Neonatal outcomes of macrosomic births in diabetic and non-diabetic women.

OBJECTIVE: To compare the neonatal outcomes and birth injuries of macrosomic infants born to diabetic mothers (IDM) and non-diabetic mothers (non-IDM). STUDY DESIGN: This is a retrospective survey of all live born, singleton neonates with a birth weight of > or = 4000 g, delivered at the Albert Einstein Medical Center, Philadelphia during a 3-year period (2003 through 2005). 305 infants of the 7158 delivered during this period met entry criteria. Data were analysed using chi(2) and Fisher's exact test. Logistic regression analysis was also performed. RESULT: Compared to IDMs, non-IDMs were born later (40 vs 38 weeks) and were more likely to be delivered vaginally (70% vs 34%). Half of the non-IDMs (49.6%) had at least one morbidity compared with 73.2% of the IDMs. Non-IDMs had a higher incidence of birth injury than IDMs (8% vs 2.4%). Logistic regression showed an increased risk of poor outcome with weight > or = 4500 g and vaginal delivery. CONCLUSION: All macrosomic infants represent a high-risk group, regardless of maternal diabetes status.

Speaking of research advance directives: planning for future research participation.

OBJECTIVE: To examine one model of research advance directive as a possible way to reduce the mismatch between patient and proxy choices and also to learn more about how patients with mild to moderate dementia may want to keep decision making or cede it to their proxies in the future. METHODS: Separate interviews were conducted with 149 dyads of dementia patients and family proxies about future enrollment in five types of research. Subsequent joint interviews were conducted with 69 of those dyads to discuss their separately articulated decisions and ask whether the patient prefers future enrollment decisions to be made as he or she directs today or as the proxy deems best in the future. RESULTS: Patients chose to cede future decision making to their proxies in 82.9% of the trials. Patients ceded decisions to their proxies in 80.7% of those trials about which the dyad had given opposite answers (n = 74, 49.7%). Patients who had expressed discomfort about the prospect of the proxy making an enrollment decision in a trial (n = 49, 32.9%) ceded decision making to their proxies in 45.7% of those trials. CONCLUSIONS: Both patients and proxies were willing to discuss future research enrollment in the context of an advance directive for research. Such a document may be helpful to proxies and researchers in the future to judge the types of research and associated risks patients are willing to enroll in. Although most patients willingly cede future decisions to their proxies, a sizeable minority do not wish to do so.

A longitudinal study of the relationship between levels of depression among persons with Alzheimer's disease and levels of depression among their family caregivers.

The purpose of this study was to examine the effects, over time, of depressive symptoms in persons with Alzheimer's disease on depression in their family caregivers. In a sample of 353 patients and caregivers, multilevel longitudinal analysis was used to accommodate an observational design in which the number of observation points and the intervals between points varied across caregivers. The rate of change (increase) in caregiver depression was predicted by the rate of change (increase) in patient depressive symptoms and by increase in patient dependency in instrumental activities of daily living (ADLs). Acceleration of the increase in caregiver depression was predicted by acceleration in patient dependency in instrumental and basic ADLs but not by acceleration in patient depressive symptoms. These findings indicate the importance of measuring the rate and acceleration of change in patient characteristics in order to understand caregiver depression. They also support early interventions for caregivers.

Effects of aging on visuospatial attention: an ERP study.

The effects of aging on visuospatial attention were investigated with event-related brain potentials (ERPs). A central arrow pointed towards (75% valid cues) or away from (25% invalid cues) the location of upcoming visual targets to which subjects made two choice discriminations. Young and older adults responded faster following valid than invalid cues. The absolute magnitude of the cueing effect was larger for older than young subjects, but cueing effects were similar between groups when estimated proportionally to overall response time. Under the present conditions, the electrophysiological manifestations of visuospatial attention were similar for young and older adults. Early ERP components following the target stimulus (P1, N1, Nd1) were slower for older than young subjects, but amplitude was similarly affected by cueing in each group. The temporal correspondence between component latencies and the observed cueing effects are consistent with theories positing that attention amplifies the sensory gain of early perceptual processes. The observation that aging slowed latency of the ipsilateral but not the contralateral P1, is consistent with age differences in interhemispheric transfer times. A broadly distributed 200-400 ms validity effect on ERP amplitude was similar between groups in timing, spatial distribution, and magnitude. The 200-400 ms attention effect appeared to be a modulation of the P3 in younger subjects, as earlier observed. However, the present study dissociated the 200-400 ms attention effects from the P3 component because the P3 did not peak until 526 ms in older subjects.

Performance of elderly and young normals on the Gollin Incomplete Pictures Test.

Our study compared 26 young and 28 elderly subjects on the Gollin Incomplete Pictures Test. Young and elderly subjects differed, the older group requiring less fragmentation and more time for identification; response accuracy and latency were not correlated with one another.

Behavior Rating Scale for Dementia: development of test scales and presentation of data for 555 individuals with Alzheimer's disease.

We studied 555 Alzheimer's disease patients on the Behavior Rating Scale for Dementia (BRSD), which uses informant interviews to measure behavioral pathology in demented patients. For the 45 items, ratings of present ranged from 5% to 66% of the subjects, with 39 rated present in at least 10%. Twenty-nine items were significantly correlated with dementia severity. The mean number of items present per subject was 13.5; only two subjects had none rated present. Factor analysis identified six factors common to mildly and moderately demented subjects. Six subscales were developed: Depressive Symptoms, Inertia, Vegetative Symptoms, Irritability/Aggression, Behavioral Dysregulation, and Psychotic Symptoms. Interitem consistency was high for three subscales (alpha's from .75 to .80) and moderate for three (alpha's from .48 to .56). Four subscale scores and total scores were significantly but weakly correlated with dementia severity. Detailed results and test instructions are presented in the BRSD manual, available from The Consortium to Establish a Registry for Alzheimer's Disease.

Characterization of depression in Alzheimer's disease by the CERAD Behavior Rating Scale for Dementia (BRSD).

The authors selected 69 participants from an Alzheimer's disease research registry and diagnosed them as depressed or nondepressed by use of a semi-structured clinical interview. Responses to selected BRSD items were compared between the depressed and nondepressed groups. Differences between responses of the two groups on BRSD items related to anxiety and depression were significant. The groups did not significantly differ in their responses to items related to other content areas. On the basis of their responses to the BRSD anxiety and depression items, 70% of participants were correctly classified as depressed or nondepressed.

Validation of a Telephone Cognitive Assessment Battery.

OBJECTIVE: To present and evaluate an instrument, the Telephone Cognitive Assessment Battery (TCAB), designed to be administered over the telephone to assess the cognitive status of older individuals. The TCAB addresses mental status, reasoning and executive ability, primary and secondary memory, and language. It consists of six neuropsychological tests and takes approximately 15 to 20 minutes to complete. DESIGN: The instrument is evaluated with a comparative cross-sectional design, with data collected both prospectively and retrospectively. SETTING: The University Hospitals of Cleveland/Case Western Reserve University Alzheimer Center Research Registry. PARTICIPANTS: Forty Alzheimer's Disease cases selected from among those most recently recruited into the Registry and 40 cognitively intact Registry controls. Controls were selected randomly so that the two groups had similar distributions of age, sex, and education. MEASUREMENTS: The cognitive status of all participants was assessed utilizing both the TCAB and the usual in-person Registry evaluation, which includes medical history data and in-person assessment of cognitive status. In order to measure the potential learning effect of repeated testing, half of the cases and half of the controls were recruited and assessed over the telephone with the TCAB before their in-person Registry evaluation (with a waiting period of at least 2 weeks between evaluations), whereas the other two halves received the TCAB after they had become part of the Registry. The TCAB was administered to all participants by a single investigator. Two clinical evaluators, blinded to the Registry diagnosis of the subjects, independently classified the subjects as cognitively impaired, normal, or questionable on the basis of the results of the TCAB and a brief listing of medical illness and depressive symptoms. A final classification was achieved through consensus and subsequently compared with the Registry diagnosis, taken here to be the gold standard. RESULTS: Test scores of subjects assessed by TCAB before receiving the in-person assessment were compared with those of subjects receiving the in-person assessment first. There were no significant differences between mean scores of the two groups (those with TCAB first and those with TCAB last) for either cases or normal controls. High values of the kappa statistic were obtained for the two initial evaluators of the TCAB classification, demonstrating excellent interrater reliability. Regarding the reconciled TCAB classification, the ability of the TCAB to correctly classify subjects according to cognitive status, while controlling for potential confounders such as age and educational level, was assessed by means of discriminant analysis techniques. Knowledge of the TCAB classification and age allowed the correct classification of 95% of the participants; this was not significantly improved by knowledge of other potential determinants. Sensitivity and specificity were calculated under two schema for classifying those subjects in the "questionable" category. Positive and negative predictive values of the TCAB were computed assuming a prevalence of cognitive impairment of 10% in the older population. High negative predictive values (over 99%) were obtained under both schema, whereas the positive predictive values were seen to be more dependent on the classification of questionables. CONCLUSION: Research studies involving ascertainment of cognitive status of older people, particularly those that require periodic follow-up, such as those focusing on healthy aging, commonly suffer from lack of representativeness of subjects, often brought about by problems related to mobility of potential participants. It is also crucial that normal individuals who are recruited initially to serve as controls in epidemiologic studies of dementing illnesses be reevaluated periodically, and this may be hindered by the same obstacles. (ABSTRACT TRUNCATED)

A longitudinal study of behavioral pathology across five levels of dementia severity in Alzheimer's disease: the CERAD Behavior Rating Scale for Dementia. The Alzheimer's Disease Cooperative Study.

As part of the Alzheimer's Disease Cooperative Study (ADCS) Instrument Development Project, the CERAD Behavior Rating Scale for Dementia (BRSD) was examined for its sensitivity to degree of cognitive impairment, its test-retest reliability, and its sensitivity to longitudinal change. Sixty-four normal elderly participants and 261 patients with AD stratified into severity groups based on Mini-Mental State Exam (MMSE) scores were rated on the BRSD at baseline and 12-month follow-up visits. A subset of subjects was evaluated at a 1-month follow-up visit. Baseline BRSD Total Score discriminated the normal group from each AD group, and mean Total Score significantly increased with increasing dementia severity. Test-retest reliability between baseline and 1-month Total Scores was satisfactory for all AD groups. Longitudinal change was evaluated by 12-month change scores, which were significant in only the normal and in one AD group. From the results, we argue that the value of behavioral pathology assessment in clinical trials would be enhanced if additive scores were based on groups of correlated items rather than on a broad array of behaviors, some of which may increase and others may decrease in frequency as AD progresses.

The Behavior Rating Scale for Dementia of the Consortium to Establish a Registry for Alzheimer's Disease. The Behavioral Pathology Committee of the Consortium to Establish a Registry for Alzheimer's Disease.

OBJECTIVE: The purpose of the study was to develop a standardized instrument, the Behavior Rating Scale for Dementia, for rating psychopathology in patients with probable Alzheimer's disease and to conduct a multicenter pilot study of this instrument. METHOD: The rating scale was developed collaboratively on the basis of clinical experience and existing instruments. Items were scaled according to frequency of psychopathology and were administered to an informant who was familiar with the subject. The scale was administered in a standardized manner by trained examiners who had met predetermined certification standards. The study group consisted of 303 subjects with probable Alzheimer's disease who had undergone standardized clinical evaluations by the Consortium to Establish a Registry for Alzheimer's Disease. RESULTS: Subjects had an average of 15 problems rated as present in the preceding month. Wide variability in the nature of disturbances was found, with a number of items rated as present since the illness began but not in the past month. Interrater agreement was high. Factor analysis suggested eight preliminary factors that mapped onto clinically relevant domains: depressive features, psychotic features, defective self-regulation, irritability/agitation, vegetative features, apathy, aggression, and affective lability. CONCLUSIONS: The Behavior Rating Scale for Dementia provides a standardized, reliable measure that can be administered to caregivers of demented subjects. On the basis of the present study, the scale has been revised slightly. After additional studies in progress, the Behavior Rating Scale for Dementia will be available for general use in assessing a wide range of psychopathology in dementia.

The evaluation of behavioral disturbances in Alzheimer's disease: the utility of three rating scales.

Behavioral disturbances, eg, wandering, irritability, depression, and delusions, are observed in Alzheimer's disease (AD). Determining the importance of such symptoms requires that they be evaluated objectively. The Behavioral Pathology in Alzheimer's Disease Rating Scale (Behave-AD), Cornell Scale for Depression in Dementia (Cornell), and Brief Psychiatric Rating Scale (BPRS) were administered to 61 AD and 20 elderly control subjects. Only one AD subject showed no behavioral symptoms. All scales were reliably rated for presence or absence of symptoms. However, assessment of reliability of severity ratings was limited, because symptom frequency and severity were low. Although the Cornell and Behave-AD appeared more appropriate for AD subjects than did the BPRS, neither scale provided a complete description of behavioral symptoms, and each showed problems that interfere with its use. We recommend the development of a comprehensive scale with a well-anchored system of scaling and detailed rater instructions.

Concomitants of visual hallucinations in Alzheimer's disease.

Visual hallucinations (VH) are the most common hallucinations in Alzheimer's disease (AD), but their relationships with other behavioral symptoms and measures of cognitive performance are unclear. Using the BE-HAVE/AD, a semistructured behavioral inventory, we identified 20/160 AD patients (13%) who were currently having VH. Patients with VH performed worse on the Mini-Mental State Examination and had more behavioral symptoms than patients without VH. Symptoms particularly associated with VH included auditory hallucinations, verbal outbursts, delusions, and paranoid ideation. Principal factor analysis of the BEHAVE/AD yielded four factors accounting for 47% of the total variance. VH loaded on two factors involving symptoms of "paranoia" and "agitation/hallucinations." Our findings suggest that VH in AD patients are common, often occur in the presence of specific behavioral disturbances, and may have management implications.

Influence of letter size on age differences in letter matching.

We tested healthy young and older adults on a simultaneous presentation, letter-matching task that varied letter size. The goal of the experiment was to determine if older adults' higher baseline level of internal noise would affect age differences in letter-matching performance as letter size was varied. The results indicated that both young and older adults evidenced "fast-same" effects for RT and "false-different" effects for errors. However, older adults (compared to young adults) showed a larger "false-different" effect for errors, and this effect was especially pronounced for smaller letter pairs. These results imply that older adults' higher baseline levels of internal noise result in these individuals setting "compromise criteria" that underestimate the impact of internal noise.

Performance of subjects with probable Alzheimer disease and normal elderly controls on the Gollin Incomplete Pictures Test.

Our study was designed to evaluate perceptual ability measured by the Gollin Incomplete Pictures Test (in which subjects identify fragmented pictures of common objects) in Alzheimer Disease. We developed a standardized procedure for administering Gollin's test and compared the performance of 58 Alzheimer patients and 37 elderly controls on the Gollin, two design copying tests, the Mini-Mental State Examination, a verbal version of the Knox Cubes test, a recognition memory test, and a verbal fluency test. Alzheimer patients performed significantly more poorly than controls on all tests. Factor analysis demonstrated a visual perceptual factor, with loadings on the Gollin test and design copying, and three other factors representing primary memory, secondary memory, and language. Results indicate the Gollin test measures visual perceptual ability, but the precise nature of the task requires further study. Identification of fragmented pictures appears a practical and potentially useful measure for evaluating at least some aspects of visual perception in patients with generalized cognitive impairment.

Memory evaluation in Alzheimer's disease. Caregivers' appraisals and objective testing.

OBJECTIVES: To evaluate if caregivers are reliable informants concerning memory deficits in patients with Alzheimer's disease (AD). DESIGN: Responses of caregivers of patients with probable AD and responses of healthy control subjects on a standardized memory questionnaire were compared with objective measures of cognition (Consortium to Establish a Registry for Alzheimer's Disease neuropsychological battery) and with clinical estimates of activities of daily living, depression, and psychopathology (Consortium to Establish a Registry for Alzheimer's Disease [CERAD] clinical assessment battery) using the Self-report Memory Questionnaire. SETTING: A federally funded AD research center. SUBJECTS: The referred sample included 117 patients with probable AD, their informants, and 41 healthy control subjects age-matched to the patients. Patients and control subjects were between the ages of 58 and 85 years, had between 9 and 19 years of education, and were in good health. EXCLUSIONS: Patients who did not meet NINCDS-ADRDA criteria of probable AD. MAIN OUTCOME MEASURE: The optimal number of questionnaire items yielding the best combination of sensitivity and specificity. RESULTS: An abbreviated version of the scale, renamed the Short-Memory Questionnaire, had excellent specificity and sensitivity for identifying dementia. Positive and negative predictive values were 63.5% and near 100%, respectively. The Short-Memory Questionnaire showed good reliability, internal consistency, and external validity. Caregiver appraisals of memory deficits significantly correlated with objective measures of memory and also with generalized cognitive dysfunction. CONCLUSIONS: Caregivers of patients with AD are reliable informants of their relatives' deficits. The Short-Memory Questionnaire is an easily administered, informant-based scale that may be useful in clinical settings or epidemiologic studies to screen out persons with memory difficulties.

Impact of adult age and Alzheimer's disease on levels of neural noise for letter matching.

We tested healthy young and older adults as well as higher-scoring (Mini-Mental State Exam, MMSE, scores between 14-20) and lower-scoring patients diagnosed with probable Alzheimer's disease (AD) on a letter-matching task. Subjects were instructed to respond "same" if two simultaneously presented letters were identical, or "different" if the letters did not match. Healthy older adults showed a larger "fast-same" effect than healthy young adults. Also, higher-scoring AD patients showed a large "false-different" effect for errors, but lower-scoring AD patients showed a large "false-same" effect. These data indicate that older adults exhibit higher neural noise levels than younger adults. The cross-over error pattern for AD suggests that moderately demented AD patients show evidence of forming degraded visual percepts whereas more severely demented AD patients show evidence of forming incomplete percepts.