Predicting MCI outcome with clinically available MRI and CSF biomarkers

Department of Radiology, University of California, San Diego, La Jolla, CA 92093-0841, USA.
Neurology (Impact Factor: 8.29). 10/2011; 77(17):1619-28. DOI: 10.1212/WNL.0b013e3182343314
Source: PubMed


To determine the ability of clinically available volumetric MRI (vMRI) and CSF biomarkers, alone or in combination with a quantitative learning measure, to predict conversion to Alzheimer disease (AD) in patients with mild cognitive impairment (MCI).
We stratified 192 MCI participants into positive and negative risk groups on the basis of 1) degree of learning impairment on the Rey Auditory Verbal Learning Test; 2) medial temporal atrophy, quantified from Food and Drug Administration-approved software for automated vMRI analysis; and 3) CSF biomarker levels(.) We also stratified participants based on combinations of risk factors. We computed Cox proportional hazards models, controlling for age, to assess 3-year risk of converting to AD as a function of risk group and used Kaplan-Meier analyses to determine median survival times.
When risk factors were examined separately, individuals testing positive showed significantly higher risk of converting to AD than individuals testing negative (hazard ratios [HR] 1.8-4.1). The joint presence of any 2 risk factors substantially increased risk, with the combination of greater learning impairment and increased atrophy associated with highest risk (HR 29.0): 85% of patients with both risk factors converted to AD within 3 years, vs 5% of those with neither. The presence of medial temporal atrophy was associated with shortest median dementia-free survival (15 months).
Incorporating quantitative assessment of learning ability along with vMRI or CSF biomarkers in the clinical workup of MCI can provide critical information on risk of imminent conversion to AD.

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Available from: David Heister, Jan 09, 2014
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    • "Indeed, the notion of " pure " AD pathology is increasingly thought to be far more rare than multiple underlying neuropathologies (e.g., AD, cerebrovascular disease, Lewy bodies, hippocampal sclerosis, TDP-43) [40] [41] [42] for the vast majority of late-onset AD. Thus, a combination of biomarkers and sensitive neuropsychological tests that detect these various underlying pathologies is an improvement on any individual biomarker and can substantially improve prediction of dementia risk [17]. A strength of the present study was the use of individual test scores and actuarial neuropsychological criteria to operationalize subtle cognitive decline within the same conceptual framework we have previously used to define MCI [27]. "
    Journal of Alzheimer's disease: JAD 07/2015; 47(1):231-242. DOI:10.3233/JAD-150128 · 4.15 Impact Factor
    • "The conversion rate is usually believed to be 10%–25% per year, and a higher conversion rate may be observed within the first two to three years [7]. Many recent studies have tried to identify useful biomarkers, first for the diagnosis of the underlying etiology to promote tailored therapeutic management and potential neuroprotective strategies, and, second for the determination of the likelihood and timing of cognitive and functional progression to dementia and its specific type [3] [8]. "
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    ABSTRACT: Polysomnographic (PSG) studies in mild cognitive impairment (MCI) are not conclusive and are limited only to conventional sleep parameters. The aim of our study was to evaluate sleep architecture and cyclic alternating pattern (CAP) parameters in subjects with MCI, and to assess their eventual correlation with cognition. Eleven subjects with MCI (mean age 68.5 ± 7.0 years), 11 patients with mild probable Alzheimer's disease (AD; mean age 72.7 ± 5.9 years), referred to the Outpatient Cognitive Disorders Clinic, and 11 cognitively intact healthy elderly individuals (mean age 69.2 ± 12.6 years) underwent ambulatory PSG for the evaluation of nocturnal sleep architecture and CAP parameters. Rapid eye movement sleep, CAP rate, and CAP slow components (A1 index) were decreased in MCI subjects and to a greater extent in AD patients, compared to cognitively intact controls. AD showed also decreased slow wave sleep (SWS) relative to healthy elderly individuals. MCI nappers showed decreased nocturnal SWS and A1 subtypes compared to non-nappers. Several correlations between sleep variables and neuropsychological tests were found. MCI and AD subjects showed a decreased sleep instability correlated with their cognitive decline. Such a decrease may be considered as a potential biomarker of underlying neurodegeneration. Copyright © 2015 Elsevier B.V. All rights reserved.
    Sleep Medicine 06/2015; 16(9). DOI:10.1016/j.sleep.2015.04.027 · 3.15 Impact Factor
    • "In the early stages of AD, neuropathologic changes are already present in medial temporal regions (hippocampal formations, parahippocampal gyrus, and entorhinal cortex), areas which are critical for long-term episodic memory (Blennow, de Leon, & Zetterberg, 2006; Morris et al., 2001; Sarazin et al., 2010). Consequently, this early involvement of medial temporal structures leads to a deficit in episodic memory, rendering it a reliable neuropsychological marker of AD (Heister et al., 2011; Richard, Schmand, Eikelenboom, Van Gool, & The Alzheimer's Disease Neuroimaging Initiative 2013). Along with the baseline diagnostic criteria, severity of the memory deficit is also a dominant predictor of progression to dementia (Dubois et al., 2007; Fleisher et al., 2007; Geerlings, Jonker, Bouter, Ad er, & Schmand, 1999; Morris et al., 2001). "
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    ABSTRACT: Amnestic mild cognitive impairment (aMCI) patients carry a greater risk of conversion to Alzheimer's disease (AD). Therefore, the International Working Group (IWG) on AD aims to consider some cases of aMCI as symptomatic prodromal AD. The core diagnostic marker of AD is a significant and progressive memory deficit, and the Free and Cued Selective Reminding Test (FCSRT) was recommended by the IWG to test memory in cases of possible prodromal AD. This study aims to investigate whether the performance on the FCSRT would enhance the ability to predict conversion to AD in an aMCI group. A longitudinal study was conducted on 88 aMCI patients, and neuropsychological tests were analysed on the relative risk of conversion to AD. During follow-up (23.82 months), 33% of the aMCI population converted to AD. An impaired FCSRT TR was significantly associated with the risk of conversion to dementia, with a mean time to conversion of 25 months. The FCSRT demonstrates utility for detecting AD at its prodromal stage, thus supporting its use as a valid clinical marker. © 2015 The British Psychological Society.
    Journal of Neuropsychology 06/2015; DOI:10.1111/jnp.12075 · 2.49 Impact Factor
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