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Biomedical subjects

P J Moberg

Publications and source records attributed to P J Moberg.

At least 19 recordsLinked to original sources

[99mTc]TRODAT-1 SPECT imaging correlates with odor identification in early Parkinson disease.

BACKGROUND: In vivo imaging of the dopamine transporter with [99mTc]TRODAT-1 (TRODAT) and olfactory testing have both been proposed as potential biomarkers in Parkinson disease (PD). OBJECTIVE: To evaluate the relationship between TRODAT SPECT imaging, odor identification skills, and motor function in patients with early PD. METHODS: Twenty-four patients with a clinical diagnosis of early-stage PD (mean Hoehn & Yahr stage = 1.4) underwent TRODAT imaging, Unified PD Rating Scale (UPDRS) ratings of motor function, and administration of the University of Pennsylvania Smell Identification Test (UPSIT). Brain images were obtained using a standardized processing protocol and specific uptake ratios for striatal regions of interest were calculated. Partial correlations between the imaging indices, disease duration, UPSIT scores, and UPDRS motor scores were then calculated. RESULTS: UPSIT scores were correlated with TRODAT uptake in the striatum as a whole (r = 0.66, p = 0.001). The putamen showed the strongest correlation with the UPSIT (r = 0.74; p < 0.001). The correlation between dopamine transporter density in the caudate and UPSIT was moderate (r = 0.36, p = 0.11), but was not significant. CONCLUSIONS: Olfactory function is highly correlated with dopamine transporter imaging abnormalities in early Parkinson disease (PD). Further studies are warranted to determine whether changes over time in these two measures are also correlated in early PD.

Agnosia↗

Dysregulation of olfactory receptor neuron lineage in schizophrenia.

BACKGROUND: Growing evidence implicates abnormal neurodevelopment in schizophrenia. While neuron birth and differentiation is largely completed by the end of gestation, the olfactory epithelium (OE) is a unique part of the central nervous system that undergoes regeneration throughout life, thus offering an opportunity to investigate cellular and molecular events of neurogenesis and development postmortem. We hypothesized that OE neurons exhibit deviant progress through neurodevelopment in schizophrenia characterized by an increase in immature neurons. METHODS: Olfactory epithelium was removed at autopsy from 13 prospectively assessed elderly subjects who had schizophrenia and 10 nonpsychiatric control subjects. Sections were immunolabeled with antibodies that distinguish OE neurons in different stages of development, including basal cells (low-affinity nerve growth factor receptor, p75NGFR), postmitotic immature neurons (growth-associated protein 43 [GAP43]), and mature olfactory receptor neurons (olfactory marker protein). Absolute and relative densities of each cell type were determined. RESULTS: We observed a significantly lower density of p75NGFR basal cells (37%) in schizophrenia and increases in GAP43 + postmitotic immature neurons (316%) and ratios of GAP43 + postmitotic immature neurons to p75NGFR + cells (665%) and olfactory marker protein + mature neurons to p75NGFR + basal cells (328%). Neuroleptic-free schizophrenia subjects exhibited the highest GAP43 + postmitotic immature neuron values. CONCLUSIONS: Abnormal densities and ratios of OE neurons at different stages of development indicate dysregulation of OE neuronal lineage in schizophrenia. This could be because of intrinsic factors controlling differentiation or an inability to gain trophic support from axonal targets in the olfactory bulb. While caution is necessary in extrapolating developmental findings in mature OE to early brain development, similarities in molecular events suggest that such studies may be instructive.

Aged↗

Cognitive impairment and functional status in elderly institutionalized patients with schizophrenia.

OBJECTIVE: The relationship of cognitive impairment to functional status in older adults with schizophrenia was investigated. PATIENTS: Ninety-three psychiatric inpatients with schizophrenia between the ages of 65 and 88 years. Two subsets of this sample, consisting of 48 and 24 patients, were studied with a greater number of assessment instruments. MEASURES: The Mini-Mental State Examination (MMSE) was used for brief assessment of overall cognitive functioning, and the Psychogeriatric Dependency Rating Scale (PGDRS) was administered to assess functional status. The cognitive test battery from the Consortium to Establish a Registry for Alzheimer's Disease (CERAD) and/or an expanded neuropsychological battery, was given to a subset of the patients. RESULTS: In the overall sample, patients with greater global cognitive impairment had higher levels of rated impairment on the individual items that comprised the Orientation and Physical, but not Behavior, subscales of the PGDRS. Furthermore, in the two subsamples, specific neuropsychological measures of problem-solving, word list learning, naming and constructional praxis were related to overall measures of outcome. CONCLUSIONS: Neuropsychological deficit and psychosocial outcome are multi-dimensional entities that relate to one another in complex ways.

Activities of Daily Living↗

Computerized neurocognitive scanning: I. Methodology and validation in healthy people.

Neuropsychological testing batteries are applied in neurobehavioral evaluations of brain disorders, including neuropsychiatric populations. They are lengthy, require expert administrators and professional scorers, and are prone to data handling errors. We describe a brief computerized neurocognitive "scan" that assesses similar domains with adequate reliability. The scan and a traditional battery were administered to a sample of 92 healthy individuals (44 men, 48 women) in a counterbalanced order. Both approaches showed a significant "sex-typical" gradient, with women outperforming men in verbal memory relative to spatial tasks. Both methods also yielded similar profiles of sex differences, with the additional computerized measure of face memory showing better performance in women. Age effects were evident for both methods, but the computerized scan isolated the effects to speed rather than accuracy. Therefore, the computerized scan has favorable reliability and construct validity and can be applied efficiently to study healthy variability related to age and gender.

Adult↗

Computerized neurocognitive scanning: II. The profile of schizophrenia.

Cognitive dysfunction in schizophrenia is well established with neuropsychological batteries, which have assessed multiple domains indicating diffuse deficits especially in processing related to frontotemporal systems. Two studies are reported examining the feasibility of the computerized neurocognitive scan to assess differential deficits in schizophrenia. In Study 1, we tested 53 patients and 71 controls with the traditional and computerized assessments counterbalanced in order. Both showed comparable generalized impairment in schizophrenia with differential deficits in executive functions and memory. The profile was replicated in Study 2 in a new sample of 68 patients and 37 controls, receiving only the computerized scan. The combined sample showed robust correlations between performance on both speed and accuracy measures of the neurocognitive scan and clinical variables, including premorbid adjustment, onset age, illness duration, quality of life, and severity of negative symptoms. These correlations were higher and more prevalent in women than men, who showed correlations predominantly for speed rather than accuracy. Neuroleptic exposure was associated with poorer performance only for speed of memory processing, and in men, this association was seen only for typical neuroleptics. We conclude that the computerized neurocognitive scan can be applied reliably in people with schizophrenia, yielding data that support its construct and criterion validity.

Adult↗

Approaches to cognitive remediation of neuropsychological deficits in schizophrenia: a review and meta-analysis.

A review and critique of the literature pertaining to the use of cognitive remediation techniques in patients with schizophrenia is presented. The review is organized into three sections, according to the neuropsychological deficit targeted for remediation: 1) executive-function, 2) attention, and 3) memory. With regards to executive-function, despite an initial report suggesting that Wisconsin Card Sorting Test performance cannot be remediated, subsequent studies suggest that performance can be improved on a variety of dependent measures including perseverative errors, categories achieved, and conceptual level responses. These observations were confirmed by a meta-analytic investigation that revealed large mean effects sizes (d+ = 0.96) for these studies. Effect sizes were homogenous across discrepant remediation strategies and dependent measures. With regards to attention, serial scanning can be improved with instruction and reinforcement, whereas there is mixed evidence suggesting that practice-based attention drills can improve performance on measures of sustained attention in schizophrenia. With regards to memory, relatively simple semantic and affective elaborate encoding strategies elevates verbal list-learning memory in patients with schizophrenia to levels consistent with controls. A similar encoding procedure, combined with vigilance training, produces substantial improvement in social cue recognition. Avenues for future research are discussed.

Attention↗

Olfactory-evoked regional cerebral blood flow in Alzheimer's disease.

Olfaction is impaired in Alzheimer's disease (AD). It was hypothesized that AD would reduce olfactory-evoked perfusion in mesial temporal olfactory (piriform) cortex, where neuropathology begins. Seven AD patients and 8 elderly controls (ECs) underwent olfactory threshold and identification tests and olfactory stimulation during positron emission tomography. Odor identification was impaired in AD, but threshold was not. Olfactory stimulation in ECs activated right and left piriform areas and right anterior ventral temporal cortex. AD patients had less activation in right piriform and anterior ventral temporal cortex but not in the left piriform area. Although orbital cortex did not activate in ECs, there was a significant between-groups difference in this area. Right piriform activation correlated with odor identification. Impaired odor identification likely reflects sensory cortex dysfunction rather than cognitive impairment. Given olfactory bulb projections to the mesial temporal lobe, olfactory stimulation during functional imaging might detect early dysfunction in this region.

Aged↗

Effectiveness of an attention- and memory-training program on neuropsychological deficits in schizophrenia.

The effect of two cognitive remediation procedures developed for closed head injury, Attention Process Training (APT) and Prospective Memory Training (PROMT), on neuropsychological deficits in schizophrenia was investigated. Six patients with schizophrenia, varying in baseline intellectual function and symptoms, were studied; three in a remediation condition and three in a nonremediated control condition. Results were evaluated individually for each of the three treated patients. Two of three remediation-treated subjects showed marked improvement on tests of sustained and divided attention. Untreated patients showed little evidence of change in neuropsychological test performance across a similar time interval, when tested on a subset of the measures administered to remediation-treated patients. The results of this study are discussed with a view toward future studies using larger sample sizes with homogeneous subject populations.

Adult↗

Comparison of the standard and structured interview guide for the Hamilton Depression Rating Scale in depressed geriatric inpatients.

The interrater reliability of the standard Hamilton Depression Rating Scale (Ham-D) and a structured interview guide for the Ham-D (the SIGH-D) were compared in a sample of 20 elderly inpatients with major depression. Each patient was independently interviewed by four raters; two used the standard 24-item Ham-D, and the other two used a 24-item modified version of the Structured Interview Guide for the Ham-D. Systematic counterbalancing of raters and scales and a stringent evaluation schedule were used to counter position effects, spontaneous symptom change, or diurnal variation. The modified SIGH-D produced uniformly higher item- and summary-scale reliabilities than the unstructured Ham-D.

Aged↗

Controlled and automatic processing during animal word list generation in schizophrenia.

Controlled and automatic aspects of semantic-associative functioning in schizophrenia were investigated by evaluating performance on animal word list generation (WLG). Responses from control (n = 47) and patient (n = 38) participants were subjected to multidimensional scaling (MDS), cluster analysis (CA), and indices on the basis of number of shared attributes (SA) between consecutive responses. Patient MDS results accounted for less variance and contained more error than control data. CA results yielded fewer and less clear animal-response subgroups among patients yet demonstrated intact associations among strongly related exemplars. The SA indices revealed better clustering and more effective switching among response clusters in controls than patients. Results suggest that animal WLG in schizophrenia is compromised both by aberrant automatic semantic-associative network activation and by controlled processes such as search, access, and selection. This pattern is consistent with prominent frontotemporal pathology evident in the disorder.

Adult↗

Ten-year follow-up survey of clinical neuropsychologists: part I. Practices and beliefs.

A 21-item questionnaire previously used to survey practices and beliefs of clinical neuropsychologists (Sweet & Moberg, 1990; Sweet, Moberg, & Westergaard, 1996) was mailed in February 1999 to all ABPP Diplomates in clinical neuropsychology and a larger sample of randomly selected non-ABPP members of Division 40 (Clinical Neuropsychology) of the American Psychological Association. Results were compared with data previously collected in 1989 and 1994. Across 10 years there have been some persistent differences between neuropsychologists based on board certification status. These differences include degree of involvement in neuropsychological practice and forensic practice, involvement in research and teaching, frequency of subscribing to or regularly reading a variety of relevant journals, employment settings, use of assistants, and use of projective assessment. There are also a number of areas of shared belief and common practice. These important areas of agreement are unrelated to board certification status and are interpreted as signs of cohesiveness and maturity in the continuing evolution of the subspecialty. Shared beliefs and common practices include: appropriate field of training, type of degree, assessment philosophy, most types of information to be gathered in evaluations, and time spent per assessment. In general, the use of assistants is correlated significantly with the number of evaluations performed per month. Although sometimes viewed as exclusively providing assessment, the majority of neuropsychologists are also involved in treating patients with brain dysfunction. Survey data appear useful in characterizing and monitoring professional status and trends of clinical neuropsychology.

Adult↗

Ten-year follow-up survey of clinical neuropsychologists: part II. Private practice and economics.

Analyses of a 10-year follow-up survey of clinical neuropsychologists demonstrated significant changes in employment settings away from institutions, placing a clear majority of the field in private practice settings in 1999 (Sweet, Moberg, & Suchy, 2000). The present paper compares characteristics of practices and beliefs of clinical neuropsychologists who work in institutions versus private practice, using data from 1989, 1994, and 1999. Previous survey data had not been analyzed along the dimension of work setting. Among the significant findings are differences in age, referral sources, hours per week engaged in specific professional activities (clinical, neuropsychological, forensic, supervisory, research, teaching), ages of patients, type and frequency of data gathered in assessments, hours spent per evaluation, use of an assistant to gather data, and journal subscriptions. Economic changes within the last 5 years have had a differential impact for the two groups in terms of yearly income and hourly reimbursement. However, approximately half of the neuropsychologists in both groups have increased hours performing clinical work, hours performing administrative duties, and patient load to compensate for economic changes in the last 5 years. Decreases in clinical research and teaching activities are apparent in both groups, but in different amounts.

Female↗

Reduced olfactory bulb volume in patients with schizophrenia.

OBJECTIVE: The authors' goal in this study was to compare the size of olfactory bulbs of patients with schizophrenia and those of healthy subjects. METHOD: Magnetic resonance imaging scans of olfactory bulbs were obtained from 26 patients with schizophrenia and 22 healthy comparison subjects. A reliable region of interest procedure was used to measure olfactory bulb volume. RESULTS: Patients exhibited 23% smaller bilateral bulb volume than comparison subjects, independent of acute clinical, demographic, or treatment measures. Bulb volume correlated with odor detection sensitivity in healthy subjects but not in patients with schizophrenia. CONCLUSIONS: Patients with schizophrenia exhibit structural olfactory deficits as well as functional olfactory deficits. The olfactory system may be a model system in which to study the neurobiology of the disorder.

Adult↗

Olfactory dysfunction in schizophrenia: a qualitative and quantitative review.

Olfactory dysfunction in patients with schizophrenia has been a topic of increasing interest, with deficits in odor identification, detection threshold sensitivity, discrimination, and memory being reported. Despite increasing knowledge, controversy has existed about possible differential deficits among olfactory tests as well as the influences of gender, smoking, and medication status on olfactory measures. To help elucidate some of this controversy, we conducted a qualitative and quantitative (meta-analytic) review of the English language literature on olfaction in schizophrenia. Moderator variables such as gender, medication status, and smoking history were also examined. Results indicated that substantial olfactory deficits, across all domains, are observed in patients with schizophrenia. No differential deficits were observed across domains of odor identification, detection threshold sensitivity, discrimination, and memory. The influences of gender, medication status, and smoking on effect sizes were not significant across studies. This supports the hypothesis of primary dysfunction in the olfactory system that is regulated by brain regions where structural and functional abnormalities have also been reported in neuroimaging studies.

Humans↗

Cellular and molecular neuropathology of the olfactory epithelium and central olfactory pathways in Alzheimer's disease and schizophrenia.

Specific deficits in odor detection threshold, identification, and memory have been recognized in a variety of disorders including the neurodegenerative disorder, Alzheimer's disease (AD), and the psychiatric illness, schizophrenia, which is likely due to abnormalities in neurodevelopment. Neuropathological abnormalities in peripheral and central olfactory systems have been described in both disorder. In the olfactory, epithelium, dystrophic neurites that are immunoreactive for tau, neurofilaments and other polypeptides, as well as deposits of beta-amyloid have been observed, and these findings have been thought to contribute to the olfactory dysfunction of these disorders. However, similar findings also occur in the olfactory epithelium of many normal individuals and those with various other neurodegenerative diseases. In contrast, neuropathological studies have reported selective vulnerability of central olfactory pathways for the accumulation of neurofibrillary pathology in AD, and for cytoarchitectural, neuronal morphometric, and cytoskeletal protein abnormalities suggestive of abnormal neurodevelopment in schizophrenia. Thus, it is likely that the olfactory impairments associated with these diseases are due to damage within central olfactory pathways, and that they are further amplified by the less specific impairments associated with age-related sensory neuroepithelial abnormalities. Finally, both the olfactory epithelium and central olfactory pathways represent model systems in which to study the neurobiology of these disorders, which ultimately may yield clues with diagnostic and therapeutic utility.

Alzheimer Disease↗

Olfaction in neurodegenerative disease: a meta-analysis of olfactory functioning in Alzheimer's and Parkinson's diseases.

BACKGROUND: Olfactory deficits in Alzheimer's disease (AD) and idiopathic Parkinson's disease (PD) have been well established. OBJECTIVE: To clarify and review the literature by evaluating the evidence for olfactory deficits in 3 olfactory domains, including odor identification, recognition, and detection threshold. DATA SOURCES: A literature search of English-language studies of olfaction in AD, PD, and healthy controls was conducted via online databases (PsycInfo and MEDLINE) and reference lists from review articles. STUDY SELECTION: To meet selection criteria for meta-analysis, each study required a control group and complete and usable data. This review yielded 26 publications of olfactory identification, recognition, and/or detection threshold. Because of the inclusion of more than 1 relevant study of olfaction in several of these publications (eg, both identification and threshold assessed), 43 studies were ultimately appropriate for meta-analysis. DATA EXTRACTION: Effect sizes were calculated for each study by expressing differences between patient and control group means in SD units (Cohen's d). DATA SYNTHESIS: Extremely large effect sizes were shown across all tasks in both AD and PD groups. Both between-group analyses using the Mann-Whitney U test and within-group analyses using Friedman 2-way analysis of variance did not reveal any significant differences (all P > .30). CONCLUSIONS: As expected, severe deficits were found for both patients with AD and PD in each of the 3 olfactory domains relative to controls. However, no discriminating olfactory deficits were seen between patient groups or among the 3 measured olfactory domains, suggesting a similar disturbance in olfactory function between patients with AD and PD.

Adult↗

Parallel loss of presynaptic and postsynaptic dopamine markers in normal aging.

Aging of the human brain is associated with a decline in dopamine (DA) function, generally interpreted as reflecting DA cell loss. Positron emission tomography studies revealed that in healthy individuals, the age-related losses in DA transporters (presynaptic marker) were associated with losses in D2 receptors (postsynaptic marker) rather than with increases as is known to occur with DA cell loss. This association was specific for DA synaptic markers, because they were not correlated with striatal metabolism. Furthermore, the association was independent of age, suggesting that a common mechanism regulates the expression of receptors and transporters irrespective of age.

Adult↗