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Psychiatry Research: Neuroimaging, 40:18I - 194 Elsevier

Topography of the Quantitative Electroencephalogram in Dementia of the Alzheimer Type: Relation to Severity of Dementia Thomas

Dierks. lvanca Perisic, Lutz Friilich,

Ralf Ihl. and Konrad Maurer

Received September 17, 1990; revised version received February 22, 1991; accepted March 31, 1991. Abstract. Conventional electroencephalographic (EEG) frequency bands and peak frequency were investigated in patients with probable dementia of the Alzheimer type (DAT). Measures of EEG topography and activity were also related to the severity of dementia, as assessed by neuropsychological tests. EEG activity measured in conventional frequency bands proved to be the most sensitive parameter for the quantitative differentiation of DAT, whereas the topography of peak frequency was the better qualitative discriminator between healthy subjects and DAT patients. Key Words. Alzheimer’s disease, dementia, ele~trophysiology,

peak frequency.

Numerous studies have investigated the influence of aging on the electroencephalogram (EEG) (Celesia, 1986), but there are relatively few reports regarding topographic abnormalities of the EEG in patients with dementia of the Alzheimer type (DAT). Duffy et al. (1984) reported that increased slow activity in right temporal areas distinguished between presenile patients and control subjects, whereas the maximal difference between senile patients and control subjects involved the midfrontal and anterior frontal areas bilaterally. Miyauchi et al. (1989) also described increased slowing over frontal areas and decreased alpha activity in rightposterior-temporal areas. Breslau et al. (1989) showed by confirmatory statistical analysis that delta activity shifted from the midsaggital plane in normal elderly subjects toward frontal areas in DAT patients, but did not find significant topographic differences between DAT patients and control subjects in any other frequency band. EEG studies that have taken the severity of dementia into account have found it difficult to differentiate between patients in early stages of DAT and healthy control subjects (Drake et al., 1989). However, a correlation between severity of illness and the number of EEG changes could be readily demonstrated in DAT patients with an established course of the disease (Coben et al., 1983). In the present study, we have compared the EEG activity of elderly control

Thomas Dierks, M.D., is Research Associate; Konrad Maurer, M.D., is Professor of Psychiatry; and Ivanka Perisic, Ph.D., is Staff Psychofogist, Neurophysiology Laboratory, Department of Psychiatry, University of Wiirzburg. Lutz FrC%ch, M.D., and Ralf Ihl, M.D., are Staff Psychiatrists, Department of Psychiatry, University of Wiirzburg. (Reprint requests to Dr. T. Dierks, Dept. of Psychiatry, Univ. of Wiirzburg, Fiichsleinstr. 15, D-W-8700 Wiirzburg, Germany.) 0165-1781/91/$03.50 @ 1991 Elsevier Scientific Publishers Ireland Ltd.

1x2 subjects with that in patients with presemle and senile DA’I‘. ‘This stud) extends earlier reports by correlating peak frequency, and its topographical alteration. to the severity of DAT.

Methods Subjects. We studied 14 healthy geriatric subjects (12 women, 2 men; mean age =- 73 years. SD = 7; age range = 64-85 years) and 48 patients suffering from probable DAT (22 women, 26 men, mean age = 67 years, SD = t 1; age range = 45-84 years; mean duration of illness = 3. I years, SD = 1.2). All subjects were right handed. The elderly healthy control subjects were volunteers from the Senior Day Center in Wiirzburg. They were screened to exclude neurological or psychiatric disorders, epilepsy, drug or alcohol dependence, head injury. and psychopharmacologically active medications. All patients met the criteria for probable DAT (McKhann et al., 1984). They were hospitafized for a period of 2-3 weeks for diagnostic evaluation. Diagnostic assessment included medical history, physical and neurologica1 examinations, and routine laboratory tests (including thyroid hormone levels and Vitamin BtZ and folate). The modified Hachinski ischemic score (score < 4) (Rosen et al., 1984) was used to exclude multi-infarct dementia. Further selection was based on computed tomographic scans in all patients which, if abnormal, showed only cerebral atrophy, ventricular dilatation, and no more than one lacunar infarction. In no case were there territorial infarctions. In most patients, single photon emission computed tomography with Tc~99m-hexamethylpropyleneamine-oxime was performed and did not reveal signs of multifocal flow deficits. Typically, temporo-parietal or frontal flow deficits were found (Friilich et al., 1989). Only patients who were not using psychopharmacologically active medication were included in the study. All patients were investigated with a battery of neuropsychological tests for cognitive function, language. apraxia, agnosia, visuospatial abilities, and mood and behavioral changes. The stage of mental impairment was assessed by the Brief Cognitive Rating Scale (BCRS; Reisberg et al.. 1983). For a better comparison of different ages at onset of DAT, the patients were subdivided into three groups with age ranges of 45-64 years, 65-74 years, and 75 years and above. The DAT group was also subdivided into three severity groupings on the basis of their BCRS scores: (I) slight degree of dementia (BCRS < 29, n = 9); (2) moderate degree of dementia (BCRS 29-39. n = 27), and (3) severe degree of dementia (BCRS > 39, n = 12). Data Acquisition. EEG was recorded using a l9-channel Bio-logic Brain Atlas III Plus. The electrodes were placed according to the international lo-20 system, Fpl, Fp2, F7$ F3, Fz, F4. F8, T3, C3, Cz, C4, T4, T5, P3, Pz, P4, T6, 01, and 02. Correct placement of the electrodes was ensured by exact measurement of the electrode locations. The areas of electrode placement were cleaned to ensure low impedances, and the electrodes were fastened into place with paste. Before recording, the impedances were measured, and low and similar values were ensured in all channels. The EEG was sampled at 128 Hz per channel and stored on magnetic disks for further analysis off-line. Before A-D conversion, however, the EEG was analogfiltered with a band pass of 1.O-30.0 Hz, precluding aliasing of data. The subjects were asked to close their eyes and relax during the recording. The technician monitored the subject’s vigilance state continuously to made sure that the subject did not become drowsy, Quantification. Spectral analysis of the EEG data was performed with a Fast Fourier Transformation (FFT; Hartley algorithm, Hanning window). Before spectral analysis, the stored EEG was visually inspected to assure that no EEG portions contaminated with artifacts were used for analysis. EEG epochs (mean i: SD = 18 -l- 8; range = 8-40 epochs) of 2-set duration, which allowed a resolution of 0.5 Hz in the frequency spectrum, were averaged. For map construction, the values for all channels were put into a matrix of 64 X 64 pixels. The pixels between real measured values were linearly interpolated using the four nearest electrodes and subsequently color coded to produce an image of the activity of a frequency or

183 frequency band. The following frequency bands were studied: delta (1.O-3.5 Hz), theta (4.0-7.5 Hz), alpha (8.0-l 1.5 Hz), beta, (12.0-15.5 Hz), beta, (16.0-19.5 Hz), and betas (20.0-23.5 Hz). The data in the frequency bands were logarithmically transformed for better Gaussian distribution (Gasser et al., 1982). Further analysis involved calculation of peak frequency (frequency component with the highest amplitude in the entire frequency spectrum) in each channel. Statistics. In each of the four groups, all channels were individually normalized (z-transformed) to give a mean value of 0.0 and a standard deviation of 1.O for each channel in each group. On these normalized data, a principal component analysis (PCA) was performed for each frequency band to search for regions of topographic similarity to reduce data. Each electrode was assigned to the component with which it showed the highest correlation after varimax rotation. A mean of the logarithmic values of the electrodes that were assigned to

each component was calculated (see Fig. 3). A split-plot repeated measures (repeated measurements over components) analysis of variance (ANOVA; Winer, 1971)was computed for statistical evaluation of effects between groups, effects between components (regions), and the group X component interaction. A significant interaction would indicate a topographic change between the groups. The Newman-Keuls test was used for post hoc analyses. A PCA was also computed on peak frequencies to find regions that were independent of one another, which were then tested in the same way as the frequency bands. The amplitude of the peak frequency was determined, and the localization of the channel with the highest amplitude of the peak was digitized for quantification by a coordinate system, with electrode rows from 1 (frontal) to 5 (occipital) and electrode columns 1 (left) to 5 (right). For example, electrode P3 would have the coordinates 4 (electrode row 4) and 2 (electrode column 2). The resuhs of the localizations were compared between groups with the nonparametric Mann-Whitney U test. Pearson linear correlation coefficients were calculated to estimate the relationships among loga~thmically transfo~ed EEG frequency-band data, peak-frequency data, and neuropsychoiogical test rest&s. To estimate the ability of each channel to discriminate between groups, a descriptive discriminant analysis was performed. From the resulting Wilk’s lambda values, the x2 values were calculated and displayed as a map of discriminant power. All tests were performed using the SPSS statistical package (SPSS, 1983).

Results Subdividing the DAT group into three age ranges revealed no differences in BCRS scores among the groups. Mean (zk SD) BCRS scores for the three subgroups were as follows: youngest group (45-64 years), 32 f 2.7; middle group (65-74 years), 32.6 + 7.1; and oldest group (75 years and above), 35.9 f 6.3. No significant correlation Hence the age of patients between age and BCRS score emerged (r = 0.21, p = 0.15). did not influence the severity of dementia. Maps were constructed from the values of the six frequency bands. Fig. 1 shows the activity of the alpha band, where there was a slight tendency toward greater frontal activity with increasing severity of dementia.

Frequency Band Analysis. The PCA rendered in all frequency bands two topographic components with an eigenvalue > 1.0, indicating that regions o# independent electrodes were located in frontal or in occipital regions. Figs. 2a to 2f show the correlation between an electrode and a component, with red values indicating electrodes with higher correlation with the first component and blue values indicating electrodes with higher correlation with the second component. For the delta band and all the beta bands, the first main component was located occipital-

Alpha (8.0-I 1.5 Hz) activity in (A) healthy controls, (6) slightly demented patiecits jBCRS c--29). /C) moderately demented patlents (SCRS 29-39). and (0) severely demented @XS >29) patients. Note that the alpha activity In the slightly demented group is at least as htgh as in the control group. ECRS = Brief Cogmtwe Rating Scale. DAT -.. dementia of the Alzheimer type.

Fig. 1s Topographicdistributionof alpha activity in healthy cantrals and DAT patients

Display of correlation coefficients between electrodes and the component/region (region 1, red values: region12, blue values), resulting from PCA, on which the electrode loads highest. Frequency bands: (A) delta band, (B) theta band, (C) alpha band, (D) beta, band, (E) betan band, and (I’) beta3 band. PCA = principal component analysis.

Fig. 2. Correlatioin between electrodes and components of PCA

ly, whereas for the theta frontally.

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the first mam component

wits iocate~;

The two topographic components detected by K’A were used tctr further descriptive presentation of’ the data. Fig. 3 graphically depicts the log-transt‘ormcd values of the EEG activity in the various frequency bands for the two components (regions) and for each group (controls. slightly demented patients. moderatel> demented patients, and severely demented patients). ‘The statistical comparison ot the data ~split-plot design) showed significant differences for the theta t p 6:. 0.01 i. alpha (p < 0.05), beta, @ < 0.01). beta, (p < O.OI), and beta, (y < 0.01) activtt! bands among the four groups. Post hoc testing showed that statistically significant differences (level at p < 0.05)could be seen between both the control group and the slightly demented group in comparison with the severely demented group. Nn difference could be observed in any frequency band or in peak frequency between the control group and the slightly demented group (Table I). The group X region interaction only showed significant changes for the beta bands. Figs. 3a-3f graphically depict the relationship between region and group. In the delta band, the activity is equally high frontally and occipitally (interaction. p = 0.47); in the theta band, all groups have higher activity frontally compared with occipitally (between regions: ft 2~.0.001; interaction: p = 0.78). In the alpha band, the control group showed a clearly increased and the slightly demented group showed a slightly increased activity in the occipital region, whereas in the moderately and the severely demented groups, activity was similarly distributed between the frontal and occipital region (between regions: p -= 0.02; interaction: p = 0.18). In the beta,-beta, bands, a similar but more pronounced pattern could be discerned, with higher activity occipitalIy in the contro1 and siightly demented groups, and higher amplitudes frontally in the moderately and severely demented groups (between regions: p > 0.05;interaction: p < 0.05). This suggests that beta activity and possibly alpha activity show a topographic change over the course of DAT. The dominant occipital pattern of activity found in the control group shifts to frontal regions in the severel? demented group. Peak Frequency Analysis. Results of PCA for the peak frequency revealed four topographic components with an eigenvalue > 1.0. Fig. 4a displays the peak frequencies for the four components. A decline of peak frequency in the moderately and the severely demented groups can best be seen in the region characterized by factor 3, the occipital region. A multivariate analysis of variance showed an overall significant difference between the groups with respect to peak frequency. A post hoc Newman-Keuls test indicated that the frontal component did not contribute to this difference at all. For the temporo-parietal regions, a significant difference between the control group and the slightly and moderately demented groups in comparison with the severely demented group could be observed. The difference between the control group and the moderately demented group was likewise sjgnificant for the occipital component (Table I I No significant interaction between groups and regions could be detected.

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Diagrams show the mean and standard deviation of logarithmically transformed values of activity in the frontal (Fr) and the occipital (Occ) localized component/region for the control group (Controls),the slightly demented (BCRS < 29), the moderately demented (BARS 29-39). and the severely demented (BARS > 39) group in 6 frequency bands (A) delta band, (B) theta band, (C) alpha band, (D) beta+ band, (E) beta? band, and (F) beta, band. BCRS = Brief Cognitive Rating Scale.

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Fig. 3. Electroencephalographic activity in 6 frequency bands in relation to topography and severity of dementia

Table 1. Mean values of electroencephalographic bands and peak frequency Group

-.- Delta

Theta

activity

Alpha _ ~.___~ Beta, -__-_ Beta2

in 6 frequency Betas

Peak (3)

Controls Slightly demented Moderately demented Severely demented

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Note. Mean values of logarithmically transformed values of activity in 6 frequency bands subdivided into 4 groups: control group, slightly demenmd group with a Brief Cognitive Rating Scale (BCRS) score < 29, moderately demented group with a BCRS score between 29 and 39. and severely demented group with a BCRS score > 39. Lines connect groups that diired significantly in the post hoc testing at the p < 0.05 level. Furthermore, the mean values of peak frequency (Hz) in the occipital component/region (3) are shown.

Regarding the amplitude of the peak frequencies, Figs. 4b and 4c display the number of subjects (in Yc) peaking with highest amplitude at which electrode. In the control group, most subjects peaked in the occipital region (Fig. 4b), whereas the DAT patients were peaking more frontally (Fig. 4~). Fig. 4d illustrates that the mean peak frequency of subjects (both groups together) peaking at an electrode was slightly (not significantly) faster occipitally than frontally. The mean location of peak frequency is shown in Fig. 5, where the control group had a significantly more occipital localization compared with all DAT groups @ < 0.05). In the DAT groups, there was a slight tendency (NS) toward a more frontal localization with increasing severity of dementia. Descriptive Regional Discriminant Analysis. To investigate which region on the scalp could best differentiate among the four groups, a descriptive discriminant analysis was performed for each channel. The discriminant analysis included the log-transformed values of the frequency bands. Fig. 6 maps the resulting x* values. The higher the x2 value, the higher is the discriminant ability of the channel. The results indicate that the highest differentiating capability is located in temporoparietal regions and is more pronounced on the left side than on the right. Correlation Between Psychometric Testing and EEG. For DAT patients, EEG parameters, in regions determined by PCA, and BCRS scores showed a nonsignificant positive correlation for the slow frequencies (delta and theta; Fig. 7a), which was more marked over the frontal components. For the other frequency bands, the highest correlations, which were negative, with BCRS scores could be found over occipital regions (Fig. 7a). The peak frequency showed negative correlations with BCRS scores, and significant correlations were found between the temporo-parietal components and BCRS scores (Fig. 7a). Since both regions of alpha activity showed significant negative correlations with the BCRS score, the correlation coefficient between each channel and the BCRS score was computed. Fig. 7b displays the coefficients as a descriptive map of significance of the correlation between alpha activity and BCRS score. All temporal (except T4), central, parietal, and occipital electrodes showed a significant negative correlation with the BCRS score.

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OccipIPl

[A) Diagrams show the mean and SD of peak frequency in the 4 com~nents/regions as determined by principal component analysis: (1) Frontal, (2) left parteto-tem~ral, (3) occipital, and (4) right temporo-pa&al component/region subdivided in one control group (Controls), slightly demented (BCRS < 29), moderately demented (BCRS 29-39), and severely demented (BCRS > 39) group. Relative number of subjects (in %) peaking with highest amplitude at each electrode in the (B) control group and (C) in the DAT group. (D) Mean peak frequency of the subjects (both groups together) peaking at each single electrode. BCRS = Brief Cognitive Rating Scale. DAT = dementia of the Alzheimer type.

90

c

Fig. 4. Peak frequency analysis

Fig. 5. Topography of peak frequency

Fig. 6. Topographic distribution of d~~~minant power of eiectmdes between groups with different stages of cognitive deterioration Chi-Square

1 0

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Mean location (rt- SE in horizontal and vertical dir~tion) of the highest amplitude of the peak frequency in the control group (*), the slightly demented group (BCRS < 29, “0”). the moderately demented group (BCRS 29-39, “X”), and the severely demented group (BCRS > 39 “+“I

9 Map of resultingx2 values of discriminantanalysis (seetext1

Fig. 7. Correlation between electroencsphalographic parameters and neuropsychological testing .5

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Topography of the quantitative electroencephalogram in dementia of the Alzheimer type: relation to severity of dementia.

Conventional electroencephalographic (EEG) frequency bands and peak frequency were investigated in patients with probable dementia of the Alzheimer ty...
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