Does Alzheimer's disease affect hippocampal asymmetry? Evidence from a cross-sectional and longitudinal volumetric MRI study

OBJECTIVE: To determine whether Alzheimer's disease (AD) is associated with preferential atrophy of either the left or right hippocampus. METHODS: We examined right-left asymmetry in hippocampal volume and atrophy rates in 32 subjects with probable AD and 50 age-matched controls. Hippocampi were measured on two serial volumetric MRI scans using a technique that minimizes laterality bias. RESULTS: We found a non-significant trend for right > left (R > L) asymmetry in controls at both time points (R > L: 1.7%; CI: -0.3-3.7%; p = 0.1). AD subjects showed a similar non-significant trend for R > L asymmetry at baseline (R > L: 1.8%; CI: -1.9-5.5%; p = 0.32), but not at repeat (p = 0.739). Change in R/L ratio between visits in AD patients was significant (p = 0.02). The AD group had significantly higher variance in these ratios than the controls at baseline (p = 0.02), but not repeat (p = 0.06). AD patients had higher atrophy rates than controls (p < 0.001). Mean (CI) annualized atrophy rates for left and right hippocampi were 1.2% (0.5-1.8%) and 1.1% (0.5-1.8%) for the controls, and 4.6% (3.3-6.0%) and 6.3% (4.9-7.8%) for AD subjects. There was no significant asymmetry in atrophy rates in controls (p = 0.9), but borderline significantly higher atrophy rates in the right hippocampus of the AD group (p = 0.05) compared to the left. Presence of an APOEepsilon4 allele had no significant effect on the size, asymmetry or atrophy rates in AD (p > 0.20). CONCLUSIONS: We report minor R > L asymmetry in hippocampal volumes in controls and present some evidence to suggest that there is a change in the natural R > L asymmetry during the progression of AD.     

New MRI markers for Alzheimer's disease: a meta-analysis of diffusion tensor imaging and a comparison with medial temporal lobe measurements

The aim of the present study is to evaluate the diagnostic value of diffusion tensor imaging (DTI) for early Alzheimer's disease (AD) in comparison to widely accepted medial temporal lobe (MTL) atrophy measurements. A systematic literature research was performed into DTI and MTL atrophy in AD and mild cognitive impairment (MCI). We included seventy-six studies on MTL atrophy including 8,122 subjects and fifty-five DTI studies including 2,791 subjects. Outcome measure was the effect size (ES) expressed as Hedges g. In volumetric studies, atrophy of the MTL significantly differentiated between AD and controls (ES 1.32-1.98) and MCI and controls (ES 0.61-1.46). In DTI-Fractional anisotropy (FA) studies, the total cingulum differentiated best between AD and controls (ES = 1.73) and the parahippocampal cingulum between MCI and controls (ES = 0.97). In DTI-Mean diffusivity (MD) studies, the hippocampus differentiated best between AD and controls (ES = -1.17) and between MCI and controls (ES = -1.00). We can conclude that in general, the ES of volumetric MTL atrophy measurements was equal or larger than that of DTI measurements. However, for the comparison between controls and MCI-patients, ES of hippocampal MD was larger than ES of hippocampal volume. Furthermore, it seems that MD values have somewhat more discriminative power than FA values with higher ES in the frontal, parietal, occipital and temporal lobe.     

Hippocampal atrophy correlates with the severity of cognitive decline

BACKGROUND: The aim of this study is to compare the results of magnetic resonance (MR) imaging, particularly the decline in hippocampal volume, of patients with Alzheimer's disease (AD) and mild cognitive impairment (MCI) with healthy age-matched controls, to examine the reliability of hippocampal volumetry in the early diagnosis of AD and the correlation of the severity of hippocampal atrophy with the severity of cognitive decline. METHODS: Twenty-six AD, 22 MCI and 15 normal cognitive status (NCS) patients were scanned with a 3 Tesla MR scanner. Hippocampus volumes were detected manually by Osiris 4.18. RESULTS: Multivariate regression analysis, which was performed to adjust the covariate effects of education, age, gender, hypertension and diabetes mellitus, showed that hippocampal atrophy was correlated with AD and MCI for right hippocampus; AD, MCI and age for left hippocampus independent of other parameters. A second regression analysis revealed that MMSE was correlated with hippocampal volume. CONCLUSIONS: Hippocampal volumetry can be used in early diagnosis of cognitive impairment, as well as grading cognitive decline.     

Measurements of the amygdala and hippocampus in pathologically confirmed Alzheimer disease and frontotemporal lobar degeneration

BACKGROUND: Differentiating between Alzheimer disease (AD) and frontotemporal lobar degeneration (FTLD) can be difficult, particularly in the earliest stages of the diseases. Patterns of atrophy on magnetic resonance imaging may help distinguish these diseases and aid diagnosis. OBJECTIVE: To assess the diagnostic utility of magnetic resonance imaging-derived amygdala and hippocampal volumes from patients with pathologically proved AD and FTLD. DESIGN: Cross-sectional volumetric magnetic resonance imaging study of the hippocampus and amygdala. SETTING: Specialist cognitive disorders clinic.Subjects Thirty-seven subjects, including 10 patients with pathologically proved AD, 17 patients with pathologically proved FTLD, and 10 age-matched control subjects. MAIN OUTCOME MEASURES: Hippocampal and amygdala volumes. RESULTS: Geometric mean amygdala and hippocampal volumes were, respectively, 15.0% (95% confidence interval [CI], 4.2%-24.5%) and 16.4% (95% CI, 5.9%-25.6%) lower in the AD than in the control group. In FTLD, the equivalent differences were 43.1% (95% CI, 31.9%-52.6%) in the amygdala and 36.1% (95% CI, 27.5%-43.7%) in the hippocampus. Volumes were significantly lower in the FTLD than in the AD group (P<.01 in both regions). Within the FTLD clinical subgroups, there was evidence of a difference in pattern of atrophy with greater asymmetry (left smaller than right) in semantic dementia compared with frontal variant FTLD (P<.001). On average, the left hippocampus was 14% smaller in semantic dementia than in frontal variant FTLD, whereas the right hippocampus was 37% larger. On average, the left amygdala was 39% smaller in semantic dementia than in frontal variant FTLD, whereas the right amygdala was only 1% smaller. CONCLUSIONS: Hippocampal atrophy is not specific to AD or FTLD. However, severe or asymmetrical amygdala atrophy should suggest FTLD. Atrophy patterns follow clinical syndromes rather than pathology.     

Ultrastructural hippocampal and white matter alterations in mild cognitive impairment: a diffusion tensor imaging study

Mild cognitive impairment (MCI) is considered to be a transitional stage between normal aging and dementia. In Alzheimer's disease (AD), white matter structural pathology is due to Wallerian degeneration and central angiopathy. However, in MCI patients, the presence and extent of white matter alterations as a possible correlate of impaired memory function and as predictor of subsequent progression to AD is not clarified yet. Diffusion tensor imaging (DTI) reveals the ultrastructural integrity of cerebral white matter tracts. Therefore, it could detect pathological processes that modify tissue integrity in patients with MCI. In our prospective study, conventional and diffusion tensor MR scans were obtained from 14 patients with MCI, 19 patients with AD, and 10 healthy controls. Mean diffusivity (MD) and fractional anisotropy (FA) were measured in temporal, frontal, parietal and occipital white matter regions as well as in the corpus callosum (genu and splenium) and the hippocampus. MCI patients showed higher MD values in the left centrum semiovale (p = 0.013; right: p = 0.026), in the left temporal (p = 0.006), the right temporal (p = 0.014) and the left hippocampal (p = 0.002) region as compared to the control group. FA values of MCI patients and controls did not differ significantly in any region. Compared to controls, AD patients had increased MD values in the left centrum semiovale (p = 0.012), the left parietal (p = 0.001), the right parietal (p = 0.028), the left temporal (p = 0.018), the right temporal (p = 0.011) and the left hippocampal region (p = 0.002). Decreased FA values were measured in the left temporal area (p = 0.017) and in the left hippocampus (p = 0.031) in AD patients compared to controls. FA and MD values did not differ significantly between AD and MCI patients. Elevated MD values indicating brain tissue alterations in MCI patients were found in regions that are typically involved in early changes due to AD, particularly the left hippocampus. The sensitivity of distinguishing MCI patients from controls was 71.4% (with a specificity set at 80%). Therefore, the DTI technique validates the MCI concept, and diffusion tensor MR measurement can be a helpful tool to quantify MCI pathology in vivo.     

Gray matter asymmetries in aging and neurodegeneration: A review and meta‐analysis

Inter‐hemispheric asymmetries are a common phenomenon of the human brain. Some evidence suggests that neurodegeneration related to aging and disease may preferentially affect the left—usually language‐ and motor‐dominant—hemisphere. Here, we used activation likelihood estimation meta‐analysis to assess gray matter (GM) loss and its lateralization in healthy aging and in neurodegeneration, namely, mild cognitive impairment (MCI), Alzheimer's dementia (AD), Parkinson's disease (PD), and Huntington's disease (HD). This meta‐analysis, comprising 159 voxel‐based morphometry publications (enrolling 4,469 patients and 4,307 controls), revealed that GM decline appeared to be asymmetric at trend levels but provided no evidence for increased left‐hemisphere vulnerability. Regions with asymmetric GM decline were located in areas primarily affected by neurodegeneration. In HD, the left putamen showed converging evidence for more pronounced atrophy, while no consistent pattern was found in PD. In MCI, the right hippocampus was more atrophic than its left counterpart, a pattern that reversed in AD. The stability of these findings was confirmed using permutation tests. However, due to the lenient threshold used in the asymmetry analysis, further work is needed to confirm our results and to provide a better understanding of the functional role of GM asymmetries, for instance in the context of cognitive reserve and compensation. Hum Brain Mapp 38:5890–5904, 2017. © 2017 Wiley Periodicals, Inc.     

Structure and function of medial temporal and posteromedial cortices in early Alzheimer's disease

Medial temporal lobe (MTL) atrophy and posteromedial cortical hypometabolism are consistent imaging findings in Alzheimer's disease (AD). As the MTL memory structures are affected early in the course of AD by neurofibrillary tangle pathology, the posteromedial metabolic abnormalities have been postulated to represent remote effects of MTL alterations. In this study, we investigated with functional MRI (fMRI) the structure-function relationship between the MTL and posteromedial regions, including the retrosplenial, posterior cingulate and precuneal cortices, in 21 older controls (OCs), 18 subjects with amnestic mild cognitive impairment (MCI) and 16 AD patients during a word list learning task. In the voxel-based morphometric and volumetric analyses, the MCI subjects showed smaller entorhinal volume than OCs (P = 0.0001), whereas there was no difference in the hippocampal or posteromedial volume. AD patients, as compared with MCI patients, showed pronounced loss of volume in the entorhinal (P = 0.0001), hippocampal (P = 0.01) and posteromedial (P = 0.001) regions. The normal pattern of posteromedial fMRI task-induced deactivation during active encoding of words was observed bilaterally in the OCs, but only in restricted unilateral left posteromedial areas in the MCI and AD patients. Across all subjects, more extensive impairment of the retrosplenial and posterior cingulate function was significantly related to smaller entorhinal (P = 0.001) and hippocampal (P = 0.0002) volume. These findings demonstrate that entorhinal atrophy and posteromedial cortical dysfunction are early characteristics of prodromal AD, and precede and/or overwhelm atrophy of the hippocampus and posteromedial cortices. Disturbances in posteromedial cortical function are associated with morphological changes in the MTL across the continuum from normal aging to clinical AD.     

Accelerated hippocampal atrophy rates in stable and progressive amnestic mild cognitive impairment

Studies suggest that smaller hippocampal volume predicts Alzheimer's disease (AD) in mild cognitive impairment (MCI). However, few studies have demonstrated decline rates in cognition and hippocampal volume in MCI subjects with stable clinical presentation. Furthermore, the effects of apolipoprotein E (ApoE) on the change rates of medial temporal structures and cognition in MCI are rarely investigated. Fifty-eight subjects with amnestic MCI and 20 normal aging elderly controls received annual neuropsychological and magnetic resonance imaging (MRI) assessments. Annual decline rates in neuropsychological test scores, hippocampal and amygdalar volumes were calculated. ApoE genotypes were examined. Nineteen (32.7%) MCI subjects converted to AD during an average 22.5-month follow-up period. The annual hippocampal atrophy rate was correlated with a decline in memory test scores. The presence of the ApoE ?4 allele did not affect the change rates in neuropsychological test scores and medial temporal structures volume. Compared to subjects with stable MCI (MCI-S) and normal aging, progressive MCI (MCI-P) had the highest annual decline rates in cognition and hippocampal volume. Logistic regression analysis showed that higher annual decline rates in hippocampal volume and global cognitive test scores were associated with conversion to AD. Furthermore, although MCI-S subjects had little cognitive decline, their hippocampal atrophy rates were higher than those of normal aging controls. Therefore, accelerated hippocampal atrophy rates may be an early and important presentation in MCI subjects.     

Hippocampal atrophy patterns in mild cognitive impairment and Alzheimer's disease

Background:

Histopathological studies and animal models suggest that hippocampal subfields may be differently affected by aging, Alzheimer's disease (AD), and other diseases. High‐resolution images at 4 Tesla depict details of the internal structure of the hippocampus allowing for in vivo volumetry of different subfields. The aims of this study were as follows: (1) to determine patterns of volume loss in hippocampal subfields in normal aging, AD, and amnestic mild cognitive impairment (MCI). (2) To determine if measurements of hippocampal subfields provide advantages over total hippocampal volume for differentiation between groups.

Methods:

Ninety‐one subjects (53 controls (mean age: 69.3 ± 7.3), 20 MCI (mean age: 73.6 ± 7.1), and 18 AD (mean age: 69.1 ± 9.5) were studied with a high‐resolution T2 weighted imaging sequence aimed at the hippocampus. Entorhinal cortex (ERC), subiculum, CA1, CA1‐CA2 transition zone (CA1‐2), CA3 & dentate gyrus (CA3&DG) were manually marked in the anterior third of the hippocampal body. Hippocampal volume was obtained from the Freesurfer and manually edited.

Results:

Compared to controls, AD had smaller volumes of ERC, subiculum, CA1, CA1‐2, and total hippocampal volumes. MCI had smaller CA1‐2 volumes. Discriminant analysis and power analysis showed that CA1‐2 was superior to total hippocampal volume for distinction between controls and MCI.

Conclusion:

The patterns of subfield atrophy in AD and MCI were consistent with patterns of neuronal cell loss/reduced synaptic density described by histopathology. These preliminary findings suggest that hippocampal subfield volumetry might be a better measure for diagnosis of early AD and for detection of other disease effects than measurement of total hippocampus. Hum Brain Mapp, 2010. © 2010 Wiley‐Liss, Inc.

     

轻度认知障碍的海马、内嗅体积变化研究

目的研究轻度认知功能障碍(MCI)和阿尔兹海默病(AD)患者的海马、内嗅体积萎缩情况,评价利用高分辨影像学测定海马、内嗅体积对MCI、AD的诊断及预测价值。方法应用西门子3.0T磁共振分别对32例MCI患者,25例AD患者,32例正常的对照者进行3D T1WI扫描,并用freesurfer软件计算三组海马、内嗅体积,后用SPSS 17.0统计学软件进行资料的统计学处理,比较三组之间灰质体积的差异。评价在判断MIC中的价值。结果与对照组比较,MCI组[左侧(3.07±0.56)cm3,右侧(3.24±0.61)cm3]、AD组[左侧(2.81±0.64)cm3,右侧(3.01±0.67)cm3]的海马体积萎缩,其差异有统计学意义(P<0.01),且AD组比MCI组在海马体积(左侧0.26 cm3,右侧0.23cm3)均值上有更明显的萎缩;海马体积减小的程度与简易智能检查量表(MMSE)积分呈正相关性,而内嗅的体积变化在三组间的比较无统计学差异。结论通过Freesurfer测量的MRI形态学研究能够客观揭示AD早期阶段海马体积的萎缩改变,且海马体积萎缩与MMSE积分相结合对轻度认知障碍的诊断更准确。     

Spatial correlation maps of the hippocampus with cerebrospinal fluid biomarkers and cognition in Alzheimer's disease: A longitudinal study

This study is an observational study that takes the existing longitudinal data from Alzheimer''s disease Neuroimaging Initiative to examine the spatial correlation map of hippocampal subfield atrophy with CSF biomarkers and cognitive decline in the course of AD. This study included 421 healthy controls (HC), 557 patients of stable mild cognitive impairment (s‐MCI), 304 Alzheimer''s Disease (AD) patients, and 241 subjects who converted to be AD from MCI (c‐MCI), and 6,525 MRI scans in a period from 2004 to 2019. Our findings revealed that all the hippocampal subfields showed their accelerated atrophy rate from cognitively normal aging to stable MCI and AD. The presubiculum, dentate gyrus, and fimbria showed greater atrophy beyond the whole hippocampus in the HC, s‐MCI, and AD groups and corresponded to a greater decline of memory and attention in the s‐MCI group. Moreover, the higher atrophy rates of the subiculum and CA2/3, CA4 were also associated with a greater decline in attention in the s‐MCI group. Interestingly, patients with c‐MCI showed that the presubiculum atrophy was associated with CSF tau levels and corresponded to the onset age of AD and a decline in attention in patients with c‐MCI. These spatial correlation findings of the hippocampus suggested that the hippocampal subfields may not be equally impacted by normal aging, MCI, and AD, and their atrophy was selectively associated with declines in specific cognitive domains. The presubiculum atrophy was highlighted as a surrogate marker for the AD prognosis along with tau pathology and attention decline.     

Three-dimensional surface mapping of hippocampal atrophy progression from MCI to AD and over normal aging as assessed using voxel-based morphometry

The hippocampus is the brain structure of highest and earliest structural alteration in Alzheimer's disease (AD). New developments in neuroimaging methods recently made it possible to assess the respective involvement of the different hippocampal subfields by mapping atrophy on a 3D hippocampal surface view. In this longitudinal study on patients with mild cognitive impairment (MCI), we used such an approach to map the profile of hippocampal atrophy and its progression over an 18-month follow-up period in rapid converters to AD and "non-converters" compared to age-matched controls. For the sake of comparison, we also assessed the profile of hippocampal atrophy associated with AD and with increasing age in a healthy control population ranging from young adult to elderly. We found major involvement of the lateral part of the superior hippocampus mainly corresponding to the CA1 subfield in MCI and AD while increasing age was mainly associated with subiculum atrophy in the healthy population. Moreover, the CA1 subfield also showed highest atrophy rates during follow-up, in both rapid converters and "non-converters" although increased effects were observed in the former group. This study emphasizes the differences between normal aging and AD processes leading to hippocampal atrophy, pointing to a specific AD-related CA1 involvement while subiculum atrophy would represent a normal aging process. Our findings also suggest that the degree of hippocampal atrophy, more than its spatial localization, predicts rapid conversion to AD in patients with MCI.     

The role of volumetric MRI in understanding mild cognitive impairment and similar classifications

We review nineteen empirical studies of mild cognitive impairment (MCI), age-associated memory impairment (AAMI) and related classifications reporting volumetric data on the hippocampus, entorhinal cortex and amygdala. Studies varied considerably in terms of the selection of participants, sample characteristics, the definitions of regions of interest and normalization techniques. Effect sizes for differences in left hippocampal volume and right hippocampal volumes of AAMI, MCI and pre-clinical dementia groups compared with controls ranged from 0.47 to 1.34. Effect sizes for left and right hippocampal volumes for Alzheimer's disease (AD) versus control were 1.88 and 1.75 respectively. Longitudinal results confirm that initial hippocampal volume is predictive of conversion to AD. Greater standardization in methodology and the development of normative age-referenced databases of regional brain volumes is required.     

Hippocampal and amygdalar volume changes in elderly patients with Alzheimer's disease and schizophrenia

Patients with Alzheimer's disease (AD) and schizophrenia display cognitive, behavioural disturbances and morphological abnormalities. Although these latter reflect progressive neurodegeneration in AD, their significance in schizophrenia is still unclear. We explored the patterns of hippocampal and amygdalar atrophy in those patients and their associations with clinical parameters. Structural magnetic resonance imaging was performed in 20 elderly schizophrenia patients, 20 AD and 19 healthy older controls. Hippocampal and amygdalar volumes were obtained by manual segmentation with a standardized protocol and compared among groups. In both schizophrenia and AD patients, left hippocampal and amygdalar volumes were significantly smaller. The hippocampus/amygdala ratio was significantly lower in schizophrenia compared to both AD cases [2.4 bilaterally, 95% C.I. 2.2 to 2.7] and healthy controls bilaterally [2.5, 95% C.I. 2.3 to 2.9 in left and 2.7, 95% C.I. 2.4 to 3.1 in right hemisphere]. In schizophrenia patients, a significant positive correlation was found between age at disease onset and the right hippocampus/amygdala volume ratio (Spearman rho=0.56). Negative symptoms correlated with higher right/left amygdala volume ratio (Spearman's rho=0.43). Our data show that unlike AD, the hippocampus/amygdala ratio is abnormally low and correlates with the age at onset in schizophrenia, being a neurodevelopmental signature of the disease.     

Hippocampal and amygdalar volume changes in elderly patients with Alzheimer's disease and schizophrenia

Patients with Alzheimer's disease (AD) and schizophrenia display cognitive, behavioural disturbances and morphological abnormalities. Although these latter reflect progressive neurodegeneration in AD, their significance in schizophrenia is still unclear. We explored the patterns of hippocampal and amygdalar atrophy in those patients and their associations with clinical parameters. Structural magnetic resonance imaging was performed in 20 elderly schizophrenia patients, 20 AD and 19 healthy older controls. Hippocampal and amygdalar volumes were obtained by manual segmentation with a standardized protocol and compared among groups. In both schizophrenia and AD patients, left hippocampal and amygdalar volumes were significantly smaller. The hippocampus/amygdala ratio was significantly lower in schizophrenia compared to both AD cases [2.4 bilaterally, 95% C.I. 2.2 to 2.7] and healthy controls bilaterally [2.5, 95% C.I. 2.3 to 2.9 in left and 2.7, 95% C.I. 2.4 to 3.1 in right hemisphere]. In schizophrenia patients, a significant positive correlation was found between age at disease onset and the right hippocampus/amygdala volume ratio (Spearman rho = 0.56). Negative symptoms correlated with higher right/left amygdala volume ratio (Spearman's rho = 0.43). Our data show that unlike AD, the hippocampus/amygdala ratio is abnormally low and correlates with the age at onset in schizophrenia, being a neurodevelopmental signature of the disease.     

Dementia, asymmetry of temporal lobe structures, and apolipoprotein E genotype: relationships to cerebral atrophy and neuropsychological impairment.

We examined asymmetry of hippocampal volume as well as other temporal lobe structures (temporal lobe, temporal horn of the lateral ventricular system, parahippocampal and fusiform gyri) in 194 subjects from the Cache County, Utah study, with varying disorders [85 with Alzheimer's disease (AD), 59 with some cognitive or neuropsychiatric disorder-referenced as a Mixed Neuropsychiatric group, 30 with mild ambiguous/mild cognitive impairment (MA/MCI) and 20 controls] and APOE genotypes. Asymmetry was determined by subtracting left-side volume from the right corrected by total intracranial volume. No significant asymmetry was observed to be associated with presence of the epsilon4 allele. Since the AD-epsilon4 allele risk effect may be expressed early in the course of the disorder, we also examined asymmetry indices in AD, MA/MCI and Mixed Neuropsychiatric subjects early in the course of their disorder (2 years or less) to those with longer duration illness (greater than 2 years). We observed a leftward asymmetry (i.e., left side larger) regardless of APOE genotype in hippocampal volume where both AD and MCI subjects demonstrated a leftward shift in hippocampal size when length of disease (LOD) was less but not more than 2 years. Leftward asymmetry was not associated with LOD in the Mixed Neuropsychiatric group. These findings do not support an association between epsilon4 and hippocampal asymmetry in dementia. We also examined whether asymmetry influenced neuropsychological performance, but minimal effects were observed. Where significance or strong trends were observed, better neuropsychological performance was associated with larger parenchymal volume of temporal lobe structures. These findings were interpreted as representing cognitive reserve effects where larger volume was protective against impairment. The role of asymmetry research in understanding neuropsychological performance in dementia is discussed.     

Conversion of mild cognitive impairment to Alzheimer disease predicted by hippocampal atrophy maps

BACKGROUND: While most patients with mild cognitive impairment (MCI) transition to Alzheimer disease (AD), others develop non-AD dementia, remain in the MCI state, or improve. OBJECTIVE: To test the following hypotheses: smaller hippocampal volumes predict conversion of MCI to AD, whereas larger hippocampal volumes predict cognitive stability and/or improvement; and patients with MCI who convert to AD have greater atrophy in the CA1 hippocampal subfield and subiculum. DESIGN: Prospective longitudinal cohort study. SETTING: University of California-Los Angeles Alzheimer's Disease Research Center. PATIENTS: We followed up 20 MCI subjects clinically and neuropsychologically for 3 years. MAIN OUTCOME MEASURE: Baseline regional hippocampal atrophy was analyzed with region-of-interest and 3-dimensional hippocampal mapping techniques. RESULTS: During the 3-year study, 6 patients developed AD (MCI-c), 7 remained stable (MCI-nc), and 7 improved (MCI-i). Patients with MCI-c had 9% smaller left and 13% smaller right mean hippocampal volumes compared with MCI-nc patients. Radial atrophy maps showed greater atrophy of the CA1 subregion in MCI-c. Patients with MCI-c had significantly smaller hippocampi than MCI-i patients (left, 24%; right, 27%). Volumetric analyses showed a trend for greater hippocampal atrophy in MCI-nc relative to MCI-i patients (eg, 16% volume loss). After permutation tests corrected for multiple comparison, the atrophy maps showed a significant difference on the right. Subicular differences were seen between MCI-c and MCI-i patients, and MCI-nc and MCI-i patients. Multiple linear regression analysis confirmed the group effect to be highly significant and independent of age, hemisphere, and Mini-Mental State Examination scores at baseline. CONCLUSIONS: Smaller hippocampi and specifically CA1 and subicular involvement are associated with increased risk for conversion from MCI to AD. Patients with MCI-i tend to have larger hippocampal volumes and relative preservation of both the subiculum and CA1.     

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

We used a new method we developed for automated hippocampal segmentation, called the auto context model, to analyze brain MRI scans of 400 subjects from the Alzheimer's disease neuroimaging initiative. 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. Forty 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. Hum Brain Mapp 2009. © 2009 Wiley‐Liss, Inc.     

轻度认知障碍和轻度Alzeimer病的海马体积MRI测量

目的研究轻度认知功能障碍（mildcognitiveimpairment,MCI）和轻度阿尔兹海默病（A1zheimerdisease,AD）患者的海马体积萎缩情况,评价利用影像学测定海马体积对MCI、AD的诊断价值。方法应用3．0T磁共振分别对20例MCI患者,20例轻度AD患者,20例认知功能正常的对照者的海马体积进行测量,所得数值用头颅体积进行标准化处理。采用计算机SPSS13．0统计学软件进行资料的统计学处理,比较三组之间体积的差异。结果对照组与MCI组,对照组与AD组的两侧海马体积均存在显著的统计学差异,轻度AD与MCI组两侧的海马体积无显著的统计学差异。结论认知功能障碍与海马体积具有一定的相关性,海马萎缩对早期认知障碍有一定的诊断意义。     

Regional pattern of increased water diffusivity in hippocampus and corpus callosum in mild cognitive impairment

BACKGROUND: Corpus callosum atrophy possibly indicates neuronal degeneration in association cortex in Alzheimer's disease (AD). Water diffusivity allows detecting physiological changes that probably occur earlier than structural shrinkage in cerebral regions during the development of AD. Objective: To simultaneously investigate the focal volumetric and early structural changes with apparent diffusion coefficient (ADC) of corpus callosum in mild cognitive impairment (MCI), and to explore the regional pattern of ADC increase in hippocampus and corpus callosum. METHODS: Thirteen subjects with MCI and 13 healthy age-matched control subjects were studied. With three-dimensional volumetric spoiled gradient recalled echo MRI images, we measured the volume of hippocampus and corpus callosum. Using MRI-guided diffusion-weighted imaging analysis, we calculated ADCs from hippocampus and corpus callosum. Within the receiver-operation curve (ROC) statistical framework, areas under ROC curves from hippocampal and callosal ADCs were compared in differentiating between MCI and controls. RESULTS: After normalization to intracranial volume, hippocampal, not callosal, volume was significantly reduced in MCI. ADC values were increased in hippocampus and corpus callosum in MCI. The extent of ADC increase was similar between hippocampus and corpus callosum. CONCLUSION: Alterations in water diffusivity may precede corpus callosum atrophy during the development of MCI. Diffusion changes might occur simultaneously in allocortex and neocortex in MCI.