Article

Structural Brain Alterations before Mild Cognitive Impairment in ADNI: Validation of Volume Loss in a Predefined Antero-Temporal Region

Department of Neurology, Chandler Medical Center, University of Kentucky, Lexington, KY, USA Department of Anatomy and Neurobiology, Chandler Medical Center, University of Kentucky, Lexington, KY, USA Sanders-Brown Center on Aging Alzheimer's Disease Center, University of Kentucky, Lexington, KY, USA Magnetic Resonance Imaging and Spectroscopy Center, University of Kentucky, Lexington, KY, USA.
Journal of Alzheimer's disease: JAD (Impact Factor: 3.61). 03/2012; 31:S49-58. DOI: 10.3233/JAD-2012-120157
Source: PubMed

ABSTRACT Volume losses in the medial temporal lobe, posterior cingulated, and orbitofrontal region have been observed in Alzheimer's disease (AD). Smaller reductions in similar regions have also been reported in amnestic mild cognitive impairment (aMCI), a canonical precursor to AD. We previously demonstrated that volume loss in bilateral anteromedial temporal lobe is present at baseline in longitudinally followed normal subjects who later developed MCI or AD. In this study we compared grey matter volumes within this predefined anteromedial temporal region (AMTR) at baseline between: 1) normal subjects enrolled in the Alzheimer's Disease Neuroimaging Initiative (ADNI) who subsequently developed cognitive complaints as reflected in a CDR memory box score of 0.5; and 2) normal subjects who remained normal over a median of 48 months of follow-up (CDR sum of boxes 0). We found significantly decreased volume within AMTR in the ADNI memory complainers. To relate AMTR results to those from conventional anatomy, we demonstrate that volumes extracted with the ICBM amygdala region had the best correspondence with AMTR volumes. In contrast, regions that have demonstrated volume loss in frank MCI and AD in ADNI, e.g., the posterior cingulate, did not show volume loss. These findings provide independent confirmation that volume changes preceding MCI occur in AMTR, a region of overlap between amygdala and anterior hippocampus.

0 Bookmarks
 · 
73 Views
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Background and purpose: Despite a strong correlation to severity of AD pathology, the measurement of medial temporal lobe atrophy (MTA) is not being widely used in daily clinical practice as a criterion in the diagnosis of prodromal and probable AD. This is mainly because the methods available to date are sophisticated and difficult to implement for routine use in most hospitals-volumetric methods-or lack objectivity-visual rating scales. In this pilot study we aim to describe a new, simple and objective method for measuring the rate of MTA in relation to the global atrophy using clinically available neuroimaging and describe the rationale behind this method. Description: This method consists of calculating a ratio with the area of 3 regions traced manually on one single coronal MRI slide at the level of the interpeduncular fossa: (1) the medial temporal lobe (MTL) region (A); (2) the parenchima within the medial temporal region, that includes the hippocampus and the parahippocampal gyrus-the fimbria taenia and plexus choroideus are excluded-(B); and (3) the body of the ipsilateral lateral ventricle (C). Therefrom we can compute the ratio "Medial Temporal Atrophy index" at both sides as follows: MTAi = (A - B)× 10/C. Conclusions: The MTAi is a simple 2D-method for measuring the relative extent of atrophy in the MTL in relation to the global brain atrophy. This method can be useful for a more accurate diagnosis of AD in routine clinical practice. Further studies are needed to assess the usefulness of MTAi in the diagnosis of early AD, in tracking the progression of AD and in the differential diagnosis of AD with other dementias.
    Frontiers in Aging Neuroscience 03/2014; 6:23. DOI:10.3389/fnagi.2014.00023 · 2.84 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: In recent years, numerous laboratories and consortia have used neuroimaging to evaluate the risk for and progression of Alzheimer's disease (AD). The Alzheimer's Disease Neuroimaging Initiative is a longitudinal, multicenter study that is evaluating a range of biomarkers for use in diagnosis of AD, prediction of patient outcomes, and clinical trials. These biomarkers include brain metrics derived from magnetic resonance imaging (MRI) and positron emission tomography scans as well as metrics derived from blood and cerebrospinal fluid. We focus on Alzheimer's Disease Neuroimaging Initiative studies published between 2011 and March 2013 for which structural MRI was a major outcome measure. Our main goal was to review key articles offering insights into progression of AD and the relationships of structural MRI measures to cognition and to other biomarkers in AD. In Supplement 1, we also discuss genetic and environmental risk factors for AD and exciting new analysis tools for the efficient evaluation of large-scale structural MRI data sets such as the Alzheimer's Disease Neuroimaging Initiative data.
    Biological psychiatry 11/2013; DOI:10.1016/j.biopsych.2013.11.020 · 8.93 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: A wide range of vascular burden factors has been identified to impact vascular function and structure as indicated by carotid intima-media thickness (IMT). On the basis of their impact on IMT, vascular factors may be selected and clustered in a vascular burden index (VBI). Since many vascular factors increase the risk of Alzheimer's disease (AD), a multifactorial neurodegenerative VBI may be related to early pathological processes in AD and cognitive decline in its preclinical stages. We investigated an elderly cohort at risk for neurodegeneration (TREND study, n = 1102) for the multifactorial influence of vascular burden factors on IMT measured by ultrasound. To create a VBI for this cohort, vascular factors and their definitions (considering medical history, medication, and/or blood marker data) were selected based on their statistical effects on IMT in multiple regressions including age and sex. The impact of the VBI on cognitive performance was assessed using the Trail-Making Test (TMT) and the consortium to establish a registry for Alzheimer's disease (CERAD) neuropsychological battery. IMT was significantly predicted by age (standardized β = 0.26), sex (0.09; males > females) and the factors included in the VBI: obesity (0.18), hypertension (0.14), smoking (0.08), diabetes (0.07), and atherosclerosis (0.05), whereas other cardiovascular diseases or hypercholesterolemia were not significant. Individuals with 2 or more VBI factors compared to individuals without had an odds ratio of 3.17 regarding overly increased IMT ( ≥ 1.0 mm). The VBI showed an impact on executive control [log(TMT B-A), p = 0.047] and a trend toward decreased global cognitive function (CERAD total score, p = 0.057) independent of age, sex, and education. A VBI established on the basis of IMT may help to identify individuals with overly increased vascular burden linked to decreased cognitive function indicating neurodegenerative processes. The longitudinal study of this risk cohort will reveal the value of the VBI as prodromal marker for cognitive decline and AD.
    Frontiers in Aging Neuroscience 07/2014; 6:161. DOI:10.3389/fnagi.2014.00161 · 2.84 Impact Factor

Full-text (2 Sources)

Download
20 Downloads
Available from
May 28, 2014