Visual rating and volumetric measurement of medial temporal atrophy in the Alzheimer's Disease Neuroimaging Initiative (ADNI) cohort: baseline diagnosis and the prediction of MCI outcome.

OBJECTIVE: This study aims to determine the clinical utility of visual ratings and volumetric measurements of medial temporal atrophy among subjects from the Alzheimer's Disease Neurorimaging Initiative (ADNI) cohort. METHODS: A sample of 189 subjects from the ADNI, Phase 1 (ADNI-1), was chosen as follows: 49 cognitively normal (CN), 89 with mild cognitive impairment (MCI), and 50 with Alzheimer's disease (AD). Structural MRI images were downloaded from the ADNI website, and a visual rating system (VRS) was used to obtain semi-quantitative ratings of the hippocampus (HPC) and entorhinal cortex (ERC). VRS ratings and FreeSurfer measures of the HPC and ERC were used to predict (i) baseline diagnosis and (ii) progression to AD among subjects with MCI at baseline. RESULTS: VRS and FreeSurfer measures of ERC were equivalent in classifying subjects at baseline, but FreeSurfer measures of HPC were superior to VRS measures for classifying CN versus MCI subjects. VRS and FreeSurfer measures of both HPC and ERC were significant predictors of progression from MCI to AD. However, VRS ratings of ERC were superior to other MRI measures. MCI subjects with minimal ERC atrophy by VRS had a threefold lower progression rate to AD at 3.2 years compared with those with mild, moderate, or severe atrophy (23% vs 63%, 69%, and 87%, respectively). CONCLUSIONS: Visual ratings of HPC and ERC provide useful information to a physician in a clinical setting. Visual ratings of ERC may be especially useful in following patients with MCI.

The utility of age-specific cut-offs for visual rating of medial temporal atrophy in classifying Alzheimer's disease, MCI and cognitively normal elderly subjects.

BACKGROUND: New research criteria for diagnosing Alzheimer's disease (AD) in the mild cognitive impairment stage (MCI-AD) incorporate biomarkers to assign a level of certainty to the diagnosis. Structural MRI is widely available but greatly under-utilized for assessing atrophy of structures affected in early AD, such as the hippocampus (HP), because the quantification of HP volumes (HP-v) requires special expertise, and normative values have not been established. METHODS: Elderly subjects (n =273) from the Florida ADRC were classified as having no cognitive impairment (cognitively normal, CN), amnestic mild cognitive impairment (aMCI) or AD. Volumes for the hippocampus (HP-v) were measured on structural MRI scans. A validated visual rating system for measuring medial temporal atrophy (VRS-MTA), including hippocampal, entorhinal cortex and perirhinal cortex atrophy was employed. The participants were subdivided into younger (less than or equal to 75 years of age) and older (greater than 75 years of age) subgroups. RESULTS: Volumetric and VRS-MTA measures were equivalent in predicting classification of CN vs. aMCI for older (area under the receiver operator curves [aROC]: 0.652 vs. 0.723) and younger subjects (aROC: 0.764 vs. 0.736). However, for younger AD subjects, aROC values were significantly higher for VRS-MTA measures (0.920) than for volumetric measures (0.847). Relative to HP-v, VRS-MTA score was significantly more correlated to impairment on a range of memory tests and was more associated with progression of aMCI to AD than HP-v. CONCLUSION: Structural MRI with VRS-MTA assessment can serve as a biomarker for supporting the diagnosis of MCI-AD. Age-adjusted VRS-MTA scores are at least as effective as HP-v for distinguishing aMCI and AD from CN and for predicting progression from aMCI to AD. VRS-MTA is convenient for use in the clinic as well as for clinical trials and can readily be incorporated into a standardized radiological report.

Minimal atrophy of the entorhinal cortex and hippocampus: progression of cognitive impairment.

BACKGROUND: In Alzheimer's disease, neurodegenerative atrophy progresses from the entorhinal cortex (ERC) to the hippocampus (HP), limbic system and neocortex. The significance of very mild atrophy of the ERC and HP on MRI scans among elderly subjects is unknown. METHODS: A validated visual rating system on coronal MRI scans was used to identify no atrophy of the HP or ERC (HP(0); ERC(0)), or minimal atrophy of the HP or ERC (HP(ma); ERC(ma)), among 414 participants. Subjects fell into the following groups: (1) ERC(0)/HP(0), (2) ERC(ma)/HP(0), (3) ERC(0)/HP(ma), and (4) ERC(ma)/HP(ma). HP volume was independently measured using volumetric methods. RESULTS: In comparison to ERC(0)/HP(0) subjects, those with ERC(0)/HP(ma) had impairment on 1 memory test, ERC(ma)/HP(0) subjects had impairment on 2 memory tests and the Mini Mental State Examination (MMSE), while ERC(ma)/HP(ma) subjects had impairment on 3 memory tests, the MMSE and Clinical Dementia Rating. Progression rates of cognitive and functional impairment were significantly greater among subjects with ERC(ma). CONCLUSION: Minimal atrophy of the ERC results in greater impairment than minimal atrophy of the HP, and the combination is additive when measured by cognitive and functional tests. Rates of progression to greater impairment were higher among ERC(ma) subjects.