Alzheimer's Disease Neuroimaging Initiative

About: This article is published in NeuroImage.The article was published on 2008-01-01 and is currently open access. It has received 1276 citations till now. The article focuses on the topics: Alzheimer's Disease Neuroimaging Initiative.

Figures

Figure 2. Seven regions of interest generated from the regions demonstrating the greatest magnitude of Alzheimer disease (AD)–specific thinning in the exploratory analysis of the Open Access Series of Imaging Studies data, shown on an inflated surface representation, with dark gray regions representing sulci and light gray regions representing gyri. For illustration purposes, only the right hemisphere is presented. A, Statistical significance values of the difference between healthy control individuals and patients with incipient AD. This exploratory analysis was not corrected for multiple comparisons; therefore, this map is not intended to be an accurate reflection of early AD-specific thinning. However, the overall pattern is in general agreement with reported results. B, The regions of interest.

Figure 4. Best second-order polynomial fit for Alzheimer disease (AD)–specific cortical thinning rates and hippocampal volume loss rates as functions of Mini-Mental State Examination (MMSE) score. Shown are scatterplots of rates of AD-specific hippocampal volume loss (A) and cortical thinning (B) vs MMSE score. Each dot represents an individual with an AD-like cerebrospinal fluid molecular profile. The curves represent best-fit quadratic functions. The curve for the hippocampus is approximately linear (but slightly convex due to a nonsignificant positive coefficient in the quadratic term). The curve for AD-specific cortical thinning is concave, with an optimum at approximately the MMSE score of 21. To examine the sensitivity of the fit to outliers, we reanalyzed these data without the 2 individuals with extreme data, namely, those with MMSE scores of 16 and 15, respectively. All results remained approximately the same. Crucially, the quadratic term for AD-specific thinning was statistically significant, and the optimum score was approximately 21.

Figure 3. Baseline hippocampal volume measurements and the annual rates of Alzheimer disease (AD)–specific cortical thinning and hippocampal volume loss. Shown are mean hippocampal volume (A) and cortical thickness in AD-vulnerable regions of interest (B) across healthy control individuals, presymptomatic individuals, and symptomatic (ie, having amnestic mild cognitive impairment [aMCI] and AD) individuals with an AD-like cerebrospinal fluid molecular profile. Mean rates of hippocampal volume loss (C) and AD-specific cortical thinning (D) are shown for each group. Error bars indicate SEM. Asterisk indicates P .05 for group differences.

Figure 1. Rates of atrophy. A, Hypothetical curve of longitudinal atrophy according to the cumulative diffusion model; B, corresponding rate of atrophy; and C, rate of atrophy as a function of the total amount of Alzheimer disease (AD)–specific atrophy.

Frequently asked questions

Q1. What contributions have the authors mentioned in the paper "The dynamics of cortical and hippocampal atrophy in alzheimer disease" ?

Analysis of the second derivative of imaging measurements revealed that AD-specific cortical thinning exhibited early acceleration followed by deceleration. 

Q2. What is the effect of the sigmoidal pattern on the hippocampal atrophy?

Cortical atrophy exhibited a pattern of acceleration in the first group (ie, the second derivative is positive) and deceleration in the second group. 

Q3. What is the significance of the bell-shaped derivative of the sigmoid?

the bell-shaped derivative of the sigmoid implies that early in the disease process, atrophy rates are likely to be indistinguishable from those of controls and therefore probably will be of limited use in tracking progression. 

Q4. What is the way to evaluate the fit of the cumulative diffusion model?

To evaluate the fit of the cumulative diffusion model on individual-level data, the authors used a model selection strategy based on stepwise logistic regression. 

Q5. What software package was used to process MRIs?

The authors processed all MRIs automatically using the FreeSurfer software package developed at the A. A. Martinos Center for Biomedical Imaging at Massachusetts General Hospital.1 

Q6. What is the recent research on the evolution of neuropathologic insults?

Postmortem studies1,2 indicate that an evolution of neuropathologic insults can be observed during the initial stages of AD, with intracellular tau-associated neurofibrillary tangles first appearing in medial temporal and limbic isocortical regions and extracellular amyloid- (A )–associated plaques affecting heteromodal association cortices. 

Q7. Who has been a member of the editorial board of CoMentis Inc?

He has served on the editorial board for Alzheimer’s & Dementia, has received honoraria from GE Healthcare Japan, Research Association for Biotechnology, The Johns Hopkins University, the Rotman Research Institute, the American Academy of Neurology, Ipsen Group, NeuroVigil Inc, and Institut Català de Neurociències Aplicades; has received commercial entities research support from Merck & Co Inc and Avid Radiopharmaceuticals Inc; has received government entities research support from the NIH, the US Department of Defense, and the US Department of Veterans Affairs; and has stock options in SYNARC Inc and Elan Pharmaceuticals Inc.ARCH NEUROL / VOL 68 (NO. 8), AUG 2011 WWW. 

Q8. What is the significance of the thinning of the hippocampal?

The recently demonstrated tight coupling between hippocampal atrophy and episodic memory impairment42 further suggests that significant volume loss in the hippocampus may be associated with clinical symptoms and therefore is unlikely to occur during a preclinical phase. 

Q9. What is the common mechanism that predicts the rate of atrophy?

One mechanism that yields such a dynamic is the cumulative diffusion model,25 which predicts that the rate of atrophy is proportional to that of aggregated atrophy (ie, tissue loss at a location is aggravated by accumulating damage in its neighborhood). 

Q10. What is the clinical manifestation of the cumulative burden of multiple neuropathologic insults?

DECLINE ANDthe dementia stage of Alz-heimer disease (AD) arethe clinical manifesta-tions of the cumulative burden of multiple neuropathologic insults. 

Q11. What is the way to test the cumulative diffusion model of atrophy?

For the primary motor and sensory cortices (ie, the control region), stepwise linear regression yielded no support for the cumulative diffusion model (ie, the alternative outcome). 

Q12. What is the MRI stream used to determine the thickness of the cortical mantle?

The authors used FreeSurfer’s longitudinal stream to process a set of serial MRIs from each study participant; this stream yields accurate and unbiased estimates of subtle changes over time. 

Q13. What is the significance of the ad-vulnerable ROIs?

This finding suggests that cortical thickness in AD-vulnerable ROIs may be a sensitive biomarker in the earliest stages of the disease process. 

Q14. What is the reason for the apparent slowing of AD-specific cortical thinning?

the apparent slowing of AD-specific cortical thinning may not occur due to the underlying biology but may be a consequence of the technical difficulty of resolving thickness changes around and beyond the voxel resolution.