Injury markers predict time to dementia in subjects with MCI and amyloid pathology
Open accessAbstract
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 β-amyloid(1-42) (Aβ(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 Aβ(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.
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CSF T-tau likely indicates the intensity of neuronal injury at a given point in time.
“CSF T-tau likely indicates the intensity of neuronal injury at a given point in time [108,114,157,158].”
From NIA‐AA Research Framework: Toward a biological definition of Alzheimer's disease (2018) · cites this paper as [157]
The introduction describes CSF tau as a marker of neuronal injury that may reflect more advanced pathology, and the Discussion links high baseline t-tau to more rapid cognitive decline in subjects with MCI and amyloid pathology. Neither passage says that CSF t-tau indicates the intensity of neuronal injury at a given point in time. (LLM, conf=0.82)
Experimental — accuracy not yet measuredPatients with prodromal Alzheimer's disease and elevated cerebrospinal fluid total tau tend to convert to Alzheimer's disease dementia sooner.
“The patients with prodromal AD and increased CSF t-tau levels tended to convert sooner to AD dementia [19, 20].”
From Duration of preclinical, prodromal, and dementia stages of Alzheimer's disease in relation to age, sex, and <i>APOE</i> genotype (2019) · cites this paper as [19]
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References 31 · Cited by 136
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- Authors
- van Rossum, I. A., Vos, S. J. B., Burns, L., Knol, D. L., Scheltens, P., Soininen, H., Wahlund, L.-O., Hampel, H., Tsolaki, M., Minthon, L., L'Italien, G., van der Flier, W. M., Teunissen, C. E., Blennow, K., Barkhof, F., Rueckert, D., Wolz, R., Verhey, F., & Visser, P. J.
- Affiliations
- From the Departments of Neurology (I.A.v.R., P.S., W.M.v.d.F., P.J.V.), Epidemiology and Biostatistics (D.L.K., W.M.v.d.F.), and Radiology (F.B.), Alzheimer Center, VU University Medical Center, Amsterdam, the Netherlands; Department of Psychiatry and Neuropsychology (S.J.B.V., F.V., P.J.V.), School for Mental Health and Neuroscience, Alzheimer Center Limburg, Maastricht, the Netherlands; Global Health Economics and Outcomes Research (L.B., G.L.), Bristol-Myers Squibb, Wallingford, CT; Department of...
- Karolinska University Hospital (SE)
- ORCID
- Venue
- Neurology
- Published
- 2012-10-23
- Volume
- 79
- Issue
- 17
- Pages
- 1809-1816
- ISSN
- 0028-3878 (ISSN-L)
- 1526-632X
- PMC
- PMC3475623
- OpenAlex
- W2096742242
- Cited by
- 136
- References
- 31
- Citations by year
- 2025: 2 · 2024: 5 · 2023: 5 · 2022: 9 · 2021: 10 · 2020: 10 · 2019: 14 · 2018: 11 · 2017: 11 · 2016: 13 · 2015: 14 · 2014: 10 · 2013: 20 · 2012: 1
- FWCI
- 10.25
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Neurology (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Research Publications (Maastricht University) (publishedVersion, other-oa)
- Pure Amsterdam UMC (publishedVersion, other-oa)
- Amsterdam UMC (VU Amsterdam) - Institutional Repository (publishedVersion, other-oa)
- VU Research Portal (acceptedVersion, other-oa)
- Digital Academic REpository of VU University Amsterdam (Vrije Universiteit Amsterdam) (submittedVersion)
- UCL Discovery (University College London) (submittedVersion)
- Lund University Publications (Lund University) (submittedVersion)
- Research Publications (Maastricht University) (submittedVersion)
- Data Archiving and Networked Services (DANS) (submittedVersion, other-oa)
- Topics
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Cancer-related cognitive impairment studies
- Keywords
- mild cognitive impairment, Alzheimer's disease, conversion to dementia, amyloid pathology, total tau, phosphorylated tau, hippocampal atrophy, APOE genotype, prognostic factors, cognitive decline, Mini-Mental State Examination, cerebrospinal fluid biomarkers, hippocampal volume, tau phosphorylation, APOE ε4 carriers
- MeSH terms
- Aged, Alzheimer Disease, Apolipoproteins E, Female, Hippocampus, Humans, Male, Neuropsychological Tests, Predictive Value of Tests, Psychiatric Status Rating Scales, Time Factors, Cohort Studies, Multicenter Studies as Topic, Biomarkers, Amyloid beta-Peptides, tau Proteins, Disease Progression, Cognitive Dysfunction
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