Dataset Information

Injury markers predict time to dementia in subjects with MCI and amyloid pathology.

ABSTRACT:

Objectives

Alzheimer disease (AD) can now be diagnosed in subjects with mild cognitive impairment (MCI) using biomarkers. However, little is known about the rate of decline in those subjects. In this cohort study, we aimed to assess the conversion rate to dementia and identify prognostic markers in subjects with MCI and evidence of amyloid pathology.

Methods

We pooled subjects from the VU University Medical Center Alzheimer Center and the Development of Screening Guidelines and Criteria for Predementia Alzheimer's Disease (DESCRIPA) study. We included subjects with MCI, an abnormal level of ?-amyloid(1-42) (A?(1-42)) in the CSF, and at least one diagnostic follow-up visit. We assessed the effect of APOE genotype, CSF total tau (t-tau) and tau phosphorylated at threonine 181 (p-tau) and hippocampal volume on time to AD-type dementia using Cox proportional hazards models and on decline on the Mini-Mental State Examination (MMSE) using linear mixed models.

Results

We included 110 subjects with MCI with abnormal CSF A?(1-42) and a mean MMSE score of 26.3 ± 2.8. During a mean follow-up of 2.2 ± 1.0 (range 0.4-5.0) years, 63 subjects (57%) progressed to AD-type dementia. Abnormal CSF t-tau (hazard ratio [HR] 2.3, 95% confidence interval [CI] 1.1-4.6, p = 0.03) and CSF p-tau (HR 3.5, 95% CI 1.3-9.2, p = 0.01) concentration and hippocampal atrophy (HR 2.5, 95% CI 1.1-5.6, p = 0.02) predicted time to dementia. For subjects with both abnormal t-tau concentration and hippocampal atrophy, HR was 7.3 (95% CI 1.0-55.9, p = 0.06). Furthermore, abnormal CSF t-tau and p-tau concentrations and hippocampal atrophy predicted decline in MMSE score.

Conclusions

In subjects with MCI and evidence of amyloid pathology, the injury markers CSF t-tau and p-tau and hippocampal atrophy can predict further cognitive decline.

SUBMITTER: van Rossum IA

PROVIDER: S-EPMC3475623 | biostudies-literature | 2012 Oct

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Injury markers predict time to dementia in subjects with MCI and amyloid pathology.

van Rossum Ineke A IA Vos Stephanie J B SJ Burns Leah L Knol Dirk L DL Scheltens Philip P Soininen Hilkka H Wahlund Lars-Olof LO Hampel Harald H Tsolaki Magda M Minthon Lennart L L'italien Gilbert G van der Flier Wiesje M WM Teunissen Charlotte E CE Blennow Kaj K Barkhof Frederik F Rueckert Daniel D Wolz Robin R Verhey Frans F Visser Pieter Jelle PJ

Neurology 20120926 17

<h4>Objectives</h4>Alzheimer disease (AD) can now be diagnosed in subjects with mild cognitive impairment (MCI) using biomarkers. However, little is known about the rate of decline in those subjects. In this cohort study, we aimed to assess the conversion rate to dementia and identify prognostic markers in subjects with MCI and evidence of amyloid pathology.<h4>Methods</h4>We pooled subjects from the VU University Medical Center Alzheimer Center and the Development of Screening Guidelines and Cr ...[more]

PMID: 23019259

Similar Datasets

Project description:BackgroundAmyloid pathology in subjects with mild cognitive impairment (MCI) is an important risk factor for progression to dementia due to Alzheimer's disease. Predicting the onset of dementia is challenging even in the presence of amyloid, as time to progression varies considerably among patients and depends on the onset of neurodegeneration. Survival analysis can account for variability in time to event, but has not often been applied to MRI measurements beyond singular predefined brain regions such as the hippocampus. Here we used a voxel-wise survival analysis to identify in an unbiased fashion brain regions where decreased gray matter volume is associated with time to dementia, and assessed the effects of amyloid on these associations.MethodsWe included 276 subjects with MCI (mean age 67?±?8, 41% female, mean Mini-Mental State Examination 26.6?±?2.4), baseline 3D T1-weighted structural MRI, baseline cerebrospinal fluid (CSF) biomarkers, and prospective clinical follow-up. We fitted for each voxel a proportional Cox hazards regression model to study whether decreased gray matter volume predicted progression to dementia in the total sample, and stratified for baseline amyloid status.ResultsDementia at follow-up occurred in 122 (44%) subjects over an average follow-up period of 2.5?±?1.5 years. Baseline amyloid positivity was associated with progression to dementia (hazard ratio 2.4, p?<?0.001). Within amyloid-positive subjects, decreased gray matter volume in the hippocampal, temporal, parietal, and frontal regions was associated with more rapid progression to dementia (median (interquartile range) hazard ratio across significant voxels 1.35 (1.32-1.40)). Repeating the analysis in amyloid-negative subjects revealed similar patterns (median (interquartile range) hazard ratio 1.76 (1.66-1.91)).ConclusionsIn subjects with MCI, both abnormal amyloid CSF and decreased gray matter volume were associated with future progression to dementia. The spatial pattern of decreased gray matter volume associated with progression to dementia was consistent for amyloid-positive and amyloid-negative subjects.

Project description:BackgroundMeasurement of beta-amyloid (Aβ) and phosphorylated tau (p-tau) levels offers the potential for early detection of neurocognitive impairment. Still, the probability of developing a clinical syndrome in the presence of these protein changes (A+ and T+) remains unclear. By performing a systematic review and meta-analysis, we investigated the risk of mild cognitive impairment (MCI) or dementia in the non-demented population with A+ and A- alone and in combination with T+ and T- as confirmed by PET or cerebrospinal fluid examination.MethodsA systematic search of prospective and retrospective studies investigating the association of Aβ and p-tau with cognitive decline was performed in three databases (MEDLINE via PubMed, EMBASE, and CENTRAL) on January 9, 2024. The risk of bias was assessed using the Cochrane QUIPS tool. Odds ratios (OR) and Hazard Ratios (HR) were pooled using a random-effects model. The effect of neurodegeneration was not studied due to its non-specific nature.ResultsA total of 18,162 records were found, and at the end of the selection process, data from 36 cohorts were pooled (n= 7,793). Compared to the unexposed group, the odds ratio (OR) for conversion to dementia in A+ MCI patients was 5.18 [95% CI 3.93; 6.81]. In A+ CU subjects, the OR for conversion to MCI or dementia was 5.79 [95% CI 2.88; 11.64]. Cerebrospinal fluid Aβ42 or Aβ42/40 analysis and amyloid PET imaging showed consistent results. The OR for conversion in A+T+ MCI subjects (11.60 [95% CI 7.96; 16.91]) was significantly higher than in A+T- subjects (2.73 [95% CI 1.65; 4.52]). The OR for A-T+ MCI subjects was non-significant (1.47 [95% CI 0.55; 3.92]). CU subjects with A+T+ status had a significantly higher OR for conversion (13.46 [95% CI 3.69; 49.11]) than A+T- subjects (2.04 [95% CI 0.70; 5.97]). Meta-regression showed that the ORs for Aβ exposure decreased with age in MCI. (beta = -0.04 [95% CI -0.03 to -0.083]).ConclusionsIdentifying Aβ-positive individuals, irrespective of the measurement technique employed (CSF or PET), enables the detection of the most at-risk population before disease onset, or at least at a mild stage. The inclusion of tau status in addition to Aβ, especially in A+T+ cases, further refines the risk assessment. Notably, the higher odds ratio associated with Aβ decreases with age.Trial registrationThe study was registered in PROSPERO (ID: CRD42021288100).

Dataset Information

Injury markers predict time to dementia in subjects with MCI and amyloid pathology.

Objectives

Methods

Results

Conclusions

Publications

Injury markers predict time to dementia in subjects with MCI and amyloid pathology.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets