| 1. |
- Buchhave, Peder, et al.
(författare)
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Longitudinal study of CSF biomarkers in patients with Alzheimer's disease.
- 2009
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Ingår i: PloS one. - : Public Library of Science (PLoS). - 1932-6203. ; 16:Suppl 3, s. 337-337
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: The CSF biomarkers tau and Abeta42 can identify patients with AD, even during the preclinical stages. However, previous studies on longitudinal changes of tau and Abeta42 in individual patients with AD and elderly controls report somewhat inconsistent results. METHODOLOGY/PRINCIPAL FINDINGS: We investigated the levels of tau and Abeta42 at baseline and after 1 year in 100 patients with AD. In a second cohort of 45 AD patients we measured the CSF biomarkers at baseline and after 2 years. Moreover, in 34 healthy elderly controls the CSF biomarkers were followed for 4 years. The baseline levels of tau were increased with >60% in AD patients compared to controls (p<0.001), while baseline Abeta42 levels were decreased with >50% (p<0.001). In the AD group followed for 2 years, tau increased with 16% compared to the baseline levels (p<0.05). However, the levels of tau were stable over 4 years in the controls. The levels of Abeta42 did not change significantly over time in any of the groups. In the patients with AD, tau was moderately associated with worse cognitive performance already at baseline (p<0.05). CONCLUSIONS/SIGNIFICANCE: Tau and Abeta42 in CSF seem to reflect the underlying disease state in both early and late stages of AD. The slight increase in tau over time observed in the patients with AD is modest when compared to the relatively large difference in absolute tau levels between AD patients and controls. Therefore, these markers maintain their usefulness as state markers over time and might serve as surrogate markers for treatment efficacy in clinical trials.
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| 2. |
- Hansson, Oskar, et al.
(författare)
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Combined rCBF and CSF biomarkers predict progression from mild cognitive impairment to Alzheimer's disease.
- 2009
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Ingår i: Neurobiology of aging. - : Elsevier BV. - 1558-1497 .- 0197-4580. ; 30:2, s. 165-73
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Tidskriftsartikel (refereegranskat)abstract
- This study aimed to identify preclinical Alzheimer's disease (AD) in patients with mild cognitive impairment (MCI) using measurements of both regional cerebral blood flow (rCBF) and cerebrospinal fluid (CSF) biomarkers. Baseline rCBF assessments ((133)Xe method) were performed in 70 patients with MCI who were cognitively stable for 4-6 years, 69 patients with MCI who subsequently developed AD, and 33 healthy individuals. CSF was collected at baseline and analyzed for beta-amyloid(1-42), total tau and phophorylated tau. In contrast to patients with stable MCI, those who subsequently developed AD had decreased rCBF in the temporo-parietal cortex already at baseline. The relative risk of future progression to AD was particularly increased in MCI patients with decreased rCBF in parietal cortex (hazard ratio 3.1, P<0.0001). Subjects with pathological levels of both CSF tau and beta-amyloid(1-42) were also at high risk of developing AD (hazard ratio 13.4, P<0.0001). The MCI patients with a combination of decreased parietal rCBF and pathological CSF biomarkers at baseline had a substantially increased risk of future development of AD, with a hazard ratio of 24.3 (P<0.0001), when compared to those with normal CSF biomarkers. Moreover, decreased parietal rCBF (but not CSF biomarkers) was associated with a more rapid progression to AD. In conclusion, the combination of rCBF and CSF biomarkers improves the risk assessment of progression to AD in patients with MCI.
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| 3. |
- Buchhave, Peder, et al.
(författare)
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Cube copying test in combination with rCBF or CSF A beta(42) predicts development of Alzheimer's disease
- 2008
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Ingår i: Dementia and Geriatric Cognitive Disorders. - : S. Karger AG. - 1420-8008 .- 1421-9824. ; 25:6, s. 544-552
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Tidskriftsartikel (refereegranskat)abstract
- <i>Background/Aim: </i>The aim was to identify subjects with incipient Alzheimer’s disease (AD) among patients with mild cognitive impairment (MCI) using brief cognitive tests. <i>Methods: </i>A total of 147 MCI patients were followed for 4–6 years and the incidence of AD was 11.6%/year. At baseline, the cube copying test, clock drawing test, MMSE and measurements of regional cerebral blood flow (rCBF) and cerebrospinal fluid (CSF) β-amyloid<sub>1–42</sub> (Aβ<sub>42</sub>) were performed. <i>Results: </i>The cube copying test, but not the clock drawing test, could predict AD among MCI patients with an area under the receiver operating characteristic curve of 0.64 (p < 0.01). The relative risk for future AD was increased in MCI subjects with impaired cube copying test (sex- and age-adjusted hazard ratio = 1.8, p < 0.05) and the incidence of AD was 18.2% in this subgroup. Combining the cube copying test with either rCBF or CSF Aβ<sub>42</sub> had additive effects on the risk assessment for future development of AD. MCI patients achieving high scores on both MMSE and cube copying test had a very low risk of developing AD (incidence of AD = 1.6%). <i>Conclusion: </i>In conclusion, combinations of the cube copying test with MMSE, rCBF and CSF Aβ<sub>42</sub> measurements can identify subgroups of MCI subjects with either substantially reduced or increased risk for future development of AD.
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| 4. |
- Hansson, Oskar, et al.
(författare)
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Prediction of Alzheimer's disease using the CSF A beta 42/A beta 40 ratio in patients with mild cognitive impairment
- 2007
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Ingår i: DEMENTIA AND GERIATRIC COGNITIVE DISORDERS. - : S. Karger AG. - 1420-8008 .- 1421-9824. ; 23:5, s. 316-320
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Tidskriftsartikel (refereegranskat)abstract
- Evidence supports an important role for β-amyloid (Aβ) in the pathogenesis of Alzheimer’s disease (AD). Here, we investigate baseline levels of the 40- and 42-amino-acid-long Aβ peptides (Aβ40 and Aβ42) in cerebrospinal fluid (CSF) from a cohort of patients with mild cognitive impairment (MCI, n = 137) in relation to the final diagnosis after 4–6 years of follow-up time. CSF Aβ42 concentration at baseline and the Aβ42/Aβ40 ratio were significantly decreased in the MCI patients who developed AD as compared to cognitively stable MCI patients and MCI patients who developed other forms of dementia (p < 0.001). The baseline levels of Aβ40 were similar in all MCI groups but correlated with change in Mini Mental State Examination scores in converters to AD. The Aβ42/Aβ40 ratio was superior to Aβ42 concentration with regard to identifying incipient AD in MCI (p < 0.05). In conclusion, the data provide further support for the view that amyloid precursor protein metabolism is disturbed in early sporadic AD and points to the usefulness of the Aβ42/Aβ40 ratio as a predictive biomarker for AD.
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| 5. |
- Johansson, Annica, 1969, et al.
(författare)
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Genetic association of CDC2 with cerebrospinal fluid tau in Alzheimer's disease
- 2005
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Ingår i: Dementia and Geriatric Cognitive Disorders. - : S. Karger AG. - 1420-8008 .- 1421-9824. ; 20:6, s. 367-374
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Tidskriftsartikel (refereegranskat)abstract
- We have recently reported that a polymorphism in the cell division cycle <i>(CDC2) </i>gene, designated Ex6 + 7I/D, is associated with Alzheimer’s disease (AD). The <i>CDC2</i> gene is located on chromosome 10q21.1 close to the marker D10S1225 linked to AD. Active cdc2 accumulates in neurons containing neurofibrillary tangles (NFT), a process that can precede the formation of NFT. Therefore, <i>CDC2 </i>is a promising candidate susceptibility gene for AD. We investigated the possible effects of the <i>CDC2</i> polymorphism on cerebrospinal fluid (CSF) biomarkers in AD patients. <i>CDC2</i> genotypes were evaluated in relation to CSF protein levels of total tau, phospho-tau and β-amyloid<sub>(1–42)</sub> in AD patients and control individuals, and in relation to the amount of senile plaques and NFT in the frontal cortex and in the hippocampus in patients with autopsy-proven AD and controls. The <i>CDC2</i> Ex6 + 7I allele was associated with a gene dose-dependent increase of CSF total tau levels (F<sub>2, 626</sub> = 7.0, p = 0.001) and the homozygous <i>CDC2</i> Ex6 + 7II genotype was significantly more frequent among AD patients compared to controls (p = 0.006, OR = 1.57, 95% CI 1.13–2.17). Our results provide further evidence for an involvement of cdc2 in the pathogenesis of AD.
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| 6. |
- Wallin, Anders, 1950, et al.
(författare)
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Donepezil in Alzheimer's disease : What to expect after 3 years of treatment in a routine clinical setting
- 2007
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Ingår i: Dementia and Geriatric Cognitive Disorders. - Basel : S. Karger AG. - 1420-8008 .- 1421-9824. ; 23:3, s. 150-160
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Tidskriftsartikel (refereegranskat)abstract
- Background/Aims: Clinical short-term trails have shown positive effects of donepezil treatment in patients with Alzheimer's disease. The outcome of continuous long-term treatment in the routine clinical settings remains to be investigated. Methods: The Swedish Alzheimer Treatment Study (SATS) is a descriptive, prospective, longitudinal, multicentre study. Four hundred and thirty-five outpatients with the clinical diagnosis of Alzheimer's disease, received treatment with donepezil. Patients were assessed with Mini-Mental State Examination (MMSE), Alzheimer's Disease Assessment Scale-cognitive subscale (ADAS-cog), global rating (CIBIC) and Instrumental Activities of Daily Living (IADL) at baseline and every 6 months for a total period of 3 years. Results: The mean MMSE change from baseline was positive for more than 6 months and in subgroups of patients for 12 months. After 3 years of treatment the mean change from baseline in MMSE-score was 3.8 points (95% CI, 3.0-4.7) and the ADAS-cog rise was 8.2 points (95% CI, 6.4-10.1). This is better than expected in untreated historical cohorts, and better than the ADAS-cog rise calculated by the Stern equation (15.6 points, 95% CI, 14.5-16.6). After 3 years with 38% of the patients remaining, 30% of the them were unchanged or improved in the global assessment. Conclusion: Three-year donepezil treatment showed a positive global and cognitive outcome in the routine clinical setting. Copyright © 2007 S. Karger AG.
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| 7. |
- Wallin, Åsa, et al.
(författare)
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Five-year outcome of cholinergic treatment of Alzheimer's disease: Early response predicts prolonged time until nursing home placement, but does not alter life expectancy
- 2004
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Ingår i: Dementia and Geriatric Cognitive Disorders. - : S. Karger AG. - 1420-8008 .- 1421-9824. ; 18:2, s. 197-206
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Tidskriftsartikel (refereegranskat)abstract
- Fifty consecutive outpatients with Alzheimer’s disease (AD) received treatment with the cholinesterase inhibitor tacrine in an open longitudinal study. Assessments using Mini-Mental State Examination, Alzheimer’s Disease Assessment Scale – cognitive subscale, and a global rating were made at baseline and at 6, 12, 24, 36, 48 and 60 months. Three outcome groups were characterized: responders, unchanged and deteriorated. Additional outcome measures were time until nursing home placement, and mortality rate. At 6 months –75%, at 12 months –42%, at 24 months –20%, and after that 10% of the patients still on medication had improved or remained stable. The mortality rate did not differ between the outcome groups. Response to tacrine treatment at 6 or 12 months was found to predict a prolonged time until nursing home placement. No predictors for a positive treatment response could be identified at baseline.
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| 8. |
- Johansson, Annica, 1969, et al.
(författare)
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Homocysteine levels in patients with Alzheimer's disease are influenced by the glutathione s-transferase omega-1 (GSTO1) gene
- 2005
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Ingår i: Haematologica Reports. - 1824-9337. ; 2005:1(3):June
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Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- Background: A substantial body of literature confirms an association between elevated blood levels of homocysteine and cognitive dysfunction, including Alzheimer’s disease (AD). Oxidative stress is a risk factor for AD. Elevated homocysteine levels might partially reflect redox status; its remethylation to methionine is coordinated by the redox-sensitive enzyme methionine synthase. Glutathione S-transferase omega-1 (GSTO1) is protective against oxidative stress, and the polymorphism Ala140Asp modifies the age-of-onset of AD. Aim: To investigate whether the GSTO1 Ala140Asp polymorphism is related to homocysteine levels in AD patients. Methods: Plasma homocysteine levels and the GSTO1 polymorphism Ala140Asp were analysed in 244 consecutive patients with clinically diagnosed AD. Results: Homocysteine levels differed significantly between the three genotypes (p=0.002) analysis of variance, Durbin-Watson D Statistic. The levels were 11.8±3.6 µmol/L in patients with the Ala/Ala genotype (n=118), 13.5±5.0 µmol/L in the Ala/Asp group (n=105), and 14.1±6.0 µmol/L in patients with the Asp/Asp genotype (n=21). Carriers of at least one Asp allele showed significantly higher plasma homocysteine levels compared to non-carriers (p=0.002) two-sample t-test. Conclusion: The association between homocysteine levels and this GSTO1 polymorphism supports the suggestion that increased homocysteine in AD patients may be a consequence of oxidative stress.
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| 9. |
- Boström, Fredrik, et al.
(författare)
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Cerebrospinal fluid total tau is associated with shorter survival in dementia with Lewy bodies.
- 2009
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Ingår i: Dementia and geriatric cognitive disorders. - : S. Karger AG. - 1421-9824 .- 1420-8008. ; 28:4, s. 314-9
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Tidskriftsartikel (refereegranskat)abstract
- A pathology typical of dementia with Lewy bodies (DLB) has been demonstrated to increase mortality to a greater extent than the pathology of Alzheimer's disease (AD). However, mortality in DLB has also been shown to increase with concomitant AD pathology. Furthermore, in a recent publication, we showed that there is a robust and specific increase in CSF calcium and magnesium in DLB patients compared to both AD patients and controls. Thus, in order to explore the influence of CSF AD markers and trace element concentrations on mortality in DLB, we undertook a longitudinal prospective study of 47 clinically diagnosed DLB patients and 157 AD patients as well as 49 healthy volunteers. Both AD and DLB patients showed an increased mortality compared to the healthy controls (relative risk: 10 and 8, respectively; p < 0.001). Increased levels of CSF total tau were associated with increased mortality among the DLB patients (p < 0.05), but not among the AD patients or controls. Gender, age, MMSE score, Abeta42 concentration and phosphorylated tau, and CSF trace element concentrations did not influence survival in the obtained models.
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| 10. |
- Boström, Fredrik, et al.
(författare)
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CSF Mg and Ca as diagnostic markers for dementia with Lewy bodies.
- 2008
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Ingår i: Neurobiology of aging. - : Elsevier BV. - 1558-1497 .- 0197-4580. ; 30:8, s. 1265-1271
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Tidskriftsartikel (refereegranskat)abstract
- Accumulating evidence implicates a role for altered metal homeostasis in the pathogenesis of neurodegenerative disorders such as Alzheimer's disease (AD). However, few investigations have addressed this issue in dementia with Lewy bodies (DLB). The aim of the present study was to investigate metal concentrations in cerebrospinal fluid (CSF) and plasma from patients with DLB and other neurodegenerative disorders. To that end, CSF and plasma samples were collected from 29 patients with DLB, 174 patients with AD, 90 patients with AD with minor vascular components, and 51 healthy volunteers. Total concentrations of Mg, Ca, Mn, Fe, Cu, Zn, Rb, Sr, and Cs were determined using mass spectrometry. Patients with DLB had elevated Ca and Mg levels in CSF and Mg levels in plasma as compared to all other groups (p<0.001). Furthermore, a combination of CSF-Mg and CSF-Ca could distinguish DLB from AD with a sensitivity of 93% and a specificity of 85%. Cu levels in both CSF and plasma tended to be higher in DLB compared to the other groups, but these trends failed to reach significance after correction for multiple comparisons. Mn, Fe, Zn, Rb, and Sr concentration in CSF or plasma were similar in all groups. The observed elevations of CSF-Mg, CSF-Ca and CSF-Cu may contribute to or be associated with the neurodegenerative process in DLB. Furthermore, determination of CSF-Mg and CSF-Ca concentration may be a valuable tool in distinguishing DLB from AD.
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