| 1. |
- Aronsson, Fredrik, et al.
(author)
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Is cognitive impairment associated with reduced syntactic complexity in writing? Evidence from automated text analysis
- 2021
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In: Aphasiology. - : ROUTLEDGE JOURNALS, TAYLOR & FRANCIS LTD. - 0268-7038 .- 1464-5041. ; 35:7, s. 900-913
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Journal article (peer-reviewed)abstract
- Background: Written language impairments are common in Alzheimers disease and reduced syntactic complexity in written discourse has been observed decades before the onset of dementia. The validity of average dependency distance (ADD), a measure of syntactic complexity, in cognitive decline needs to be studied further to evaluate its clinical relevance. Aims: The aim of the study was to determine whether ADD is associated with levels of cognitive impairment in memory clinic patients. Methods & procedures: We analyzed written texts collected in clinical practice from 114 participants with subjective cognitive impairment, mild cognitive impairment, and Alzheimers disease during routine assessment at a memory clinic. ADD was measured using automated analysis methods consisting of a syntactic parser and a part-of-speech tagger. Outcomes & results: Our results show a significant association between ADD and levels of cognitive impairment, using ordinal logistic regression models. Conclusion: These results suggest that ADD is clinically relevant with regard to levels of cognitive impairment and indicate a diagnostic potential for ADD in cognitive assessment.
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| 2. |
- Chiotis, Konstantinos, et al.
(author)
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Imaging in-vivo tau pathology in Alzheimer's disease with THK5317 PET in a multimodal paradigm
- 2016
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In: European Journal of Nuclear Medicine and Molecular Imaging. - : Springer Science and Business Media LLC. - 1619-7070 .- 1619-7089. ; 43:9, s. 1686-1699
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Journal article (peer-reviewed)abstract
- Purpose The aim of this study was to explore the cerebral distribution of the tau-specific PET tracer [F-18]THK5317 (also known as (S)-[F-18]THK5117) retention in different stages of Alzheimer's disease; and study any associations with markers of hypometabolism and amyloid-beta deposition. Methods Thirty-three individuals were enrolled, including nine patients with Alzheimer's disease dementia, thirteen with mild cognitive impairment (MCI), two with non-Alzheimer's disease dementia, and nine healthy controls (five young and four elderly). In a multi-tracer PET design [F-18]THK5317, [C-11] Pittsburgh compound B ([C-11]PIB), and [F-18]FDG were used to assess tau pathology, amyloid-beta deposition and cerebral glucose metabolism, respectively. The MCI patients were further divided into MCI [C-11]PIB-positive (n=11) and MCI [C-11]PIB-negative (n=2) groups. Results Test-retest variability for [F-18]THK5317-PET was very low (1.17-3.81 %), as shown by retesting five patients. The patients with prodromal (MCI [C-11]PIB-positive) and dementia-stage Alzheimer's disease had significantly higher [F-18]THK5317 retention than healthy controls (p=0.002 and p=0.001, respectively) in areas exceeding limbic regions, and their discrimination from this control group (using the area under the curve) was >98 %. Focal negative correlations between [F-18]THK5317 retention and [F-18]FDG uptake were observed mainly in the frontal cortex, and focal positive correlations were found between [F-18]THK5317 and [C-11] PIB retentions isocortically. One patient with corticobasal degeneration syndrome and one with progressive supranuclear palsy showed no [C-11]PIB but high [F-18]THK5317 retentions with a different regional distribution from that in Alzheimer's disease patients. Conclusions The tau-specific PET tracer [F-18]THK5317 images in vivo the expected regional distribution of tau pathology. This distribution contrasts with the different patterns of hypometabolism and amyloid-beta deposition.
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| 3. |
- Cselenyi, Zsolt, et al.
(author)
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[C-11]PBB3 binding in A beta(-) or A beta(+) corticobasal syndrome
- 2023
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In: Synapse. - : Wiley. - 0887-4476 .- 1098-2396. ; 77:4
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Journal article (peer-reviewed)abstract
- Corticobasal syndrome (CBS) is associated with 4-repeat tauopathy and/or Alzheimers disease pathologies. To examine tau and amyloid-beta (A beta) deposits in CBS patients using positron emission tomography (PET). Eight CBS patients and three healthy individuals lacking amyloid pathology underwent PET with [C-11]PBB3 for tau imaging, and [C-11]AZD2184 for A beta. Subcortical and cortical binding of [C-11]PBB3 was compared between A beta(-) and A beta(+) CBS patients and reference group. Postmortem analysis was done in one CBS patient. Three CBS patients were considered A beta(+). Total binding was higher in all patients compared to the reference group. Similar regional binding profiles of [C-11]PBB3 in A beta(+) and A beta(-) CBS patients were found. Elevated [C-11]PBB3 binding in pallidum was observed in all CBS patients. Cortical [C-11]PBB3 binding was higher in A beta(+) compared to A beta(-) patients. Postmortem analysis of a CBS patient revealed corticobasal degeneration neuropathology and [C-11]PBB3 autofluorescence in some tau-positive structures. [C-11]PBB3 is elevated in CBS patients with binding in relevant areas capturing some, but not all, 4-repeat tauopathy in CBS.
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| 4. |
- Enache, Daniela, et al.
(author)
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CAIDE Dementia Risk Score and biomarkers of neurodegeneration in memory clinic patients without dementia
- 2016
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In: Neurobiology of Aging. - : Elsevier BV. - 0197-4580 .- 1558-1497. ; 42, s. 124-131
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Journal article (peer-reviewed)abstract
- The aim of this study was to explore cross-sectional associations between Cardiovascular Risk Factors, Aging and Dementia Study (CAIDE) Dementia Risk Score and dementia-related cerebrospinal fluid and neuroimaging biomarkers in 724 patients without dementia from the Memory Clinic at Karolinska University Hospital, Huddinge, Sweden. We additionally evaluated the score's capacity to predict dementia. Two risk score versions were calculated: one including age, gender, obesity, hyperlipidemia, and hypertension; and one additionally including apolipoprotein E (APOE) ε4 carrier status. Cerebrospinal fluid was analyzed for amyloid β (Aβ), total tau, and phosphorylated tau. Visual assessments of medial temporal lobe atrophy (MTA), global cortical atrophy-frontal subscale, and Fazekas scale for white matter changes (WMC) were performed. Higher CAIDE Dementia Risk Score (version without APOE) was significantly associated with higher total tau, more severe MTA, WMC, and global cortical atrophy-frontal subscale. Higher CAIDE Dementia Risk Score (version with APOE) was associated with reduced Aβ, more severe MTA, and WMC. CAIDE Dementia Risk Score version with APOE seemed to predict dementia better in this memory clinic population with short follow-up than the version without APOE.
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| 5. |
- Eriksdotter-Jönhagen, Maria, et al.
(author)
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Encapsulated cell biodelivery of nerve growth factor to the Basal forebrain in patients with Alzheimer's disease.
- 2012
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In: Dementia and geriatric cognitive disorders. - : S. Karger AG. - 1421-9824 .- 1420-8008. ; 33:1, s. 18-28
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Journal article (peer-reviewed)abstract
- Degeneration of cholinergic neurons in the basal forebrain correlates with cognitive decline in patients with Alzheimer's disease (AD). Targeted delivery of exogenous nerve growth factor (NGF) has emerged as a potential AD therapy due to its regenerative effects on the basal forebrain cholinergic neurons in AD animal models. Here we report the results of a first-in-man study of encapsulated cell (EC) biodelivery of NGF to the basal forebrain of AD patients with the primary objective to explore safety and tolerability.
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| 6. |
- Garcia-Ptacek, Sara, et al.
(author)
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Subjective cognitive impairment subjects in our clinical practice
- 2014
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In: Dementia and Geriatric Cognitive Disorders Extra. - : S. Karger AG. - 1664-5464. ; 4:3, s. 419-430
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Journal article (peer-reviewed)abstract
- BACKGROUND:The clinical challenge in subjective cognitive impairment (SCI) is to identify which individuals will present cognitive decline. We created a statistical model to determine which variables contribute to SCI and mild cognitive impairment (MCI) versus Alzheimer's disease (AD) diagnoses.METHODS:A total of 993 subjects diagnosed at a memory clinic (2007-2009) were included retrospectively: 433 with SCI, 373 with MCI and 187 with AD. Descriptive statistics were provided. A logistic regression model analyzed the likelihood of SCI and MCI patients being diagnosed with AD, using age, gender, Mini-Mental State Examination score, the ratio of β-amyloid 42 divided by total tau, and phosphorylated tau as independent variables.RESULTS:The SCI subjects were younger (57.8 ± 8 years) than the MCI (64.2 ± 10.6 years) and AD subjects (70.1 ± 9.7 years). They were more educated, had less medial temporal lobe atrophy (MTA) and frequently normal cerebrospinal fluid biomarkers. Apolipoprotein E4/E4 homozygotes and apolipoprotein E3/E4 heterozygotes were significantly less frequent in the SCI group (6 and 36%) than in the AD group (28 and 51%). Within the regression model, cardiovascular risk factors, confluent white matter lesions, MTA and central atrophy increased the AD likelihood for SCI subjects.CONCLUSIONS:SCI patients form a distinct group. In our model, factors suggesting cardiovascular risk, MTA and central atrophy increased the AD likelihood for SCI subjects.
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| 7. |
- Handels, Ron L. H., et al.
(author)
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Predicting progression to dementia in persons with mild cognitive impairment using cerebrospinal fluid markers
- 2017
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In: Alzheimer's & Dementia. - : Elsevier. - 1552-5260 .- 1552-5279. ; 13:8, s. 903-912
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Journal article (peer-reviewed)abstract
- INTRODUCTION: We aimed to determine the added value of cerebrospinal fluid (CSF) to clinical and imaging tests to predict progression from mild cognitive impairment (MCI) to any type of dementia.METHODS: The risk of progression to dementia was estimated using two logistic regression models based on 250 MCI participants: the first included standard clinical measures (demographic, clinical, and imaging test information) without CSF biomarkers, and the second included standard clinical measures with CSF biomarkers.RESULTS: Adding CSF improved predictive accuracy with 0.11 (scale from 0-1). Of all participants, 136 (54%) had a change in risk score of 0.10 or higher (which was considered clinically relevant), of whom in 101, it was in agreement with their dementia status at follow-up.DISCUSSION: An individual person's risk of progression from MCI to dementia can be improved by relying on CSF biomarkers in addition to recommended clinical and imaging tests for usual care.
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| 8. |
- Idrizbegovic, Esma, et al.
(author)
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Central auditory function in early Alzheimer's disease and in mild cognitive impairment.
- 2011
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In: Age and Ageing. - : Oxford University Press (OUP). - 0002-0729 .- 1468-2834. ; 40:2
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Journal article (peer-reviewed)abstract
- OBJECTIVE: to investigate auditory function in subjects with early Alzheimer's disease, mild cognitive impairment and with subjective memory complaints, in search of signs of central auditory processing dysfunction even in early stages of cognitive impairment.DESIGN AND SUBJECTS: a consecutive group of men and women, referred to the Memory Clinic at the Karolinska University Hospital, was approached for inclusion in this prospective study. One hundred and thirty-six subjects, mean age 64 years (range 50-78 years), diagnosed with Alzheimer's disease (n = 43), mild cognitive impairment (n = 59) or with subjective memory complaints (n = 34), were included.METHODS: auditory function was assessed with pure tone audiometry, speech perception in quiet and in background noise and dichotic digits tests with two or three digits.RESULTS: pure tone audiometry and speech perception scores in quiet and in background noise were normal for age and without between-group differences. Dichotic digits tests showed strongly significant differences between the three groups, where the Alzheimer's disease group performed significantly poorer than the other two groups, with the mild cognitive impairment group in an intermediate position.CONCLUSIONS: our results demonstrate that central auditory processing dysfunction is highly evident in subjects with Alzheimer's disease, and to a considerable extent even in subjects with mild cognitive impairment.
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| 9. |
- Jaremo, Petter, et al.
(author)
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Alzheimers Disease: Erythrocyte 2,3-diphosphoglycerate Content and Circulating Erythropoietin
- 2019
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In: Current Alzheimer Research. - : BENTHAM SCIENCE PUBL LTD. - 1567-2050 .- 1875-5828. ; 16:9, s. 834-835
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Journal article (peer-reviewed)abstract
- Background: Alzheimers Disease (AD) features the accumulation of beta-amyloid in erythrocytes. The subsequent red cell damage may well affect their oxygen-carrying capabilities. 2,3-diphosphoglycerate (2,3-DPG) binds to the hemoglobin thereby promoting oxygen release. It is theorized that 2,3-DPG is reduced in AD and that the resulting hypoxia triggers erythropoietin (EPO) release. Methods amp; Objective: To explore this theory, we analyzed red cell 2,3-DPG content and EPO in AD, mild cognitive impairment, and the control group, subjective cognitive impairment. Results: We studied (i) 2,3-DPG in red cells, and (ii) circulating EPO in AD, and both markers were unaffected by dementia. Disturbances of these oxygen-regulatory pathways do not appear to participate in brain hypoxia in AD.
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| 10. |
- Jaremo, Petter, et al.
(author)
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Erythrocyte Amyloid Beta Peptide Isoform Distributions in Alzheimer and Mild Cognitive Impairment
- 2019
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In: Current Alzheimer Research. - : BENTHAM SCIENCE PUBL LTD. - 1567-2050 .- 1875-5828. ; 16:11, s. 1050-1054
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Journal article (peer-reviewed)abstract
- Introduction: We recently showed that Amyloid Beta (A beta)(40) accumulates in erythrocytes and possibly causes cell damage as evidenced by an increased number of assumed injured low-density (kg/L) erythrocytes. Furthermore, we have suggested a separation technique to isolate and concentrate such damaged red blood cells for subsequent analysis. Objectives: We isolated high- and low-density erythrocytes and investigated the accumulation patterns of the A beta peptides (A beta(40), A beta(42), and A beta(43) ) in Alzheimer (AD), mild cognitive impairment (MCI), and Subjective Cognitive Impairment (SCI). Methods: Whole blood was fractionated through a density gradient, resulting in two concentrated high-and presumed injured low-density erythrocyte fractions. After cell lysis, intracellular A beta(40) , A beta 4(2), and A beta (43) were quantified by ELISA. Results: In both high- and low-density erythrocytes, A beta(40) displayed the lowest concentration in MCI, while it was equal and higher in AD and SCI. A beta(40) was detected at a 10-fold higher level than A beta(42), and in injured low-density erythrocytes, the lowest quantity of A beta(42) was found in AD and MCI. A beta(40) exhibited a 100-fold greater amount than A beta(43). and lighter erythrocytes of MCI subjects displayed less intracellular A beta(43) than SCI. Conclusion: Red blood cell accumulation patterns of A beta(40), A beta(42), and A beta(43) differ significantly between AD, MCI, and SCI. The data must be verified through larger clinical trials. It is, however, tenable that AP peptide distributions in erythrocyte subpopulations have the potential to be used for diagnostic purposes.
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