PubMed Health⌕ Search

Biomedical subjects

N Andreasen

Publications and source records attributed to N Andreasen.

At least 19 recordsLinked to original sources
PubMed1999

Sensitivity, specificity, and stability of CSF-tau in AD in a community-based patient sample.

OBJECTIVE: To evaluate the sensitivity and specificity of CSF-tau in clinical practice as a diagnostic marker for AD compared with normal aging and depression, to study the stability of CSF-tau in longitudinal samples, and to determine whether CSF-tau levels are influenced by different covariates such as gender, age, duration or severity of disease, or possession of the APOE-epsilon4 allele. METHODS: Consecutive AD patients from a community-based sample were studied, including 407 patients with AD (274 with probable AD and 133 with possible AD), 28 patients with depression, and 65 healthy elderly control subjects. A follow-up lumbar puncture was performed in 192 AD patients after approximately 1 year. CSF-tau was determined using a sandwich ELISA, which was run as a routine clinical neurochemical analysis. RESULTS: CSF-tau was increased in probable (690+/-341 pg/mL; p < 0.0001) and possible (661+/-447 pg/mL; p < 0.0001) AD, but not in depression (231+/-110 pg/mL) compared with control subjects (227+/-101 pg/mL). Receiver operating characteristics analysis showed that a cutoff level of 302 pg/mL resulted in a sensitivity of 93% (95% CI, 90-96%) and a specificity of 86% (95% CI, 75-94%), with an area under the curve of 0.95 to discriminate AD from control subjects. Within the AD group, CSF-tau did not differ significantly between baseline and follow-up investigations, and was relatively stable between baseline and 1-year follow-up levels, with a coefficient of variation of 21.0%. High CSF-tau levels were also found in most AD patients with very short duration of dementia, and with Mini-Mental State Examination scores >23 (n = 205). In total, 193 of 205 patients (sensitivity, 94%) had a CSF-tau level higher than 302 pg/mL. CONCLUSIONS: CSF-tau has a high sensitivity and specificity to differentiate AD from normal aging and depression, as demonstrated in a large community-based series of consecutive AD patients during which analyses were run continually in a clinical neurochemical laboratory. The increase in CSF-tau is found very early in the disease process in AD, is stable over time, and has a low interindividual variation on repeated sampling. Although high CSF-tau is found in some neurologic conditions (e.g., stroke), these findings suggest that CSF-tau may be of use to help in differentiating AD from normal aging and depression, especially early in the course of the disease, when the symptoms are vague and the diagnosis is especially difficult.

Aged↗
PubMed1999

Cerebrospinal fluid tau and Abeta42 as predictors of development of Alzheimer's disease in patients with mild cognitive impairment.

We studied CSF-tau and CSF-Abeta42 in 16 patients with mild cognitive impairment (MCI) who at follow-up investigations 6-27 months later had progressed to Alzheimer's disease (AD) with dementia. For comparison, we studied 15 age-matched healthy individuals. At baseline, 14/16 (88%) of MCI patients had high CSF-tau and/or low CSF-Abeta42 levels. These findings show that these CSF-markers are abnormal before the onset of clinical dementia and that they may help to identify MCI patients that will develop AD. This is especially important when drugs with potential effects on the progression of AD will reach the clinical phase.

Aged↗
PubMed1999

Cerebrospinal fluid beta-amyloid(1-42) in Alzheimer disease: differences between early- and late-onset Alzheimer disease and stability during the course of disease.

OBJECTIVES: To study the diagnostic potential of the 42 amino acid form of beta-amyloid (beta-amyloid(1-42)) in cerebrospinal fluid (CSF) as a biochemical marker for Alzheimer disease (AD), the intra-individual biological variation of CSF-beta-amyloid(1-42) level in patients with AD, and the possible effects of differential binding between beta-amyloid and apolipoprotein E isoforms on CSF-beta-amyloid(1-42) levels. DESIGN: A 20-month prospective follow-up study. SETTING: Community population-based sample of consecutive patients with AD referred to the Piteå River Valley Hospital, Piteå, Sweden. PATIENTS: Fifty-three patients with AD (mean +/- SD age, 71.4 +/- 7.4 years) diagnosed according to the National Institute of Neurological and Communicative Disorders and Stroke and Alzheimer's Disease and Related Disorders Association criteria and 21 healthy, age-matched (mean +/- SD age, 68.8 +/- 8.0 years) control subjects. MAIN OUTCOME MEASURES: Cerebrospinal fluid beta-amyloid(1-42) level--analyzed using enzyme-linked immunosorbent assay--and severity of dementia--analyzed using the Mini-Mental State Examination. RESULTS: Mean +/- SD levels of CSF-beta-amyloid(1-42) were decreased (P<.001) in patients with AD (709 +/- 304 pg/mL) compared with controls (1678 +/- 436 pg/mL). Most patients with AD (49 [92%] of 53 patients) had reduced levels (<1130 pg/mL). A highly significant correlation (r = 0.90; P<.001) between baseline and 1-year follow-up CSF-beta-amyloid(1-42) levels was found. There were no significant correlations between CSF-beta-amyloid(1-42) level and duration (r = -0.16) or severity (r = -0.02) of dementia. Low levels were also found in patients with mild dementia (Mini-Mental State Examination score, >25). CONCLUSIONS: The sensitivity of CSF-beta-amyloid(1-42) level as a diagnostic marker for AD is high. The intra-individual biological variation in CSF-beta-amyloid(1-42) level is low. Low CSF-beta-amyloid(1-42) levels are also found in the earlier stages of dementia in patients with AD. These findings suggest that CSF-beta-amyloid(1-42) analyses may be of value in the clinical diagnosis of AD, especially in the early course of the disease, when drug therapy may have the greatest potential of being effective but clinical diagnosis is particularly difficult.

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

Prevalence and incidence of clinically diagnosed memory impairments in a geographically defined general population in Sweden. The Piteå Dementia Project.

In the Piteå River Valley all persons with memory impairment that interferes with normal life are referred to one hospital department for clinical workup and diagnosis. 619 patients were assessed in the department during the years 1990-1995. Of these, 36.9% had Alzheimer's disease (AD), 30.4% had vascular dementia (VaD), 3.0% had a mixed AD/VaD, 3.2% had frontotemporal dementia and 5.3% had other forms of dementia. Another 7% had memory impairment but no dementia. The overall mean annual incidence rate of clinically relevant dementia was 295/100,000 persons at risk and the mean prevalence rate was 755/100,000 persons. For persons 65 years and older the incidence and prevalence rates were 840 and 2,150/100,000 persons, respectively. This means that annually, approximately 300 persons/100,000 population over the age of 40 need medical attention or social services.

Adult↗
PubMed1998

Morphometry in schizophrenia revisited: height and its relationship to pre-morbid function.

BACKGROUND: Morphometry, the measurement of forms, is an ancient practice. In particular, schizophrenic somatology was popular early in this century, but has been essentially absent from the literature for over 30 years. More recently, evidence has grown to support the notion that aberrant neurodevelopment may play a role in the pathophysiology of schizophrenia. Is the body, like the brain, affected by abnormal development in these patients? METHODS: To evaluate global deficit in development and its relationship to pre-morbid function, height was compared in a large group (N = 226) of male schizophrenics and a group of healthy male controls (N = 142) equivalent in parental socio-economic status. Patients in the lower quartile of height were compared to those in the upper quartile of height. RESULTS: The patient group had a mean height of 177.1 cm, which was significantly shorter than the mean height of the control group of 179.4 (P < 0.003). Those in the lower quartile had significantly poorer pre-morbid function as measured by: (1) psychosocial adjustment using the pre-morbid adjustment scales for childhood and adolescence/young adulthood, and (2) cognitive function using measures of school performance such as grades and need for special education. In addition, these measures of pre-morbid function correlated significantly with height when analysed using the entire sample. CONCLUSIONS: These findings provide further support to the idea that abnormal development may play a key role in the pathophysiology of schizophrenia. Furthermore, this is manifested as a global deficit in growth and function resulting in smaller stature, poorer social skills, and deficits in cognitive abilities.

Adolescent↗
PubMed1998

Cerebrospinal fluid tau protein as a biochemical marker for Alzheimer's disease: a community based follow up study.

OBJECTIVES: Biochemical markers for Alzheimer's disease would be of great value, especially to help in diagnosis early in the course of the disease. A pronounced increase in CSF tau protein (CSF-tau) is found in most patients with Alzheimer's disease. However, the specificity has to be further studied, as an increase in CSF-tau has also been found in other dementias, especially in vascular dementia. As most previous CSF studies have been based on selected inpatients, it was considered of special interest to examine the diagnostic potential of CSF-tau in a community population based sample of consecutive patients with dementia. Such patient material has been examined at the Piteå River Valley Hospital in Northern Sweden since 1986, and includes all those with memory disturbances in the community. The aim was also to study if an increase in CSF-tau is found early in the disease process, and whether CSF-tau changes during the progression of disease. METHODS PARTICIPANTS: Community population based sample of 75 demented patients (43 with Alzheimer's disease, 21 with vascular dementia, and 11 with mixed Alzheimer's disease/vascular dementia), 18 healthy subjects, and 18 neurological controls. A follow up investigation (including analysis of a new CSF sample) was performed in all patients after about one year. MAIN OUTCOME MEASURES: Concentrations of total (both normal tau and PHF-tau) tau in CSF, clinical measures (duration and severity of dementia), and apoE polymorphism. RESULTS: CSF-tau was markedly increased in Alzheimer's disease, 41/43 (95%) patients had values above the cut off level (mean+2 SD) in controls (306 pg/ml). High CSF-tau concentrations were also found in most patients with vascular dementia, preferentially in patients with vascular dementia without progressive leukoaraiosis on CT, whereas patients with vascular dementia with progressive leukoaraiosis had normal CSF-tau. Concentrations of CSF-tau were stable at one year follow up in both patients with Alzheimer's disease and patients with vascular dementia, and there was no correlation between CSF-tau and either duration or severity of dementia. CONCLUSIONS: The findings confirm the high sensitivity of CSF-tau for the diagnosis of Alzheimer's disease, but high CSF-tau was also found in vascular dementia, resulting in a lower specificity. However, high CSF-tau is preferentially found in patients with vascular dementia without progressive leukoaraiosis, which may constitute a group with concomitant Alzheimer's disease pathology. High CSF-tau may be present during the whole course of the disease in Alzheimer's disease. Possibly, therefore, the same high CSF-tau concentrations may be present before the onset of clinical dementia. Follow up studies on such patients will tell whether analysis of CSF-tau is useful as a biochemical marker for early Alzheimer's disease.

Aged↗
PubMed1997

Dependence on public financial support early in the course of schizophrenia.

Although most patients with schizophrenia rely on public financial support, little is known about how soon after the onset of illness such dependence occurs. Forty-eight patients with schizophrenia were followed for a mean of five years after their first hospitalization to examine their reliance on public support. At one year after their first hospitalization, 27 subjects (56 percent) were primarily supported by social service agencies. Once such support was initiated, it was maintained throughout the entire follow-up period for all patients except two. The findings indicate that dependence on public financial assistance begins very early in the course of illness for most hospitalized patients with schizophrenia.

Adult↗
PubMed1996

Regional brain enlargement in autism: a magnetic resonance imaging study.

OBJECTIVE: To determine whether increased brain volume in autism, suggested in previous studies, is the result of general or regional brain size differences and to study the effect of gender on brain size and pattern of enlargement. METHOD: Total brain volume and cerebral cortical lobe volumes were examined in 35 autistic and 36 comparison subjects using magnetic resonance imaging and an automated method of brain volume measurement. RESULTS: After controlling for height and nonverbal IQ, the authors detected a significant diagnosis x gender effect (F = 7.4; p = .009) for total brain volume. A repeated-measures analysis of variance indicated that the pattern of enlargement (brain region x diagnosis) in autistic subjects differed from that in controls (F = 4.88; p = .0004). Subsequent sex-specific analysis revealed significantly increased total brain volume in autistic males but not females. Analysis of lobe sizes showed significant enlargement in autistic subjects in temporal, parietal, and occipital, but not frontal lobes. CONCLUSIONS: These results suggest that brain size is increased in autism and that differences are not generalized but appear to be the result of a pattern of enlargement with increases in the size of specific cortical lobes.

Adolescent↗
PubMed1994

Stability of cognitive functioning early in the course of schizophrenia.

This study evaluated the longitudinal course of neuropsychological deficits in a group of patients with new or recent onset schizophrenia. Thirty-five inpatients with DSM-III-R diagnoses of schizophrenia were administered a comprehensive battery of neuropsychological tests during their index hospitalization, and either 1 or 2 years after intake. Cognitive function remained stable in most domains, including motor speed, verbal and nonverbal memory, and verbal learning. Significant improvement in neuropsychological performance was observed on a task of complex attention (Trails B) and a set response shifting task (Stroop). These improvements were correlated with changes in clinical symptoms, but not with changes in medication dose. These findings suggest that most of the neuropsychological functioning in schizophrenia is stable over the first few years of the illness. Moreover, those neuropsychological deficits that remain unchanging appear to be independent of significant change in clinical symptoms, suggesting they may be a trait of the illness. However, a small subset of functions such as complex attention and response inhibition appear to fluctuate with time, and in particular, with clinical symptomatology, and may be considered 'state' dependent.

Adult↗
PubMed1993

Pseudoautosomal locus for schizophrenia excluded in 12 pedigrees.

A pseudoautosomal locus for schizophrenia has been proposed based on observations of an excess of same-sex affected sibling pairs over opposite-sex pairs when the transmitting parent is the father. Such a pattern of partial concordance by sex related to paternal transmission would be difficult to explain by any biologic mechanism other than pseudoautosomal transmission of schizophrenia. To test the pseudoautosomal hypothesis, 37 sibling pairs concordant for the schizophrenia spectrum were identified from 24 nuclear pedigrees. No significant difference in concordance for sex was found between sibships of paternal and maternal transmission of schizophrenia. Next, a linkage analysis was performed in 12 informative pedigrees, examining seven marker loci spanning the pseudoautosomal region. Both strict schizophrenia and a broader schizophrenia spectrum were analyzed as the affected phenotype, and both autosomal dominant and autosomal recessive models were tested. None of the markers supported linkage to either schizophrenia or the schizophrenia spectrum. Lod scores of less than -4 were obtained across the entire pseudoautosomal region by means of multipoint linkage analyses in the autosomal dominant model. In the autosomal recessive model, the respective lod scores were less than -2. We conclude that there is no evidence of a pseudoautosomal locus for schizophrenia in our pedigrees in any of the genetic models we tested.

Chromosome Mapping↗
PubMed1989

Bipolar II illness: course and outcome over a five-year period.

A five year semi-annual follow-up of patients with non-bipolar (N = 442), bipolar II (N = 64) and bipolar I (N = 53) major depression tracked the courses of prospectively observed major depressive, hypomanic and manic syndromes. In all three groups, depression was much more likely in any given week than was hypomania or mania. However, during the majority of weeks, no full syndrome was present and none of the groups exhibited evidence of continuing psychosocial deterioration. Though all three groups exhibited similar times to recovery from index and subsequent major depressive episodes, both bipolar groups had substantially higher relapse rates and developed more episodes of major depression, hypomania and mania. The two bipolar groups, in turn, differed by the severity of manic-like syndromes and thus remained diagnostically stable; the bipolar II patients were much less likely to develop full manic syndromes or to be hospitalized during follow-up. In conjunction with family study data showing that bipolar II disorder breeds true, these data support the separation of bipolar I and bipolar II affective disorder.

Adult↗
PubMed1989

Bipolar affective disorder and high achievement: a familial association.

The authors studied 442 probands with nonbipolar major depression, 64 with bipolar II disorder, and 88 with bipolar I disorder. Although the proband groups did not differ in occupational or educational achievement, the first-degree relatives of probands with bipolar disorders had significantly higher mean levels of achievement than did those of probands with nonbipolar disorder. This pattern applied whether or not the relatives themselves had bipolar illness. The authors conclude that the socioeconomic advantage previously associated with affective disorder in general may be limited to the bipolar forms.

Achievement↗
PubMed1987

The antisocial and the nonantisocial alcoholic: clinical distinctions in men with major unipolar depression.

Depressed, alcoholic men were divided into those with and those without antisocial personality (ASP). The ASP alcoholics had a more severe, cross-sectional clinical picture; they had a higher rate of drug use disorder and more alcohol-related symptomatology. The medical complications of alcoholism were related to the duration of heavy drinking whereas the nonmedical complications (the psychosocial and pathologic-intake problems) were related to ASP, duration of heavy drinking, and their interaction.

Adult↗
PubMed1986

Structural abnormalities in the frontal system in schizophrenia. A magnetic resonance imaging study.

Thirty-eight schizophrenics and 49 normal controls underwent magnetic resonance imaging. Midline sagittal cuts indicated that the schizophrenics had significantly smaller frontal lobes, as well as smaller cerebrums and craniums. The findings are consistent with some type of early developmental abnormality that might retard brain growth and therefore skull growth. These findings are confirmed on a smaller sample of patients on whom we have coronal cuts. Decreased cerebral and cranial size are associated with prominent negative symptoms, although decreased frontal size is not. Decreased cranial and cerebral size was also associated with impairment on some cognitive tests. These findings are consistent with the hypothesis that some schizophrenics may have a type of early developmental abnormality associated with prominent negative symptoms and cognitive impairment. Further, the results suggest that schizophrenics may have a type of structural frontal system impairment. Thus, they provide anatomic evidence for the "hypofrontality hypothesis."

Adult↗