Combined rCBF and CSF biomarkers predict progression from mild cognitive impairment to Alzheimer's disease

Hansson, Oskar; Buchhave, Peder; Zetterberg, Henrik; Blennow, Kaj; Minthon, Lennart; Warkentin, Siegbert

doi:10.1016/j.neurobiolaging.2007.06.009

Cited by 70 publications

(60 citation statements)

References 36 publications

(74 reference statements)

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“…clinics (39)(40)(41)(42)(43)(44)(45)(46)(47)(48)(49)(50)(51)(52) and eight were population studies conducted in the community (53)(54)(55)(56)(57)(58)(59)(60). Sixteen were conducted using modified (non-Mayo) criteria.…”

Section: Search Resultsmentioning

confidence: 99%

Rate of progression of mild cognitive impairment to dementia – meta‐analysis of 41 robust inception cohort studies

Mitchell

Shiri-Feshki

2009

Acta Psychiatr Scand

1,374

932

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Objective: To quantify the risk of developing dementia in those with mild cognitive impairment (MCI).Method: Meta‐analysis of inception cohort studies.Results: Forty‐one robust cohort studies were identified. To avoid heterogeneity clinical studies, population studies and clinical trials were analysed separately. Using Mayo defined MCI at baseline and adjusting for sample size, the cumulative proportion who progressed to dementia, to Alzheimer’s disease (AD) and to vascular dementia (VaD) was 39.2%, 33.6% and 6.2%, respectively in specialist settings and 21.9%, 28.9% and 5.2%, respectively in population studies. The adjusted annual conversion rate (ACR) from Mayo defined MCI to dementia, AD and VaD was 9.6%, 8.1% and 1.9%, respectively in specialist clinical settings and 4.9%, 6.8% and 1.6% in community studies. Figures from non‐Mayo defined MCI and clinical trials are also reported.Conclusion: The ACR is approximately 5–10% and most people with MCI will not progress to dementia even after 10 years of follow‐up.

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Section: Search Resultsmentioning

confidence: 99%

Rate of progression of mild cognitive impairment to dementia – meta‐analysis of 41 robust inception cohort studies

Mitchell

Shiri-Feshki

2009

Acta Psychiatr Scand

1,374

932

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“…Even though the cognitively stable MCI patients were followed for almost an average of 5 years, it is still unclear if all MCI cases with abnormal CSF biomarkers will develop AD in the future. However, the positive predictive value of CSF biomarkers can be increased if they are combined with other diagnostic methods, such as measurements of regional cerebral blood flow [37]. Interestingly, the negative predictive value of tau and Aβ 42 was found to be very high (94%) in the MCI cohort, indicating that MCI patients with normal CSF Aβ 42 or tau levels do not run an increased risk of developing AD compared to the normal population.…”

Section: Discussionmentioning

confidence: 99%

Evaluation of CSF Biomarkers as Predictors of Alzheimer's Disease: A Clinical Follow-Up Study of 4.7 Years

Hertze

Minthon

Zetterberg

et al. 2010

JAD

Self Cite

115

111

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Abstract. In this study, we determined the diagnostic accuracy of cerebrospinal fluid (CSF) biomarkers to predict development of Alzheimer's disease (AD) within five years in patients with mild cognitive impairment (MCI). To do so, the levels of tau, phosphorylated tau, Aβ42, Aβ40, Aβ38, sAβPPα, and sAβPPβ were analyzed in 327 CSF samples obtained at baseline from patients with AD (n = 94), MCI (n = 166), depressive disorder (n = 29), and cognitively healthy controls (n = 38). In the cohort with MCI at baseline, 33% subsequently developed AD and 16% developed other types of dementia; however, 51% were still cognitively stable after a follow-up of 4.7 years (range 3.0-7.2). Optimal cut-offs for each biomarker or combinations of biomarkers were defined in the AD, control, and depressive disorder groups. Several combinations resulted in sensitivity and specificity levels > 85% for differentiation of AD from controls and depressive disorder. Using the previously established cut-offs, a combination of Aβ42 and tau could predict future development of AD in MCI patients with a sensitivity of 88%, specificity 82%, positive predictive value 71%, and negative predictive value 94%. MCI patients with both low Aβ42 and high tau levels had a substantially increased risk of developing AD (OR 20; 95% CI 6-58), even after adjustment for confounding factors. Ultimately, CSF biomarkers can stratify MCI patients into those with very low or high risk for future development of AD. However, the specificities and positive predictive values are still too low to be able to diagnose AD before the patients fulfill the clinical criteria.

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“…16,18,38 Additionally, the combination of these diagnostic strategies seems to increase the predictive power to identify AD patients at the prodromal stages of the disease. 39 According to a recent task-force that proposed the revised NINCDS-ADRDA diagnostic criteria for research, 40 the presence of AD-compatible pathological findings, as indicated by one or more of these biomarkers, endorses the diagnosis of incipient (pre-dementia) AD given the clinical characterization of episodic memory impairment.…”

Section: Discussionmentioning

confidence: 99%

Clinical and biological predictors of Alzheimer's disease in patients with amnestic mild cognitive impairment

Forlenza

Diniz

Talib

et al. 2010

Rev. Bras. Psiquiatr.

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Preditores clínicos e biológicos da evolução para doença de AbstractObjective: To identify predictors of the progression from pre-dementia stages of cognitive impairment in Alzheimer's disease is relevant to clinical management and to substantiate the decision of prescribing antidementia drugs. Method: Longitudinal study of a cohort of elderly adults with amnestic mild cognitive impairment and healthy controls, carried out to estimate the risk and characterize predictors of the progression to Alzheimer's disease. Results: Patients with amnestic mild cognitive impairment had a higher risk to develop Alzheimer's disease during followup (odds ratio = 4.5, CI 95% [1.3-13.6], p = 0.010). At baseline, older age, lower scores on memory tests and presence of the APOE*4 allele predicted the progression from amnestic mild cognitive impairment to Alzheimer's disease. In a sub sample of amnestic mild cognitive impairment patients, those who progressed to Alzheimer's disease had lower cerebrospinal fluid concentrations of amyloid-beta peptide (Aβ 42 , p = 0.020) and higher concentrations of total TAU (p = 0.030) and phosphorylated TAU (p = 0.010), as compared to non-converters. Discussion: This is the first Brazilian study to report cerebrospinal fluid biomarkers in the prediction of the conversion from MCI to Alzheimer's disease. Our data are in accordance with those reported in other settings. The measurement of cerebrospinal fluid total-TAU, phospho-TAU and Aβ 42 may help identify patients with mild cognitive impairment at higher risk for developing Alzheimer's disease. [1,3-13,6], p = 0,012 Descriptors

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Combined rCBF and CSF biomarkers predict progression from mild cognitive impairment to Alzheimer's disease

Cited by 70 publications

References 36 publications

Rate of progression of mild cognitive impairment to dementia – meta‐analysis of 41 robust inception cohort studies

Rate of progression of mild cognitive impairment to dementia – meta‐analysis of 41 robust inception cohort studies

Evaluation of CSF Biomarkers as Predictors of Alzheimer's Disease: A Clinical Follow-Up Study of 4.7 Years

Clinical and biological predictors of Alzheimer's disease in patients with amnestic mild cognitive impairment

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