不同认知功能障碍程度阿尔茨海默病患者海马、内嗅皮层体积变化及其与MMSE评分的关系

目的 探讨不同认知功能障碍程度的患者阿尔兹海默病（AD）海马、内嗅皮层体积的变化,及其与简易精神状态检查表（MMSE）评分的相关性。方法 横断面研究。纳入2017年9月—2021年9月联保部队第九六〇医院淄博院区86例AD患者临床和影像学资料,其中男54例、女32例,年龄55~87（73.9±8.1）岁。根据临床痴呆评定量表（CDR）评分将86例患者分为3组,其中36例CDR评分0.5分患者为轻度认知障碍（MCI）组,21例1分患者为轻度AD组,29例2~3分患者为中重度AD组。患者均应用MRI测量双侧海马体积、内嗅皮层体积,采用MMSE评分评估患者认知功能。观察指标：（1）比较3组患者性别、年龄、受教育年限等临床基线资料,以及MMSE评分;（2）比较3组患者海马体积和内嗅皮层体积;（3）分析AD患者MMSE评分与海马、内嗅皮层体积的相关性。结果 （1）3组患者性别、年龄、受教育年限等临床基线资料比较差异均无统计学意义（P值均>0.05）。MCI组、轻度AD组、中重度AD组患者MMSE评分依次降低,差异有统计学意义（F=113.29,P<0.001）。（2）MCI组、轻度AD组、中重度AD组左右侧海马体积MRI测量值分别为（3.24±0.32）cm³和（3.22±0.31）cm³、（2.72±0.53）cm³和（2.84±0.56）cm³、（2.31±0.55）cm³和（2.46±0.54）cm³,左右侧内嗅皮层体积分别为（1.42±0.26）cm³和（1.39±0.27）cm³、（1.28±0.24）cm³和（1.24±0.25）cm³、（1.04±0.31）cm³和（1.06±0.34）cm³。3组患者左右侧海马体积、内嗅皮层体积MRI测量值比较,均为MCI组>轻度AD组>中重度AD组,差异均有统计学意义（P值均<0.05）。（3）86例AD患者MMSE评分10~27（20.9±5.2）分,与左右两侧海马体积、内嗅皮层体积MRI测量值均呈正相关（r=0.82、0.81、0.73、0.72,P值均<0.001）。结论 随着认知功能障碍程度的加重,AD患者海马、内嗅皮层体积MRI测量值逐渐减小,且MMSE评分与海马、内嗅皮层体积存在相关性。     

MRI of hippocampus and entorhinal cortex in mild cognitive impairment: a follow-up study

The concept of mild cognitive impairment (MCI) has been proposed to represent a transitional stage between normal aging and dementia. We studied the predictive value of the MRI-derived volumes of medial temporal lobe (MTL) structures, white matter lesions (WML), neuropsychological tests, and Apolipoprotein E (APOE) genotype on conversion of MCI to dementia and AD. The study included 60 subjects with MCI identified from population cohorts. During the mean follow-up period of 34 months, 13 patients had progressed to dementia (9 to Alzheimer's disease (AD)). In Cox regression analysis the baseline volumes of the right hippocampus, the right entorhinal cortex and CDR sum of boxes predicted the progression of MCI to dementia during the follow-up. In a bivariate analysis, only the baseline volumes of entorhinal cortex predicted conversion of MCI to AD. The Mini-Mental State Examination (MMSE) score at baseline, WML load, or APOE genotype were not significant predictors of progression. The MTL volumetry helps in identifying among the MCI subjects a group, which is at high risk for developing AD.     

Hippocampus and entorhinal cortex in mild cognitive impairment and early AD

Magnetic resonance imaging (MRI) has been suggested as a useful tool in early diagnosis of Alzheimer's disease (AD). Based on MRI-derived volumes, we studied the hippocampus and entorhinal cortex (ERC) in 59 controls, 65 individuals with mild cognitive impairment (MCI) and 48 patients with AD. The controls and individuals with MCI were derived from population-based cohorts. Volumes of the hippocampus and ERC were significantly reduced in the following order: control > MCI > AD. Stepwise discriminant function analysis showed that the most efficient overall classification between controls and individuals with MCI subjects was achieved with ERC measurements (65.9%). However, the best overall classification between controls and AD patients (90.7%), and between individuals with MCI and AD patients (82.3%) was achieved with hippocampal volumes. Our results suggest that the ERC atrophy precedes hippocampal atrophy in AD. The ERC volume loss is dominant over the hippocampal volume loss in MCI, whereas more pronounced hippocampal volume loss appears in mild AD.     

Rate of entorhinal and hippocampal atrophy in incipient and mild AD: relation to memory function

In the present study, as part of a more extensive longitudinal investigation of the in vivo anatomical markers of early and incipient AD in our laboratory, three groups of elderly participants were followed with yearly clinical evaluations and high resolution MRI scans over a 6-year period (baseline and 5 years of follow-up). At baseline, participants consisted of: (1) 35 old subjects with no cognitive impairment (controls); (2) 33 participants with amnestic mild cognitive impairment (MCI); and (3) 14 patients with very mild AD. 11 participants with amnestic MCI received a diagnosis of AD over the follow-up period and 9 controls declined in cognitive function. T1 weighted MRI scans were acquired using a 3D SPGR pulse sequence. At baseline, both the amnestic MCI and mild AD groups differed from the controls in hippocampal and entorhinal cortex volume, but not from each other. Longitudinal analyses showed that the rate of atrophy of the entorhinal cortex and hippocampus for the stable controls differed significantly from MCI participants who converted to AD and the AD groups. Furthermore, longitudinal decreases in hippocampal and entorhinal volume were related to longitudinal decline in declarative memory performance. These findings suggest that the rate of atrophy of mesial temporal lobe structures can differentiate healthy from pathological aging.     

MRI-derived entorhinal and hippocampal atrophy in incipient and very mild Alzheimer's disease.

With high resolution, quantitative magnetic resonance imaging (MRI) techniques, it is now possible to examine alterations in brain anatomy in vivo and to identify regions affected in the earliest stages of Alzheimer's disease (AD). In this study, we compared MRI-derived entorhinal and hippocampal volume in healthy elderly controls, patients who presented at the clinic with cognitive complaints, but did not meet criteria for dementia (non-demented), and patients with very mild AD. The two patient groups differed significantly from controls in entorhinal volume, but not from each other; in contrast, they differed from each other, as well as from controls, in hippocampal volume, with the mild AD cases showing the greatest atrophy. Follow-up clinical evaluations available on 23/28 non-demented patients indicated that 12/23 had converted to AD within 12-77 months from the baseline MRI examination. Converters could be best differentiated from non-converters on the basis of entorhinal, but not hippocampal volume. These data suggest that although both the EC and hippocampal formation degenerate before the onset of overt dementia, EC volume is a better predictor of conversion.     

Posterior cingulate cortex atrophy and regional cingulum disruption in mild cognitive impairment and Alzheimer's disease

This study aimed to investigate the atrophy of the posterior cingulate cortex (PCC) and medical temporal lobe (MTL) structures (i.e., the entorhinal cortex (ERC) and hippocampus) and the regional disruption of the cingulum bundle in mild cognitive impairment (MCI) and Alzheimer's disease (AD) patients. The relationships between atrophy of these structures and regional cingulum disruption were also explored. Three-dimensional MRI and diffusion tensor imaging were applied to 19 MCI, 19 probable AD patients, and 18 normal controls (NC). Fractional anisotropy (FA) values were obtained from three different regions of the cingulum. Both MCI and AD patients showed decreased PCC volumes compared with NC. ERC atrophy was also significant in AD and MCI, while hippocampus atrophy was significant only in AD. MCI patients showed a significant FA decrease in the parahippocampal cingulum (PH-C), whereas AD patients had lower FA values in the posterior cingulate cingulum (PC-C) and PH-C, as compared with NC. However, the middle cingulate cingulum (MC-C) showed no significant FA differences between groups. Moreover, the volumes of MTL structures were significantly correlated with PH-C and PC-C FA values. In terms of PCC functional deficit in MCI or early AD, our results support both the direct effect of PCC atrophy itself and the indirect effect of cingulum fiber degeneration secondary to MTL atrophy.     

Prediction of conversion from mild cognitive impairment to Alzheimer's disease dementia based upon biomarkers and neuropsychological test performance

The current study tested the accuracy of primary MRI and cerebrospinal fluid (CSF) biomarker candidates and neuropsychological tests for predicting the conversion from mild cognitive impairment (MCI) to Alzheimer's disease (AD) dementia. In a cross-validation paradigm, predictor models were estimated in the training set of AD (N = 81) and elderly control subjects (N = 101). A combination of CSF t-tau/Aβ(1-4) ratio and MRI biomarkers or neuropsychological tests (free recall and trail making test B (TMT-B)) showed the best statistical fit in the AD vs. HC comparison, reaching a classification accuracy of up to 64% when applied to the prediction of MCI conversion (3.3-year observation interval, mean = 2.3 years). However, several single-predictor models showed a predictive accuracy of MCI conversion comparable to that of any multipredictor model. The best single predictors were right entorhinal cortex (prediction accuracy = 68.5% (95% CI (59.5, 77.4))) and TMT-B test (prediction accuracy 64.6% (95% CI (55.5, 73.4%))). In conclusion, short-term conversion to AD is predicted by single marker models to a comparable degree as by multimarker models in amnestic MCI subjects.     

Prediction of Alzheimer's disease in mild cognitive impairment: a prospective study in Taiwan

The relationship between apolipoprotein E (ApoE) and clinical manifestations of mild cognitive impairment (MCI) has not been investigated in non-Caucasian populations. This prospective study was conducted in an ethnic Chinese population to evaluate the correlations of ApoE genotype, cognitive performance, medial temporal structure volumes, and clinical outcome in amnestic MCI. Twenty normal elders, 58 MCI, and 20 mild Alzheimer's disease (AD) patients received neuropsychological, MRI, and ApoE genotype assessments at baseline. Patients with MCI had intermediate cognitive performance and hippocampal volumes between those in normal and AD groups. In each diagnostic group, 4 carriers (E4+) consistently had smaller hippocampal volume than non-carriers (E4−) did. Nineteen MCI subjects (32.7%) converted to AD during the 3-year study period. Compared with MCI non-converters and E4− MCI converters, E4+ MCI converters had the smallest hippocampal volume. However, 4 was not a predictor for AD. Both cognitive performance and hippocampal volume were predictive for progression to AD. However, stepwise Cox regression model integrating both neuropsychological and radiological variables showed that global cognitive performance was the only significant predictor for AD. A poor global cognitive score may be more crucial than a small hippocampal volume in the prediction of AD.     

Hippocampal formation glucose metabolism and volume losses in MCI and AD.

We used MRI volume sampling with coregistered and atrophy corrected FDG-PET scans to test three hypotheses: 1) hippocampal formation measures are superior to temporal neocortical measures in the discrimination of normal (NL) and mild cognitive impairment (MCI); 2) neocortical measures are most useful in the separation of Alzheimer disease (AD) from NL or MCI; 3) measures of PET glucose metabolism (MRglu) have greater diagnostic sensitivity than MRI volume. Three groups of age, education, and gender matched NL, MCI, and AD subjects were studied. The results supported the hypotheses: 1) entorhinal cortex MRglu and hippocampal volume were most accurate in classifying NL and MCI; 2) both imaging modalities identified the temporal neocortex as best separating MCI and AD, whereas widespread changes accurately classified NL and AD; 3) In most between group comparisons regional MRglu measures were diagnostically superior to volume measures. These cross-sectional data show that in MCI hippocampal formation changes exist without significant neocortical changes. Neocortical changes best characterize AD. In both MCI and AD, metabolism reductions exceed volume losses.     

Differential effects of aging and Alzheimer's disease on medial temporal lobe cortical thickness and surface area

The volume of parcellated cortical regions is a composite measure related to both thickness and surface area. It is not clear whether volumetric decreases in medial temporal lobe (MTL) cortical regions in aging and Alzheimer's disease (AD) are due to thinning, loss of surface area, or both, nor is it clear whether aging and AD differ in their effects on these properties. Participants included 28 Younger Normals, 47 Older Normals, and 29 patients with mild AD. T1-weighted MRI data were analyzed using a novel semi-automated protocol (presented in a companion article) to delineate the boundaries of entorhinal (ERC), perirhinal (PRC), and posterior parahippocampal (PPHC) cortical regions and calculate their mean thickness, surface area, and volume. Compared to Younger Normals, Older Normals demonstrated moderately reduced ERC and PPHC volumes, which were due primarily to reduced surface area. In contrast, the expected AD-related reduction in ERC volume was produced by a large reduction in thickness with minimal additional effect (beyond that of aging) on surface area. PRC and PPHC also showed large AD-related reductions in thickness. Of all these MTL morphometric measures, ERC and PRC thinning were the best predictors of poorer episodic memory performance in AD. Although the volumes of MTL cortical regions may decrease with both aging and AD, thickness is relatively preserved in normal aging, while even in its mild clinical stage, AD is associated with a large degree of thinning of MTL cortex. These differential morphometric effects of aging and AD may reflect distinct biologic processes and ultimately may provide insights into the anatomic substrates of change in memory-related functions of MTL cortex.     

Neuropathological correlates of volumetric MRI in autopsy-confirmed Lewy body dementia

The objective of this study was to determine the neuropathological correlates of regional medial temporal lobe volume measures on magnetic resonance imaging (MRI) in subjects with Lewy body dementia (LBD). Twenty-three autopsy-confirmed LBD cases with an MRI scan close to death (mean 1.5 years) were studied. MRI-based volumetric measures were calculated for total intracranial volume, hippocampus, entorhinal cortex, and amygdala. Quantitative neuropathological analysis of plaques, tangles, and Lewy bodies were carried out in the same regions. Spearman's rho was used to examine correlations between MRI volumes and neuropathology measures and linear regression to assess the relationship between neuropathology and MRI volumes. A significant inverse correlation was observed between normalized amygdala volume and percent area of Lewy bodies in the amygdala (r = -0.461, p = 0.035). There were no other significant correlations between regional MRI volume and measures of neuropathology. Lewy body, but not Alzheimer's disease (AD) pathology was associated with reduced amygdala volume in pathologically-verified LBD cases but neither Lewy body nor Alzheimer's disease pathology was associated with volume loss in the hippocampus or entorhinal cortex, suggesting other neuropathological factors account for atrophy in these structures in LBD.     

Regional Magnetic Resonance Imaging Measures for Multivariate Analysis in Alzheimer’s Disease and Mild Cognitive Impairment

Automated structural magnetic resonance imaging (MRI) processing pipelines are gaining popularity for Alzheimer’s disease (AD) research. They generate regional volumes, cortical thickness measures and other measures, which can be used as input for multivariate analysis. It is not clear which combination of measures and normalization approach are most useful for AD classification and to predict mild cognitive impairment (MCI) conversion. The current study includes MRI scans from 699 subjects [AD, MCI and controls (CTL)] from the Alzheimer’s disease Neuroimaging Initiative (ADNI). The Freesurfer pipeline was used to generate regional volume, cortical thickness, gray matter volume, surface area, mean curvature, gaussian curvature, folding index and curvature index measures. 259 variables were used for orthogonal partial least square to latent structures (OPLS) multivariate analysis. Normalisation approaches were explored and the optimal combination of measures determined. Results indicate that cortical thickness measures should not be normalized, while volumes should probably be normalized by intracranial volume (ICV). Combining regional cortical thickness measures (not normalized) with cortical and subcortical volumes (normalized with ICV) using OPLS gave a prediction accuracy of 91.5 % when distinguishing AD versus CTL. This model prospectively predicted future decline from MCI to AD with 75.9 % of converters correctly classified. Normalization strategy did not have a significant effect on the accuracies of multivariate models containing multiple MRI measures for this large dataset. The appropriate choice of input for multivariate analysis in AD and MCI is of great importance. The results support the use of un-normalised cortical thickness measures and volumes normalised by ICV.     

Combined 99mTc-ECD SPECT and neuropsychological studies in MCI for the assessment of conversion to AD

Identifying pre-clinical Alzheimer's disease (AD) in subjects with mild cognitive impairment (MCI) is a major issue in clinical diagnosis. Establishing a combination of predictive markers from different fields of research might help in increasing the diagnostic accuracy. Aim of this study was to evaluate the potential role of 99mTc-ECD single photon emission computed tomography (SPECT) and memory scores in predicting conversion to AD in MCI subjects. Thirty-one MCI subjects underwent a clinical and neuropsychological examination, and a regional cerebral blood flow (rCBF) SPECT scan at baseline. Subjects had been followed periodically through 2 years in order to monitor the progression of cognitive symptoms. Canonical variate analysis of principal components was able to separate all subjects who converted to AD from those who remained stable, the former being characterized by a specific hypometabolic pattern, involving the parietal and temporal lobes, precuneus, and posterior cingulate cortex. Canonical correlation analysis of combined baseline memory deficits and rCBF SPECT images identified pre-clinical AD with a sensitivity and specificity of 77.8%. The pattern of hypoperfusion 99mTc-ECD SPECT and the severity of memory deficits predict the risk of progression to probable AD dementia in MCI subjects.     

Effects of ApoE4 and maternal history of dementia on hippocampal atrophy

We applied an automated hippocampal segmentation technique based on adaptive boosting (AdaBoost) to the 1.5 T magnetic resonance imaging (MRI) baseline and 1-year follow-up data of 243 subjects with mild cognitive impairment (MCI), 96 with Alzheimer's disease (AD), and 145 normal controls (NC) scanned as part of the Alzheimer's Disease Neuroimaging Initiative (ADNI). MCI subjects with positive maternal history of dementia had smaller hippocampal volumes at baseline and at follow-up, and greater 12-month atrophy rates than subjects with negative maternal history. Three-dimensional maps and volumetric multiple regression analyses demonstrated a significant effect of positive maternal history of dementia on hippocampal atrophy in MCI and AD after controlling for age, ApoE4 genotype, and paternal history of dementia, respectively. ApoE4 showed an independent effect on hippocampal atrophy in MCI and AD and in the pooled sample.     

How early can we predict Alzheimer's disease using computational anatomy?

Computational anatomy with magnetic resonance imaging (MRI) is well established as a noninvasive biomarker of Alzheimer's disease (AD); however, there is less certainty about its dependency on the staging of AD. We use classical group analyses and automated machine learning classification of standard structural MRI scans to investigate AD diagnostic accuracy from the preclinical phase to clinical dementia. Longitudinal data from the Alzheimer's Disease Neuroimaging Initiative were stratified into 4 groups according to the clinical status—(1) AD patients; (2) mild cognitive impairment (MCI) converters; (3) MCI nonconverters; and (4) healthy controls—and submitted to a support vector machine. The obtained classifier was significantly above the chance level (62%) for detecting AD already 4 years before conversion from MCI. Voxel-based univariate tests confirmed the plausibility of our findings detecting a distributed network of hippocampal-temporoparietal atrophy in AD patients. We also identified a subgroup of control subjects with brain structure and cognitive changes highly similar to those observed in AD. Our results indicate that computational anatomy can detect AD substantially earlier than suggested by current models. The demonstrated differential spatial pattern of atrophy between correctly and incorrectly classified AD patients challenges the assumption of a uniform pathophysiological process underlying clinically identified AD.     

Olfactory identification deficits and MCI in a multi-ethnic elderly community sample

Odor identification deficits occur in Alzheimer's disease (AD) and mild cognitive impairment (MCI), and predict clinical conversion from MCI to AD. In an epidemiologic study conducted in a multi-ethnic community elderly sample (average 80 years old), the University of Pennsylvania Smell Identification Test (UPSIT, range 0-40) was administered to 1092 non-demented subjects. Women (mean 26.6, S.D. 6.6) scored higher than men (mean 24.4, S.D. 7.4, p<.02), and ethnic differences were not significant after controlling for age and education. UPSIT scores correlated inversely with age (r=-0.24, p<.0001) and positively with Selective Reminding Test immediate recall (r=0.33), delayed recall (r=0.28), category fluency (r=0.28) and the 15-item Boston Naming Test (r=0.23), all ps<.0001. In a sub-sample in which MRI was done, UPSIT scores showed a significant correlation with hippocampal volume (n=571, r=0.16, p<.001) but not entorhinal cortex volume nor total number of white matter hyperintensities. In ANOVA, UPSIT scores differed (p<.0001) as a function of MCI classification: no MCI (mean 26.6, S.D. 6.8), non-amnestic MCI (mean 24.4, S.D. 7.2), and amnestic MCI (mean 23.5, S.D. 6.7). The difference between amnestic MCI and no MCI remained significant after controlling for relevant covariates. These findings indicate that the predictive utility of olfactory identification deficits for decline from no MCI to MCI and AD needs to be assessed in longitudinal studies of elderly community samples.     

Longitudinal MRI findings from the vitamin E and donepezil treatment study for MCI

The vitamin E and donepezil trial for the treatment of amnestic mild cognitive impairment (MCI) was conducted at 69 centers in North America; 24 centers participated in an MRI sub study. The objective of this study was to evaluate the effect of treatment on MRI atrophy rates; and validate rate measures from serial MRI as indicators of disease progression in multi center therapeutic trials for MCI. Annual percent change (APC) from baseline to follow-up was measured for hippocampus, entorhinal cortex, whole brain, and ventricle in the 131 subjects who remained in the treatment study and completed technically satisfactory baseline and follow-up scans. Although a non-significant trend toward slowing of hippocampal atrophy rates was seen in APOE is an element of 4 carriers treated with donepezil; no treatment effect was confirmed for any MRI measure in either treatment group. For each of the four brain atrophy rate measures, APCs were greater in subjects who converted to AD than non-converters, and were greater in APOE is an element of 4 carriers than non-carriers. MRI APCs and changes in cognitive test performance were uniformly correlated in the expected direction (all p<0.000). Results of this study support the feasibility of using MRI as an outcome measure of disease progression in multi center therapeutic trials for MCI.     

Structural MRI changes detectable up to ten years before clinical Alzheimer's disease

Structural brain changes have been described in both mild cognitive impairment (MCI) and Alzheimer's disease (AD). However, less is known about whether structural changes are detectable earlier, in the asymptomatic phase. Using voxel-based morphometry (VBM) and shape analyses of magnetic resonance imaging (MRI) data, we investigated structural brain differences between groups of healthy subjects, stratified by subsequent diagnoses of MCI or AD during a 10-year follow-up. Images taken at baseline, at least 4 years before any cognitive symptoms, showed that subjects with future cognitive impairment (preclinical AD and MCI) had reduced brain volume in medial temporal lobes, posterior cingulate/precuneus, and orbitofrontal cortex, compared with matched subjects who remained cognitively healthy for 10 years (HC). For only those subjects later diagnosed as AD, significantly greater atrophy at baseline was detected in the right medial temporal lobe, which was also confirmed by shape analysis of the right hippocampus in these subjects. Our results demonstrate that structural brain changes occur years before clinical cognitive decline in AD and are localized to regions affected by AD neuropathology.     

Prediction of MCI to AD conversion, via MRI, CSF biomarkers, and pattern classification

Magnetic resonance imaging (MRI) patterns were examined together with cerebrospinal fluid (CSF) biomarkers in serial scans of Alzheimer's Disease Neuroimaging Initiative (ADNI) participants with mild cognitive impairment (MCI). The SPARE-AD score, summarizing brain atrophy patterns, was tested as a predictor of short-term conversion to Alzheimer's disease (AD). MCI individuals that converted to AD (MCI-C) had mostly positive baseline SPARE-AD (Spatial Pattern of Abnormalities for Recognition of Early AD) and atrophy in temporal lobe gray matter (GM) and white matter (WM), posterior cingulate/precuneous, and insula. MCI individuals that converted to AD had mostly AD-like baseline CSF biomarkers. MCI nonconverters (MCI-NC) had mixed baseline SPARE-AD and CSF values, suggesting that some MCI-NC subjects may later convert. Those MCI-NC with most negative baseline SPARE-AD scores (normal brain structure) had significantly higher baseline Mini Mental State Examination (MMSE) scores (28.67) than others, and relatively low annual rate of Mini Mental State Examination decrease (−0.25). MCI-NC with midlevel baseline SPARE-AD displayed faster annual rates of SPARE-AD increase (indicating progressing atrophy). SPARE-AD and CSF combination improved prediction over individual values. In summary, both SPARE-AD and CSF biomarkers showed high baseline sensitivity, however, many MCI-NC had abnormal baseline SPARE-AD and CSF biomarkers. Longer follow-up will elucidate the specificity of baseline measurements.     

Atrophy of the medial occipitotemporal, inferior, and middle temporal gyri in non-demented elderly predict decline to Alzheimer's disease

Our goal was to ascertain, among normal elderly and individuals with mild cognitive impairment, which temporal lobe neocortical regions predicted decline to dementia of the Alzheimer's type (DAT). Individuals received an MRI at baseline and a clinical and cognitive evaluation at baseline and follow-up. By using the baseline MRI we assessed the anatomical subdivisions of the temporal lobe: anteromedial temporal lobe (hippocampus and parahippocampal gyrus), medial occipitotemporal (fusiform) gyrus, middle and inferior temporal gyri, and superior temporal gyrus. We studied two groups of carefully screened age- and education-matched elderly individuals: 26 normal elderly (NL) and 20 individuals with mild cognitive impairment (MCI). Fourteen individuals (12 from the MCI group and two from the NL group) declined to DAT within the 3.2-year follow-up interval. We used logistic regression analyses to ascertain whether the baseline brain volumes were useful predictors of decline to DAT at follow-up after accounting for age, gender, individual differences in brain size, and other variables known to predict DAT. After accounting for age, gender, and head size, adding the volume of the anteromedial temporal lobe (the aggregate of hippocampus and parahippocampal gyrus) and an index of global atrophy raised the accuracy of overall classification to 80.4%. However, the ability to detect those individuals who declined (sensitivity) was low at 57%. When baseline medial occipitotemporal and the combined middle and inferior temporal gyri were added to the logistic model, the overall classification accuracy reached 95.6% and, most importantly, the sensitivity rose to 92.8%. These data indicate that the medial occipitotemporal and the combined middle and inferior temporal gyri may be the first temporal lobe neocortical sites affected in AD; atrophy in these areas may herald the presence of future AD among nondemented individuals. No other clinical baseline variables examined predicted decline with sensitivities above 71%. The apolipoprotein APOE epsilon4 genotype was not associated with decline.