Medial temporal lobe atrophy and memory dysfunction as predictors for dementia in subjects with mild cognitive impairment

To determine whether the medial temporal lobe is atrophic in subjects with mild cognitive impairment, and whether atrophy of this structure is a better predictor of dementia than memory dysfunction. Forty-five noninstitutionalized subjects aged 65–85 years were randomly selected from a population based study to obtain a sample with Alzheimer’s disease (AD; n = 7), and a clinically nondemented sample (n = 38). Twenty of the latter subjects displayed some cognitive impairment and fulfilled CAMDEX criteria for “minimal dementia.” Coronal T1-weighted magnetic resonance imaging was used to visualize the medial temporal lobe. The volume of the parahippocampal gyrus and hippocampus was measured, and medial temporal lobe atrophy was assessed qualitatively. The memory subscore from the CAMCOG was used as a measure of memory functioning. The follow-up period was 3 years. Nine subjects who were diagnosed as being minimally demented at baseline met the criteria for AD during follow-up. At baseline the volume of the parahippocampal gyrus of these subjects was smaller than that of the other subjects with minimal dementia. The memory score was the best predictor of clinical outcome. All medial temporal lobe measures increased the accuracy of prediction compared with only the memory score, by reducing the number of false-negative classifications of dementia. Severe medial temporal lobe atrophy is present even in some subjects with mild cognitive impairment and is an indicator of subsequent AD. The absence of medial temporal lobe atrophy, however, does not exclude the development of dementia. In the majority of subjects memory impairment was a better predictor of dementia than atrophy of the medial temporal lobe. The combination of the two increased predictive accuracy. Nondemented subjects with severe atrophy of the medial temporal lobe could be enrolled in drug trials aimed at slowing the progression of AD. Received: 18 June 1998 Received in revised form: 28 September 1998Accepted: 4 November 1998     

Diagnosis of preclinical Alzheimer's disease in a clinical setting

INTRODUCTION: The aim of the study was to investigate whether the preclinical stage of Alzheimer's disease (AD) can be diagnosed in a clinical setting. To this end we investigated whether subjects with preclinical AD could be differentiated from subjects with nonprogressive mild cognitive impairment and from subjects with very mild AD-type dementia. METHODS: Twenty-three subjects with preclinical AD, 44 subjects with nonprogressive mild cognitive impairment, and 25 subjects with very mild AD-type dementia were selected from a memory clinic population. Variables that were used to differentiate the groups were demographic variables, the Mini-Mental State Examination score, performance on cognitive tests, measures of functional impairment, and measures of noncognitive symptomatology. RESULTS: Age and the scores for the delayed recall task could best discriminate between subjects with preclinical AD and subjects with nonprogressive mild cognitive impairment. The overall accuracy was 87%. The score on the Global Deterioration Scale and a measure of intelligence could best discriminate between subjects with preclinical AD and subjects with very mild AD-type dementia. The overall accuracy was 85%. CONCLUSIONS: Subjects with preclinical AD can be distinguished from subjects with nonprogressive mild cognitive impairment and from subjects with very mild AD-type dementia. This means that preclinical AD is a diagnostic entity for which clinical criteria should be developed.     

Medial temporal lobe atrophy and APOE genotype do not predict cognitive improvement upon treatment with rivastigmine in Alzheimer's disease patients

BACKGROUND: Only a subgroup of subjects with probable AD shows cognitive improvement after treatment with cholinesterase inhibitors. OBJECTIVES: To investigate whether atrophy of the medial temporal lobe and the apolipoprotein E (APOE) genotype could predict cognitive improvement in subjects with probable AD treated with rivastigmine. METHODS: 121 subjects with mild to moderate probable AD were treated for 26 weeks with escalating doses of rivastigmine. Outcome measures were change on the MMSE and the ADAS-Cog between baseline and follow-up and treatment response defined as at least 2 points improvement on the MMSE or at least 4 points improvement on the ADAS-Cog. The study was an open-label multi-centre study in The Netherlands. RESULTS: Subjects with medial temporal lobe atrophy (MTLA) tended to show more decline on the MMSE after correction for age, sex, education, baseline cognitive score, and dosage at week 26 compared with subjects without MTLA (p = 0.08). A significant interaction between MTLA and dosage at week 26 existed for change on the MMSE and ADAS-Cog: subjects with MTLA showed more cognitive decline than subjects without MTLA only in the group of patients who received a low dosage at week 26. MTLA was not associated with treatment response. The APOE genotype was not associated with change on the MMSE or ADAS-Cog or with treatment response. CONCLUSIONS: MTLA and the APOE genotype are not clinically useful predictors of cognitive response in subjects with probable AD who are treated with rivastigmine.     

Hippocampal and temporal lobe atrophy and age-related decline in memory

OBJECTIVES: To evaluate the relationship of memory decline that accompanies aging with structural changes in the medial temporal lobe, in healthy middle-aged and older subjects. MATERIAL AND METHODS: A sample of 35 neurologically non-diseased subjects, between 55 and 70 years of age, were examined in a 5-year follow-up study. Neuropsychological investigation included tests of learning, verbal memory, and visual memory. MRI was performed with a superconducting MRI system operating at 1.0 T, using coronal slices of T1-weighted images. Medial temporal lobe atrophy was rated separately in the neocortical, entorhinal and hippocampal regions. RESULTS: We did not find any statistically significant relationship between mild hippocampal or temporal atrophy and memory test performance. Nor did the longitudinal decline in memory show a relationship with temporal lobe atrophy. CONCLUSIONS: The main outcome of our study was that age-related memory decline was not related to mild temporal lobe atrophy in healthy subjects without mild cognitive impairment. There could be other factors influencing memory functions besides age-related structural changes in temporal lobes.     

Longitudinal brain structural changes in preclinical Alzheimer's disease

Introduction

Brain structural changes in preclinical Alzheimer's disease (AD) are poorly understood.

A preclinical phase in vascular dementia: cognitive impairment three years before diagnosis

Alzheimer's disease (AD) and vascular dementia (VaD) patients exhibit similar patterns of deficits in many cognitive tasks in the early clinical stages. Considering that preclinical cognitive deficits are well documented in AD, the purpose of the present study was to investigate if such deficits are also present in VaD. The cognitive outcome measure was the Mini-Mental State Examination (MMSE). The sample was taken from a population-based study and consisted of 699 persons who were nondemented at baseline, but out of whom 35 persons were diagnosed with VaD and 170 with AD at a 3-year follow-up. Both the incident VaD and AD cases exhibited baseline deficits on the total score of the MMSE and three of the subscales: orientation to time, orientation to place, and delayed memory. Further, both dementia groups exhibited precipitous decline on most MMSE subscales during the 3-year follow-up period. Logistic regression analyses showed that all subscales that revealed deficits at baseline predicted dementia status at follow-up. Delayed memory was the best predictor in both preclinical VaD and preclinical AD. Thus, these results demonstrate preclinical cognitive deficits in VaD in a measure of global cognitive functioning, which closely resemble those observed in AD. This observation suggests that circulatory disturbance is associated with cognitive problems several years before the actual VaD diagnosis.     

MRI measures and progression of cognitive decline in nondemented elderly attending a memory clinic

OBJECTIVE: To investigate whether MRI-based volumes of whole brain, medial temporal lobe and white matter hyperintensities (WMH) predict progression of cognitive decline in a sample of nondemented elderly. METHODS: Thirty-seven nondemented elderly attending a memory clinic and 28 elderly controls participated in this follow-up study. The average follow-up period was 1.8 years. Cognitive function was measured at baseline and follow-up with the Cambridge Cognitive Examination (CAMCOG). Baseline Magnetic Resonance Imaging (MRI) provided quantitative measures of whole brain, medial temporal lobe and WMH. Linear mixed models controlled for age and sex were used to assess the independent associations between MRI measures, baseline cognition, and annual decline in cognition. RESULTS: Medial temporal lobe volume was independently associated with baseline CAMCOG score (p < 0.01), whereas whole brain volume (p < 0.01) and WMH (p < 0.05) were associated with annual decline in CAMCOG score. CONCLUSIONS: These data suggest that regional damage to the medial temporal lobes underlies initial mild cognitive impairment, whereas more global brain changes, such as whole brain atrophy and WMH, contribute to further progression of cognitive decline.     

Insensitivity of visual assessment of hippocampal atrophy in familial Alzheimer’s disease

Medial temporal atrophy is a well-established marker for Alzheimer’s disease (AD). However, due to normal variation in the size of medial temporal structures and variability in how radiologists interpret images, the use of clinical reads in establishing the presence of pathological atrophy is imprecise. A limitation of studies of magnetic resonance imaging (MRI) measures in AD is diagnostic uncertainty as it can be unknown if pre- or early-symptomatic subjects go on to develop AD and most subjects do not undergo autopsy verification of the diagnosis. In persons with or at-risk for AD due to fully-penetrant autosomal dominant mutations in the PSEN1 and APP genes, the diagnosis or future development of AD can be predicted with essentially 100% accuracy. We used this predictability to assess the ability of radiologists to detect hippocampal atrophy (HA) in persons destined to develop AD. Coronal T1-weighted MRI scans of 39 persons demented from (n = 4) or at-risk for inheriting (n = 35) PSEN1 or APP mutations were independently assessed by two radiologists and the presence or absence of HA determined. Of the 39 subjects, 26 were FAD mutation carriers. Fifteen of 28 asymptomatic at-risk persons were FAD mutation carriers and four of these were rated as having atrophy for a sensitivity of 27% and a specificity of 85%. Among seven mildly affected yet non-demented subjects, atrophy was detected in three and in the four demented subjects HA was identified in two. Our results suggest that radiologists’ ability to detect HA in persons in whom the diagnosis of incipient AD is certain is sub-optimal and quantitative MRI techniques or other biological markers of the disease are needed.     

Increasing the diagnostic accuracy of medial temporal lobe atrophy in Alzheimer's disease

Medial temporal lobe (MTL) atrophy is considered to be one of the most important predictors of Alzheimer's disease (AD). This study investigates whether atrophy in parietal and prefrontal areas increases the predictive value of MTL atrophy in three groups of different cognitive status. Seventy-five older adults were classified as cognitively stable (n = 38) or cognitively declining (n = 37) after three years follow-up. At follow-up, the grey matter of the MTL, inferior prefrontal cortex (IPC), and inferior parietal lobule (IPL) was delineated on MRI scans. Six years later, a dementia assessment resulted in distinguishing and separating a third group (n = 9) who can be considered as preclinical AD cases at scan time. Ordinal logistic regressions analysis showed that the left and right MTL, as well as the right IPC and IPL accurately predicted group membership. Receiver Operating Curves showed that the MTL was best in distinguishing cognitively stable from cognitively declining individuals. The accuracy of the differentiation between preclinical AD and cognitively stable participants improved when MTL and IPL volumes were combined, while differentiating preclinical AD and cognitively declined participants was accomplished most accurately by the combined volume of all three areas. We conclude that depending on the current cognitive status of an individual, adding IPL or IPC atrophy improved the accuracy of predicting conversion to AD by up to 22%. Diagnosis of preclinical AD may lead to more false positive outcomes if only the MTL atrophy is considered.     

The Radial Width of the Temporal Horn in Mild Cognitive Impairment

BACKGROUND AND PURPOSE: The diagnosis of preclinical Alzheimer's disease (AD) (or mild cognitive impairment [MCI]) is loaded with a high degree of uncertainty. The aim was to test the accuracy of a computed tomography-based (CT-based) marker of medial temporal lobe atrophy, the radial width of the temporal horn (rWTH), in MCI. METHODS: Ten MCI and 42 AD patients and 29 nondemented controls underwent brain CT on the temporal lobe plane (slice thickness = 2 mm). The rWTH was taken on CT films with a precision caliper placed at the tip of the temporal horn radial to the curvature of the hippocampal head region. RESULTS: When specificity was fixed at 95%, the sensitivity for the detection of AD was 39/42 (93%) and that for the detection of MCI was 8/10 (80%). CONCLUSION: The rWTH is a measure sensitive to the regional brain atrophy common in early AD.     

Evaluation and clinical correlation of practical cut-offs for visual rating scales of atrophy: normal aging versus mild cognitive impairment and Alzheimer’s disease

Age-related brain atrophy is a common finding, but neurodegenerative diseases such as Alzheimer’s disease are associated with accelerated atrophy of the medial temporal lobe. In current practice for brain atrophy evaluation, several rating scales are being used such as the medial temporal atrophy (MTA), global cortical atrophy-frontal subscale (GCA-F) and posterior atrophy (PA) scales. Practical cut-offs to differentiate between normal and advanced brain atrophy are needed, because of their possible usefulness as a biomarker. A retrospective study was performed over a 1-year period resulting in a total of 79 subjects [27 patients with Alzheimer’s disease (AD), 27 patients with minimal cognitive impairment (MCI) and 25 control subjects]. The MTA, GCA-F and PA scales were applied blinded and independent by two raters. Possible age- and disease-related cut-offs were computed. The MTA scale showed significantly better diagnostic performances and inter-rater agreement than the PA and GCA-F scales. We could not confirm the suggested MTA cut-off for each decade. However, an MTA score of >1 and >1.75 was considered pathological, respectively, in the population under and over 70 years. MTA can be of use in making distinction between age-related atrophy and abnormal increase of atrophy. Systematic assessment of regional brain atrophy through the use of MTA in MRI images could be a useful biomarker in aiding the early diagnosis of Alzheimer’s disease.     

Medial temporal lobe atrophy in memory disorders

Medial temporal lobe atrophy determined by temporal lobe oriented computed tomography (CT), 1 year before death, is strongly associated with histopathologically confirmed Alzheimer’s disease (AD). The aim of this study was to assess the diagnostic accuracy of medial temporal lobe measurement for the diagnosis of AD in patients referred to a memory disorders clinic, especially those at an early stage of the disease. CT oriented to the temporal lobe was performed in 333 subjects aged 41–93 years consecutively recruited in a Memory Disorders Clinic: 124 had probable AD, Mini Mental State score (MMS) = 17 (8); 50 possible AD [MMS = 21 (5)]; and 119 patients had miscellaneous memory disorders [MMS = 22 (7): frontotemporal lobe dementia, subcortical dementia, cortical Lewy body disease, vascular dementia, Korsakoff syndrome, focal atrophy, etc.]. There were also 19 anxious/ depressed patients [MMS = 29 (1)] with normal performance on memory tests, and 21 controls. The minimum width of the medial temporal lobe was measured. The best cut-off to distinguish AD patients from non-AD patients was 11.5 mm, in agreement with data in the literature. At this threshold, 84% of probable AD patients had a positive test and 90% of controls and anxious/depressed patients had a negative test. For the diagnosis of probable AD, sensitivity of the measurement was 0.81, specificity 0.95, predictive positive value 0.99, predictive negative value 0.45, and diagnostic accuracy 0.83. The test was positive in half the possible AD patients, and half those with miscellaneous memory disorders. It was negative in all anxious/depressed patients. Therefore, temporal lobe oriented CT might be a valuable tool for assessment of medial temporal lobe atrophy in AD routine practice. Received: 27 September 1995 Accepted: 10 October 1996     

Injury markers but not amyloid markers are associated with rapid progression from mild cognitive impairment to dementia in Alzheimer's disease

Alzheimer's disease (AD) is a common cause of mild cognitive impairment (MCI). However, the time between the diagnosis of MCI and the diagnosis of dementia is highly variable. In this study we investigated which known risk factors and biomarkers of AD pathology were associated with rapid progression from MCI to dementia. Of the 203 subjects with MCI, 91 progressed to AD-type dementia and were considered to have MCI-AD at baseline. Subjects with MCI-AD were older, more frequently female and carrier of the APOE-ε4 allele, had lower scores on the Mini-Mental State Examination (MMSE), more medial temporal lobe atrophy (MTA) and lower levels of Aβ1-42 and increased levels of t-tau and p-tau in the cerebrospinal fluid (CSF) compared to subjects without AD-type dementia at follow up. Of the 91 subjects with MCI-AD, we had data available of CSF (n = 56), MTA (n = 76), and APOE-genotype (n = 63). Among the subjects with MCI-AD, MTA (hazard ratio (HR) 2.2, p = 0.004) and low MMSE score (HR 2.0 p = 0.007) were associated with rapid progression to dementia. High CSF t-tau (HR 1.7, p = 0.07) and p-tau (1.7, p = 0.08) tended to be associated with rapid progression to dementia. CSF Aβ1-42, APOE status, age, gender, and educational level were not associated with time to dementia. Our findings implicate a different role for biomarkers in diagnosis and prognosis of MCI-AD. While amyloid markers can be used to identify MCI-AD, injury markers may predict rapid progression to dementia.     

A voxel based morphometry study on mild cognitive impairment

BACKGROUND: Mild cognitive impairment (MCI) is the most widely used concept in classifying cognitive impairment in the elderly who do not fulfil the criteria for dementia. MCI is considered to confer an increased risk of progressing to dementia and most often Alzheimer's disease (AD). Various approaches such as imaging of the brain have been applied to predict the conversion of MCI to dementia. A number of volumetric magnetic resonance imaging (MRI) studies have detected atrophy of the medial temporal lobe in subjects with MCI, but for the other cerebral regions the results have been inconsistent. OBJECTIVE: To study the pattern of brain atrophy in MCI. METHODS: Thirty two controls and 51 individuals with MCI deriving from population based cohorts were studied by MRI using voxel based morphometry. The threshold of t maps was set at p < 0.001. RESULTS: Individuals with MCI had significant unilateral atrophy in the medial temporal lobe on the right side. Less extensive atrophy was found elsewhere-for example, in the temporal lobe, left superior parietal lobule, left anterior cingulate gyrus, and bilaterally in the thalami. CONCLUSIONS: The MRI findings in MCI resemble those seen in early AD.     

Comprehensive dissection of the medial temporal lobe in AD: measurement of hippocampus, amygdala, entorhinal, perirhinal and parahippocampal cortices using MRI

Background Early pathological involvement of specific medial temporal lobe areas is characteristic for Alzheimer’s disease (AD). Objective To determine the extent of regional medial temporal lobe atrophy, including hippocampus, amygdala, and entorhinal, perirhinal, and parahippocampal cortices in mild AD patients and healthy controls, and to compare diagnostic accuracy across volumetric markers. Methods We studied 34 patients with clinically probable AD and 22 healthy elderly control subjects. Regional volumetric measures were obtained from volumetric T1–weighted MRI scans after accounting for global brain atrophy using affine transformation into standard space. Results Volumes of medial temporal lobe structures were significantly smaller in AD patients than in controls with exception of the left entorhinal cortex. The degree of atrophy was comparable between all structures. Diagnostic accuracy (number of correctly allocated cases divided by number of all cases) was highest for the right parahippocampal cortex with 85%, but only slightly lower for the right hippocampus and right entorhinal cortex with 82% and 84%. Using a linear combination of markers, the unilateral volumes of the right hippocampus, parahippocampal cortex and perirhinal cortex yielded an accuracy of 93%. Conclusion Extent of atrophy is similar between the different regions of the medial temporal lobe in mild AD.Volume measurements of medial temporal lobe structures in addition to the hippocampus only yield improved diagnostic accuracy if a combination of these structures is used.     

An empirically derived composite cognitive test score with improved power to track and evaluate treatments for preclinical Alzheimer's disease

BackgroundThere is growing interest in the evaluation of preclinical Alzheimer's disease (AD) treatments. As a result, there is a need to identify a cognitive composite that is sensitive to track preclinical AD decline to be used as a primary endpoint in treatment trials.MethodsLongitudinal data from initially cognitively normal, 70- to 85-year-old participants in three cohort studies of aging and dementia from the Rush Alzheimer's Disease Center were examined to empirically define a composite cognitive endpoint that is sensitive to detect and track cognitive decline before the onset of cognitive impairment. The mean-to-standard deviation ratios (MSDRs) of change over time were calculated in a search for the optimal combination of cognitive tests/subtests drawn from the neuropsychological battery in cognitively normal participants who subsequently progressed to clinical stages of AD during 2- and 5-year periods, using data from those who remained unimpaired during the same period to correct for aging and practice effects. Combinations that performed well were then evaluated for representation of relevant cognitive domains, robustness across individual years before diagnosis, and occurrence of selected items within top performing combinations.ResultsThe optimal composite cognitive test score comprised seven cognitive tests/subtests with an MSDR = 0.964. By comparison, the most sensitive individual test score was Logical Memory Delayed Recall with an MSDR = 0.64.ConclusionsWe have identified a composite cognitive test score representing multiple cognitive domains that has improved power compared with the most sensitive single test item to track preclinical AD decline and evaluate preclinical AD treatments. We are confirming the power of the composite in independent cohorts and with other analytical approaches, which may result in refinements, have designated it as the primary endpoint in the Alzheimer's Prevention Initiative's preclinical treatment trials for individuals at high imminent risk for developing symptoms due to late-onset AD.     

The neuropsychology of preclinical Alzheimer's disease and mild cognitive impairment

Subjects in the preclinical stages of Alzheimer's disease (AD) typically record neuropsychological performance between that of healthy older individuals and demented patients. More specifically, deficits on measures of verbal episodic memory are commonly reported in these patients, while other cognitive functions (e.g. language, praxis and executive function) seem to be spared. A similar neuropsychological profile is observed in elderly subjects with mild cognitive impairment (MCI), a disorder that is attracting increasing research interest. Evidence from lesion and functional imaging studies, as well as volumetric imaging in probable AD and MCI patients, suggests that the cognitive deficits observed in these disorders may be related to medial temporal lobe dysfunction. An issue currently under investigation is whether MCI represents the preclinical stages of AD or a distinct and static cognitive aetiology. In an attempt to address this issue, present investigations are adopting a convergent approach to the detection of preclinical AD, where multiple risk factors are considered when making a diagnosis.     

Medial Temporal Atrophy and Memory Dysfunction in Poststroke Cognitive Impairment-No Dementia

Background and Purpose

It was recently reported that the prevalence of poststroke memory dysfunction might be higher than previously thought. Stroke may exist concomitantly with underlying Alzheimer''s disease (AD), and so we determined whether post-stroke memory dysfunction indicates manifestation of underlying subclinical AD.

Methods

Of 1201 patients in a prospective cognitive assessment database, we enrolled subjects with poststroke amnestic vascular cognitive impairment-no dementia (aVCIND; n=48), poststroke nonamnestic vascular cognitive impairment-no dementia (naVCIND; n=50), and nonstroke amnestic mild cognitive impairment (aMCI; n=65). All subjects had cognitive deficits, but did not meet the criteria for dementia. A standardized neuropsychological test battery and magnetic resonance imaging were performed at least 90 days after the index stroke (mean, 473 days). Visual assessment of medial temporal atrophy (MTA) was used as a measure of underlying AD pathology.

Results

The MTA score was significantly lower in the naVCIND group (0.64±0.85, mean±SD) than in the aVCIND (1.10±1.08) and aMCI (1.45±1.13; p<0.01) groups. Multivariable ordinal logistic regression analysis revealed that compared with naVCIND, aVCIND [odds ratio (OR)=2.69; 95% confidence interval (CI)=1.21-5.99] and aMCI (OR=5.20; 95% CI=2.41-11.23) were significantly associated with increasing severity of MTA.

Conclusions

Our findings show that compared with poststroke naVCIND, the odds of having more-severe MTA were increased for poststroke aVCIND and nonstroke aMCI.     

Time course of brain volume changes in the preclinical phase of Alzheimer's disease

BackgroundStructural alterations of a large network characterize Alzheimer's disease (AD), but the time course of these changes remains unclear. The dynamic of these alterations was examined in the AD preclinical phase using data from the 10-year follow-up of a population-based cohort (Bordeaux-3City).MethodsParticipants received neuropsychological assessments every 2 years and two identical magnetic resonance imaging (MRI) exams at baseline and 4 years later. Twenty-five incident AD cases were compared with 319 subjects who remained free of dementia. Subjects were free of dementia at baseline and at follow-up MRI. Incident AD occurred after these time points.ResultsAt baseline, incident AD already presented smaller volumes only in the left amygdalo-hippocampal complex. Moreover, a higher annual rate of atrophy of the temporoparietal cortices was observed in future AD subjects during the following 4 years.ConclusionIncident AD cases present mediotemporal lesions up to 5 years before diagnosis. This neurodegenerative process seems to progressively reach the temporoparietal cortices in the AD preclinical phase.     

MRI Temporal Lobe Volume Measures and Neuropsychologic Function in Alzheimer's Disease

The authors performed quantitation of the temporal lobes using magnetic resonance imaging in 20 patients with mild-tomoderate Alzheimer's disease, 20 age-matched aged control subjects, and 26 healthy young volunteers. Compared to young subjects, aged controls showed volume reductions in amygdala (17%, p=0.02), hippocampus (15%, p=0.0001) and temporal lobe (22%, p=0.0001). Compared to aged controls, Alzheimer's subjects showed further volume reductions in amygdala (33%, p=0.0001) and hippocampus (20%, p=0.006) but not temporal lobe (7%, p=0.15). In Alzheimer's subjects, left temporal lobe volume correlated strongly with the Mini Mental State (MMSE) score (adjusted r² =0.46, p=0.0006) whereas right amygdala volume correlated inversely with the noncognitive ADAS score (adjusted r²=0.46, p=0.0006). The authors conclude that significant volume changes occur in the temporal lobe in aging and in Alzheimer's disease, with the greatest percentage reductions in the amygdala in Alzheimer's disease. Temporal neocortical atrophy and temporal limbic atrophy might be associated with different patterns of performance and behavior in Alzheimer's patients.