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Biomedical subjects

J Brandt

Publications and source records attributed to J Brandt.

At least 163 records · Page 9Linked to original sources

Adjustment to residential placement in Alzheimer disease patients: does premorbid personality matter?

AIM: To evaluate the influence of premorbid personality on adaptation to placement in a long-term care facility. SUBJECTS: Twenty-eight persons with probable Alzheimer disease (AD) residing in an academically affiliated nursing home for 6-9 months. METHODS: Premorbid personality was described retrospectively by two informants for each resident using the revised NEO Personality Inventory (NEO-PI-R). Standardized tests and rating scales were used on admission to the facility to assess cognition, mood state, physical dependency and general health. Nurses rated each AD resident's social behaviour, participation in activities and quality of sleep. RESULTS: Poorer adjustment was associated with more severe dementia but better physical health. None of the NEO-PI-R domain scores predicted adjustment. CONCLUSIONS: Contrary to popular belief, premorbid personality is relatively inconsequential for an AD patient's adaptation to a long-term care facility.

Adaptation, Psychological↗

When does Huntington's disease begin?

Recent studies have detected basal ganglia atrophy in clinically asymptomatic persons with the genetic mutation that causes Huntington's disease (HD). Whether reductions in caudate and putamen volume on MRI scans are associated with changes in cognitive and neurologic functioning was examined in 13 healthy adults with the IT-15 mutation. Reduced striatal volume was found to correlate with greater neurologic (largely motor) impairment, slower mental processing speed, and poorer verbal learning, although none of the participants met even liberal criteria for clinical diagnosis of HD. These correlations are strikingly similar to those observed in symptomatic HD patients, possibly reflecting the earliest manifestations of disease.

Adult↗

Right atrial free wall conduction velocity and degree of anisotropy in patients with stable sinus rhythm studied during open heart surgery.

AIMS: Although the perpetuation of several supraventricular arrhythmias is critically dependent upon intra-atrial conduction, the literature lacks detailed information on normal values of conduction velocity and degree of anisotropy. In order to explore these factors further, we have measured conduction velocities at the right atrial free wall during sinus rhythm and during atrial pacing in four directions parallel and perpendicular to the atrioventricular groove in patients with normal atria and stable sinus rhythm. METHODS AND RESULTS: Using a Bard Cardiac Mapping System, atrial ECGs were recorded using a 3 x 4 cm electrode array with 56 equally spaced bipolar electrodes in 12 patients undergoing open heart surgery due to ischaemic heart disease or Wolf-Parkinson-White syndrome. A bipolar pen probe connected to a Medtronic 5328 stimulator was used for pacing at a 10% higher rate than sinus rhythm. The local activation times were manually set and isochronal activation maps were created for each recording. The conduction velocities were calculated from the activation maps over a distance ranging from 2.2 to 4.2 cm. The majority of the activation maps showed no signs of anisotropy; the others had less than 15% spatial inhomogeneity of conduction. Mean conduction velocity, calculated from five consecutive beats, was 88 +/- 9 cm.s-1 (mean +/- SD), ranging between 68 +/- 4 and 103 +/- 3 cm.s-1 during sinus rhythm. Mean conduction velocity during atrial pacing was 81 +/- 16 cm.s-1 at a propagation direction of 0 degree, 74 +/- 14 cm.s-1 at a 90 degrees direction, 79 +/- 12 cm.s-1 at 180 degrees and 78 +/- 20 cm.s-1 at 270 degrees, where 0 degree was parallel to the atrioventricular groove in the cranial direction and the angle increased counter-clockwise. Mean conduction velocity during sinus rhythm was significantly higher (P < 0.05) than during atrial pacing at the 90 degrees and 180 degrees directions but not compared to atrial pacing at 0 degree or 270 degrees. There was no significant difference in mean conduction velocity in different directions during atrial pacing. CONCLUSION: Although anisotropy was documented during conduction velocity in individual cases, conduction velocity was not dependent on propagation direction at the epicardial right atrial free wall in patients with stable sinus rhythm. These findings do not exclude the presence of internodal preferential pathways as these are located sub-epicardially and a marked transmural discordance in activation has previously been documented in the vicinity of such pathways.

Adult↗

Time-dependent motor memory processes in amnesic subjects.

Functional properties of motor memory change with the passage of time. The time-dependent nature of memories in humans has also been demonstrated for certain "declarative" memories. When the declarative memory system is damaged, are the time-dependent properties associated with motor memories intact? To approach this question, we examined five subjects with global amnesia (AMN), including subject H.M., and a group of age-matched control subjects. The task was to make reaching movements to visually presented targets. We found that H.M. (but not the other subjects) was significantly impaired in the ability to perform the visuomotor kinematic transformations required in this task, to accurately move the hand in the direction specified by a target. With extensive practice, H.M.'s performance improved significantly. At this point, a force field was imposed on the hand. With practice in field A, H.M. and other AMN subjects developed aftereffects and maintained these aftereffects for 24 h. To quantify postpractice properties associated with motor memories, subjects learned field B on day 2 and at 5 min were retested in field A. In both subject groups, performance in field A was significantly worse than their own naive performance a day earlier. The aftereffects indicated persistence of the just-learned but now inappropriate motor memory. After 4 h of rest, subjects were retested in B. Performance was now at naive levels. The aftereffects at 4 h indicated a reduced influence of the memory of field A. The time-dependent patterns of motor memory perseveration, as measured at 5 min and 4 h, were not different in the AMN and normal control groups.

Aged↗

Lack of relation between race and cognitive test performance in Alzheimer's disease.

This study evaluated cognitive test performance in African-American and European-American Alzheimer's disease patients with equivalent years of education. Group differences were negligible on a variety of memory, language, and attentional measures, including several widely used neuropsychological tests. Differences between racial groups observed in earlier studies may have stemmed, in part, from differences in education, which may itself serve as a proxy for other potentially important sociologic and health variables.

Aged↗

Increased frequency of Sjögren's syndrome in patients with spondyloarthropathy.

OBJECTIVE: To determine the prevalence of sicca symptoms and Sjögren's syndrome (SS) in spondyloarthropathy (SpA) patients with ankylosing spondylitis (AS) and undifferentiated SpA (uSpA). METHODS: Patients with SpA with inflammatory back pain and/or peripheral arthritis presenting to the university outpatient clinic were diagnosed as AS (n = 40) and uSpA (n = 65) according to established criteria. Patients with SpA with sicca symptoms and/or positive antinuclear antibody (ANA) were investigated for SS by minor salivary gland biopsy and/or sialography. To assess sicca symptoms in this cohort systematically we mailed a validated questionnaire with 6 questions on dryness of eyes and mouth to all 105 SpA patients and 150 healthy controls, a positive answer to > or = 3 questions was taken as suggestive of SS. There was no significant difference in baseline characteristics between patients and controls. RESULTS: In 8/105 SpA patients (5 uSpA, 3 AS; 6 female, 2 male) SS diagnosis by the European criteria indicated a frequency of 7.6%. Of 105 SpA patients, 12 were ANA+ (11.4%), of whom 7 had SS; thus, ANA were detected in 7/8 SpA patients with SS (88%). Of the 84 SpA patients responding to the questionnaire (80%), 10 gave a positive answer to > or = 3 questions (11.9%) compared to 2 of 131 (1.5%) controls (87.3%) (odds ratio = 8.7, 95% CI 2.3-32.5, p < 0.01). CONCLUSION: The data suggest increased prevalence of sicca symptoms and SS in SpA patients with AS and uSpA. The occurrence of a secondary SS in a variety of inflammatory diseases suggests that salivary gland involvement in these conditions results from as yet unidentified shared pathogenic mechanisms resulting in nonspecific inflammation in this location.

Adult↗

Predicting time to nursing home care and death in individuals with Alzheimer disease.

OBJECTIVE: To develop and validate an approach that uses clinical features that can be determined in a standard patient visit to estimate the length of time before an individual patient with Alzheimer disease (AD) requires care equivalent to nursing home placement or dies. DESIGN: Prospective cohort study of 236 patients, followed up semiannually for up to 7 years. A second validation cohort of 105 patients was also followed. SETTING: Three AD research centers. PATIENTS: All patients met National Institute of Neurological and Communicative Disorders and Stroke-Alzheimer's Disease and Related Disorders Association (NINCDS-ADRDA) criteria for probable AD and had mild dementia at the initial visit. INTERVENTION: Predictive features, ascertained at the initial visit, were sex, duration of illness, age at onset, modified Mini-Mental State Examination (mMMS) score, and the presence or absence of extrapyramidal signs or psychotic features. MAIN OUTCOME MEASURES: (1) Requiring the equivalent of nursing home placement and (2) death. RESULTS: Prediction algorithms were constructed for the 2 outcomes based on Cox proportional hazard models. For each algorithm, a predictor index is calculated based on the status of each predictive feature at the initial visit. A table that specifies the number of months in which 25%, 50%, and 75% of patients with any specific predictor index value are likely to reach the end point is then consulted. Survival curves for time to need for care equivalent to nursing home placement and for time to death derived from the algorithms for selected predictor indexes fell within the 95% confidence bands of actual survival curves for patients. When the predictor variables from the initial visit for the validation cohort patients were entered into the algorithm, the predicted survival curves for time to death fell within the 95% confidence bands of actual survival curves for the patients. CONCLUSIONS: The prediction algorithms are a first but promising step toward providing specific prognoses to patients, families, and practitioners. This approach also has clear implications for the design and interpretation of clinical trials in patients with AD.

Age of Onset↗

The course of psychopathologic features in mild to moderate Alzheimer disease.

BACKGROUND: The onset and course of the psychopathologic features of Alzheimer disease have not been established in prospective, longitudinal studies. METHODS: Two hundred thirty-five patients with early, probable Alzheimer disease were recruited at 3 sites and observed naturalistically for up to 5 years. At 6-month intervals, the Columbia University Scale for Psychopathology in Alzheimer's Disease was administered. Markov analyses were used to predict the probability of a specific symptom developing or being maintained at the next visit. For each symptom category, the maximum frequency of occurrence at 4 consecutive points (duration, 2 years) was calculated. RESULTS: Misidentification, wandering or agitation, and physical aggression increased during follow-up. At any visit, the likelihood of a new symptom developing was greatest for behavioral disturbance, intermediate for paranoid delusions and hallucinations, and least for depressed mood with vegetative features. Wandering or agitation occurred at 3 or more of 4 consecutive visits (duration, 2 years) in the majority of patients, paranoid delusions and hallucinations were intermediate in their degree of persistence, and depressed mood with vegetative signs rarely persisted. CONCLUSIONS: Behavioral disturbance, particularly agitation, is common and persistent in patients with Alzheimer disease. Psychotic symptoms are less common and show moderate persistence over time. Depressed mood with vegetative signs is uncommon and rarely persists. These findings suggest leads about the optimal treatment duration for specific subtypes of psychopathologic features.

Aged↗

The absence of an apolipoprotein epsilon4 allele is associated with a more aggressive form of Alzheimer's disease.

We investigated the relationship between APOE genotype and rate of disease progression and survival in 99 patients with probable Alzheimer's disease (AD) who were followed biannually for up to 6 years. Patients were stratified into two groups, those with and without at least one APOE epsilon4 allele. The rate of decline in modified Mini-Mental State Examination scores was slower, the presence of extrapyramidal signs was decreased, and the development of myoclonus occurred later among patients with APOE epsilon4 alleles compared with patients with other genotypes. Compared with patients without an APOE epsilon4 allele, the risk of mortality was also decreased in patients with at least one epsilon4 allele (RR = 0.38; CI = 0.17-0.84, p < 0.02). Because the decline in mental ability as well as the development of myoclonus and extrapyramidal signs are consistent manifestations of disease progression, our results imply that APOE epsilon4 is associated with a less aggressive form of AD.

Age of Onset↗

Access to information about famous individuals in Alzheimer's disease.

Alzheimer's disease (AD) patients and normal adults were tested in two complementary recognition tasks. On each trial of the faces task, participants matched the photograph of a famous individual to one of four names. On each tial of the names task, participants matched the name of a famous individual to one of four photographs. The AD patients made enough consistent errors across the two tasks to suggest an impairment in the storage of information about the individuals. In addition, they made enough inconsistent errors to suggest a generalized retrieval deficit. The AD patients performed as well on the faces taslk as on the names task, providing no evidence of a specialized deficit in the retrieval of lexical information.

Adult↗

Predictors of psychological adjustment to genetic testing for Huntington's disease.

In the present study the authors assessed predictors of adjustment to genetic testing for Huntington's disease. Fifty-two genetically positive and 108 genetically negative persons were studied for 1 year following testing. Adjustment, defined by hopelessness and depressive symptoms, was measured at 3, 6, 9, and 12 months after disclosure and was within normal limits for both groups. Those less well adjusted had tested positive, were married, had no children, or were closer to their estimated ages of onset. The study delineated risk factors for psychological distress that should be considered by people contemplating testing for Huntington's disease.

Adaptation, Psychological↗

Perseverations during paired-associate learning in Huntington's disease.

Verbal (word) and nonverbal (design) paired-associate tasks were administered to Huntington's disease (HD) patients and healthy control subjects. An AB-AC paradigm, in which the cue stimuli were paired with different responses on the learning (e.g., BED-REST) and test trials (e.g., BED-SHEET), was used. It was hypothesized that HD patients would continue to respond with AB associations on the AC trials. The results were contrary to expectations: Patients showed impaired learning of both verbal and nonverbal associations but did not display a perseverative response style, even when the associative strength between word pairs was manipulated to elicit perseverations. Patients made more nonperseverative than perseverative errors in all conditions, an error pattern similar to that of control subjects. HD patients did not demonstrate increased susceptibility to proactive interference on these associative learning tasks.

Adult↗

Epicardial right atrial free wall mapping in chronic atrial fibrillation. Documentation of repetitive activation with a focal spread--a hitherto unrecognised phenomenon in man.

BACKGROUND: Previous studies have shown that atrial fibrillation of recent onset in man is based on a varying number of simultaneously present activation waves reentering either themselves or each other. In the present study, right atrial activation during chronic atrial fibrillation in man was studied. METHODS AND RESULTS: In 16 patients with chronic atrial fibrillation multiple epicardial recordings of 8 s each were made at the right atrial posterior free wall and at the appendage using a 20 x 35 mm electrode array with 56 bipolar measurement points. The preferable activation pattern of each recording and the propagation direction, cycle length and conduction velocity of individual activation waves within each recording were determined. Activation was characterized by unorganised activation with several simultaneously present activation waves: inconsistent preferable activation pattern (n = 5), predominantly organised activation with either frequent episodes of uniform activation: consistent preferable activation pattern (n = 7) or frequent episodes of activation with focal spread; focal preferable activation pattern (n = 4). Random re-entry was frequently documented in recordings with the inconsistent preferable activation pattern and less frequently in recordings with the consistent and focal preferable activation pattern. Complete re-entry circuits were rarely documented. The median fibrillation cycle length was 146, 159 (P < 0.05) and 165 ms (not significant) and the mean conduction velocity during uniform activation was 64, 67 and 83 cm. s-1 (not significant) in recordings with the inconsistent, consistent and focal preferable activation pattern, respectively. CONCLUSIONS: During chronic atrial fibrillation in man, right atrial free wall activation ranges from disorganised activation with multiple co-existing activation waves to predominantly organised activation characterized by either uniform activation consistent with the presence of large re-entry circuits or repetitive activation of unknown mechanism and focal spread.

Aged↗

Depression, delusions, and hallucinations in Alzheimer's disease: no relationship to apolipoprotein E genotype.

The apolipoprotein E (APOE) locus on chromosome 19 has been shown to modify risk, and age at onset, of Alzheimer's disease (AD). The authors hypothesized that the phenotypic expression of different psychiatric symptoms in patients with AD would be associated with variability in APOE locus. Neuropsychiatric and genetic testing of 120 probable AD patients revealed 28% had major depression, 17% had minor depression, 30% had delusions, and 14% had hallucinations; 69% were carriers of at least one APOE E4 allele (14% homozygous E4/E4, 49% heterozygous E3/E4, 6% heterozygous E2/E4, 29% homozygous E3/E3, 2% heterozygous E2/E3). Prevalence of the various psychiatric disturbances did not differ significantly in AD patients with different APOE genotypes. Apolipoprotein E does not appear to modify the risk of developing AD-associated psychiatric symptomatology.

Aged↗

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.

Aged↗

Mesial temporal spikes interfere with working memory.

The hippocampus and other mesial temporal structures support long-term memory and also are common foci for epilepsy. Recently it was shown that these brain structures may subserve the short-term storage and rehearsal processes called working memory in humans. We determined the accuracy of verbal and visuospatial working memory in the presence and in the absence of mesial temporal spikes in eight patients who had bilateral depth electrodes implanted to evaluate intractable epilepsy. Six of eight patients had declines in working memory performance during mesial temporal spiking, with the greatest disruption in spatial and verbal recall coincident with left hippocampal spikes (p = 0.019). Overall accuracy of working memory for all patients declined an average of 6% on spike trials. The two patients who did not have decreased accuracy during spike trials also had the best overall working memory performance. Mesial temporal spikes were not detected on extracranial recordings and yet may be associated with declines in working memory in some patients with epilepsy.

Action Potentials↗