Language and mathematical problems as precursors of psychotic-like experiences and juvenile mania symptoms.

BACKGROUND: Psychotic-like experiences (PLEs) and juvenile mania in adolescence index risk for severe psychopathology in adulthood. The importance of childhood problems with communication, reading, speech and mathematics for the development of PLEs and juvenile mania is not well understood. METHOD: Through the Child and Adolescent Twin Study in Sweden, we identified 5812 children. The parents were interviewed about their children's development at age 9 or 12 years. At age 15 or 18 years, children and parents completed questionnaires targeting current PLEs and juvenile mania symptoms. Logistic regressions were used to assess associations between problems with communication, reading, speech and mathematics and PLEs/juvenile mania symptoms. To evaluate the relative importance of genes and environment in these associations, we used bivariate twin analyses based on structural equation models. RESULTS: Children with parent-endorsed childhood problems with communication, reading and mathematics had an increased risk of developing auditory hallucinations and parental-reported juvenile mania symptoms in adolescence. The most consistent finding was that children with childhood problems with communication, reading and mathematics had an increased risk of developing auditory hallucinations [for example, the risk for self-reported auditory hallucinations at age 15 was increased by 96% for children with communication problems: OR (odds ratio) 1.96, 95% confidence interval (CI) 1.33-2.88]. The twin analyses showed that genetic effects accounted for the increased risk of PLEs and juvenile mania symptoms among children with communication problems. CONCLUSIONS: Childhood problems with communication, reading and mathematics predict PLEs and juvenile mania symptoms in adolescence. Similar to the case for schizophrenia and bipolar disorder, PLEs and juvenile mania may share genetic aetiological factors.

Putaminal volume in frontotemporal lobar degeneration and Alzheimer disease: differential volumes in dementia subtypes and controls.

BACKGROUND AND PURPOSE: Frontostriatal (including the putamen) circuit-mediated cognitive dysfunction has been implicated in frontotemporal lobar degeneration (FTLD), but not in Alzheimer disease (AD) or healthy aging. We sought to assess putaminal volume as a measure of the structural basis of relative frontostriatal dysfunction in these groups. MATERIALS AND METHODS: We measured putaminal volume in FTLD subtypes: frontotemporal dementia (FTD, n = 12), semantic dementia (SD, n = 13), and progressive nonfluent aphasia (PNFA, n = 9) in comparison with healthy controls (n = 25) and patients with AD (n = 18). Diagnoses were based on accepted clinical criteria. We conducted manual volume measurement of the putamen blinded to the diagnosis on T1 brain MR imaging by using a standardized protocol. RESULTS: Paired t tests (P < .05) showed that the left putaminal volume was significantly larger than the right in all groups combined. Multivariate analysis of covariance with a Bonferroni correction was used to assess statistical significance among the subject groups (AD, FTD, SD, PNFA, and controls) as independent variables and right/left putaminal volumes as dependent variables (covariates, age and intracranial volume; P < .05). The right putamen in FTD was significantly smaller than in AD and controls; whereas in SD, it was smaller compared with controls with a trend toward being smaller than in AD. There was also a trend toward the putamen in the PNFA being smaller than that in controls and in patients with AD. Across the groups, there was a positive partial correlation between putaminal volume and Mini-Mental State Examination (MMSE). CONCLUSIONS: Right putaminal volume was significantly smaller in FTD, the FTLD subtype with the greatest expected frontostriatal dysfunction; whereas in SD and PNFA, it showed a trend towards being smaller, consistent with expectation, compared to controls and AD; and in SD, compared with AD and controls. Putaminal volume weakly correlated with MMSE.

Cortical morphometric subclassification of frontotemporal lobar degeneration.

BACKGROUND AND PURPOSE: Frontotemporal lobar degeneration (FTLD) is a primary neurodegenerative disease comprising 3 clinical subtypes: frontotemporal dementia (FTD), semantic dementia (SD), and progressive nonfluent aphasia (PNFA). The subdivision is primarily based on the characteristic clinical symptoms displayed by each subtype. We hypothesized that these symptoms would be correlated to characteristic patterns of brain atrophy, which could be indentified and used for subclassification of subjects with FTLD. MATERIALS AND METHODS: Volumes of 9 cortical regions were manually parcellated and measured on both hemispheres on 27 controls, 12 patients with FTD, 9 patients with PNFA, and 13 patients with SD. The volumetric data were analyzed by traditional t tests and by a multivariate discriminant analysis (partial least squares discriminant analysis). RESULTS: The ensemble or pattern of atrophy was a good discriminator in pair-wise comparison between the subtypes: FTD compared with SD (sensitivity 100% [12/12], specificity 100% [13/13]); FTD compared with PNFA (sensitivity 92% [11/12], specificity 89% [8/9]); and SD compared with PNFA (sensitivity 86% [11/13], specificity 100% [9/9]). Temporal-versus-frontal atrophy was the most important pattern for discriminating SD from the other 2 subtypes. Right-sided versus left-sided atrophy was the most important pattern for discriminating between subjects with FTD and PNFA. CONCLUSIONS: FTLD subtypes generally display a characteristic pattern of atrophy, which may be considered in diagnosing patients with FTLD.

Caudate nucleus volumes in frontotemporal lobar degeneration: differential atrophy in subtypes.

BACKGROUND AND PURPOSE: Frontostriatal circuits involving the caudate nucleus have been implicated in frontotemporal lobar degeneration (FTLD). We assessed caudate nucleus volumetrics in FTLD and subtypes: frontotemporal dementia (FTD, n = 12), semantic dementia (SD, n = 13), and progressive nonfluent aphasia (PNFA, n = 9) in comparison with healthy controls (n = 27) and subjects with Alzheimer disease (AD, n = 19). MATERIALS AND METHODS: Diagnoses were based on accepted clinical criteria. Manual volume measurement of the head and body of the caudate, excluding the tail, was conducted on T1-weighted brain MR imaging scans, using a published protocol, by a single analyst blinded to the diagnosis. RESULTS: Paired t tests (P < .05) showed that the right caudate nucleus volume was significantly larger than the left in controls and PNFA. No hemispheric asymmetry was found in AD, FTD, and SD. Across the groups, there was a positive partial correlation between the left caudate nucleus volume and Mini-Mental State Examination (MMSE) scores (r = 0.393, n = 76, P = .001) with higher left caudate volumes associated with higher MMSE scores. Multivariate analysis of covariance was used to assess the statistical significance between the subject groups (AD, FTD, SD, PNFA, and controls) as independent variables and raw right/left caudate volumes at the within-subject level (covariates: age and intracranial volume; P < .05). Control volume was largest, followed by AD (93% of control volume), SD (92%), PNFA (79%), and FTD (75%). CONCLUSIONS: Volume of the head and body of the caudate nucleus differs in subtypes of FTLD, due to differential frontostriatal dysfunction in subtypes being reflected in structural change in the caudate, and is correlated with cognition.

Swedish norms for word fluency tests: FAS, animals and verbs.

Verbal fluency tests are useful measures of acquired language impairment and cognitive decline of various etiologies. The aim of this study was to provide normative data for the Swedish population on the three verbal fluency tests, FAS, Animals and Verbs. A group of 165 healthy participants ranging from 16 to 89 years of age were assessed with the verbal fluency tests and tests of level of intellectual functioning. The sample was stratified by education, age and gender. Level of education had a substantial influence on the performance on verbal fluency, most clearly so in FAS and Verbs. Intellectual level had a positive and significant correlation with all measures of word fluency. Moreover, there was an interaction between age and gender such that women aged between 30 and 64 years outperformed elderly men on FAS and Verbs. Guidelines for instructions and scoring in Swedish are given in the article.

Bioaccumulation of 14C-PCB 101 and 14C-PBDE 99 in the marine planktonic copepod Calanus finmarchicus under different food regimes.

Bioaccumulation factors (BAFs) were determined for (14)C-PCB 101 and (14)C-PBDE 99 in the pelagic copepod Calanus finmarchicus after exposure to either contaminated water or after being fed contaminated phytoplankton (the dinoflagellate Prorocentrum minimum or the diatom Thalassiosira weissflogii). BAFs in algae range from 7.6 to 8.0 for PCB 101 and from 8.5 to 8.6 for PBDE 99. BAFs in copepods were significantly lower, 6.3-6.8 for PCB 101 and 7.6 for PBDE 99. For each compound, the BAFs in copepods were independent of what algal species they had consumed, even though the bioaccumulation of both compounds were higher in P. minimum than in T. weissflogii. The ratios between BAF and the K(ow) for PCB 101 and PBDE 99 were similar within each of the three species, but varied between species. For copepods the ratios were 2-4, for T. weissfloggii 15-22 and for P. minimum 32-40. The data strongly suggest that the two compounds bioaccumulate in a similar manner and that there is no biomagnification in the transfer between phytoplankton and herbivorous copepods.

Jargonagraphia in a case of frontotemporal dementia.

Jargonagraphia is known to occur after discrete brain lesions but not in primary degenerative dementia. We report a patient with frontotemporal dementia who developed jargonagraphia and nonfluent aphasia. Written output was graphically preserved but consisted of short words intermingled with abstruse neologisms. MRI showed predominant right frontotemporal cortical atrophy accompanied by white matter hyperintensities in the right anterior subcallosal periventricular region. Diagnosis and MRI were corroborated by extensive neuropathological findings obtained 8 months later. The agraphia in this case is discussed with reference to both specific macroscopic and microscopic pathoanatomical lesions. We suggest that jargonagraphia can appear in frontotemporal dementia depending on the localization of lesions.

White matter lesions impair initiation of FAS flow.

Word fluency performance is known to rely on left frontal cortical regions and has also been shown to be affected by lesions in the white matter, which may be seen as white matter hyperintensities (WMH) on magnetic resonance imaging. However, word fluency may be divided into two independent components, initial and late performance, separated in time [J Clin Exp Neuropsychol 1998;20:137-143]. The purpose of the current study was to investigate the relationship between the two components of FAS fluency performance and WMH. Patients varying in degree of memory impairment participated: Alzheimer's disease, mild cognitive impairment and subjective memory disorder. WMH were rated with the Scheltens scale in the periventricular and deep subcortical areas. Results demonstrated that WMH in this sample of patients may be summarized in two indices according to a principal factor analysis, one anterior factor mainly related to WMH in the frontal lobes and adjacent to ventricles, and a second posterior factor related to parietal and occipital WMH. The initial FAS performance was related to anterior WMH, in particular left frontal or lateral periventricular hyperintensities, whereas the late FAS performance was not related to any index of WMH.

Tau protein in cerebrospinal fluid from semantic dementia patients.

Apolipoprotein E (APOE) genotypes and cerebrospinal fluid (CSF) tau protein concentration were evaluated in patients suffering from semantic dementia, with the aim of determining whether these markers could help to differentiate this condition from Alzheimer's disease (AD) in early stages. By strictly following diagnostic criteria for semantic dementia, we found a clinically homogeneous group comprising eight patients from a total population of 621 subjects referred for dementia investigation. CSF tau protein concentrations were moderately increased with a small intraindividual variation 437+/-36 pg/ml (mean+/-SD) compared to healthy control individuals. APOE genotype distribution showed an over representation of the epsilon4 allele (69% epsilon3, 31% epsilon4 and no epsilon2), a pattern similar to that found in AD. These results indicate that semantic dementia is a rather uncommon but clinically distinct condition which shows a moderate increase of CSF tau protein levels and for which the epsilon4 allele is a risk factor.

Bilateral temporal lobe volume reduction parallels cognitive impairment in progressive aphasia.

BACKGROUND: Patients with isolated aphasia in the absence of other cognitive abnormalities have been the focus of several studies during the past decade. It has been called primary progressive aphasia (PPA), and the typical features of this syndrome are marked atrophy of the left temporal lobe according to the radiological examination and a language disorder as the initial symptom. In previous studies of PPA, the selection of the patients was based mainly on linguistic symptoms. Now, when computed tomography or magnetic resonance imaging scans are part of the routine investigation of cognitive impairment and suspected dementia, the patients with lobar atrophy will be found at an earlier stage. In the present study, we used a new approach and defined the study group by selecting patients with obvious left temporal lobe atrophy, assessed by MRI, and we referred to them as patients with temporal lobe atrophy (TLA). OBJECTIVE: To identify the features that distinguish TLA from other primary neurodegenerative disorders. PATIENTS: Six patients with TLA were compared with patients with Alzheimer disease (AD), patients with frontal lobe dementia (FLD), and healthy control subjects. METHODS: The investigations included magnetic resonance imaging volumetry, single photon emission computed tomography, and neuropsychologic and linguistic evaluations. RESULTS: In the TLA group, the mean volume of the left temporal lobe was 35% smaller than the right, while in the AD and FLD groups, the atrophy was symmetrical and bilateral. In the TLA group, the absolute volumes of the temporal lobes were significantly smaller on the left side compared with the AD and FLD groups, whereas there was no difference on the right side. The cerebral blood flow pattern in TLA was asymmetric and differed from that in the other study groups. All patients with TLA had a history of progressive Wernicke-type aphasia, ranging from 2 to 6 years. They showed primary verbal memory impairment but had preserved visuospatial functions. The clinical condition of all patients with TLA deteriorated during the study period; severe aphasia developed, and the patients exhibited signs of frontal lobe dysfunction. Serial volumetric measurements in 4 of 6 patients showed an annual 8% to 9% decrease of both left and right temporal lobes. CONCLUSIONS: The initial marked asymmetry in cognitive function found in patients with TLA contrasts with the general decline found in patients with AD. The bilateral degenerative process evident in patients with TLA paralleled the clinical deterioration, indicating TLA to be a non-AD lobar atrophy that develops into generalized cognitive dysfunction and dementia.

Effects of contrast media on renal graft function and survival after cerebral angiography of cadaveric donors.

The effects of intravascularly administered ionic contrast media on renal graft function and survival were retrospectively evaluated in 211 recipients of cadaveric renal transplants. The renal grafts were explanted from the donors within 24 hours (mean 16 hours) after cerebral angiography. There were no differences in renal function or graft survival between those exposed and those not exposed to contrast media before nephrectomy.