Hemispheric differences in hippocampal volume predict verbal and spatial memory performance in patients with Alzheimer's disease

Atrophy of the hippocampal formation, a region important for the acquisition of new declarative knowledge, has been well-documented in Alzheimer's disease (AD), although the relation of such atrophy to the extent of memory dysfunction in these patients has been less clear. In the present study, 18 patients with a clinical diagnosis of probable AD were studied with a high-resolution, quantitative magnetic resonance imaging (MRI) protocol, as well as the verbal and spatial versions of the Buschke controlled learning task. The volumes of the hippocampal formation and, as a control for generalized atrophy, parahippocampal gyrus and temporal neocortex were computed from gapless coronal slices taken perpendicular to the long axis of the hippocampus. To correct for individual differences in brain size, volumes of regions of interest were divided by total intracranial volume. Separate stepwise regression analyses (with age, right and left hippocampal, parahippocampal gyrus, and temporal lobe volumes as the independent variables) showed that left hippocampal volume was the best predictor of free recall and delayed free recall of verbal information (P = 0.0042 and P < 0.0001, respectively). Recall and delayed recall of the spatial location of verbal items were best predicted by right hippocampal volume (P = 0.0054 and P = 0.0118, respectively). Memory scores did not correlate either with parahippocampal gyrus or temporal lobe volume. Furthermore, the relation between hippocampal volume and memory function observed in cases with AD did not hold for healthy aged control subjects.     

Visual rating of the hippocampus in non‐demented elders: Does it measure hippocampal atrophy or other indices of brain atrophy? The SMART‐MR study

Visual rating of hippocampal atrophy is often used to differentiate between normal aging and Alzheimer's disease. We investigated whether two visual rating scales of hippocampal atrophy were related to hippocampal volumes, and if visual rating was related to global, cortical and subcortical brain atrophy in persons without dementia. Within the SMART‐MR study, a prospective cohort study among patients with manifest arterial disease, medial temporal lobe atrophy was qualitatively rated in 95 participants without dementia (mean age 62 ± 10 years) using two visual rating scales: the medial temporal lobe (MTA) score was rated on coronal oriented images and the perihippocampal cerebrospinal fluid (HCSF) score was rated on axial oriented images. Hippocampal volume assessed by manual segmentation on a 3‐dimensional FFE T1‐weighted MR image. Automated segmentation was used to quantify volumes of brain tissue and cerebrospinal fluid. Total brain volume, gray matter volume, and ventricular volume were divided by intracranial volume to obtain brain parenchymal fraction (BPF), gray matter fraction (GMF) and ventricular fraction (VF). Using ANOVA, crude hippocampal volumes were smaller with increasing MTA and HSCF scores as were hippocampal volumes normalized for intracranial volume (P < 0.05). However, hippocampal volumes normalized for total brain size were not smaller with increasing MTA or HSCF scores (P = 0.33 and P = 0.49). Also, with increasing visual rating scores, BPF was smaller and VF was larger (P < 0.001), and the GMF decreased with increasing HCSF score (P = 0.008). In this nondemented population, visual rating of the medial temporal lobe reflects hippocampal atrophy as well as global and subcortical atrophy. © 2009 Wiley‐Liss, Inc.     

A comparison of medial and lateral temporal lobe atrophy in dementia with Lewy bodies and Alzheimer's disease: magnetic resonance imaging volumetric study

OBJECTIVES: To compare medial and lateral temporal lobe atrophy on magnetic resonance imaging (MRI) in dementia with Lewy bodies (DLB) and Alzheimer's disease (AD), and to examine the relationship between volumetric indices and cognitive and non-cognitive symptoms. METHODS: T(1)-weighted 1.0-tesla MRI scans were acquired in elderly subjects with DLB (n = 26; mean age = 75.8 years) and AD (n = 22; 77.3 years) and normal controls (n = 26; 76.2 years). MRI-based volume measurements of the hippocampus, parahippocampus, fusiform gyrus, combined inferior and middle temporal gyri, and superior temporal gyrus were acquired. RESULTS: Hippocampal and parahippocampal volumes were significantly larger in subjects with DLB compared to AD. Differences in hippocampal volumes between DLB and AD were observed across the entire length, and in all subjects with dementia there was a loss of hippocampal asymmetry compared to normal controls. Atrophy of temporal lobe structures correlated with memory impairment in both groups, and with age in DLB. There was no association between atrophy and psychotic symptoms in either group. CONCLUSIONS: Subjects with DLB and AD have a different pattern of temporal lobe atrophy with the most striking differences relating to medial rather than lateral temporal lobe structures. These structural differences could explain the relative preservation of memory function in DLB compared to AD.     

Disconnection of hippocampal networks contributes to memory dysfunction in individuals with temporal lobe epilepsy

A deficit in declarative memory function is common among individuals with temporal lobe epilepsy. The purpose of this study is to evaluate the relationship between the volume of the hippocampus, entorhinal cortex along with the surrounding parahippocampal white matter and memory performance in those with temporal lobe epilepsy. T1 weighted MRI scans were acquired using a 3‐D pulse sequence in 50 individuals with temporal lobe epilepsy. Hippocampal and entorhinal cortex volumes were derived by manually tracing consecutive coronal slices aligned perpendicular to the long axis of the hippocampus. In addition, parahippocampal white matter volumes were determined using voxel based morphometry. Finally, declarative memory was assessed using immediate and delayed verbal and visual memory tests from the Wechsler Memory Scale third edition. Significant correlations were seen between right and left hippocampal volumes and delayed verbal memory test scores. In addition, left parahippocampal white matter showed positive correlations with immediate and delayed verbal and visual recall. Furthermore, regression models found that the right hippocampus and left parahippocampal white matter were the best predictors of immediate and delayed verbal and visual memory performance. These results show that a decrease in white matter fibers projecting to the hippocampus may cause a disruption of incoming multi‐modal sensory information, contributing to the memory decline seen in individuals with temporal lobe epilepsy.     

Temporal lobe rating scale: application to Alzheimer's disease and frontotemporal dementia

OBJECTIVES: Temporal lobe atrophy as assessed by MRI can be measured in several ways. Volumetric measurements are quantitative but very time consuming and require extensive training to perform, so are not easily transferable to clinical practice. Visual rating scales, by contrast, are quick and widely applicable. Although medial temporal lobe atrophy is well described in Alzheimer's disease (AD), it is uncertain how early these changes can be detected and whether they discriminate AD from other neurodegenerative diseases, most notably frontotemporal dementia (FTD). The objectives were (1) to develop a widely applicable temporal lobe rating scale, and (2) to characterise and quantify the patterns of temporal lobe atrophy in AD versus temporal and frontal variants of FTD. METHODS: The temporal lobe assessments were made using an established hippocampal rating scale extended to incorporate additional temporal regions. This was firstly validated with volumetric analysis and then applied to 30 probable AD, 30 FTD (consisting of 17 temporal variant (semantic dementia) and 13 frontal variant) and 18 control coronal MRI images. RESULTS: Bilateral hippocampal atrophy was found in 50% of the patients with AD. Contrary to expectations, patients with semantic dementia also had hippocampal atrophy, which for the left side exceeded that seen in AD; other regions (temporal pole, parahippocampal gyrus, and lateral temporal lobe), spared in AD, were severely atrophied in this group. The patients with frontal variant FTD occupied an intermediate position and were largely indistinguishable from AD. CONCLUSIONS: Hippocampal atrophy is, therefore, not specific for AD. Semantic dementia can be distinguished from AD, by the presence of severe bilateral atrophy of the temporal pole, parahippocampal and lateral regions. These findings have implications for the differential diagnosis of dementias.     

Correlates of memory function in community-dwelling elderly: the importance of white matter hyperintensities.

We sought to identify magnetic resonance- (MR)-imaged structures associated with declarative memory in a community-dwelling sample of elderly Mexican-American individuals with a spectrum of cognitive decline. Measured structures were the hemispheric volumes of the hippocampus (HC), parahippocampal gyrus, and remaining temporal lobes, as well as severity of white matter signal hyperintensities (WMH). Participants were an imaged subsample from the Sacramento Area Latino Study of Aging (SALSA), N = 122. Individuals were categorized as normal, memory impaired (MI), cognitively impaired non-demented (CIND), or demented. We show that WMH was the strongest structural predictor for performance on a delayed free-recall task (episodic memory) in the entire sample. The association of WMH with delayed recall was most prominent in elderly normals and mildly cognitively impaired individuals with no dementia or impairment of daily function. However, the left HC was associated with verbal delayed recall only in people with dementia. The right HC volume predicted nonverbal semantic-memory performance. We conclude that WMH are an important pathological substrate that affects certain memory functions in normal individuals and those with mild memory loss and discuss how tasks associated with WMH may rely upon frontal lobe function.     

Medial temporal lobe atrophy in patients with refractory temporal lobe epilepsy

OBJECTIVE: The objective of this study was to assess the volumes of medial temporal lobe structures using high resolution magnetic resonance images from patients with chronic refractory medial temporal lobe epilepsy (MTLE). METHODS: We studied 30 healthy subjects, and 25 patients with drug refractory MTLE and unilateral hippocampal atrophy (HA). We used T1 magnetic resonance images with 1 mm isotropic voxels, and applied a field non-homogeneity correction and a linear stereotaxic transformation into a standard space. The structures of interest are the entorhinal cortex, perirhinal cortex, parahippocampal cortex, temporopolar cortex, hippocampus, and amygdala. Structures were identified by visual examination of the coronal, sagittal, and axial planes. The threshold of statistical significance was set to p<0.05. RESULTS: Patients with right and left MTLE showed a reduction in volume of the entorhinal (p<0.001) and perirhinal (p<0.01) cortices ipsilateral to the HA, compared with normal controls. Patients with right MTLE exhibited a significant asymmetry of all studied structures; the right hemisphere structures had smaller volume than their left side counterparts. We did not observe linear correlations between the volumes of different structures of the medial temporal lobe in patients with MTLE. CONCLUSION: Patients with refractory MTLE have damage in the temporal lobe that extends beyond the hippocampus, and affects the regions with close anatomical and functional connections to the hippocampus.     

CSF Abeta42, tau and phosphorylated tau correlate with medial temporal lobe atrophy

Cerebrospinal fluid (CSF) biomarkers and medial temporal lobe (MTL) atrophy predict the progression of mild cognitive impairment (MCI) to Alzheimer's disease (AD). We investigated the association between the CSF biomarkers and MTL atrophy and the ability of these measures to predict AD in MCI patients in the same study population. The study included 21 MCI patients of whom eight progressed to AD during the study. CSF biomarkers were measured by using ELISA method and volumes of MTL structures were assessed by magnetic resonance imaging (MRI). Abeta42 levels were lower and tau and phospho-tau levels were higher in progressive subjects. The progressive subjects had lower volumes in all MRI measures. Tau and phospho-tau correlated inversely with hippocampal volumes and left entorhinal cortex volume in the whole study group. In the stable group, tau correlated with hippocampal volumes. Abeta42 had a negative correlation whereas phospho-tau exhibited a positive correlation with left hippocampal volume in the progressive group. These results indicate that both measures may reflect the ongoing neurodegenerative process in the progressive MCI patients. However, the order of the changes in the CSF biomarkers and MTL atrophy remain unclear due to a small number of studied subjects and study design.     

Left hippocampal volume loss in Alzheimer's disease is reflected in performance on odor identification: a structural MRI study.

The very high sensitivity and specificity of odor identification tasks in discriminating between Alzheimer's patients and normals suggests that they reflect the presence of underlying neuropathology. Significant neuropathological changes are seen in areas critical to processing olfactory information, even in the early stages of Alzheimer's disease (AD). The current study was designed to investigate whether performance on olfactory tasks (odor threshold and odor identification) was related to volumetric MRI measures of mesial temporal areas central to olfactory information processing and important in the neuropathology of AD. Participants were 8 male and 5 female patients with probable AD, and 10 male and 12 female normal age-matched controls, diagnosed at the UCSD Alzheimer's Disease Research Center. The study investigated correlations between volumetric measures of hippocampus, the parahippocampal gyrus and the amygdala, and the psychophysical measures of olfactory function. Robust relationships were observed between mesial temporal lobe volumes and olfactory functional measures. The finding of a strong relationship between left hippocampal volume and performance on the odor identification task (r = .85) is compatible with a left-hemisphere superiority for verbally mediated olfactory tasks. The findings suggest a neural substrate for the breakdown in functional performance on verbally mediated odor identification tasks in Alzheimer's disease and suggest the utility of quantitative MRI measures and psychophysical performance in the assessment of AD. These results support the potential clinical utility of inclusion of odor identification tests in diagnostic batteries for detecting AD.     

Evidence of a smaller left hippocampus and left temporal horn in both patients with first episode schizophrenia and normal control subjects

Findings from cerebral magnetic resonance imaging (MRI) studies in schizophrenia indicating temporal lobe involvement have been inconsistent and controversial. In a prospective study, we quantified the volumes of temporal lobe structures in 20 male patients with first episode schizophrenia (FES; mean+/-S.D.=27.4+/-4. 8 years) and 20 healthy age-matched male control subjects (27.7+/-3. 1 years). Measurements were performed on contiguous 2.2-mm coronal MRI slices, which included, as well as the temporal lobe, the amygdala, the hippocampal formation, and the temporal horn of the lateral ventricle. The definition of the borders of the structures relied on measurement guidelines derived from mutual comparisons of MRI and histological data. The definition of the hippocampus-amygdala interface was also validated in a correlated triplanar display. We did not detect any significant volume reductions of the measured structures in the FES group, as compared with healthy control subjects, on either side. Comparisons within groups, however, revealed that in both the patients and the healthy volunteers the hippocampal formations showed a significant right-sided bias (+9%, P=0.004, in the FES group; +12%, P=0.0003 in the control subjects). A significant volume difference in favor of the right hemisphere was also observed in the temporal horns of the lateral ventricles (+17%, P=0.02 in the patients with FES; +34%, P=0. 003, in the control group). There was only a nonsignificant trend for a larger temporal horn on the left side in patients with schizophrenia as compared with the control subjects. Our findings do not indicate a loss or reversal of the normal volume asymmetry pattern in the FES group.     

Changes in the volume of temporal lobe structures related to Alzheimer's type dementia

We compared the volumes of the superior temporal gyrus, basolateral temporal area, parahippocampal gyrus, hippocampal head, amygdaloid body and the inferior horn of the lateral ventricle in 29 patients with dementia of Alzheimer's type (DAT) and in 14 cognitively normal controls. Measurements were performed on coronal MR images perpendicular to the long axis of the hippocampus then the raw data were normalised for intracranial volume. The volumes of all studied structures were significantly smaller in patients with DAT than in age-matched control group. The differences in the volume between DAT and age-matched control group were the largest for the amygdaloid body and the basolateral temporal area. The discriminant analysis including the volume of both the basolateral area and the left amygdaloid body allows for correct classification of 100% DAT patients and 93% controls. We conclude that the estimation of the volume of the amygdaloid body and basolateral temporal area seems to be the most important factor for DAT diagnosis.     

MRI volumetric study of dementia with Lewy bodies: a comparison with AD and vascular dementia

OBJECTIVE: To compare global and regional atrophy on MRI in subjects with dementia with Lewy bodies (DLB), AD, vascular dementia (VaD), and normal aging. In addition, the relationship between APOE-epsilon4 genotype and volumetric indices was examined. METHOD: MRI-based volume measurements of the whole-brain, ventricles, frontal lobe, temporal lobe, hippocampus, and amygdala were acquired in elderly subjects with DLB (n = 27; mean age = 75.9 years), AD (n = 25; 77.2 years), VaD (n = 24; 76.9 years), and normal control subjects (n = 26; 76.2 years). RESULTS: Subjects with DLB had significantly larger temporal lobe, hippocampal, and amygdala volumes than those with AD. No significant volumetric difference between subjects with DLB and VaD was observed. Compared with control subjects, ventricular volumes were increased in all patients with dementia, though those with DLB showed a relative preservation of whole-brain volume. There were no significant differences in frontal lobe volumes between the four groups. APOE-epsilon4 status was not associated with volumetric indices. CONCLUSION: The findings support the hypothesis that DLB is associated with a relative preservation of temporal lobe structures. In the differentiation of DLB and AD, this may have important implications for diagnosis.     

Basal ganglia and limbic system pathology in schizophrenia. A morphometric study of brain volume and shrinkage

The volume of several parts of the basal ganglia and of the limbic system was measured by planimetry of myelin-stained serial sections in postmortem brains of 13 schizophrenic patients and nine control cases. The medial limbic structures of the temporal lobe (amygdala, hippocampal formation, and parahippocampal gyrus) and the pallidum internum were significantly smaller in the schizophrenic group, whereas the pallidum externum showed only a modest trend toward volume reduction. The volumes of the putamen, nucleus caudatus, nucleus accumbens, and the bed nucleus of the stria terminalis did not differ between patients and controls. The volume reductions of the limbic temporal structures and of the pallidum internum of schizophrenics are interpreted as degenerative shrinkages of unknown etiology.     

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.     

Cortical and Hippocampal Volume Deficits in Temporal Lobe Epilepsy

Summary: Purpose : To use quantitative magnetic resonance imaging (MRI) methods to examine the extent of volume abnormalities in the hippocampus and in extrahippocampal brain regions in localization-related epilepsy of temporal lobe origin (TLE).
Methods : Hippocampal, temporal lobe, and extratemporal lobe volumes were examined with 3–mm spin-echo coronal MRI scans in patients with unilateral TLE who were candidates for temporal lobe resection. Measures were adjusted for normal variation due to intracranial volume and age based on 72 healthy male controls. Group differences between 14 male TLE [7 left TLE (LTLE), 7 right TLE (RTLE)] patients and a subset of 49 age range-matched controls were examined with analysis of variance (ANOVA).
Results : As compared with controls, patients with TLE had smaller temporal lobe and frontoparietal region gray matter volumes, bilaterally, smaller temporal lobe white matter volumes bilaterally, and larger ventricular volumes. In contrast to these bilateral tissue volume deficits, hippocampal volume deficits in TLE were ipsilateral to the epileptogenic temporal lobe.
Conclusions : Extrahippocampal volume abnormalities were bilateral and occurred in both temporal and extra-temporal cortical regions in TLE, whereas hippocampal deficits were related to the side of the epileptogenic focus. These data suggest that brain abnormalities in TLE are not limited to the epileptogenic region.     

Parkinson's disease is associated with hippocampal atrophy.

Patients with Parkinson's disease (PD) may have hippocampal atrophy compared with controls. We compared hippocampal, and extra-hippocampal volumes between PD, PDD (patients with PD who have mild cognitive impairment or dementia), Alzheimer's disease (AD) and controls using volumetric magnetic resonance imaging (MRI). Participants (10 patients with PD, 10 with PDD, 11 with AD, and 12 control subjects) had an informant interview, neurological examination, and psychometric testing. Established, reliable methods were used to measure the hippocampus, parahippocampal gyrus, temporal, frontal, and parieto-occipital lobes. Correction for intracranial volume was carried out before comparison. There was no age difference between groups (mean age, 74 years). On the Clinical Dementia Rating scale (CDR) cognitive impairment was mild (CDR = 0.5) in the majority of PDD and AD patients. Hippocampal (P < 0.0004) volumes were smaller in the patient groups. Effect sizes compared with the control group were: PD, 0.66; PDD, 1.22; and AD, 1.81. The other volumes did not differ significantly. Among PD and PDD patients, recognition memory (r = 0.54, P = 0.015) and Mini-Mental State Examination scores (r = 0.56, P = 0.01) correlated with left, but not right hippocampal volume. In conclusion, hippocampal volume showed a pattern (Control > PD > PDD > AD) suggesting progressive hippocampal volume loss in PD. Volumetric MRI imaging might provide an early marker for dementia in PD.     

Relation of medial temporal lobe volumes to age and memory function in nondemented adults with Down's syndrome: implications for the prodromal phase of Alzheimer's disease.

OBJECTIVE: In Down's syndrome (trisomy 21), a dementia syndrome occurs that is phenotypically similar to Alzheimer's disease; the initial phase is characterized by memory loss. The authors used an in vivo structural technique in the predementia stage of Alzheimer's disease in adults with Down's syndrome to investigate whether atrophy of medial temporal lobe structures occurs in these subjects and whether volumes of these structures correlate specifically with performance on memory tests. METHOD: The subjects were 34 nondemented Down's syndrome adults (mean age=41.6 years, 17 women and 17 men) and 33 healthy comparison subjects (mean age=41.3, 15 women and 18 men). By using T(1)-weighted magnetic resonance imaging slices taken perpendicular to the Sylvian fissure, volumes of the hippocampus, amygdala, anterior and posterior parahippocampal gyrus, and temporal pole CSF were measured in both hemispheres. These data were normalized to the total intracranial volume. RESULTS: For Down's syndrome, smaller volumes of the right and left amygdala, hippocampus, and posterior parahippocampal gyrus were significantly associated with greater age; this association was not seen in the anterior parahippocampal gyrus. The amygdala and hippocampus volumes were positively correlated with memory measures. For the comparison group, there was no relationship between volume and age in any region. CONCLUSIONS: In the predementia phase of Down's syndrome, significant volume changes in medial temporal lobe structures occur with age and are related to memory. These structures are affected early in Alzheimer's disease in Down's syndrome, and their evaluation may help identify people in the preclinical stages of Alzheimer's disease.     

Volumetric structural brain abnormalities in men with schizophrenia or antisocial personality disorder

Brain abnormalities are found in association with antisocial personality disorder and schizophrenia, the two mental disorders most implicated in violent behaviour. Structural magnetic resonance imaging was used to investigate the whole brain, cerebellum, temporal lobe, lateral ventricles, caudate nucleus, putamen, thalamus, hippocampus, amygdala and the prefrontal, pre-motor, sensorimotor, occipito-parietal regions in 13 men with antisocial personality disorder, 13 men with schizophrenia and a history of violence, 15 men with schizophrenia without violent history and 15 healthy non-violent men. Compared to controls, the antisocial personality disorder group displayed reductions in whole brain volume and temporal lobe as well as increases in putamen volume. Both schizophrenia groups regardless of violence history exhibited increased lateral ventricle volume, while the schizophrenia group with violent history showed further abnormalities including reduced whole brain and hippocampal volumes and increased putamen size. The findings suggest that individuals with antisocial personality disorder as well as those with schizophrenia and a history of violence have common neural abnormalities, but also show neuro-anatomical differences. The processes by which they came to apparently common ground may, however, differ. The finding of temporal lobe reductions prevalent among those with antisocial personality disorder and hippocampal reduction in the violent men with schizophrenia contributes support for the importance of this region in mediating violent behaviour.     

Memory relationships between MRI volumes and resting PET metabolism of medial temporal lobe structures

Prior studies of temporal lobe epilepsy (TLE) patients showed that MRI volumes and resting PET scan measures of temporal lobe structures were related to memory. Weintrob and colleagues [Ann. Neurol. 2002;51:442-7] reported that PET glucose uptake in the left perirhinal cortex predicted verbal paired associate (PA) learning, whereas MRI volume of the left hippocampus did not. We investigated whether MRI volumes could account for memory functioning if both PET and volumes were from the same region in 18 TLE patients. Volumes and glucose uptake of the hippocampus and parahippocampal gyrus (PHG) were compared with WMS-III performance. Significant correlations were observed between hippocampal volumes and PA and Logical Memory (LM) Percent Retention, but not between memory and PHG volumes or any PET measures. Multiple regression revealed that hippocampal volumes, but not PHG volumes or PET, significantly predicted PA and LM retention scores. These findings suggest that hippocampal volumes provide unique information regarding memory.     

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