| 241. |
- von Otter, Malin, 1978, et al.
(författare)
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Kinesin Light Chain 1 Gene Haplotypes in Three Conformational Diseases
- 2010
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Ingår i: NeuroMolecular Medicine. - : Springer Science and Business Media LLC. - 1535-1084 .- 1559-1174. ; 12:3, s. 229-236
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Tidskriftsartikel (refereegranskat)abstract
- A functional intracellular transport system is essential to maintain cell shape and function especially in elongated cells, e.g. neurons and lens fibre cells. Impaired intracellular transport has been suggested as a common pathological mechanism for age-related diseases characterised by protein aggregation. Here, we hypothesise that common genetic variation in the transport protein kinesin may influence the risk of Parkinson's disease (PD), Alzheimer's disease (AD) and age-related cataract. This case-control study involves a PD material (165 cases and 190 controls), an AD material (653 cases and 845 controls) and a cataract material (495 cases and 183 controls). Genetic variation in the kinesin light chain 1-encoding gene (KLC1) was tagged by six tag single nucleotide polymorphisms (SNPs). Single SNPs and haplotypes were analysed for associations with disease risk, age parameters, mini-mental state examination scores and cerebrospinal fluid biomarkers for AD using logistic or linear regression. Genetic variation in KLC1 did not influence risk of PD. Weak associations with risk of AD were seen for rs8007903 and rs3212079 (P (c) = 0.04 and P (c) = 0.02, respectively). Two SNPs (rs8007903 and rs8702) influenced risk of cataract (P (c) = 0.0007 and P (c) = 0.04, respectively). However, the allele of rs8007903 that caused increased risk of AD caused reduced risk of cataract, speaking against a common functional effect of this particular SNP in the two diseases. Haplotype analyses did not add significantly to the associations found in the single SNP analyses. Altogether, these results do not convincingly support KLC1 as a major susceptibility gene in any of the studied diseases, although there is a small effect of KLC1 in relation to cataract.
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| 242. |
- von Otter, Malin, 1978, et al.
(författare)
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Nrf2-encoding NFE2L2 haplotypes influence disease progression but not risk in Alzheimer's disease and age-related cataract
- 2010
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Ingår i: Mechanisms of Ageing and Development. - : Elsevier BV. - 0047-6374 .- 1872-6216. ; 131:2, s. 105-110
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Tidskriftsartikel (refereegranskat)abstract
- Alzheimer's disease (AD) and age-related cataract, disorders characterized by protein aggregation causing late-onset disease, both involve oxidative stress. We hypothesize that common variants of NFE2L2 and KEAP1, the genes encoding the main regulators of the Nrf2 system, an important defence system against oxidative stress, may influence risk of AD and/or age-related cataract. This case-control study combines an AD material (725 cases and 845 controls), and a cataract material (489 cases and 182 controls). Genetic variation in NFE2L2 and KEAP1 was tagged by eight and three tag single nucleotide polymorphisms (SNPs), respectively. Single SNPs and haplotypes were analyzed for associations with disease risk, age parameters, MMSE and AD cerebrospinal fluid biomarkers. NFE2L2 and KEAP1 were not associated with risk of AD or cataract. However, one haplotype allele of NFE2L2 was associated with 2 years earlier age at AD onset (pc 0.013) and 4 years earlier age at surgery for posterior subcapsular cataract (p(c) = 0.019). Another haplotype of NFE2L2 was associated with 4 years later age at surgery for cortical cataract (p(c) = 0.009). Our findings do not support NFE2L2 or KEAP1 as susceptibility genes for AD or cataract. However, common variants of the NFE2L2 gene may affect disease progression, potentially altering clinically recognized disease onset. (C) 2010 Elsevier Ireland Ltd. All rights reserved.
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| 243. |
- Waggestad, T. H., et al.
(författare)
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Improving validity of the trail making test with alphabet support
- 2023
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Ingår i: Frontiers in Psychology. - 1664-1078. ; 14
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Tidskriftsartikel (refereegranskat)abstract
- ObjectiveThe Trail Making Test (TMT) is commonly used worldwide to evaluate cognitive decline and car driving ability. However, it has received critique for its dependence on the Latin alphabet and thus, the risk of misclassifying some participants. Alphabet support potentially increases test validity by avoiding misclassification of executive dysfunction in participants with dyslexia and those with insufficient automatization of the Latin alphabet. However, Alphabet support might render the test less sensitive to set-shifting, thus compromising the validity of the test. This study compares two versions of the TMT: with and without alphabet support. MethodsWe compared the TMT-A, TMT-B, and TMT-B:A ratios in two independent normative samples with (n = 220) and without (n = 64) alphabet support using multiple regression analysis adjusted for age and education. The sample comprised Scandinavians aged 70-84 years. Alphabet support was included by adding the Latin alphabet A-L on top of the page on the TMT-B. We hypothesized that alphabet support would not change the TMT-B:A ratio. ResultsAfter adjusting for age and years of education, there were no significant differences between the two samples in the TMT-A, TMT-B, or the ratio score (TMT-B:A). ConclusionOur results suggest that the inclusion of alphabet support does not alter TMT's ability to measure set-shifting in a sample of older Scandinavian adults.
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| 244. |
- Wahlund, L. O., et al.
(författare)
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Imaging biomarkers of dementia: recommended visual rating scales with teaching cases
- 2017
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Ingår i: Insights into Imaging. - : Springer Science and Business Media LLC. - 1869-4101. ; 8:1, s. 79-90
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Tidskriftsartikel (refereegranskat)abstract
- The diagnostic work up of dementia may benefit from structured reporting of CT and/or MRI and the use of standardised visual rating scales. We advocate a more widespread use of standardised scales as part of the workflow in clinical and research evaluation of dementia. We propose routine clinical use of rating scales for medial temporal atrophy (MTA), global cortical atrophy (GCA) and white matter hyperintensities (WMH). These scales can be used for evaluation of both CT and MRI and are efficient in routine imaging assessment in dementia, and may improve the accuracy of diagnosis. Our review provides detailed imaging examples of rating increments in each of these scales and a separate teaching file. The radiologist should relate visual ratings to the clinical assessment and other biomarkers to assist the clinician in the diagnostic decision.
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| 245. |
- Wallin, Anders, 1950, et al.
(författare)
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Alzheimer's disease-subcortical vascular disease spectrum in a hospital-based setting: overview of results from the Gothenburg MCI and dementia studies.
- 2016
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Ingår i: Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism. - : SAGE Publications. - 1559-7016. ; 36:1, s. 95-113
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Forskningsöversikt (refereegranskat)abstract
- The ability to discriminate between Alzheimer's disease (AD), subcortical vascular disease, and other cognitive disorders is crucial for diagnostic purposes and clinical trial outcomes. Patients with primarily subcortical vascular disease are unlikely to benefit from treatments targeting the AD pathogenic mechanisms and vice versa. The Gothenburg mild cognitive impairment (MCI) and dementia studies are prospective, observational, single-center cohort studies suitable for both cross-sectional and longitudinal analysis that outline the cognitive profiles and biomarker characteristics of patients with AD, subcortical vascular disease, and other cognitive disorders. The studies, the first of which started in 1987, comprise inpatients with manifest dementia and patients seeking care for cognitive disorders at an outpatient memory clinic. This article gives an overview of the major published papers (neuropsychological, imaging/physiology, and neurochemical) of the studies including the ongoing Gothenburg MCI study. The main findings suggest that subcortical vascular disease with or without dementia exhibit a characteristic neuropsychological pattern of mental slowness and executive dysfunction and neurochemical deviations typical of white matter changes and disturbed blood-brain barrier function. Our findings may contribute to better healthcare for this underrecognized group of patients. The Gothenburg MCI study has also published papers on multimodal prediction of dementia, and cognitive reserve.Journal of Cerebral Blood Flow & Metabolism advance online publication, 29 July 2015; doi:10.1038/jcbfm.2015.148.
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| 246. |
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| 247. |
- Wallin, Anders, 1950, et al.
(författare)
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Biochemical markers in vascular cognitive impairment associated with subcortical small vessel disease - A consensus report.
- 2017
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Ingår i: BMC neurology. - : Springer Science and Business Media LLC. - 1471-2377. ; 17:1
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Forskningsöversikt (refereegranskat)abstract
- Vascular cognitive impairment (VCI) is a heterogeneous entity with multiple aetiologies, all linked to underlying vascular disease. Among these, VCI related to subcortical small vessel disease (SSVD) is emerging as a major homogeneous subtype. Its progressive course raises the need for biomarker identification and/or development for adequate therapeutic interventions to be tested. In order to shed light in the current status on biochemical markers for VCI-SSVD, experts in field reviewed the recent evidence and literature data.The group conducted a comprehensive search on Medline, PubMed and Embase databases for studies published until 15.01.2017. The proposal on current status of biochemical markers in VCI-SSVD was reviewed by all co-authors and the draft was repeatedly circulated and discussed before it was finalized.This review identifies a large number of biochemical markers derived from CSF and blood. There is a considerable overlap of VCI-SSVD clinical symptoms with those of Alzheimer's disease (AD). Although most of the published studies are small and their findings remain to be replicated in larger cohorts, several biomarkers have shown promise in separating VCI-SSVD from AD. These promising biomarkers are closely linked to underlying SSVD pathophysiology, namely disruption of blood-CSF and blood-brain barriers (BCB-BBB) and breakdown of white matter myelinated fibres and extracellular matrix, as well as blood and brain inflammation. The leading biomarker candidates are: elevated CSF/blood albumin ratio, which reflects BCB/BBB disruption;altered CSF matrix metalloproteinases, reflecting extracellular matrix breakdown; CSF neurofilment as a marker of axonal damage, and possibly blood inflammatory cytokines and adhesion molecules. The suggested SSVD biomarker deviations contrasts the characteristic CSF profile in AD, i.e. depletion of amyloid beta peptide and increased phosphorylated and total tau.Combining SSVD and AD biomarkers may provide a powerful tool to identify with greater precision appropriate patients for clinical trials of more homogeneous dementia populations. Thereby, biomarkers might promote therapeutic progress not only in VCI-SSVD, but also in AD.
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| 248. |
- Wallin, Anders, 1950, et al.
(författare)
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Biomarkers in vascular dementia
- 2009
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Ingår i: Vascular Cognitive Impairment in Clinical Practice. Wahlund, Erkinjuntti, Gauthier (eds.). - Cambridge : Cambridge University Press. ; , s. 77-92
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Bokkapitel (övrigt vetenskapligt/konstnärligt)
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| 249. |
- Wallin, Anders, 1950, et al.
(författare)
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Cerebral small vessel disease: Cerebrospinal fluid aspects
- 2011
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Ingår i: Cerebral Small Vessel Disease. - Cambridge : Cambridge University Press. - 9781139382694 ; , s. 200-215
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Bokkapitel (refereegranskat)abstract
- Introduction: The most common cerebral small vessel disease is the arteriolosclerotic variant located in the subcortical white and gray matter of the brain [1]. It gives rise to a characteristic phenotype called subcortical vascular dementia (SVD). However, SVD is often underdiagnosed or labeled Alzheimer’s disease (AD), although it comprises several features that are not characteristic for AD. The recently published National Institute of Aging/Alzheimer Association criteria [2] are more specific than the very often used, almost 30 years old, diagnostic guidelines for AD [3]. This suggests that now there are improved diagnostic criteria for avoiding error in the identification of SVD and AD. Another common small vessel disease is cerebral amyloid angiopathy (CAA) situated in meningeal and intracortical arteries. It is a characteristic feature of AD but may also occur without AD pathology [4]. Brains of patients with AD-related CAA often also display subcortical arteriolosclerotic vessel wall lesions [5], whereas those from patients with primary SVD usually lack signs of CAA [6]. The combination of arteriolosclerosis and CAA may underlie what is called “mixed dementia.”.
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| 250. |
- Wallin, Anders, 1950, et al.
(författare)
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Characteristic clinical presentation and CSF biomarker pattern in cerebral small vessel disease
- 2012
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Ingår i: Journal of the Neurological Sciences. - : Elsevier BV. - 0022-510X. ; 322:1-2, s. 192-196
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Tidskriftsartikel (refereegranskat)abstract
- To be able to live a good, independent life cognitive functions need to be intact. Dementia, stroke and neuropsychiatric disorders are the major disorders underlying disability. Stroke is usually a consequence of an underlying vessel wall disease that has lasted for a longer period. This vessel wall disease is commonly silent or without prominent symptoms. Damage to the small penetrating arterioles of the brain, arteriolosclerosis, induced by aging and hypertension, as well as other factors such as diabetes and genetic vulnerability, plays an important role in the origin of white matter changes. The pathological vascular wall process leads to lumen constriction, impaired ability to change lumen diameter according to metabolic needs and possible ischemic-hypoxic tissue damage in the vulnerable vascular architectural terminal areas of the long penetrating arteries. The arteriolosclerotic blood vessels are associated with inflammation and remodelling of the extracellular matrix. Enzymes connected to this process have also been found to be involved in demyelination and blood brain barrier opening but also in the repair process of angiogenesis and neurogenesis. Biochemical changes reflecting these processes might be early indicators of small vessel disease and hence increase the knowledge about the disease characteristic mechanisms. Moreover, monitoring disease modifying treatment effects can be an important application for small vessel disease specific biochemical markers. (c) 2012 Elsevier B.V. All rights reserved.
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