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- Lindberg, Olof, et al.
(författare)
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Cortical morphometric subclassification of frontotemporal lobar degeneration
- 2009
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Ingår i: American Journal of Neuroradiology. - 0195-6108 .- 1936-959X. ; 30:6, s. 1233-1239
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Tidskriftsartikel (refereegranskat)abstract
- 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.
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| 3. |
- Looi Chee Leong, Jeffrey, et al.
(författare)
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Caudate nucleus volumes in frontotemporal lobar degeneration : differential atrophy in subtypes
- 2008
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Ingår i: American Journal of Neuroradiology. - 0195-6108 .- 1936-959X. ; 29:8, s. 1537-1543
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Tidskriftsartikel (refereegranskat)abstract
- 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, ETD, 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, ETD, 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 ETD (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
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- Freund-Levi, Yvonne, 1956-, et al.
(författare)
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Effects of omega-3 fatty acids on inflammatory markers in cerebrospinal fluid and plasma in Alzheimer's disease : the OmegAD study
- 2009
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Ingår i: Dementia and Geriatric Cognitive Disorders. - : S. Karger. - 1420-8008 .- 1421-9824. ; 27:5, s. 481-490
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: omega-3 fatty acids (omega-3 FAs) found in dietary fish or fish oils are anti-inflammatory agents that may influence Alzheimer's disease (AD).OBJECTIVE: To study the effects of dietary omega-3 FA supplementation on inflammatory markers in cerebrospinal fluid (CSF) and plasma from patients with mild to moderate AD.METHODS: Thirty-five patients (70.3 +/- 8.2 years) were randomized to a daily intake of 2.3 g omega-3 FAs or placebo for 6 months. The inflammatory markers interleukin (IL)-6, tumour necrosis factor-alpha and soluble interleukin-1 receptor type II (sIL-1RII) were analysed in CSF and plasma at baseline and at 6 months. The AD markers tau-protein, hyperphosphorylated tau-protein and beta-amyloid (Abeta(1-42)) were assessed in CSF. High-sensitivity C-reactive protein was assessed in plasma. A possible relation to the APOE genotype was investigated.RESULTS: There was no significant treatment effect of omega-3 FAs on inflammatory and AD biomarkers in CSF or on inflammatory markers in plasma, nor was there any relation with APOE. A significant correlation was observed at baseline between sIL-1RII and Abeta(1-42) levels in CSF.CONCLUSIONS: Treatment of AD patients with omega-3 FAs for 6 months did not influence inflammatory or biomarkers in CSF or plasma. The correlation between sIL-1RII and Abeta(1-42) may reflect the reciprocal interactions between IL-1 and Abeta peptides.
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| 6. |
- Gabrielsson, Jon, et al.
(författare)
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Multivariate Methods in the Development of a New Tablet Formulation : Excipient Mixtures and Principal Properties
- 2006
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Ingår i: Drug Development and Industrial Pharmacy. - New York : M. Dekker. - 0363-9045 .- 1520-5762. ; 32:1, s. 7-20
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Tidskriftsartikel (refereegranskat)abstract
- A tablet formulation for direct compression has previously been studied using multivariate design. An optimization study of one of the most important tablet properties, disintegration time, revealed that excipients with Principal Properties (PP's) that were predicted as suitable by the model were not represented within the studied material.The feasibility of using mixtures of excipients in the multivariate approach to tablet formulation to solve this problem has been investigated in the present study. By mixing different excipients of the same excipient class, it should be possible to obtain mixtures with the predicted PP's, which in turn should give a formulation with the desired properties. In order to investigate the utility of this approach, separate mixture designs were applied to both binders and fillers (diluents).As reported here, the Partial Least Squares Projections to Latent Structures (PLS) model developed in the previously published screening study has been validated in the sense that the interesting region of the PP space identified in it has been shown to contain excipients, pure or mixed, that give the formulation suitable properties. Formulations with suitable properties were found with the mixture experiments. The local models also offer several alternatives for the composition of the formulation that yield the desired disintegration time.
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| 9. |
- Giordanetto, Fabrizio, et al.
(författare)
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Discovery of cyclopentane- and cyclohexane-trans-1,3-diamines as potent melanin-concentrating hormone receptor 1 antagonists
- 2007
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Ingår i: Bioorganic & Medicinal Chemistry Letters. - : Elsevier BV. - 0960-894X. ; 17:15, s. 4232-41
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Tidskriftsartikel (refereegranskat)abstract
- We herein report the optimization of cyclopentane- and cyclohexane-1,3-diamine derivatives as novel and potent MCH-R1 antagonists. Structural modifications of the 2-amino-quinoline and thiophene moieties found in the initial lead compound served to improve its metabolic stability profile and MCH-R1 affinity, and revealed unprecedented SAR when compared to other 2-amino-quinoline-containing MCH-R1 antagonists.
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