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Biomedical subjects

C R Jack

Publications and source records attributed to C R Jack.

At least 19 recordsLinked to original sources

Hippocampal atrophy correlates with clinical features of Alzheimer disease in African Americans.

CONTEXT: Imaging measurements may aid in the characterization and diagnosis of patients with Alzheimer disease (AD). Most research studies, however, have been performed on predominantly white study groups despite the fact that there may be biological differences in AD between African American and white patients. OBJECTIVE: To measure hippocampal volume in African American patients with AD and to correlate these measurements with the presence of AD and neuropsychological test performance. DESIGN: Survey study. SETTING: Academic center. PARTICIPANTS: Fifty-four healthy African American subjects and 32 African American patients with AD were studied. Hippocampal volumes were measured in all subjects from magnetic resonance images using established methods. MAIN OUTCOME MEASURE: Correlations were assessed between hippocampal volume and demographic variables, clinical group membership, and neuropsychological performance. RESULTS: The hippocampi of patients were atrophic with respect to those of healthy subjects (P<.01). Significant direct correlations were present between hippocampal volumes and performance on several different neuropsychological tests (r>0.5 and P<.01 for every test evaluated) when patients and healthy subjects were combined. CONCLUSIONS: Hippocampal atrophy is a feature of AD in African Americans as it is in white subjects. The neuropsychological-hippocampal volume correlations indicate that hippocampal volume measurements do represent a measure of the structural substrate of functional impairment in AD.

Black or African American↗

Functional inferences vary with the method of analysis in fMRI.

Neuroanatomic substrates of specific cognitive functions have been inferred from anatomic distributions of activated pixels during fMRI studies. With declarative memory tasks, interest has focused on the extent to which various medial temporal lobe anatomic structures are activated while subjects encode new information. The aim of this project was to examine how commonly used variations in fMRI data processing methods affect the distribution of activation in anatomically defined medial temporal lobe regions of interest (ROIs) during a complex scene-encoding task. ROIs were drawn on an MRI anatomic template formed from 3D SPGR scans of eight subjects combined in Talairach space. Separate ROIs were drawn for the posterior and anterior hippocampal formation, parahippocampal gyrus, and entorhinal cortex. Twelve different activation maps were created for each subject by using four correlation coefficients and three cluster volumes. Friedman's two-way ANOVA by ranks was used to test the hypothesis that the distribution of activated pixels among defined anatomic ROIs varied as a function of the data processing method. By simply varying the combination of correlation coefficient and cluster volume, significantly different distributions of activation within named medial temporal lobe structures were obtained from the same fMRI datasets (P < 0.015; P < 0.001). The number of subjects studied (n = 8) is in a range commonly found in the literature yet this clearly resulted in spurious associations between processing parameter variations and activation distribution. Using data processing methods that are independent of the arbitrary selection of cutoff values for thresholding activation maps may reduce the likelihood of obtaining spurious results.

Adult↗

The relationship between quantitative T2 relaxometry and memory in nonlesional temporal lobe epilepsy.

PURPOSE: We investigated the relationship between preoperative quantitative magnetic resonance imaging (MRI) T2 relaxometry and volumetry of the hippocampi and pre- and postoperative verbal memory in temporal lobectomy patients who had nonlesional temporal lobe epilepsy. METHODS: Pre- and postoperative memory data based on the Logical Memory (LM) subtest of the Wechsler Memory Scale-Revised (WMS-R) and the 30-min delayed recall trial of the Rey Auditory Verbal Learning Test (AVLT) were obtained from 26 left and 15 right temporal lobectomy patients. Coronal MRI T2 maps were generated for these 41 temporal lobectomy patients as well as 61 control patients. Hippocampal T2 relaxation times and hippocampal volumes, converted to z scores using control group data, were correlated with neuropsychological performance in the patients. RESULTS: In left temporal lobe-onset patients, high T2 in the left hippocampal body predicted higher LM performance after surgery. Asymmetrically high T2 in the left hippocampal body (i.e., the right-minus-left difference), compared with the right hippocampal body, also predicted higher LM performance after surgery. In right temporal lobe-onset patients, high T2 in the left hippocampal body predicted relatively lower AVLT performance after surgery. Multiple regression analysis in left temporal-onset patients revealed that high T2 in the left hippocampal body together with higher preoperative LM performance predict higher postoperative LM performance. CONCLUSIONS: Our findings suggest that elevated (i.e., abnormal) hippocampal T2 signal is associated with memory ability (or hippocampal functional capacity) independent of MRI-determined hippocampal atrophy. Therefore, our findings support the use of quantitative T2 relaxometry as an independent predictor of verbal memory outcome in both left and right TLE patients who are candidates for temporal lobectomy.

Adult↗

Mild cognitive impairment and Alzheimer disease: regional diffusivity of water.

PURPOSE: To compare the regional diffusivity of water in the brains of normally aging elderly people and patients with mild cognitive impairment (MCI) or Alzheimer disease. MATERIALS AND METHODS: Magnetic resonance images were obtained in 21 patients with Alzheimer disease, 19 patients with MCI, and 55 normally aging elderly control subjects without evidence of cognitive impairment. Regions of interest were drawn to compare the apparent diffusion coefficient (ADC) and the anisotropy index (AI) in frontal, parietal, temporal, occipital, anterior, and posterior cingulate white matter (WM), and the thalami and hippocampi. RESULTS: Hippocampal ADC was higher in MCI and Alzheimer disease patients than in control subjects. ADC of the temporal stem and posterior cingulate, occipital, and parietal WM was higher in Alzheimer disease patients than in control subjects. Except for occipital AI, which was lower in MCI patients than in control subjects, there were no differences in AI among the three groups for any of the regions. CONCLUSION: Hippocampal ADC was significantly different between control subjects and MCI patients, many of whom likely have preclinical Alzheimer disease. Elevation in hippocampal ADC may reflect early ultrastructural changes in the progression of Alzheimer disease.

Aged↗

Autocorrection of three-dimensional time-of-flight MR angiography of the Circle of Willis.

OBJECTIVE: The purpose of this study was to investigate the efficacy of a retrospective adaptive motion correction technique known as autocorrection for reducing motion-induced artifacts in high-resolution three-dimensional time-of-flight MR angiography of the circle of Willis. MATERIALS AND METHODS: Ten consecutive volunteers were imaged with an unenhanced gradient-recalled echo three-dimensional time-of-flight MR angiography sequence of the circle of Willis. Each volunteer was asked to rotate approximately 2 degrees after completion of one third and one half of the acquisition in the axial, sagittal, and oblique planes (45 degrees to the axial and sagittal planes). A single static data set was also acquired for each volunteer. Unprocessed and autocorrected maximum-intensity-projection images were reviewed as blinded image pairs by six radiologists and were compared on a five-point image quality scale. RESULTS: Mean improvement in image quality after autocorrection was 1.4 (p < 0.0001), 1.1 (p < 0.0001), and 0.2 (p = 0.003) observer points (maximum value, 2.0), respectively, for examinations corrupted by motion in the axial, oblique, and sagittal planes. All three axes had statistically significant improvement in image quality compared with the uncorrected images. Changes in image quality after the application of the autocorrection algorithm to static angiogram data were not statistically significant (mean change in score = -0.13 points; p = 0.29). CONCLUSION: Autocorrection can reduce artifacts in motion-corrupted MR angiography of the circle of Willis without distorting motion-free examinations.

Artifacts↗

Rates of hippocampal atrophy correlate with change in clinical status in aging and AD.

BACKGROUND: The cognitive continuum in the elderly population can be conceptually divided into those who are functioning normally (control subjects), those with a mild cognitive impairment (MCI), and those with probable AD. OBJECTIVES: To test the hypothesis that the annualized rates of hippocampal atrophy differ as a function of both baseline and change in clinical group membership (control, MCI, or AD). METHODS: The authors identified 129 subjects from the Mayo Clinic AD Research Center/AD Patient Registry who met established criteria for normal control subjects, MCI, or probable AD, both at entry and at the time of a subsequent clinical follow-up evaluation 3 +/- 1 years later. Each subject underwent an MRI examination of the head at the time of the initial assessment and at follow-up clinical assessment; the annualized percentage change in hippocampal volume was computed. Subjects who were classified as controls or patients with MCI at baseline could either remain cognitively stable or could decline to a lower functioning group over the period of observation. RESULTS: The annualized rates of hippocampal volume loss for each of the three initial clinical groups decreased progressively in the following order: AD > MC > control. Within the control and MCI groups, those who declined had a significantly greater rate of volume loss than those who remained clinically stable. The mean annualized rates of hippocampal atrophy by follow-up clinical group were: control-stable 1.73%, control-decliner 2.81%, MCI-stable 2.55%, MCI-decliner 3.69%, AD 3. 5%. CONCLUSION: Rates of hippocampal atrophy match both baseline cognitive status and the change in cognitive status over time in elderly persons who lie along the cognitive continuum from normal to MCI to AD.

Aged↗

Regional metabolic patterns in mild cognitive impairment and Alzheimer's disease: A 1H MRS study.

BACKGROUND: Mild cognitive impairment (MCI) is a recently described transitional clinical state between normal aging and AD. Assuming that amnestic MCI patients had pathologic changes corresponding to an early phase and probable AD patients to a later phase of the disease progression, the authors could approximate the temporal course of proton MR spectroscopic (1H MRS) alterations in AD with a cross-sectional sampling scheme. METHODS: The authors compared 1H MRS findings in the superior temporal lobe, posterior cingulate gyri, and medial occipital lobe in 21 patients with MCI, 21 patients with probable AD, and 63 elderly controls. These areas are known to be involved at different neurofibrillary pathologic stages of AD. RESULTS: The N-acetylaspartate (NAA)/creatine (Cr) ratios were significantly lower in AD patients compared to both MCI and normal control subjects in the left superior temporal and the posterior cingulate volumes of interest (VOI) and there were no between-group differences in the medial occipital VOI. Myoinositol (MI)/Cr ratios measured from the posterior cingulate VOI were significantly higher in both MCI and AD patients than controls. The choline (Cho)/Cr ratios measured from the posterior cingulate VOI were higher in AD patients compared to both MCI and control subjects. CONCLUSION: These findings suggest that the initial 1H MRS change in the pathologic progression of AD is an increase in MI/Cr. A decrease in NAA/Cr and an increase in Cho/Cr develop later in the disease course.

Aged↗

Usefulness of MRI measures of entorhinal cortex versus hippocampus in AD.

OBJECTIVE: MRI-based measurements of hippocampal atrophy are a sensitive indicator of the early pathologic degeneration of the medial temporal lobe in AD. However, AD pathology appears first in the transentorhinal/entorhinal cortex, not the hippocampus. The authors tested the hypothesis that MRI-based measurements of the entorhinal cortex are more sensitive than measurements of hippocampal volume in discriminating among three clinical groups; controls, patients with a mild cognitive impairment (MCI), and patients with mild probable AD. METHODS: The authors studied 30 controls, 30 patients with MCI, and 30 patients with AD who were matched among clinical groups on age, gender, and education. All underwent a standardized MRI protocol from which the authors made measurements of hippocampal volume, entorhinal cortex volume, and the cumulative length of the medial border of the entorhinal cortex. RESULTS: Pairwise intergroup differences (p < 0.01) were found for all MRI measurements with the exception of the cumulative length of the entorhinal cortex, which did not differentiate controls from MCI patients. Whereas the hippocampal and entorhinal cortex volume measurements provided slightly better intergroup discrimination than the entorhinal distance measurement, overall differences in discriminating ability among the three MRI measurements were minor. CONCLUSIONS: Despite the theoretical rationale for the superiority of entorhinal measurements in early AD, the authors found MRI measurements of the hippocampus and entorhinal cortex were approximately equivalent at intergroup discrimination. Measurements of the hippocampus may be preferable because MRI depiction of the boundaries of the entorhinal cortex can be obscured by anatomic ambiguity, image artifact, or both.

Aged↗

Memory and MRI-based hippocampal volumes in aging and AD.

OBJECTIVE: To demonstrate structural-functional relationships between MRI-based volumetric measurements of medial temporal lobe structures and cognitive function. BACKGROUND: Previous work has documented the ability of MRI-based measurements of the hippocampus to discriminate between age-matched control subjects and patients with very mild AD. Relatively less is known about the correlation between medial temporal lobe structures and cognitive functions. METHOD: We evaluated structural-functional relationships among the hippocampal formation, parahippocampal gyrus, and amygdala, and measures of memory, language, and general cognitive performance in 220 probable AD patients and normal control subjects. Standardized instruments of memory and general cognitive function were used to assess subjects enrolled in a longitudinal study of aging and dementia. RESULTS: The volume of the hippocampal formation predicted performance on most acquisition and recall measures across the spectrum of normal aging and AD. If the groups were segregated, most of the expected associations between medial temporal lobe structures and memory measures were observed in the AD patients. CONCLUSION: MRI-based hippocampal volumetry accurately depicts the structural-functional relationships between memory loss and hippocampal damage across the spectrum from normal aging to dementia.

Aged↗

Prospective multiaxial motion correction for fMRI.

Corruption of the image time series due to interimage head motion limits the clinical utility of functional MRI. This paper presents a method for real-time prospective correction of rotation and translation in all six degrees of rigid body motion. By incorporating an orbital navigator (ONAV) echo for each of the sagittal, axial, and coronal planes into the fMRI pulse sequence, rotation and translation can be measured and the spatial orientation of the image acquisition sequence that follows can be corrected prospectively in as little as 160 msec. Testing of the method using a computerized motion phantom capable of performing complex multiaxial motion showed subdegree rotational and submillimeter translational accuracy over a range of +/-8 degrees and +/-8 mm of motion. In vivo images demonstrate correction of simultaneous through-plane and in-plane motion and improved detection of fMRI activation in the presence of head motion.

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Factors predictive of the outcome of frontal lobe epilepsy surgery.

PURPOSE: To identify factors that predict the outcome in seizure control after frontal lobe epilepsy surgery (FLES). FLES is the second most frequent type of epilepsy surgery, but the results are generally not as good as those after anterior temporal lobectomy. METHODS: Our cohort consisted of 68 consecutive patients whose first epilepsy surgery involving the frontal lobe occurred between 1987 and 1994. Clinical history and results of imaging and electroencephalographic studies were reviewed in detail. Excellent outcome was defined as being seizure free or having only nondisabling seizures at last follow up. RESULTS: Forty of the 68 patients (58.8%) had an excellent outcome; none of the patients with a history of childhood febrile seizures had an excellent outcome, whereas outcome was excellent in 63% of those without that history (p </= 0.01). The other significant presurgical factor was the presence of a potentially epileptogenic lesion in the frontal lobe on neuroimaging (excellent outcome in 72% when present versus 41% when absent, p </= 0.001). The only significant postsurgical factor was early postoperative seizure control in the first year (excellent outcome in 96% with early control versus 25% without, p </= 0.01). CONCLUSIONS: History of childhood febrile seizures is a poor prognostic factor in FLES patients. It may suggest that the structural basis of all or some of the patients' intractable seizures is mesial temporal sclerosis. On the other hand, neuroimaging detection of a potentially epileptogenic frontal lobe lesion and early postoperative seizure control are associated with subsequent excellent outcome.

Adult↗

Significance of cerebellar atrophy in intractable temporal lobe epilepsy: a quantitative MRI study.

PURPOSE: To determine the incidence of cerebellar atrophy (CA) in patients with intractable temporal lobe epilepsy, whether any clinical factors are significantly associated with CA, whether CA is unilateral or asymmetric and whether this feature has any relationship to the side of epileptogenicity, and whether the presence of CA is related to epilepsy surgery outcome. METHODS: We developed a magnetic resonance imaging method of measuring the presurgical volumes of the cerebellar hemispheres of 185 patients who underwent temporal lobectomy for intractable epilepsy and of 80 control subjects. In addition, cerebellar volumes were normalized to the total brain volumes. CA was determined as being present when the measured volume was smaller than two standard deviations from the mean value found in control subjects. RESULTS: Both absolute and normalized cerebellar volumes were found to be significantly reduced in the epilepsy patients compared with the control subjects. Without normalization of the cerebellar volumes, CA was present in 25.9% of the epilepsy patients; with normalization, it was present in only 16.2%. The atrophy was symmetric between the cerebellar hemispheres, and there was no significant difference in volume between the hemisphere ipsilateral and the hemisphere contralateral to the side of the temporal lobectomy. The duration of epilepsy was significantly longer and the age at onset of epilepsy was younger in patients with CA than in those without CA. The presence of CA was not associated with the outcome of temporal lobectomy. CONCLUSIONS: CA is symmetric and common in patients with intractable temporal lobe epilepsy. However, the results suggest that the atrophy in one third of patients with CA also proportionately affects the cerebral hemispheres. The duration of epilepsy and the age at onset of epilepsy are associated with the occurrence of CA. Seizure control after temporal lobectomy is not influenced by the presence of CA.

Adult↗

Prediction of AD with MRI-based hippocampal volume in mild cognitive impairment.

OBJECTIVE: To test the hypothesis that MRI-based measurements of hippocampal volume are related to the risk of future conversion to Alzheimer's disease (AD) in older patients with a mild cognitive impairment (MCI). BACKGROUND: Patients who develop AD pass through a transitional state, which can be characterized as MCI. In some patients, however, MCI is a more benign condition, which may not progress to AD or may do so slowly. PATIENTS: Eighty consecutive patients who met criteria for the diagnosis of MCI were recruited from the Mayo Clinic Alzheimer's Disease Center/Alzheimer's Disease Patient Registry. METHODS: At entry into the study, each patient received an MRI examination of the head, from which the volumes of both hippocampi were measured. Patients were followed longitudinally with approximately annual clinical/cognitive assessments. The primary endpoint was the crossover of individual MCI patients to the clinical diagnosis of AD during longitudinal clinical follow-up. RESULTS: During the period of longitudinal observation, which averaged 32.6 months, 27 of the 80 MCI patients became demented. Hippocampal atrophy at baseline was associated with crossover from MCI to AD (relative risk [RR], 0.69, p = 0.015). When hippocampal volume was entered into bivariate models-using age, postmenopausal estrogen replacement, standard neuropsychological tests, apolipoprotein E (APOE) genotype, history of ischemic heart disease, and hypertension-the RRs were not substantially different from that found univariately, and the associations between hippocampal volume and crossover remained significant. CONCLUSION: In older patients with MCI, hippocampal atrophy determined by premorbid MRI-based volume measurements is predictive of subsequent conversion to AD.

Aged↗

Subtraction SPECT co-registered to MRI improves postictal SPECT localization of seizure foci.

OBJECTIVE: To determine whether the detection of focal hypoperfusion by subtraction SPECT co-registered to MRI (SISCOM) improves the sensitivity and specificity of postictal SPECT in intractable partial epilepsy. BACKGROUND: Postictal SPECT injections are easier to perform than are ictal injections, but the images are more difficult to interpret and have been reported to have lower sensitivity and specificity. METHODS: Thirty-five consecutive intractable partial epilepsy patients who had postictal SPECT studies were evaluated. The following sets of SPECT images were separately interpreted by three blinded reviewers and classified as either localizing to 1 of 16 possible sites in the brain or as nonlocalizing: unsubtracted postictal and interictal images for conventional side-by-side comparison, SISCOM images of hyperperfusion, SISCOM images of hypoperfusion, and both sets of SISCOM hyperperfusion and hypoperfusion images (combined SISCOM evaluation). RESULTS: Significantly higher proportions of the hyperperfusion SISCOM images (65.7%), the hypoperfusion SISCOM images (74.3%), and the combined SISCOM evaluation (82.9%) were localizing than were the conventional method of side-by-side comparison of unsubtracted images (31.4%; p < 0.0001). Concordance with the discharge diagnosis was higher for the combined SISCOM evaluation than it was for either the hyperperfusion or the hypoperfusion SISCOM images alone (both p < 0.05). For the hypoperfusion SISCOM and the combined SISCOM evaluations, concordance of the localization with the site of epilepsy surgery was associated with a greater probability of an excellent outcome than were nonconcordant/nonlocalizing images (both p < 0.05). CONCLUSION: The use of SISCOM to detect focal cerebral hypoperfusion, in addition to focal hyperperfusion, improves the sensitivity and specificity of postictal SPECT in intractable partial epilepsy.

Adolescent↗

Comparative study of 99mTc-ECD and 99mTc-HMPAO for peri-ictal SPECT: qualitative and quantitative analysis.

OBJECTIVES: Most studies that clinically validated peri-ictal SPECT in intractable partial epilepsy had used technetium-99m-hexamethylpropylene amine oxime (99mTc-HMPAO or 99mTc-exametazime) as the radiopharmaceutical. Because of some theoretical advantages, technetium-99m-ethyl cysteinate diethylester (99mTc-ECD or 99mTc-bicisate) is increasingly being used instead. This study compares unstabilised 99Tc-HMPAO and 99mTc-ECD in the performance of peri-ictal SPECT in partial epilepsy. METHODS: The injection timing and localisation rates in 49 consecutive patients with partial epilepsy who had peri-ictal injections with unstabilised 99mTc-HMPAO were compared with 49 consecutive patients who had peri-ictal injections with 99mTc-ECD. Quantitative cortical/subcortical and cortical/extracerebral uptake ratios were also compared. Subtraction SPECT coregistered to MRI (SISCOM) was performed in patients whose interictal SPECTS were available. RESULTS: In the 99mTc-ECD patients, the latency from seizure commencement to injection was shorter (median 34 v 80 seconds, p<0.0001) and there was a lower rate of postictal injections (16.3% v 57.1%, p<0.0001). The cortical/extracerebral and cortical/subcortical uptake ratios were greater in the 99mTc-ECD images (median 5.0 v 3.6, and 2.5 v 2.2 respectively; both p<0.005), but the relative peri-ictal increase in uptake in the cortical focus did not differ significantly (median 37.0% v 37.0%; p>0.05). Blinded review of the SISCOM images were localising in a higher proportion of the 99mTc-ECD patients (40/45 (88.9%) v 25/37 (67.6%), p<0.05), and had a better concordance with EEG, MRI, and with the discharge diagnosis. CONCLUSION: 99mTc-ECD compares favourably with unstabilised 99mTc-HMPAO as a radiopharmaceutical for peri-ictal SPECT studies. Its use results in earlier injections and less frequent postictal injections than unstabilised 99mTc-HMPAO, thereby enhancing the sensitivity and the specificity of peri-ictal SPECT for the localisation of intractable partial epilepsy.

Adolescent↗

Progressive hippocampal atrophy in chronic intractable temporal lobe epilepsy.

We report on a 28-year-old man with long-standing intractable complex partial and secondary generalized seizures, whose magnetic resonance imaging scans 4 years apart documented progressive decrease in the left hippocampal volume. Left anterior temporal lobectomy with amygdalohippocampectomy rendered the patient seizure free at 12 months' follow-up. The findings demonstrate that patients with uncontrolled temporal lobe seizures may develop progressive atrophy of the hippocampus, in the absence of status epilepticus.

Adult↗

Assessment of functional MR imaging in neurosurgical planning.

BACKGROUND AND PURPOSE: Presurgical sensorimotor mapping with functional MR imaging is gaining acceptance in clinical practice; however, to our knowledge, its therapeutic efficacy has not been assessed in a sizable group of patients. Our goal was to identify how preoperative sensorimotor functional studies were used to guide the treatment of neuro-oncologic and epilepsy surgery patients. METHODS: We retrospectively reviewed the medical records of 46 patients who had undergone preoperative sensorimotor functional MR imaging to document how often and in what ways the imaging studies had influenced their management. Clinical management decisions were grouped into three categories: for assessing the feasibility of surgical resection, for surgical planning, and for selecting patients for invasive functional mapping procedures. RESULTS: Functional MR imaging studies successfully identified the functional central sulcus ipsilateral to the abnormality in 32 of the 46 patients, and these 32 patients are the focus of this report. In epilepsy surgery candidates, the functional MR imaging results were used to determine in part the feasibility of a proposed surgical resection in 70% of patients, to aid in surgical planning in 43%, and to select patients for invasive surgical functional mapping in 52%. In tumor patients, the functional MR imaging results were used to determine in part the feasibility of surgical resection in 55%, to aid in surgical planning in 22%, and to select patients for invasive surgical functional mapping in 78%. Overall, functional MR imaging studies were used in one or more of the three clinical decision-making categories in 89% of tumor patients and 91% of epilepsy surgery patients. CONCLUSION: Preoperative functional MR imaging is useful to clinicians at three key stages in the preoperative clinical management paradigm of a substantial percentage of patients who are being considered for resective tumor or epilepsy surgery.

Adolescent↗

Hippocampal atrophy and apolipoprotein E genotype are independently associated with Alzheimer's disease.

A variety of anatomic and functional neuroimaging findings are associated with Alzheimer's disease (AD). One of the strongest imaging associations identified is between AD and hippocampal atrophy. The epsilon4 allele of the apolipoprotein E (ApoE) gene increases the risk of developing AD and lowers the mean age of onset of the disease. The purpose of this study was to assess the association between hippocampal volume and ApoE polymorphisms in elderly control subjects and in patients with probable AD. We performed magnetic resonance imaging-based volume measurements of the hippocampus in 125 cognitively normal elderly controls and 62 patients with probable AD. ApoE genotyping was performed by using standard methods. Hippocampal volumes were significantly smaller in AD cases than in control subjects. Hippocampal volumes did not differ significantly within either clinical group on the basis of ApoE genotype. Both the epsilon4 allele of ApoE and hippocampal atrophy were significantly but independently associated with AD.

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