Automated 3D mapping of hippocampal atrophy and its clinical correlates in 400 subjects with Alzheimer's disease, mild cognitive impairment, and elderly controls

Abstract

We used a new method we developed for automated hippocampal segmentation, called the auto context model (ACM), to analyze brain MRI scans of 400 subjects from the Alzheimer's Disease Neuroimaging Initiative (ADNI). After training the classifier on 21 hand-labeled expert segmentations, we created binary maps of the hippocampus for three age-and sex-matched groups: 100 subjects with Alzheimer's disease (AD), 200 with mild cognitive impairment (MCI) and 100 elderly controls (mean age: 75.84; SD: 6.64). Hippocampal traces were converted to parametric surface meshes and a radial atrophy mapping technique was used to compute average surface models and local statistics of atrophy. Surface-based statistical maps visualized links between regional atrophy and diagnosis (MCI versus controls: p = 0.008; MCI versus AD: p = 0.001), mini-mental state exam (MMSE) scores, and global and sum-of-boxes clinical dementia rating scores (CDR; all p < 0.0001, corrected). Right but not left hippocampal atrophy was associated with geriatric depression scores (p = 0.004, corrected); hippocampal atrophy was not associated with subsequent decline in MMSE and CDR scores, educational level, ApoE genotype, systolic or diastolic blood pressure measures, or homocysteine. We gradually reduced sample sizes and used false discovery rate curves to examine the method's power to detect associations with diagnosis and cognition in smaller samples. 40 subjects were sufficient to discriminate AD from normal and correlate atrophy with CDR scores; 104, 200 and 304 subjects, respectively, were required to correlate MMSE with atrophy, to distinguish MCI from normal, and MCI from AD.

A commonly carried allele of the obesity-relatedFTOgene is associated with reduced brain volume in the healthy elderly

“…We estimated the minimal number of subjects (n = 96) needed to repeat the finding by successively removing subjects, at random but without bias, from our sample and calculating the critical P value for FDR threshold, until the results were no longer significant. This gives a rough estimate of how many subjects are needed to find the effect in an independent sample (on the premise that in very small samples, the FTO effect would not explain enough of the variance) as in prior studies (50). A cumulative distribution function (CDF) plot displays the results from smaller sample sizes having lower critical P values than those computed from larger sample sizes (Fig.…”

APOE ε4 worsens hippocampal CA1 apical neuropil atrophy and episodic memory

“…[10][11][12] Perhaps these divergent findings arise from disproportionate effects of the e4 allele on individual hippocampal subfields that are not always evident in global volumetric analyses.…”

Effects of music and art education in early life and oral functions on the QOL of the Takarazuka Revue Company OG compared with general elderly females

“…Currently, there is a report by Morra JH et al 24 regarding the relationship between the presence of hippocampal atrophy and decreases in cognitive function in healthy subjects, but no conclusions have been reached. Therefore, regarding the interpretation of the present study results, further examinations will be necessary by obtaining image data of brain functions from positron emission tomography and single photon emission computed tomography imaging and temporal changes by year using MRI tests while conducting more detailed examinations of the cognitive function.…”

“…atrophy) from the earliest stages from among cerebral degeneration associated with Alzheimer's disease (AD), 21,22 and there are several reports that support the conclusion that a relationship between hippocampal atrophy and decline in cognitive function exist based on the findings of MRI. 23 First, regarding the relationship between the hippocampal volume and decline in cognitive function in cases of mild cognitive impairment (MCI) and AD, some reports have stated that significantly higher levels of brain atrophy were observed in several areas of the brain, including the hippocampus in cases of MCI 24,25 and cases of AD 24,26 compared with healthy subjects. In addition, other reports have stated that higher degrees of advancement of hippocampal atrophy are expressed in AD, MCI and healthy subjects in that order, and that this advancement is correlated with the first MMSE score and subsequent temporal changes.…”

“…27 Furthermore, another report states that hippocampal atrophy advances more rapidly in healthy subjects with ApoE4 compared with subjects without ApoE4 and that hippocampal atrophy advanced more rapidly in cases transitioning from MCI to AD in comparison with non-transitioning cases. 27 At the same time, it has been reported that in cases of AD and MCI, and in healthy elderly people, there is no relationship between hippocampal atrophy and decreases in cognitive function (MMSE, Clinical Dementia Rating (CDR)), ApoE genotype or blood pressure, 24 and that in cases of MCI, the presence of hippocampal atrophy is a prognostic factor of increases in the advancement rate of subsequent hippocampal atrophy. 22 In the results of the present study, significant differences in the hippocampal volume were observed between the two groups; however, the implications of these results for subjects without dementia are unknown.…”