Voxel-level comparison of arterial spin-labeled perfusion MRI and FDG-PET in Alzheimer disease.

OBJECTIVE: We compared the ability of arterial spin labeling (ASL), an MRI method that measures cerebral blood flow (CBF), to that of FDG-PET in distinguishing patients with Alzheimer disease (AD) from healthy, age-matched controls. METHODS: Fifteen patients with AD (mean age 72 ± 6 years, Mini-Mental State Examination score [MMSE] 20 ± 6) and 19 age-matched controls (mean age 68 ± 6 years, MMSE 29 ± 1) underwent structural MRI. Participants were injected with 5 mCi of FDG during pseudocontinuous ASL scan, which was followed by PET scanning. Statistical parametric mapping and regions of interest (ROI) analysis were used to compare the ability of the 2 modalities in distinguishing patients from controls. Similarity between the 2 modalities was further assessed with linear correlation maps of CBF and metabolism to neuropsychological test scores. RESULTS: Good agreement between hypoperfusion and hypometabolism patterns was observed, with overlap primarily in bilateral angular gyri and posterior cingulate. ROI results showed similar scales of functional deficit between patients and controls in both modalities. Both ASL and FDG-PET were able to distinguish neural networks associated with different neuropsychological tests with good overlap between modalities. CONCLUSIONS: Our voxel-wise results indicated that ASL-MRI provides largely overlapping information with FDG-PET. ROI analysis demonstrated that both modalities detected similar degrees of functional deficits in affected areas. Given its ease of acquisition and noninvasiveness, ASL-MRI may be an appealing alternative for AD studies.

Can dynamic susceptibility contrast magnetic resonance imaging replace single-photon emission computed tomography in the diagnosis of patients with Alzheimer's disease? A pilot study.

PURPOSE: To compare single-photon emission computed tomography (SPECT) and magnetic resonance imaging (MRI) in a cohort of patients examined for suspected dementia, including patients with no objective cognitive impairment (control group), mild cognitive impairment (MCI), and Alzheimer's disease (AD). MATERIAL AND METHODS: Twenty-four patients, eight with AD, 10 with MCI, and six controls were investigated with SPECT using 99mTc-hexamethylpropyleneamine oxime (HMPAO) and dynamic susceptibility contrast magnetic resonance imaging (DSC-MRI) with gadobutrol. Three observers performed a visual interpretation of the SPECT and MR images using a four-point visual scale. RESULTS: SPECT was superior to DSC-MRI in differentiating normal from pathological. All three observers showed statistically significant results in discriminating between the control group, AD, and MCI by SPECT, with a P value of 0.0006, 0.04, and 0.01 for each observer. The statistical results were not significant for MR (P values 0.8, 0.1, and 0.2, respectively). CONCLUSION: DSC-MRI could not replace SPECT in the diagnosis of patients with Alzheimer's disease. Several patient- and method-related improvements should be made before this method can be recommended for clinical practice.

Evaluation of linear registration algorithms for brain SPECT and the errors due to hypoperfusion lesions.

The semiquantitative analysis of perfusion single-photon emission computed tomography (SPECT) images requires a reproducible, objective method. Automated spatial standardization (registration) of images is a prerequisite to this goal. A source of registration error is the presence of hypoperfusion defects, which was evaluated in this study with simulated lesions. The brain perfusion images measured by 99mTc-HMPAO SPECT from 21 patients with probable Alzheimer's disease and 35 control subjects were retrospectively analyzed. An automatic segmentation method was developed to remove external activity. Three registration methods, robust least squares, normalized mutual information (NMI), and count difference were implemented and the effects of simulated defects were compared. The tested registration methods required segmentation of the cerebrum from external activity, and the automatic and manual methods differed by a three-dimensional displacement of 1.4+/-1.1 mm. NMI registration proved to be least adversely effected by simulated defects with 3 mm average displacement caused by severe defects. The error in quantifying the patient-template parietal ratio due to misregistration was 2.0% for large defects (70% hypoperfusion) and 0.5% for smaller defects (85% hypoperfusion).

Discrimination of Alzheimer's disease and mild cognitive impairment by equivalent EEG sources: a cross-sectional and longitudinal study.

OBJECTIVES: The spatial aspects of brain electrical activity can be assessed by equivalent EEG frequency band generators. We aimed to describe alterations of these EEG generators in Alzheimer's disease (AD) and healthy aging and whether they could serve as predictive markers of AD in subjects at risk. METHODS: The amplitude and 3-dimensional localization of equivalent EEG sources were evaluated using FFT dipole approximation in 38 mild AD patients, 31 subjects with mild cognitive impairment (MCI) and 24 healthy control subjects. RESULTS: AD patients showed an increase of delta and theta global field power (GFP), which corresponds to the generalized EEG amplitude, as well as a reduction of alpha GFP when compared to the controls. A decrease of alpha and beta GFP was found in AD patients, as compared to the MCI subjects. With respect to topography in the antero-posterior direction, sources of alpha and beta activity shifted more anteriorly in AD patients compared to both the controls and MCI subjects. No significant difference was found between MCI and controls. Combined alpha and theta GFP were the best discriminating variables between AD patients and controls (84% correct classification) and AD and MCI subjects (78% correctly classified). MCI subjects were followed longitudinally (25 months on average) in order to compare differences in baseline EEG variables between MCI subjects who progressed to AD (PMCI) and those who remained stable (SMCI). Compared to SMCI, PMCI had decreased alpha GFP and a more anterior localization of sources of theta, alpha and beta frequency. In a linear discriminant analysis applied on baseline values of the two MCI subgroups, the best predictor of future development of AD was found to be antero-posterior localization of alpha frequency. CONCLUSIONS: FFT dipole approximation and frequency analysis performed by conventional FFT showed comparable classification accuracy between the studied groups. We conclude that localization and amplitude of equivalent EEG sources could be promising markers of early AD.

Visual rating and volumetry of the medial temporal lobe on magnetic resonance imaging in dementia: a comparative study.

OBJECTIVES: It has been shown that atrophy of medial temporal lobe structures such as the hippocampus and entorhinal cortex shown on MRI may distinguish patients with Alzheimer's disease from healthy controls. However, the diagnostic value of visual inspection and volumetry of medial temporal lobe atrophy (MTA) on MRI in a clinical setting is insufficiently known. METHODS: Medial temporal lobe atrophy in 143 patients was visually rated from hard copies, using a 0-4 rating scale and a comparison was made with the volumes (cm(3)) of the medial temporal lobe as estimated with volumetry, using a stereological method. All patients were recruited in an unselected way in a clinical setting in the centre for memory impairments at the Huddinge University Hospital. Patients with Alzheimer's disease (n=41), patients with other dementias (vascular dementia, frontotemporal dementia, and unspecified dementia; n=36) as well as non-demented subjects (n=66) were included. Medial temporal atrophy and volumetry were evaluated as a diagnostic tool by performing logistic regression analysis including age, sex, and mini mental state examination (MMSE) score and calculating the sensitivity and specificity and percentage correct classification. RESULTS: Visual and volumetric analysis yielded statistically significant differences between patients with Alzheimer's disease and non-demented subjects, as well as between those with other dementias and non-demented subjects. Combining MMSE scores and visually rated MTA ratings yielded a sensitivity of 95% for Alzheimer's disease, 85% for other dementias. Non-demented subjects were identified with a specificity of 96%. Volumetry did not have an added value over the MMSE score alone. CONCLUSIONS: Visual rating of MTA is a clinically useful method for differentiating Alzheimer's disease from controls and is both quicker and more accurate than volumetry.

Spatial pattern of cerebral glucose metabolism (PET) correlates with localization of intracerebral EEG-generators in Alzheimer's disease.

BACKGROUND: Since the measurement of human cerebral glucose metabolism (GluM) by positron emission tomography (PET) and that of human cerebral electrical activity by EEG reflect synaptic activity, both methods should be related in their cerebral spatial distribution. Healthy subjects do indeed demonstrate similar metabolic and neuroelectric spatial patterns. OBJECTIVE: The aim of the study was to show that this similarity of GluM and EEG spatial patterns holds true in a population with a high variability of glucose metabolism. METHODS: We investigated healthy control subjects and patients with varying degrees of cognitive dysfunction and varying GluM patterns by applying [18F]FDG PET and EEG. RESULTS: We demonstrated that the localization of intracerebral generators of EEG correlates with spatial indices of GluM. CONCLUSION: These results indicates that EEG provides similar spatial information about brain function as GluM-PET. Since EEG is a non-invasive technique, which is more widely available and can be repeated more often than PET, this may have important implications both for neuropsychiatric research and for clinical diagnosis. However, further studies are required to determine whether equivalent EEG dipole generators can yield a diagnostic specificity and sensitivity similar to that of GluM-PET.

Quantitative electroencephalography in mild cognitive impairment: longitudinal changes and possible prediction of Alzheimer's disease.

The present study evaluated the clinical course of patients with mild cognitive impairment (MCI), the pattern of electroencephalography (EEG) changes following cognitive deterioration, as well as the potential of neurophysiological measures in predicting dementia. Twenty-seven subjects with MCI were followed for a mean follow up period of 21 months. Fourteen subjects (52%) progressed (P MCI) to clinically manifest Alzheimer's disease (AD), and 13 (48%) remained stable (S MCI). The two MCI subgroups did not differ in baseline EEG measures between each other and the healthy controls (n = 16), but had significantly lower theta relative power at left temporal, temporo-occipital, centro-parietal, and right temporo-occipital derivation when compared to the reference AD group (n = 15). The P MCI baseline alpha band temporo-parietal coherence, alpha relative power values at left temporal and temporo-occipital derivations, theta relative power values at frontal derivations, and the mean frequency at centro-parietal and temporo-occipital derivations overlapped with those for AD and control groups. After the follow-up, the P MCI patients had significantly higher theta relative power and lower beta relative power and mean frequency at the temporal and temporo-occipital derivations. A logistic regression model of baseline EEG values adjusted for baseline Mini-Mental Test Examination showed that the important predictors were alpha and theta relative power and mean frequency from left temporo-occipital derivation (T5-O1), which classified 85% of MCI subjects correctly.

A follow-up study of the family with the Swedish APP 670/671 Alzheimer's disease mutation.

OBJECTIVE: To study the progression of Alzheimer's disease (AD) at a very early stage and to evaluate clinical markers of presymptomatic AD. SETTING: Longitudinal study at a university hospital. SUBJECTS: A Swedish family harboring a double mutation at codons 670/671 of the APP gene on chromosome 21 was followed longitudinally for 3 years. Both mutation carriers and noncarriers participated. OUTCOME MEASUREMENTS: Results from clinical investigations, electroencephalography, neuropsychological and neuroradiological examinations including magnetic resonance imaging, single-photon emission computed tomography and positron emission tomography were assessed and compared on two or more occasions. MAIN OUTCOME: During follow-up, 1 initially asymptomatic mutation carrier who was near the expected age of onset for this family, developed cognitive symptoms, and at the end of the follow-up fulfilled the diagnostic criteria for AD. One mutation carrier with cognitive symptoms at the first examination showed clinical deterioration and was diagnosed with AD. One demented mutation carrier died and was shown to have typical AD neuropathology at autopsy. The two remaining asymptomatic mutation carriers, as well as all the noncarriers were asymptomatic. These mutation carriers who were near the expected age of onset of AD but without clinical signs of the disease, did not show changes in either electrophysiological parameters or volumes of the temporal lobes. However, in these 2 individuals the blood flow in the temporal lobe showed intermediate values between the symptomatic mutation carriers and healthy noncarriers. Two neuropsychological tests showed a deterioration that paralleled clinical symptoms in 1 of the mutation carriers who was close to the expected age of onset and who at the end of the follow-up had clinical signs of AD. In the same subject, brain glucose metabolism was pathologically reduced in the temporal lobes before other clinical symptoms were obvious. CONCLUSION: In this familial form of AD a reduced temporal lobe glucose metabolism was indicative of AD before the expected clinical onset. Reduced glucose metabolism even preceded the development of subjective or objective cognitive dysfunction and might therefore serve as a clinical marker for AD before the onset of clinical symptoms. Reduced cerebral blood flow in the temporal lobes and cognitive deterioration paralleled the clinical decline in the early stage of the disease. Copyrightz1999S.KargerAG,Basel

Visual assessment of medical temporal lobe atrophy in demented and healthy control subjects: correlation with volumetry.

The present study evaluated the validity of visual rating of medial temporal lobe atrophy on coronal magnetic resonance imaging scans in a population of demented and non-demented individuals. Medial temporal lobe atrophy in 194 subjects was visually rated from hard copies, using a 0-4 rating scale, and a comparison was made with the absolute volumes (ccm) of the medial temporal lobe as estimated with volumetry, using a stereological method. We found a highly significant correlation between the estimated and stereologically measured volumes. There was a 10-fold difference in time spent on rating medial temporal lobe atrophy (1-2 min) vs. time spent calculating the medial temporal lobe volume (10-12 min) on a single subject. The diagnostic accuracy of both methods showed that visual rating was more efficient than volumetry in differentiating Alzheimer's disease from control subjects, We conclude that visual rating is a reliable and fast method to estimate medial temporal lobe atrophy in demented subjects in a clinical setting.

Inheritance of the ApoE epsilon4 allele increases the rate of brain atrophy in dementia patients.

We investigated the influence of the apolipoprotein (ApoE) epsilon4 allele on the rate of brain atrophy in patients with clinical dementia and in subjects at risk for dementia. Eighty-one subjects, consecutively referred to a memory clinic due to symptoms of dementia, went through a comprehensive examination, including cerebral magnetic resonance imaging. After an initial investigation these subjects were divided into one of six diagnostic groups; Alzheimer's disease (AD, n = 23), objective cognitive impairment (OCI, n = 27), subjective cognitive impairment (SCI, n = 17), vascular dementia (VaD), frontotemporal dementia (FTD) and unspecified dementia (USD). The last three groups were joined into one diagnostic group designated 'other dementia' (OD, altogether n = 14). In order to study the progression of cognitive impairment as well as the rate of atrophy in different brain regions all subjects were reinvestigated after an average period of 16 months. Interest was focused on investigating if those subjects with one or two epsilon4 alleles differed in either dementia progression or rate of brain atrophy compared to those without the epsilon4 allele. We found that the ApoE epsilon4 carriers had a statistically significantly larger increase in ventricular volume as compared with the ApoE epsilon4 noncarriers. In all diagnostic groups the ApoE epsilon4 carriers showed a greater rate of ventricular volume increase, as compared to the noncarriers. However, this difference was statistically significant only for the OD subjects. No statistical significant changes over time were seen for whole brain volume or volume of the temporal lobes and the medial temporal lobes. The diagnostic groups differed in dementia progression with the AD subjects having the most pronounced reduction in MMSE scores as compared to subjects at risk for AD (OCI and SCI subjects). The presence of ApoE epsilon4 allele did not influence the change in MMSE in any of the diagnostic groups.

EEG slowing and cerebrospinal fluid tau levels in patients with cognitive decline.

We explored the relationship between cerebrospinal fluid (CSF) tau levels as indirect markers of tau-related pathology in Alzheimer's disease (AD) and EEG slowing, a typical neurophysiological finding in the disease. A positive correlation between CSF tau levels and ratio of alpha/delta global field power was found in 14 AD patients (r = 0.65, p = 0.01). This relationship was better approximated by polynomial fit of 2nd degree (p = 0.002). A subgroup of AD patients (n = 7) with higher tau levels and shorter duration of illness showed a strong relationship between CSF tau levels and alpha/theta (r = 0.83, p = 0.02), and alpha/delta (r = 0.87, p = 0.01) ratios of the global field power. There were no significant correlations between EEG slowing and CSF tau levels in 12 patients with mild cognitive dysfunction or in 14 healthy control subjects. That a strong inverse linear correlation exists in AD patients with higher levels of tau and shorter duration of illness may imply that with longer illness duration CSF tau levels decrease due to neuronal death.

Brain volumes and regional cerebral blood flow in carriers of the Swedish Alzheimer amyloid protein mutation.

As a preliminary part of a longitudinal clinical study of carriers of the Swedish amyloid precursor protein (APP) 670/671 mutation, 13 members of a family were investigated with magnetic resonance imaging (MRI) brain volumetry and single photon emission computed tomography (SPECT) cerebral blood flow (CBF) measurements. Five of the family members were mutation carriers; eight were not carriers. Two carriers were younger than 40 years of age and had no evidence of cognitive dysfunction or structural or functional brain changes. One carrier with 4 years to expected disease onset showed poor performance in episodic memory tests and also slightly low temporal lobe CBF, although there were no clearly abnormal findings. One carrier with mild Alzheimer disease (AD) had no clear structural brain changes, although CBF measurements showed clear reduction of temporal lobe CBF. One carrier with severe AD had both temporal lobe atrophy and CBF reduction. This indicates that in carriers of the APP 670/671 mutation, reduction of regional CBF is more severe than regional atrophy. The clearest change related to development of clinical AD was a reduction of CBF in the basal and lateral temporal lobes. Further longitudinal studies of these subjects are needed to confirm these preliminary findings, which might provide important data regarding early brain changes in AD.

Global dimensional complexity of multichannel EEG in mild Alzheimer's disease and age-matched cohorts.

Multichannel EEG as sequence of momentary brain field maps constitutes a trajectory through K-dimensional state space (K = number of channels); the complexity of this trajectory is assessed by the nonlinear measure of global correlation dimension (Global Dimensional Complexity, GDC) with the number of electrodes as embedding dimension. We analyzed eyes-closed EEG of three age-matched subject groups: mild Alzheimer's disease (AD; n = 21), mild cognitive impairment (29) and subjective memory complaint (29). Kruskal-Wallis statistics showed an overall effect between groups. AD patients differed significantly (GDC = 4.56) from mild cognitive impairments (GDC = 4.98) and from subjective memory complaints (GDC = 4.93). GDC also had significant positive correlations with mental condition and performance (MMSE and WAIS-R scores). Thus, the dynamics of brain state development over time in mild AD differs from that in mild cognitive impairment and in subjective memory complaint cases.

Bilateral temporal lobe volume reduction parallels cognitive impairment in progressive aphasia.

BACKGROUND: Patients with isolated aphasia in the absence of other cognitive abnormalities have been the focus of several studies during the past decade. It has been called primary progressive aphasia (PPA), and the typical features of this syndrome are marked atrophy of the left temporal lobe according to the radiological examination and a language disorder as the initial symptom. In previous studies of PPA, the selection of the patients was based mainly on linguistic symptoms. Now, when computed tomography or magnetic resonance imaging scans are part of the routine investigation of cognitive impairment and suspected dementia, the patients with lobar atrophy will be found at an earlier stage. In the present study, we used a new approach and defined the study group by selecting patients with obvious left temporal lobe atrophy, assessed by MRI, and we referred to them as patients with temporal lobe atrophy (TLA). OBJECTIVE: To identify the features that distinguish TLA from other primary neurodegenerative disorders. PATIENTS: Six patients with TLA were compared with patients with Alzheimer disease (AD), patients with frontal lobe dementia (FLD), and healthy control subjects. METHODS: The investigations included magnetic resonance imaging volumetry, single photon emission computed tomography, and neuropsychologic and linguistic evaluations. RESULTS: In the TLA group, the mean volume of the left temporal lobe was 35% smaller than the right, while in the AD and FLD groups, the atrophy was symmetrical and bilateral. In the TLA group, the absolute volumes of the temporal lobes were significantly smaller on the left side compared with the AD and FLD groups, whereas there was no difference on the right side. The cerebral blood flow pattern in TLA was asymmetric and differed from that in the other study groups. All patients with TLA had a history of progressive Wernicke-type aphasia, ranging from 2 to 6 years. They showed primary verbal memory impairment but had preserved visuospatial functions. The clinical condition of all patients with TLA deteriorated during the study period; severe aphasia developed, and the patients exhibited signs of frontal lobe dysfunction. Serial volumetric measurements in 4 of 6 patients showed an annual 8% to 9% decrease of both left and right temporal lobes. CONCLUSIONS: The initial marked asymmetry in cognitive function found in patients with TLA contrasts with the general decline found in patients with AD. The bilateral degenerative process evident in patients with TLA paralleled the clinical deterioration, indicating TLA to be a non-AD lobar atrophy that develops into generalized cognitive dysfunction and dementia.

Apolipoprotein E epsilon4 allele decreases functional connectivity in Alzheimer's disease as measured by EEG coherence.

OBJECTIVES: The epsilon4 allele of apolipoprotein E (APOE) represents a major biological risk factor for late onset Alzheimer's disease. However, it is still not known whether the APOE genotype affects the progression of the disease, assessed by different functional methods. METHODS: The study sample included 41 patients with probable Alzheimer's disease. Subjects had similar severity of disease, age of onset, and duration of illness, and were subcategorised according to their APOE genotypes: 17 with no epsilon4 allele, 14 with one epsilon4 allele, and 10 with two epsilon4 alleles. The control group consisted of 18 healthy subjects comparable with the patients in age and education. Analysed quantitative EEG (qEEG) variables were the ratio of alpha and theta absolute power and EEG coherence in alpha frequency band, representing major cortical association pathways. RESULTS: There was pronounced EEG slowing in all three patient subgroups compared with the controls for the alpha/theta ratio, but there was no significant difference across the patient subgroups. Patients homozygous for the APOE epsilon4 allele had reduced right and left temporoparietal, right temporofrontal, and left occipitoparietal coherence. Patients without and with one epsilon4 allele showed an overlap between the control group and group with two epsilon4 alleles in coherence measures. CONCLUSIONS: APOE epsilon4 does not influence EEG slowing, an index which reflects severity of the disease in patients with Alzheimer's disease, but seems to be associated with selective decreases in functional connectivity as assessed by EEG coherence. This finding might be of clinical importance when considering different pathogenetic mechanisms.

MRI-guided SPECT measurements of medial temporal lobe blood flow in Alzheimer's disease.

UNLABELLED: In this study, we assessed the accuracy and reliability of MRI-guided SPECT measurements of medial temporal lobe blood flow in Alzheimer's disease (AD). METHODS: Interactively aligned three-dimensional MP-RAGE MRI and 99mTc-HMPAO SPECT images were used for MRI-guided measurement of medial temporal lobe CBF in eight control subjects and eight patients with probable AD. Intraoperator reliability was assessed by repeated alignment and measurement by one experienced operator. Accuracy was assessed by examining two subjects with fiducial markers. RESULTS: The alignment error was less than 1 SPECT pixel size (3.5 mm) and the coefficient of variation in repeated measures of medial temporal-to-cerebellar CBF ratios was 3.2%. The difference in mean medial temporal-to-cerebellar CBF ratios between eight control subjects and eight AD patients was 12%. Also by using three-dimensional seed-grow defined healthy brain reference regions, there were significant differences between control subjects and AD patients in medial temporal blood flow. Furthermore, the volumes of the MRI-defined medial temporal ROIs were smaller in the AD patients. The best separation between AD patients and control subjects was achieved by combining MRI measurements of atrophy and SPECT measurements of CBF. CONCLUSION: These data show that the accuracy and reliability of MRI-guided SPECT measurements of medial temporal CBF clearly allow the detection of changes in AD. Also, a direct comparison of structural and functional changes is possible by this methodology, which might improve the early diagnosis of AD.

EEG-microstates in mild memory impairment and Alzheimer's disease: possible association with disturbed information processing.

The only available functional neuroimaging methods reaching the time resolution of human information processing are EEG and MEG. Since spectral analysis implies analysis of longer time epochs, the high temporal resolution of EEG is partly lost. By dividing the EEG in the time-domain into segments of similar spatial distribution on the scalp (microstates) it has been possible to assess patterns of neuronal activity representing the information process currently performed by the brain. In the present study alterations of EEG microstates in subjective (n = 31) and objective (n = 38) memory impairment as well as in probable Alzheimer disease (DAT: n = 64) compared to healthy controls (n = 21) were investigated. The main findings were reduced segment durations and a more anterior center of gravity of the microstate topography in DAT. With more pronounced cognitive dysfunction larger window sizes were found. Shorter microstates and larger windows reflect more rapidly changing spatial activation patterns, and are interpreted as an impaired capability to establish stable brain states necessary for normal brain function. The anteriorization of the microstates is consistent with results in the frequency domain and may reflect neuropathological changes in DAT.

Reliability of interactive three-dimensional brain volumetry using MP-RAGE magnetic resonance imaging.

We assessed the reliability of an interactive 3-dimensional methodology for magnetic resonance imaging (MRI) brain tissue segmentation and volumetry using a 3-dimensional magnetization prepared rapid gradient echo pulse sequence (3D MP-RAGE). The methodology was intended to be practically useful to study structural brain changes in larger groups of patients investigated for suspected dementia. The pulse sequence combines volume acquisition, excellent tissue contrast and short patient scan-time. The volumetric method is fully interactive, requiring a minimum of image pre-processing. Ten healthy controls and 10 patients with dementia were included in the study. Six healthy controls were scanned twice. The method is based on thresholding combined with manual tracing in a 3D volume. The 3-dimensional measurement method reduces the measurement time considerably compared to that of slice by slice measurement and permits 3-dimensional display of measured volumes. For different brain regions the intra-study (0.5-1.3%), study-study (1.8-4.7%) and inter-operator (7.1%) variability of this method compared favourably with other manual or automated methods reported. The major advantages of the method are its simplicity and speed, which permits measurement and display of regional brain volumes and tissues in larger patient groups.

Quantitative electroencephalography power and coherence in Alzheimer's disease and mild cognitive impairment.

In this study the best combination of quantitative electroencephalographic variables (qEEG) for the discrimination of groups with mild to moderate Alzheimer's disease (AD), mild cognitive impairment and healthy subjects was defined and related to neuropsychological performance. The study population included 18 patients with mild to moderate probable AD, 19 subjects with objective memory disturbance, 17 subjects with subjective memory complaints who did not have clinical evidence of memory disturbance, and 16 healthy controls. AD patients had significantly increased theta and decreased alpha relative power, mean frequency, and temporoparietal coherence. There was no significant difference in the mean frequency in the left temporal region between AD patients and subjects with objective memory disturbances. Temporoparietal coherence appeared as a discriminant variable together with alpha and theta relative power only between AD patients and controls giving 77.8% sensitivity and 100% specificity. Significant correlations between regional changes in qEEG variables and cognitive functions were found.

MRI in successful aging, a 5-year follow-up study from the eighth to ninth decade of life.

PURPOSE: This study aimed at evaluate the effect of aging on the central nervous system in "successfully aged" elderly subjects. The brain was studied with magnetic resonance imaging and neuropsychological tests at three different occasions during a time period of 5 yr. MATERIALS AND METHODS: Twenty-four successfully aged elderly were repeatedly examined with cerebral MRI and neuropsychological tests. The first examinations were performed in 1987 and then followed-up in 1989 and 1993. Two different MRI systems were used, in 1987 and 1989, a system operating at 0.02 T and in 1993 a system operating at 0.5 T. Ten subjects (42%) did not participate in the follow-up studies. MRI was used to study the degree of and increase in signal hyperintensities in the cerebrum, the basal ganglia, and in the infratentorial areas as well as changes in the volumes of the cerebro spinal fluid (CSF) spaces. RESULTS: At the start of the study in 1987, mild signal hyperintensities were observed in 11 of the 13 subjects who completed the follow up study. A modest increase in signal hyperintensity was found in almost all of the subjects, with the increases in cerebral white matter and basal ganglia signal hyperintensity being statistically significant (p < .03 and p < .05). The increases in periventricular hyperintensity and the hyperintensity from the infratentorial areas did not reach statistical significance. Volumes of the lateral ventricles and the frontal CSF spaces increased significantly (p < .03 in both cases) during the observation period, whereas the other volumes remained unchanged. The neuropsychological tests were unchanged during the observation period with the exception of the psychomotor capacity, which deteriorated. No statistical significant correlations were seen between the degree of or increase in signal hyperintensities and results from any of the neuropsychological tests. CONCLUSION: During a 5-yr observation of successfully aged elderly it was found that there was a mild increase in signal hyperintensity in the cerebral white matter and basal ganglia, as well as an increase in the frontal and ventricular CSF volumes. These changes were not related to changes in psychometric test results, nor were they related to the clinical outcome during the time of observation.