate decline but remained persistent regardless of cognitive status. Hallucinations, despite some fluctuations, were relatively stable during the follow-up period (8-17%) and moderately persistent. CONCLUSION: Psychopathological features, particularly wandering/agitation and delusions, in AD were common throughout the disease course. The natural history and persistence of the four psychopathological features varied. These findings provide important information to clinicians and caregivers regarding the course, predictability, and possible treatment of psychopathological behaviors in patients with probable AD