Biomedical subjects

J S Paulsen

Publications and source records attributed to J S Paulsen.

At least 19 recordsLinked to original sources

PubMed2004

In vivo evidence of cerebellar atrophy and cerebral white matter loss in Huntington disease.

OBJECTIVE: To investigate the regional pattern of white matter and cerebellar changes, as well as subcortical and cortical changes, in Huntington disease (HD) using morphometric analyses of structural MRI. METHODS: Fifteen individuals with HD and 22 controls were studied; groups were similar in age and education. Primary analyses defined six subcortical regions, the gray and white matter of primary cortical lobes and cerebellum, and abnormal signal in the cerebral white matter. RESULTS: As expected, basal ganglia and cerebral cortical gray matter volumes were significantly smaller in HD. The HD group also demonstrated significant cerebral white matter loss and an increase in the amount of abnormal signal in the white matter; occipital white matter appeared more affected than other cerebral white matter regions. Cortical gray and white matter measures were significantly related to caudate volume. Cerebellar gray and white matter volumes were both smaller in HD. CONCLUSIONS: The cerebellum and the integrity of cerebral white matter may play a more significant role in the symptomatology of HD than previously thought. Furthermore, changes in cortical gray and cerebral white matter were related to caudate atrophy, supporting a similar mechanism of degeneration.

Adult↗

PubMed2004

A new model for prediction of the age of onset and penetrance for Huntington's disease based on CAG length.

Huntington's disease (HD) is a neurodegenerative disorder caused by an unstable CAG repeat. For patients at risk, participating in predictive testing and learning of having CAG expansion, a major unanswered question shifts from "Will I get HD?" to "When will it manifest?" Using the largest cohort of HD patients analyzed to date (2913 individuals from 40 centers worldwide), we developed a parametric survival model based on CAG repeat length to predict the probability of neurological disease onset (based on motor neurological symptoms rather than psychiatric onset) at different ages for individual patients. We provide estimated probabilities of onset associated with CAG repeats between 36 and 56 for individuals of any age with narrow confidence intervals. For example, our model predicts a 91% chance that a 40-year-old individual with 42 repeats will have onset by the age of 65, with a 95% confidence interval from 90 to 93%. This model also defines the variability in HD onset that is not attributable to CAG length and provides information concerning CAG-related penetrance rates.

Age of Onset↗

PubMed2003

Behavioural abnormalities contribute to functional decline in Huntington's disease.

The independent and relative contributions of motor, cognitive, and behavioural deficits to functional decline in patients with Huntington's disease are examined. Twenty two patients with Huntington's disease were assessed with rating scales for motor dysfunction, cognitive measures of executive functions, and behavioural measures of apathy, executive dysfunction, and disinhibition. Their functional status was assessed with informant based and clinician based ratings of activities of daily living (ADL). A composite apathy/executive dysfunction behavioural index was strongly related to decline in ADL independently and after controlling for motor and cognitive deficits. These results suggest that behavioural dysfunction contributes to functional decline in patients with Huntington's disease and may impede their ability to utilise motor or cognitive skills that remain available in the early stages of the disease.

Activities of Daily Living↗

PubMed2001

Clinical markers of early disease in persons near onset of Huntington's disease.

OBJECTIVE: There is increasing evidence that neuron loss precedes the phenotypic expression of Huntington's disease (HD). As genes for late-onset neurodegenerative diseases are identified, the need for accurate assessment of phenoconversion (i.e., the transition from health to the disease phenotype) will be important. METHODS: Prospective longitudinal evaluation using the Unified Huntington's Disease Rating Scale (UHDRS) was conducted by Huntington Study Group members from 36 sites. There were 260 persons considered "at risk" for HD who initially did not have manifest disease and had at least one subsequent evaluation. Repeat UHDRS data, obtained an average of 2 years later, showed that 70 persons were given a diagnosis of definite HD based on the quantified neurologic examination. RESULTS: Baseline cognitive performances were consistently worse for the at-risk group who demonstrated conversion to a definitive diagnosis compared with those who did not. Longitudinal change scores showed that the at-risk group who did not demonstrate manifest disease during the follow-up study period demonstrated improvements in all cognitive tests, whereas performances in the at-risk group demonstrating conversion to disease during the study declined across cognitive domains. CONCLUSIONS: Neuropsychological measures show impairment 2 years before the development of more manifest motor disease. Findings suggest that these brief cognitive measures administered over time may capture early striatal neural loss in HD.

Adult↗

PubMed2001

Neuropsychiatric assessment of Gilles de la Tourette patients: comparative study with other hyperkinetic and hypokinetic movement disorders.

The role of the basal ganglia in conditions with co-occurring movement disorders and neuropsychiatric symptoms is not well known. It has been hypothesized that hyperkinesia -disinhibited behaviors and hypokinesia-inhibited behaviors result from an imbalance between the direct and indirect striatal output pathways, and that differential involvement of these pathways could account for the concurrent abnormalities in movement and behavior observed in these disorders. This study aimed to evaluate whether the pattern and the extent of the neuropsychiatric manifestations of patients with GTS, a hyperkinetic movement disorder of basal ganglia origin, differs from that of patients with other basal ganglia hyperkinetic (e.g., HD) or hypokinetic (e.g., PSP) movement disorders, and to determine whether patients with GTS show a greater frequency of hyperactive behaviors (e.g., agitation, irritability, euphoria, or anxiety) than PSP patients, and are comparable to patients with HD. The Neuropsychiatric Inventory (NPI), a scale with established validity and reliability, was administered to 26 patients with GTS (mean age, 30.2 +/- 2.2 years), and the results were compared with that of 29 patients with HD (mean age, 43.8 +/- 2 years) and 34 with PSP (mean +/- S.D. age, 66.6 +/- 1.2 years). There was no difference between the groups in the total NPI scores. However, there was a double dissociation in behaviors: patients with hyperkinetic disorders (HD and GTS) exhibited significantly more agitation, irritability, anxiety, euphoria, and hyperkinesia, whereas hypokinetic patients (PSP) exhibited more apathy. Patients with GTS showed greater scores than HD patients in all those scores differentiating HD and GTS from PSP patients (e.g., agitation, irritability, anxiety and euphoria), and were differentiated in a logistic regression analysis from both HD and PSP patients in having significantly more anxiety. We found that patients with GTS manifested predominantly hyperactive behaviors similar but more pronounced than those presented by patients with HD, while those with PSP manifested hypoactive behaviors. Based on our findings and the proposed models of basal ganglia dysfunction in these disorders, we suggest that the hyperactive behaviors in GTS are comparable to those observed in HD, being both secondary to an excitatory subcortical output through the medial and orbitofrontal cortical circuits, while in PSP the hypoactive behaviors are secondary to hypostimulation of these circuits. Abnormalities of other brain structures (e.g., amygdala, brainstem nuclei) may account for the significantly higher anxiety scores differentiating GTS from HD patients.

Adult↗

PubMed2001

Detection of mild cognitive deficits in Parkinson's disease patients with the WAIS-R NI.

The relative insensitivity of traditional IQ tests to mild cognitive deficits has led investigators to develop a version of the widely used Wechsler intelligence scales that allows quantitative analysis of underlying qualitative responses. This instrument, the Wechsler Adult Intelligence Scale-Revised as a Neuropsychological Instrument (WAIS-R NI) was administered to 16 Parkinson's disease (PD) patients and 30 normal controls (NC). The 2 groups did not differ significantly in mean age or education, or on their mean Mattis Dementia Rating Scale score. Relative to NC participants, PD patients showed decreased visual attention span, longer response latencies, slower visuomotor processing, and more stimulus-bound errors. Many of the WAIS-R NI measures were able to detect cognitive impairment in a greater percentage of patients than the traditional WAIS-R measures, making it easier to identify deficits that could affect quality of life early in the course of the disease.

Adult↗

PubMed2001

Bupropion SR vs. methylphenidate vs. placebo for attention deficit hyperactivity disorder in adults.

Despite the increasing recognition of attention-deficit hyperactivity disorder (ADHD) in adults, there are few controlled trials demonstrating the effectiveness of pharmacological treatments, particularly with nonstimulants. One controlled trial found bupropion SR more effective than placebo in the treatment of ADHD adults. We conducted a controlled study to contrast the effectiveness of bupropion SR and methylphenidate to placebo in ADHD adults. A randomized, double-blind, parallel design was used in this study. Following a 7-day placebo lead-in, 30 ADHD (DSM-IV) subjects (18-60 years old) were randomized to bupropion, methylphenidate, or placebo for 7 weeks. Methylphenidate was titrated over 1 week to a maximum dose of 0.9 mg/kg/d divided into 3 doses while bupropion was titrated over 2 weeks to a maximum dose of 200 mg A.M. and 100 mg P.M. Response rates based on Clinical Global Impression improvement ratings in patients receiving bupropion, methylphenidate, and placebo were 64, 50, and 27%, respectively. The difference in response rates between active treatment and placebo was not statistically significant (p = 0.14). Neuropsychological testing demonstrated trends favoring drug treatment on measures of immediate recall and verbal fluency. While bupropion SR may be a viable clinical alternative for adults with ADHD, further investigation is needed.

Adrenergic Agents↗

PubMed2001

Ecological validity of neuropsychological and personality measures of executive functions.

Associations between two types of measures of executive functions, namely, neuropsychological and personality, and measures of real-world behavior were investigated. Undergraduate students were administered neuropsychological measures of executive functions and completed a personality questionnaire developed to measure traits central to the construct of executive functions. Participants also reported on their behavior. Hierarchical regressions indicated that neuropsychological and personality measures of executive functions were significant predictors of different types of behavior. Neuropsychological measures predicted work behaviors and personality measures predicted substance use, risk-taking, and aggressive behaviors. Findings highlight the importance of including personality assessment in standard neuropsychological assessment in order to maximize ability to predict real-world behaviors relevant to independent and socially responsible functioning.

Adolescent↗

PubMed2001

Neuropsychiatric aspects of Huntington's disease.

OBJECTIVE: Neuropsychiatric symptoms are common in Huntington's disease and have been considered its presenting manifestation. Research characterising these symptoms in Huntington's disease is variable, however, encumbered by limitations within and across studies. Gaining a better understanding of neuropsychiatric symptoms is essential, as these symptoms have implications for disease management, prognosis, and quality of life for patients and caregivers. METHOD: Fifty two patients with Huntington's disease were administered standardised measures of cognition, psychiatric symptoms, and motor abnormalities. Patient caregivers were administered the neuropsychiatric inventory. RESULTS: Ninety eight per cent of the patients exhibited neuropsychiatric symptoms, the most prevalent being dysphoria, agitation, irritability, apathy, and anxiety. Symptoms ranged from mild to severe and were unrelated to dementia and chorea. CONCLUSIONS: Neuropsychiatric symptoms are prevalent in Huntington's disease and are relatively independent of cognitive and motor aspects of the disease. Hypothesised links between neuropsychiatric symptoms of Huntington's disease and frontal-striatal circuitry were explored. Findings indicate that dimensional measures of neuropsychiatric symptoms are essential to capture the full range of pathology in Huntington's disease and are vital to include in a comprehensive assessment of the disease.

Adult↗

PubMed2001

Effects of depression on working memory in presymptomatic Huntington's disease.

Cognitive decline may precede motor symptoms in Huntington's disease (HD). Depression is common in HD and has also been linked with cognitive impairment. The contribution of depression to cognition in individuals presymptomatic for HD (N=15) was investigated. Tests from the Cambridge Automated Neuropsychological Assessment Battery measured visual and working memory. Depression was assessed with the Beck Depression Inventory and the Unified Huntington's Disease Rating Scale. Depressed mood and estimated time to disease onset, calculated by using DNA mutation length, both were significant predictors of working memory performance. Findings are consistent with and contribute to existing research with individuals presymptomatic for HD, identifying a potentially remediable contribution to cognitive decline (i.e., depressed mood).

Adult↗

PubMed2000

Incidence of and risk factors for hallucinations and delusions in patients with probable AD.

OBJECTIVE: To examine the incidence of and risk factors for hallucinations and delusions associated with patients clinically diagnosed with probable AD. BACKGROUND: Estimates of the incidence of psychosis in AD range widely from 10% to 75%. The risk factors for psychosis of AD are not known, although multiple studies indicate that AD patients with psychosis demonstrate greater cognitive and functional impairment. METHODS: The authors conducted psychiatric evaluations of 329 patients with probable AD from the University of California at San Diego Alzheimer's Disease Research Center to determine the incidence of hallucinations and delusions. They examined data from annual clinical and neuropsychological evaluations to determine whether there were specific risk factors for the development of hallucinations and delusions. RESULTS: Using Cox survival analyses, the cumulative incidence of hallucinations and delusions was 20.1% at 1 year, 36.1% at 2, 49.5% at 3, and 51.3% at 4 years. Parkinsonian gait, bradyphrenia, exaggerated general cognitive decline, and exaggerated semantic memory decline were significant predictors. Age, education, and gender were not significant predictors. CONCLUSIONS: The authors found a relatively high incidence of hallucinations and delusions in patients diagnosed with probable AD and suggest that specific neurologic signs, cognitive abilities, and accelerated decline may be predictive markers for their occurrence.

Alzheimer Disease↗

PubMed2000

Neurobehaviors and psychotic symptoms in Alzheimer's disease.

Psychotic symptoms are common in Alzheimer's disease (AD) and clinicoanatomical and neuropsychological evidence indicate an association between these symptoms and frontal lobe dysfunction. Neuro-behaviors associated with frontal dysfunction were assessed in Alzheimer's disease (AD) patients with (n = 20) and without psychotic symptoms (n = 21) matched for mean age, education, gender, and dementia severity. The Frontal Lobe Personality Scale (FLOPs) was completed by patient caregivers to measure behaviors typically associated with frontal dysfunction. Findings indicated that AD patients with psychotic symptoms exhibited significantly greater neurobehavioral dysfunction (FLOPs M = 130.69, SD = 24.70) than AD patients without psychotic symptoms (FLOPs M = 111.10, SD = 25.83). Subscale analyses indicated that psychotic AD patients were more dis-inhibited (M = 28.28, SD = 7.54) than patients without psychotic symptoms (M = 20.92, SD = 4.9). Findings are consistent with and contribute to previous neuropsychological and clinicoanatomical research suggesting increased frontal dysfunction in AD with psychotic symptoms and lend additional empirical support to subtyping AD based on the presence of psychotic symptoms. Furthermore, findings provide preliminary evidence indicating which specific type of neurobehavioral abnormalities are related to the presence of distressing psychotic symptoms.

Aged↗

PubMed2000

Estimation of premorbid intelligence: the word accentuation test-- Buenos Aires version.

We have sought to adapt and validate a NART-like Spanish test, the Word Accentuation Test (WAT: Del Ser, Montalvo, Espinosa, Villapalos, & Bermejo, 1997) to estimate acquired intelligence in local normal older adults. The test requires examinees to read aloud infrequent, irregularly stressed Spanish words, a situation that presumably requires lexical knowledge. Results in a sample of 74 participants show that the revised WAT (i.e., the WAT for Buenos Aires) has good concurrent validity with the WAIS Vocabulary subtest and number of years of formal education, as well as high internal consistency. Performance on this test was dissociated from age, memory, or frontal/executive measures.

Aged↗

PubMed1999

Generalized cognitive deficits in schizophrenia: a study of first-episode patients.

BACKGROUND: Cognitive impairment is recognized as a core characteristic of schizophrenia. There has always been a debate about the nature, selectivity, and time of onset of these deficits in relationship to the onset of illness and treatment factors. To our knowledge, the present study represents the largest sample of mostly neuroleptic-naive patients with first-episode schizophrenia that has been reported to date. METHODS: A group of 94 patients experiencing their first episode of schizophrenic illness and 305 normal comparison subjects were administered a comprehensive clinical and neuropsychological evaluation. Seventy-three patients were neuroleptic naive, 14 had received treatment for less than 1 week, and the remaining 7 had been medicated for less than 2 weeks. RESULTS: Patients performed significantly worse than the comparison subjects on every neuropsychological variable except those assessing savings scores (ie, forgetting over time). Twenty-five of 30 tests had an effect size (ES) greater than 0.75 when the 2 groups were compared. An ES analysis within the schizophrenia group revealed that the greatest relative impairments were on the Wechsler Adult Intelligence Scale-Revised digit symbol (ES, -0.52) and comprehension (ES, -0.42) subscales. CONCLUSIONS: Our findings are in concert with others demonstrating that significant cognitive impairment across multiple ability domains is a core characteristic of schizophrenia and is not caused by chronic illness, treatment, or institutionalization. The ES analysis emphasizes that patients with schizophrenia have a generalized deficit that is not easily explained by a single anatomical region or ability area.

Adult↗

PubMed1999

Odor detection, learning, and memory in Huntington's disease.

We compared 7 mildly affected Huntington's disease (HD) patients to 7 age- and education-matched healthy controls (NC) on an odor detection test, the California Odor Learning Test, and the California Verbal Learning Test. Results demonstrated that odor detection sensitivity, but not group membership, accounted for significant variance in total olfactory learning. Both groups learned fewer items in the olfactory modality compared to the verbal modality, but retained a similar amount following a delay. No group differences were demonstrated for verbal recognition discriminability, but the HD group demonstrated significantly impaired odor recognition discriminability. Finally, odor detection provided excellent classification sensitivity and specificity between the patients and controls, suggesting that olfactory testing may provide a sensitive measure of the early disease process in HD.

Cognition Disorders↗

PubMed1999

The disparate effects of Alzheimer's disease and Huntington's disease on semantic memory.

Alzheimer's disease (AD) and Huntington's disease (HD) impair performance on semantic memory tasks, but researchers disagree on whether AD and HD cause these impairments in the same manner. According to one view, AD disrupts the storage of semantic memories, whereas HD disrupts the retrieval of semantic memories. Dissenters argue that AD, like HD, disrupts retrieval. In this study, participants generated category exemplars (e.g., kinds of fruits) for 1 min, and response latencies were examined. Relative to healthy controls, the 12 AD patients produced a larger proportion of responses earlier in the recall period, consistent with the view that AD patients quickly exhaust their limited supply of items in storage. By contrast, the 12 HD patients produced a larger proportion of their responses late in the recall period, consistent with the view that HD slows retrieval.

Aged↗

PubMed1999

A test of odor fluency in patients with Alzheimer's and Huntington's disease.

In the present study, an olfactory analog to the verbal fluency test was designed and administered to 40 patients with Alzheimer's disease (AD) and 11 patients with Huntington's disease (HD). Because onset of AD is typically in the sixties while onset of HD is typically in the mid-thirties, the patient groups had their own control group, an older (ONC) and younger (YNC) control group, respectively. Both control groups included 40 participants who were age- and education-matched to their respective patient group. Odor threshold, odor identification, and odor fluency measures were administered to each participant. Results of the study indicate that patients with dementia perform more poorly on all three measures of olfactory functioning. Our results suggest that tests of odor memory show differential performance in healthy and demented patients, leading to the suggestion that tests of olfactory functioning may be useful in detection and diagnosis of neurodegenerative disease.

Adult↗

PubMed1999

Cognitive deficits and psychopathology in institutionalized versus community-dwelling elderly schizophrenia patients.

We evaluated psychiatric symptoms and neurocognitive functioning among 25 institutionalized and 25 outpatient DSM-IV-diagnosed schizophrenia patients, as well as 25 middle-aged and elderly normal comparison subjects. All subjects were assessed with the Positive and Negative Syndrome Scale, Hamilton Rating Scale for Depression, modified Simpson-Angus Extrapyramidal Symptom Scale, the Abnormal Involuntary Movement Scale, and the Mattis Dementia Rating Scale (DRS). The two patient groups had similar levels of depressive symptoms, but the institutionalized patients had more severe positive and negative symptoms and were on higher doses of neuroleptic medication. The institutionalized patients had significantly more cognitive impairment on the DRS than outpatients and normal comparison subjects, particularly on the subscales of initiation/perseveration, conceptualization, and memory. Results are discussed in terms of the possible neuropathology associated with cognitive impairment in chronic schizophrenia.

Aged↗