Alzheimer Disease: Jelic V

Palmer K, Jelic V, Winblad B. · Division of Geriatric Epidemiology and Medicine, Neurotec, Karolinska Institutet and Stockholm Gerontology Research Center, Stockholm, Sweden. · Acta Neurol Scand Suppl. · Pubmed #12603243 No free full text.

This publication has no abstract.

Jelic V, Wahlund LO. · Division of Clinical Geriatrics, NVS Department, Karolinska Institutet, Karolinska University Hospital, Hudddinge, 141 86 Stockholm, Sweden. · Expert Rev Med Devices. · Pubmed #17605683 No free full text.

Abstract: This review discusses current imaging devices in the diagnosis of Alzheimer's disease, their neurobiological correlates and future perspectives in the development of these techniques. The challenge of diagnostic devices is to achieve high accuracy in early, preferably preclinical disease stages at the individual patient level. This is of utmost importance for the development of disease-modifying strategies and monitoring their efficacy. In order to achieve this goal, larger validation trials with prospective designs in unselected and mixed patient populations are needed. A combination of imaging methods of different modalities, both structural and functional, will probably provide optimal diagnostic sensitivity in early cases and specificity towards other dementia syndromes, as well as give in vivo insight into the distribution of disease pathology and residual brain capacity for coping with cognitive decline.

Jelic V, Kivipelto M, Winblad B. · Karolinska Institutet, Neurotec Department, Division of Geriatric Medicine, Karolinska University Hospital-Huddinge, Stockholm, Sweden. · J Neurol Neurosurg Psychiatry. · Pubmed #16306154 links to  free full text

Abstract: Mild cognitive impairment (MCI) is an operational definition for a cognitive decline in individuals with a greater risk of developing dementia. The amnestic subtype of MCI is of particular interest because these individuals most likely progress to Alzheimer's disease (AD). Currently hypothesised therapeutic approaches in MCI are mainly based on AD treatment strategies. Long term secondary prevention randomised clinical trials have been completed in amnestic MCI populations, encompassing agents with various mechanisms of action: acetylcholinesterase inhibitors (donepezil, rivastigmine, galantamine), antioxidants (vitamin E), anti-inflammatories (rofecoxib), and nootropics (piracetam). The design of clinical trials in MCI is influenced by study objectives and definition of primary end points: time to clinical diagnosis of dementia, and AD in particular, or symptom progression. As none of the drugs previously shown to have clinical efficacy in AD trials or benefit in everyday practice have met the primary objectives of the respective trials, design of future clinical trials in MCI should be further developed particularly as regards the selection of more homogeneous samples at entry, optimal treatment duration, and multidimensional and reliable outcomes.

Winblad B, Jelic V. · Karolinska Institutet, Alzheimer's Disease Research Center, Neurotec Department, Division of Geriatric Medicine, Karolinska University Hospital-Huddinge, Stockholm, Sweden. · Alzheimer Dis Assoc Disord. · Pubmed #15249842 No free full text.

Abstract: During the past 20 years, research on Alzheimer disease (AD) and other dementias has increased our understanding of these disorders and has opened doors to new methods of treatment. Acetylcholinesterase inhibitors (AChEIs) have been successful in reducing symptoms in patients with mild-to-moderate AD and led to the US Food and Drug Administration's approval of four AChEIs for the treatment of AD. Although these agents are approved for only mild-to-moderate AD, and the available data for most of them are from trials of only 6 months' duration, long-term studies suggest that the benefits of AChEI treatment can endure for up to 4 years. A common pattern of response to treatment is initial improvement in cognition, followed by maintenance of cognitive gains above baseline for up to 1 year. Generally there is a decline in cognition to below baseline levels after approximately 1 year of treatment, but the level of cognition remains above that predicted for those not receiving pharmacologic treatment. Furthermore, long-term studies suggest that early diagnosis and treatment with AChEIs yield better long-term outcomes. Patients who received continuous pharmacologic treatment from the outset generally had better long-term outcomes than those who received placebo in the double-blind phase of these trials.

Wolf H, Jelic V, Gertz HJ, Nordberg A, Julin P, Wahlund LO. · Karolinska Institutet, Neurotec, Division of Geriatric Medicine, Huddinge University Hospital, Sweden. · Acta Neurol Scand Suppl. · Pubmed #12603252 No free full text.

Abstract: OBJECTIVE: In this paper, the current neuroimaging literature is reviewed with regard to characteristic findings in mild cognitive impairment (MCI). Particular attention is drawn to the possible value of neuroimaging modalities in the prediction and early diagnosis of Alzheimer's disease (AD). METHODS: First, the potential contribution of neuroimaging to an early, preclinical diagnosis of degenerative disorders is discussed at the background of our knowledge about the pathogenesis of AD. Second, relevant neuroimaging studies focusing on MCI are explored and summarized. Neuroimaging studies were found through Medline search and by systematically checking through the bibliographies of relevant articles. RESULTS: Structural volumetric magnetic resonance imaging (MRI) and positron emission tomography (PET)/single photon emission tomography (SPECT) are currently the most commonly used neuroimaging modalities in studies focusing on MCI. There were considerable variations in demographical and clinical characteristics across studies. However, significant hippocampal and entorhinal cortex volume reductions were consistently found in subjects with MCI as compared with cognitively unimpaired controls. While hippocampal and entorhinal cortex atrophy in subjects with MCI are also well-established risk factors for the development of AD, these measures cannot be regarded as being of high predictive value in an individual case. Evidence for other typical neuroimaging changes in MCI is still scarce. In PET and SPECT studies, reduced blood flow and/or glucose metabolism in temporoparietal association areas, posterior cingulate and hippocampus were associated with a higher risk of progressive cognitive decline in MCI. In quantitative electroencephalogram (QEEG), low beta, high theta, low alpha and slowed mean frequency were associated with development of dementia. CONCLUSIONS: Existing studies suggest that neuroimaging measures have the potential to become valuable tools in the early diagnosis of AD. To establish their value in routine use, larger studies, preferably with long prospective follow-up are needed.

Jelic V, Nordberg A. · Karolinska Institute, Department of Clinical Neuroscience, Huddinge University Hospital, Sweden. · Alzheimer Dis Assoc Disord. · Pubmed #10850738 No free full text.

Abstract: The emergence of drugs that may slow progression of Alzheimer disease, if administered early during its course, has necessitated early diagnosis of the disease itself. Among the functional imaging methods that could assist in early diagnosis, positron emission tomography has an important role in providing quantitative measures of various aspects of brain function affected by the disease. Positron emission tomography studies in patients with Alzheimer disease have revealed a typical pattern of metabolic deficits in the temporal and parietal lobes. Additionally, converging evidence from numerous studies indicates that a similar pattern of deficits can be observed in nondemented subjects who are at risk of developing the disease, such as those with recognized genetic traits such as familial Alzheimer disease with mutations in chromosomes 21 and 14, Down syndrome, subjects with the epsilon4 allele of the apolipoprotein E gene, and individuals with mild cognitive impairment. These findings might have implications for the selection of patients for clinical trials, defining the outcome measures and evaluation of treatment efficacy and responder characteristics, but should be confirmed by prospective studies comprising larger samples and include clinicopathologic correlations.

Almkvist O, Jelic V, Amberla K, Hellström-Lindahl E, Meurling L, Nordberg A. · Division of Geriatric Medicine, Department of Clinical Neuroscience, Occupational Therapy and Elderly Care Research (NEUROTEC), Huddinge University Hospital, Huddinge, Sweden. · Dement Geriatr Cogn Disord. · Pubmed #11125238 No free full text.

Abstract: A proportion of Alzheimer's disease (AD) patients treated for several months with cholinesterase (ChE) inhibitors have shown some favorable response on cognition, but the characteristics of the responders are still unclear. This study attempts to identify the characteristics of individuals with a positive behavioral response after a double-blind randomized administration of a single oral dose of tacrine (40 mg) and placebo to AD patients. Furthermore, the relationship between single-dose and long-term responders are examined. Twenty-four mildly to very mildly demented AD patients participated in the study. They all fulfilled the diagnosis of probable AD according to NINCDS-ADRDA criteria. Active treatment (tacrine 40 mg) and placebo was administered in random order on 2 consecutive days, and the effects were evaluated within 2 h using neuropsychological tests (assessing visuospatial ability, episodic memory and attention), registration of EEG activity and measurement of red blood cells (RBC) acetylcholinesterase (AChE), ChE activity and concentrations of tacrine and its metabolites in plasma. Results demonstrated significant improvement, tacrine compared to placebo, in measures of attention, but not in episodic memory or visuospatial ability. A single-dose response was therefore defined in terms of improvement in attention. The tacrine plasma concentration (pcTHA) showed a positively skewed distribution (mean +/- SD: 10.5 +/- 11.8, range: 1.0-51.8 ng/ml). There were no significant differences between single-dose responders compared to nonresponders in pcTHA, metabolites of tacrine, inhibition of AChE in RBC, tau levels in CSF, AChE activity in CSF or plasma and demographic variables. However, single-dose responders showed a higher right frontal alpha/theta ratio on EEG and had lower glucose metabolism in the parietal-temporal association cortex at baseline. In addition, the frequency of apolipoprotein E (APOE) epsilon 4 alleles was higher in responders. Interestingly, the single-dose response was related to the long-term response, although not significantly, which probably was due to lack of power. To conclude, the present study identified single-dose responders in terms of improved attentional performance associated with a relatively higher alpha/theta activity in the right frontal regions of the brain measured on EEG and predominance of APOE epsilon 4 allele.

Wahlund LO, Basun H, Almkvist O, Julin P, Axelman K, Shigeta M, Jelic V, Nordberg A, Lannfelt L. · Department of Clinical Neuroscience and Family Medicine, Division of Geriatric Medicine, B-56, Huddinge University Hospital, Karolinska Institute, Huddinge, Sweden. · Dement Geriatr Cogn Disord. · Pubmed #10559570 No free full text.

Abstract: 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

Herholz K, Nordberg A, Salmon E, Perani D, Kessler J, Mielke R, Halber M, Jelic V, Almkvist O, Collette F, Alberoni M, Kennedy A, Hasselbalch S, Fazio F, Heiss WD. · Max-Planck-Institut für neurologische Forschung, Köln, Germany. · Dement Geriatr Cogn Disord. · Pubmed #10559566 No free full text.

Abstract: Progression rates of Alzheimer's disease (AD) vary considerably, and they are particularly difficult to predict in patients with mild cognitive impairment. We performed a prospective multicenter cohort study in 186 patients with possible or probable AD, mostly with presenile onset. In a cross-sectional analysis at entry, impairment of glucose metabolism in temporoparietal or frontal association areas measured with positron emission tomography was significantly associated with dementia severity, clinical classification as possible versus probable AD, presence of multiple cognitive deficits and history of progression. A prospective longitudinal analysis showed a significant association between initial metabolic impairment and subsequent clinical deterioration. In patients with mild cognitive deficits at entry, the risk of deterioration was up to 4.7 times higher if the metabolism was severely impaired than with mild or absent metabolic impairment. Copyrightz1999S.KargerAG, Basel

Jelic V, Haglund A, Kowalski J, Langworth S, Winblad B. · Division of Geriatric Medicine, Department of NVS, Karolinska Institutet, Karolinska University Hospital-Huddinge, Stockholm, Sweden. · Dement Geriatr Cogn Disord. · Pubmed #18984956 No free full text.

Abstract: BACKGROUND/AIMS: Our objective was to define clinically meaningful outcomes in donepezil versus placebo treatment in severe Alzheimer's disease (AD) and to describe characteristics of responders. METHODS: Analyses were performed on data from a 6-month, double-blind, parallel-group, placebo-controlled study on the efficacy of donepezil in 248 nursing home residents. Various individual responses were defined as stabilisation or improvement on the Severe Impairment Battery (SIB), Alzheimer's Disease Cooperative Study-activities of daily living scale (ADCS-ADL), Mini-Mental State Examination, Neuropsychiatric Inventory (NPI) or Clinical Global Impression of Improvement. Three composite measures were defined by combining the individual response criteria on these outcomes. The impact of baseline disease severity and of concomitant use of psychotropic drugs was also analysed. RESULTS: At 6 months, greater proportions of patients defined as responders to donepezil on individual efficacy measures showed significant stabilisation or improvement compared with placebo on the SIB (>or=0, >or=4 or >or=7 points) and Mini-Mental State Examination (>or=0 or >or=3 points), and positive trends on the ADCS-ADL-severe (>or=3 points) and the NPI cluster based on mood items. All 3 composite measures of efficacy showed a significantly higher proportion of responders in the donepezil group. The responders had a similar distribution between the 2 subgroups of cognitive and functional disease severity at baseline. The donepezil-treated patients taking psychotropic drugs showed significantly greater improvement on the SIB, less deterioration on the ADCS-ADL, and had higher Clinical Global Impression of Improvement scores and a trend towards lower NPI scores. The baseline demographic and clinical profile did not differ between the non-responders and responders on the composite outcome measures. CONCLUSION: The results demonstrate that donepezil treatment of patients with severe AD consistently shows stabilisation or improvement across multiple outcome measures in individual patients, including cognitive, functional and behavioural symptoms.

Winblad B, Jelic V, Kershaw P, Amatniek J. · Alzheimer Disease Research Center and Department of Clinical Geriatrics, Karolinska Institute, Stockholm, Sweden. · Drugs Aging. · Pubmed #17233547 No free full text.

Abstract: BACKGROUND AND OBJECTIVE: A number of reports have been published on the possible involvement of changes in brain cholesterol metabolism in the origin of Alzheimer's disease (AD) and the potential for influencing these changes by administration of HMG-CoA reductase inhibitors ('statins'). The aim of this study was to evaluate a potential association between use of statins and maintenance of cognitive function in patients with AD in galantamine clinical trials. METHOD: A post hoc analysis was conducted on data pooled from three double-blind, placebo-controlled, clinical trials of galantamine in patients with AD. Patients were divided into four treatment groups: statin plus galantamine (n = 42), statin alone (n = 50), galantamine alone (n = 614) or neither galantamine nor statin (n = 619). RESULTS: Galantamine was associated with a significant beneficial effect on cognitive status (p < 0.001). The association of use of statins with changes in cognitive status was not significant (p = 0.083). There was no significant interaction between the effects on cognition of statins and galantamine (p = 0.183) and no statistically significant changes in adverse effect rates were observed. CONCLUSION: These findings suggest the need for larger long-term trials to confirm or refute possible effects of statins on cognitive function and the potential interaction of statins with acetylcholinesterase inhibitors in the treatment of AD.

Lehmann C, Koenig T, Jelic V, Prichep L, John RE, Wahlund LO, Dodge Y, Dierks T. · University Hospital of Clinical Psychiatry, Department of Psychiatric Neurophysiology, University of Berne, Bolligenstrasse 111, CH-3000 Bern 60, Switzerland. · J Neurosci Methods. · Pubmed #17156848 No free full text.

Abstract: The early detection of subjects with probable Alzheimer's disease (AD) is crucial for effective appliance of treatment strategies. Here we explored the ability of a multitude of linear and non-linear classification algorithms to discriminate between the electroencephalograms (EEGs) of patients with varying degree of AD and their age-matched control subjects. Absolute and relative spectral power, distribution of spectral power, and measures of spatial synchronization were calculated from recordings of resting eyes-closed continuous EEGs of 45 healthy controls, 116 patients with mild AD and 81 patients with moderate AD, recruited in two different centers (Stockholm, New York). The applied classification algorithms were: principal component linear discriminant analysis (PC LDA), partial least squares LDA (PLS LDA), principal component logistic regression (PC LR), partial least squares logistic regression (PLS LR), bagging, random forest, support vector machines (SVM) and feed-forward neural network. Based on 10-fold cross-validation runs it could be demonstrated that even tough modern computer-intensive classification algorithms such as random forests, SVM and neural networks show a slight superiority, more classical classification algorithms performed nearly equally well. Using random forests classification a considerable sensitivity of up to 85% and a specificity of 78%, respectively for the test of even only mild AD patients has been reached, whereas for the comparison of moderate AD vs. controls, using SVM and neural networks, values of 89% and 88% for sensitivity and specificity were achieved. Such a remarkable performance proves the value of these classification algorithms for clinical diagnostics.

Koenig T, Prichep L, Dierks T, Hubl D, Wahlund LO, John ER, Jelic V. · Department of Psychiatric Neurophysiology, University Hospital of Clinical Psychiatry, Bolligenstrasse 111, CH-3000 Berne 60, Switzerland. · Neurobiol Aging. · Pubmed #15582746 No free full text.

Abstract: The hypothesis of a functional disconnection of neuro-cognitive networks in patients with mild cognitive impairment (MCI) and Alzheimer Dementia was investigated using baseline resting EEG data. EEG databases from New York (264 subjects) and Stockholm (155 subjects), including healthy controls and patients with varying degrees of cognitive decline or Alzheimer Dementia were analyzed using Global Field Synchronization (GFS), a novel measure of global EEG synchronization. GFS reflects the global amount of phase-locked activity at a given frequency by a single number; it is independent of the recording reference and of implicit source models. Patients showed decreased GFS values in Alpha, Beta, and Gamma frequency bands, and increased GFS values in the Delta band, confirming the hypothesized disconnection syndrome. The results are discussed within the framework of current knowledge about the functional significance of the affected frequency bands.

Dierks T, Jelic V. · Department of Psychiatric Neurophysiology, University Hospital of Clinical Psychiatry, Bern, Switzerland. · Methods Find Exp Clin Pharmacol. · Pubmed #12809081 No free full text.

This publication has no abstract.

Lindau M, Jelic V, Johansson SE, Andersen C, Wahlund LO, Almkvist O. · Karolinska Institutet, Department of Clinical Neuroscience, Occupational Therapy and Elderly Care Research, Huddinge University Hospital, Stockholm, Sweden. · Dement Geriatr Cogn Disord. · Pubmed #12566600 No free full text.

Abstract: OBJECTIVE: To investigate the relationship between quantitative EEG (qEEG) measurements in frontotemporal dementia (FTD), Alzheimer's disease (AD) and healthy controls and to study to what extent qEEG in FTD and AD or neuropsychological test results of FTD and AD patients or a combination of both contribute to classification accuracy. METHOD: The FTD sample consisted of 19 patients, the AD sample of 16 patients, and the control group of 19 subjects. Groups were matched on the group level with respect to demographic variables. For qEEG the global field power was calculated for six frequency bands: delta (1.0-3.5 Hz), theta (4.0-7.5 Hz), alpha (8.0-11.0 Hz), beta1 (12.0-15.5 Hz), beta2 (16.0-19.5 Hz), beta3 (20.0-23.5 Hz), and spectral ratio as the ratio of the sum of fast frequency bands alpha + beta1 + beta2 + beta3 and slow frequency bands delta + theta. RESULTS: In comparison to controls FTD patients were marked by an absence of an increase in slow qEEG activities and a decrease in fast activities, whereas AD patients were marked by an increase in slow activities and a smaller decrease in fast activities. According to the Mann-Whitney U test the cognitive functions of attention, visuospatial thinking and episodic memory were significantly better in FTD than in AD. Using logistic regression analysis the best predictors of FTD and AD were in a model using the delta and theta activities, and high levels of visuospatial ability and episodic memory. Classification accuracy of the model was 93.3%. CONCLUSION: FTD patients reveal a different pattern of qEEG changes than AD patients. This result demonstrates the importance of qEEG for FTD diagnosis. Cognition is selectively better in FTD than in AD. A combination of qEEG and neuropsychology is recommended for differential diagnoses of FTD and AD.

Arnáiz E, Jelic V, Almkvist O, Wahlund LO, Winblad B, Valind S, Nordberg A. · Karolinska Institutet, Department of Clinical Neuroscience, Occupational Therapy, and Elderly Care Research (NEUROTEC), Huddinge University Hospital, Sweden. · Neuroreport. · Pubmed #11277595 No free full text.

Abstract: The objective of this study was to assess whether reduced glucose metabolism (rCMRGlu) and cognitive functioning could predict development of Alzheimer's disease (AD) in subjects with mild cognitive impairment (MCI). Twenty MCI patients underwent baseline and follow-up investigations of rCMRGlu, as measured by PET, and cognitive function measured by neuropsychological test assessments. Subjects were clinically followed up with an average interval of 36.5 months. Two groups were obtained after the second clinical assessment. Nine patients were diagnosed as AD and classified as progressive MCI (P-MCI), whereas 11 patients remained clinically stable and were classified as stable MCI (S-MCI). There were no differences in demographic variables or baseline MMSE between the two subgroups. Logistic regression indicated the two variables that most effectively predicted future development of AD were rCMRGlu from the left temporoparietal area and performance on the block design. These combined measures gave an optimal 90% correct classification rate, whereas only rCMRGlu or neuropsychology alone gave 75% and 65% correct classification, respectively. Measures of temporoparietal cerebral metabolism and visuospatial function may aid in predicting the evolution to AD for patients with MCI.

Huang C, Wahlund L, Dierks T, Julin P, Winblad B, Jelic V. · Karolinska Institutet, Department of Clinical Neuroscience, Occupational Therapy and Elderly Care Research (NEUROTEC), Divison of Geriatric Medicine, B-84, Huddinge University Hospital, Huddinge, Sweden. · Clin Neurophysiol. · Pubmed #11068230 No free full text.

Abstract: 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.

Dierks T, Jelic V, Pascual-Marqui RD, Wahlund L, Julin P, Linden DE, Maurer K, Winblad B, Nordberg A. · Department of Psychiatric Neurophysiology, University Hospital of Clinical Psychiatry, University of Bern, Bern, Switzerland. · Clin Neurophysiol. · Pubmed #11018498 No free full text.

Abstract: 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.

Jelic V, Johansson SE, Almkvist O, Shigeta M, Julin P, Nordberg A, Winblad B, Wahlund LO. · Karolinska Institutet, NEUROTEC, Division of Geriatric Medicine, B-84, Huddinge University Hospital, S-141 86, Huddinge, Sweden. · Neurobiol Aging. · Pubmed #10924766 No free full text.

Abstract: 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.