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- Buerger, Katharina, et al.
(author)
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Prediction of Alzheimer's disease using midregional proadrenomedullin and midregional proatrial natriuretic peptide: a retrospective analysis of 134 patients with mild cognitive impairment.
- 2011
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In: The Journal of clinical psychiatry. - 1555-2101 .- 0160-6689. ; 72:4, s. 556-63
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Journal article (peer-reviewed)abstract
- OBJECTIVE: Development of biomarkers for early detection of Alzheimer's disease (AD) is a major clinical research goal. On the basis of the hypothesis that cardiovascular risk factors contribute to the pathogenesis of AD, we investigated whether the cardiovascular risk markers midregional proadrenomedullin (MR-proADM) and midregional proatrial natriuretic peptide (MR-proANP) predict a major clinical milestone, ie, conversion from predementia mild cognitive impairment (MCI) to manifest AD. METHOD: A group of 134 MCI patients, among 137 originally prospectively recruited at the memory disorder clinic at Malmö University Hospital, Malmö, Sweden, between July 1998 and June 2001, was clinically followed for 4-6 years. We determined whether plasma concentrations of MR-proADM and MR-proANP at baseline predicted time to conversion from MCI to clinically diagnosed AD (DSM-III-R). MCI was diagnosed according to Petersen criteria. RESULTS: During follow-up, 41.8% of MCI patients remained cognitively stable, 42.5% converted to possible and probable AD, and 15.7% converted to other forms of dementia (MCI-other). MCI converters and MCI-other patients showed increased concentrations of MR-proANP and MR-proADM compared to the stable MCI patients (P = .0001). At a cutoff of 87 pmol/L, MR-proANP yielded a sensitivity of 73.7% and a specificity of 64.3% for predicting conversion to AD. The survival analysis showed that higher values of MR-proANP and MR-proADM were associated with progression to AD. In a multivariate Cox regression model including known risk factors, MR-proANP and MR-proADM remained independent risk factors for conversion to AD for patients below the age of 72 years. CONCLUSIONS: Our study shows that plasma concentrations of MR-proANP and MR-proADM have predictive value in the progression from predementia MCI to clinical AD. Sensitivity was particularly high, which may recommend this test for first-stage screening in patients at risk for AD.
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| 2. |
- Buerger, Katharina, et al.
(author)
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Validation of Alzheimer's disease CSF and plasma biological markers: the multicentre reliability study of the pilot European Alzheimer's Disease Neuroimaging Initiative (E-ADNI).
- 2009
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In: Experimental gerontology. - : Elsevier BV. - 1873-6815 .- 0531-5565. ; 44:9, s. 579-85
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Journal article (peer-reviewed)abstract
- BACKGROUND: Alzheimer's Disease Neuroimaging Initiatives ("ADNI") aim to validate neuroimaging and biochemical markers of Alzheimer's disease (AD). Data of the pilot European-ADNI (E-ADNI) biological marker programme of cerebrospinal fluid (CSF) and plasma candidate biomarkers are reported. METHODS: Six academic EADC centres recruited 49 subjects (healthy controls, subjects with mild cognitive impairment (MCI) and AD). We measured CSF beta-amyloid 42 (CSF Abeta42), total tau-protein (t-tau), phosphorylated tau-proteins (P-tau181, P-tau231), plasma beta-amyloid 40 and 42 (Abeta40/Abeta42). Immediate fresh shipment was compared to freezing and later shipment on dry ice. RESULTS: CSF T-tau (fresh samples) was increased in AD versus controls (p=0.049), CSF Abeta42 (frozen samples) was decreased in MCI and AD (p=0.02), as well as plasma Abeta40 (fresh and frozen samples) in AD (p=0.049 and p=0.016). Pooled values of neurochemical parameters and ratios thereof were different between centres (p<0.005). Analysis of frozen samples yielded higher diagnostic accuracy than immediate fresh shipment with 100% (fresh: 100%) correctly classified in control subjects, 100% (78%) in MCI, 91% (91%) in AD. CONCLUSION: The use of frozen rather than fresh samples renders higher diagnostic accuracy within a multicentre context. We confirmed the feasibility of a multicentre AD biomarker programme for future clinical trials.
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