Evaluating Alzheimer’s Disease Progression Using Rate of Regional Hippocampal Atrophy

Abstract

Alzheimer’s disease (AD) is characterized by neurofibrillary tangle and neuropil thread deposition, which ultimately results in neuronal loss. A large number of magnetic resonance imaging studies have reported a smaller hippocampus in AD patients as compared to healthy elderlies. Even though this difference is often interpreted as atrophy, it is only an indirect measurement. A more direct way of measuring the atrophy is to use repeated MRIs within the same individual. Even though several groups have used this appropriate approach, the pattern of hippocampal atrophy still remains unclear and difficult to relate to underlying pathophysiology. Here, in this longitudinal study, we aimed to map hippocampal atrophy rates in patients with AD, mild cognitive impairment (MCI) and elderly controls. Data consisted of two MRI scans for each subject. The symmetric deformation field between the first and the second MRI was computed and mapped onto the three-dimensional hippocampal surface. The pattern of atrophy rate was similar in all three groups, but the rate was significantly higher in patients with AD than in control subjects. We also found higher atrophy rates in progressive MCI patients as compared to stable MCI, particularly in the antero-lateral portion of the right hippocampus. Importantly, the regions showing the highest atrophy rate correspond to those that were described to have the highest burden of tau deposition. Our results show that local hippocampal atrophy rate is a reliable biomarker of disease stage and progression and could also be considered as a method to objectively evaluate treatment effects.

Basic MR sequence parameters systematically bias automated brain volume estimation

“…This is in the same range as early disease-related brain volume alterations, for example in Alzheimer's Disease 11 . Automated brain segmentation software packages should therefore require strict MR parameter selection or include compensatory algorithms 12 to avoid MR-parameter-related bias of brain morphometry results.…”

Can multi-modal neuroimaging evidence from hippocampus provide biomarkers for the progression of amnestic mild cognitive impairment?

“…Jack and colleagues have also reported that the odds ratio for progression to sporadic AD over 1.2-4.8 years is 1.75 in aMCI patients with smaller hippocampal volumes when compared to those with larger hippocampal volumes [32] . In a 3-year donepezil/vitamin E/placebo study of aMCI, Jack and colleagues further demonstrated a higher hippocampal atrophy rate (5.44%) in the placebo group than in the others [23] . Using hippocampal atrophy data from different time points (0, 6, 12, 18, 24, and 36 months), Leung and colleagues demonstrated that the rates in aMCI patients accelerated by 0.22%/ year 2 , and the acceleration of hippocampal loss may contribute to the progression of aMCI to AD [33] .…”

“…Most of the studies found that smaller hippocampal volumes, predominantly in the subicular and CA1 areas, are related to an increased risk for conversion from aMCI to AD [20][21][22][23][24] , despite some inconsistent findings [25,26] .…”

A fast approach for hippocampal segmentation from T1-MRI for predicting progression in Alzheimer's disease from elderly controls

“…6). Although the difference in hippocampal volume had the same trend in many previous studies (Leung et al, 2010;Nestor et al, 2013;Frankó and Joly, 2013), the reported volumes substantially differed. The remarkable difference among studies could be due to the manual segmentation protocols used to define the atlases.…”

“…These techniques require the correspondence between the hippocampal segmentation of each subject to a template, and then a local analysis is performed (Styner et al, 2006;Gerardin et al, 2009;Frankó and Joly, 2013). In contrast, the surface roughness does not require any non-rigid registration.…”