Subtypes based on cerebrospinal fluid and magnetic resonance imaging markers in normal elderly predict cognitive decline

Abstract Cerebrospinal fluid (CSF) and structural magnetic resonance imaging (MRI) show patterns of change in Alzheimer's disease (AD) that precede dementia. The Alzheimer's Disease Neuroimaging Initiative (ADNI) studied normal controls (NC), subjects with mild cognitive impairment (MCI),...

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Bibliographic Details
Published in:Neurobiology of aging 2010-08, Vol.31 (8), p.1419-1428
Main Authors: Nettiksimmons, J, Harvey, D, Brewer, J, Carmichael, O, DeCarli, C, Jack, C.R, Petersen, R, Shaw, L.M, Trojanowski, J.Q, Weiner, M.W, Beckett, L
Format: Article
Language:English
Subjects:
Aged
Aged, 80 and over
Alzheimer Disease - cerebrospinal fluid
Alzheimer Disease - classification
Alzheimer Disease - pathology
Alzheimer's disease
Amyloid beta-protein
Biomarkers - cerebrospinal fluid
Cerebrospinal fluid
Clustering
Cognition
Cognition Disorders - cerebrospinal fluid
Cognition Disorders - classification
Cognition Disorders - pathology
Cross-Sectional Studies
Dementia
Early diagnosis
Female
Follow-Up Studies
Hippocampal volume
Humans
Internal Medicine
Longitudinal Studies
Magnetic Resonance Imaging - methods
Male
Neurology
Normal controls
Predictive Value of Tests
Prospective Studies
Structural magnetic resonance imaging
Tau protein
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Summary:Abstract Cerebrospinal fluid (CSF) and structural magnetic resonance imaging (MRI) show patterns of change in Alzheimer's disease (AD) that precede dementia. The Alzheimer's Disease Neuroimaging Initiative (ADNI) studied normal controls (NC), subjects with mild cognitive impairment (MCI), and subjects with AD to identify patterns of biomarkers to aid in early diagnosis and effective treatment of AD. Two hundred twenty-two NC underwent baseline MRI and clinical examination at baseline and at least one follow-up. One hundred twelve also provided CSF at baseline. Unsupervised clustering based on initial CSF and MRI measures was used to identify clusters of participants with similar profiles. Repeated measures regression modeling assessed the relationship of individual measures, and of cluster membership, to cognitive change over 3 years. Most individuals showed little cognitive change. Individual biomarkers had limited predictive value for cognitive decline, but membership in the cluster with the most extreme profile was associated with more rapid decline in ADAS-cog. Subtypes among NC based on multiple biomarkers may represent the earliest stages of subclinical cognitive decline and AD.
ISSN:0197-4580
1558-1497
DOI:10.1016/j.neurobiolaging.2010.04.025