Magnetx Resonance Printed in the USA.
Imaging. Vol. IO, pp. 859-865, All rights reserved.
1992 Copyright
0
0730-725X/92 $5.00 + .oO 1992 Pergamon Press Ltd.
l Original Contribution
QUANTITATIVE ESTIMATION OF BRAIN WHITE MATTER ABNORMALITIES IN ELDERLY SUBJECTS USING MAGNETIC RESONANCE IMAGING WAHLUND,* G. ANDERSSON-LUNDMAN,* P. JULIN,* M. NORDSTROM,* M. VIITANEN,~ AND J. S~F *Karolinska Institute, Department of Psychiatry at S:t G6ran’s Hospital, and TDepartment of Geriatric Medicine at Huddinge Hospital, Stockholm, Sweden L.O.
Twenty-five elderly subjects were examined with brain magnetic resonance imaging (MRI). The subjects were divided into two groups: those with Mini-Mental State Examination (MMSE) scores above 25, and those subjects with MMSE scores between 18 and 24. The degree of white matter abnormalities (WMA) (expressed as relative volumes) as well as the presence of cerebrovascular risk factors were evaluated in the two groups. We found that a) subjects with low MMSE scores had significantly larger relative volumes of WMA than the subjects with higher scores, b) a significant correlation (r, = 0.53, p c O.OO!J) between MMSE scores and the relative volume of WMA was also established, and c) a weak significant correlation (r, = -0.51, p c 0.05) between arterial blood pressure and WMA was found in the subjects with high MMSE scores. Besides these findings no other correlations between the presence of cerebrovascular risk factors and WMA were found in any of the groups. Keywords: MRI; White matter abnormalities; Dementia; Cerebrovascular risk factors; Cognitive; Normal controls.
often selected by advertisements or from among relatives of demented patients, and sometimes they have been selected from patients referred for a brain MRI examination with no pathological findings. In a recent study a group of “successfully aged” persons were examined with brain MRI scans and it was found that less than 8% showed WMA. The group of patients were, however, not representative for “normally aged” persons, because those with arteriosclerosis and other diseases were excluded. Also, they showed very high intellectual and cognitive functions.’ In order to study further the occurrence and degree of WMA in “normally” aged subjects, we have studied a different group of elderly people. These subjects were randomly selected from a larger group participating in a population study aiming to investigate the frequency of dementia and mental illnesses in elderly living in a central part of Stockholm. We also aimed to evaluate if there was a correlation between the degree of WMA and cognitive functions as well as between the degree of WMA and cerebrovascular risk factors.
INTRODUCTION Magnetic resonance imaging (MRI) is highly sensitive in detecting abnormalities in the cerebral white matter. These alterations are usually demonstrated as focal areas of increased signal intensity on T2-weighted images. The abnormalities are often found in the deep cerebral white matter and in the basal ganglia. The MRI technique has been widely used in the study of dementia and many reports have discussed white matter abnormalities (WMA) in relation to different types of dementia.lm3 The degree of WMA increases with age4y5and whether these changes are a part of a normal aging process or if they are important for the development of dementia has not been fully elucidated. When studying WMA in normal aging the selection of subjects is crucial. A review article by Drayer reports that several studies have shown WMA from 30 to 80% in normal populations.6 There is a lot of discrepancy about the frequency in WMA observed in different studies. This might be due in part to different ways of selecting study participants. Subjects are
RECENED 10/8/91; ACCEPTED3/24/92. Please address all correspondence to L.O. Wahlund, De-
partment of Psychiatry, S:t G6rans Hospital, Box 12500, S-11281 Stockholm, 859
Sweden.
Magnetic Resonance Imaging0 Volume 10, Number 6, 1992
860
SUBJECTS AND METHODS In a parish in the central part of Stockholm all persons older than 75 years were examined to investigate the incidence of psychiatric disorders and dementia in elderly. This population consisted of 2,369 subjects. All the subjects were interviewed and the degree of cognitive impairments were established using the MiniMental State Examination (MMSE).’ A total of 364 were found to score 25) 86 1 Fern 77 2 Fern 3 81 Fern 85 4 Fern 84 5 Fern 6 Male 92 85 7 Male 79 8 Fern 77 9 Fern 81 10 Fern 83 11 Fern Male 82 12 Male 77 13 79 14 Fern 81 Male 15 lOF/5M 82 f 4
Stroke
-
-
+ -
-
+ + 3+/12-
+ 1+/14-
Blood glucose level
7.2 6.4 4.6 21 .d;bM) 6.0 6.2 5.1 6.8 6.2 4.9 5.0 5.2 5.1 4.1 6.7 + 4
Syst. BP
Diast. BP
MMSE
WMA
160 150 140 160 160 120 190 200 160 160 135 120 175 170 150 157 f 22
80 80 75 75 80 60 100 90 85 90 80 70 110 80 70 82 f 12
28 28 26 26 29 29 27 26 29 27 26 29 30 28 30 28 f 1
+ f
135 170 140 180 135 140 120 140 115 NI 142 f 21
80 85 80 80 75 80 75 80 75 NI 79 f 3
20 21 23 21 22 22 23 22 21 20 21 * 1
f f f f -
6+/9-
(Mean f SD) Patients 16 17 18 19
(MMSE scores 18-24) Fern 86 Fern 83 Fern 85 Fern 81
+ -
20 21
Fern Male
81 91
+ -
22 23
Fern Male
77 77
+ +
24 25 Fern 8F/2M
84 77 82 f 5
l& 5+/4-
+ NI 1+/9-
5.6 4.8 8.0 5.8 5.6 4.3 3.9 4.6 4.6 NI 5.2 + 1.2
-F + + + + + + + -
8+/2-
The following cerebrovascular risk factors were noted: History of ischemic heart disease (myocardial infarction, atria1 fibrillation, angina pectoris, congestive heart disease) or stroke. Moreover, blood glucose level and arterial blood pressure, as well as scores from the Mini-Mental State Examination (MMSE) test, are also given. The presence of white matter abnormalities (WMA) is also noted. DM: diabetes mellitus, NI: no information.
Quantitative estimation of white matter abnormalities 0 L.O. WAHLUND
sidered: 1) ischemic heart disease, 2) history of stroke, 3) diabetes mellitus, 4) arterial blood pressure, and 5) level of blood glucose. These risk factors as well as the MMSE scores are presented in Table 1. Magnetic Resonance Imaging The MRI examinations were performed with a low field magnetic resonance imager operating at 0.02 T (Acutscan 110, Instrumentarium Corp.). The brains were scanned with 12 (10 mm) transaxial slices with no gap between. A mid-sagittal image was used as localizer and the transaxial slices were positioned according to the CA-CP line. A highly 7”-weighted pulse sequence (SE 2300/130) was selected to get an optimal contrast between abnormalities in the white matter and brain tissue. Periventricular WMA were sometimes difficult to separate from the cerebrovascular fluid (CSF) on the Tz-weighted images. In these cases we used a mixed T,/T, pulse sequence (SR 500/60) to obtain a good separation between CSF and WMA. Area and Volume Measurements From the 12 slices, 8 were selected for volume measurements. The first and lowest slice was the one imaging the optic nerve and the next seven, more cranial slices were used for the volume measurements. After transferring the images to an image processor (GOP300, Struer-Vision AB) the volume estimations were made in the following way: In each slice the areas of increased signal intensity (white matter abnormalities) were detected and manually outlined by one of the authors (GAL) with a paint function in the image processor, and the areas of the WMA were calculated. This was done without knowing the MMSE scores or other clinical data of the subjects. The volume of the WMA was calculated as the area of WMA multiplied by the slice thickness (10 mm). The degree of WMA was expressed as a relative volume (a quotient between the sum of the volume(s) of the WMA and the intracranial volume from the 8 selected slices). The brain was divided into six regions as shown in Fig. 1 A-E, the regions were designated as follows: A. Left and right frontal areas (L Fr and R Fr) (Including periventricular and non-periventricular WMA); B. Left and right lateral areas (including centrum semiovale) (L L and R L); and C. Left and right posterior areas (L P and R P) (Including periventricular and non-periventricular WMA).
861
ET AL.
StatisticalAnalysis All group comparisons were made using MannWhitney U-test and x2-test, correlations were evaluated using Spearman’s rank correlation coefficient. RESULTS
Clinical data as well as the presence of brain WMA in the “patients” and “controls” are shown in Table 1. We did not find any statistically significant differences in systolic or diastolic blood pressure between the “patients” and “controls.” Nor were there any differences in the level of blood-glucose. The frequency of ischemit risk factors was not significantly different in the “patients” (6/9) as compared to the “controls” (5/15), although the “controls” had a fewer frequency of ischemit risk factors. A statistically significant (p < 0.05, x2) higher frequency of WMA was found in the “patients” (S/10) than among the “controls” (6/15). The relative volumes of WMA are presented in Table 2. We found that the “patients” had significantly larger WMA volumes in the right and left frontal areas as well as in the right and left posterior areas compared to the “controls.” Also the relative volumes of WMA in the whole brain were significantly larger in the “patients” than in the “controls.” When comparing the volumes of WMA in the posterior and anterior parts of the brains we found that there were slightly more WMA in the posterior regions than in the anterior in both groups (“patients”, 1.67 f 3.12, 0.73 + 0.95 and “controls”, 0.14 + 0.23, 0.1 + 0.17). However, the differences were not statistically significant. There were no differ-
Table 2. Volumes of white matter abnormalities in six brain-regions, in the hemispheres and in the whole brain
Brain area Frontal left Frontal right Lateral left Lateral right Posterior left Posterior right Left hemisphere Right hemisphere Total brain
Patients (n = 10) 0.37 0.37 0.08 0.21 0.71 0.99 1.50 1.53 3.0
-+ 0.60 If: 0.50 rf: 0.1 f 0.42 * 1.12 + 2.03 f 2.53 * 2.50 f 4.99
Controls (n = 15) 0.05 0.05 0.02 0.01 0.09 0.05 0.19
* 0.10 zk 0.1 f 0.05 z!c0.03 f 0.15 f 0.10 f 0.28
0.12 * 0.18 0.31 Ik 0.44
P
Imaging. Vol. IO, pp. 859-865, All rights reserved.
1992 Copyright
0
0730-725X/92 $5.00 + .oO 1992 Pergamon Press Ltd.
l Original Contribution
QUANTITATIVE ESTIMATION OF BRAIN WHITE MATTER ABNORMALITIES IN ELDERLY SUBJECTS USING MAGNETIC RESONANCE IMAGING WAHLUND,* G. ANDERSSON-LUNDMAN,* P. JULIN,* M. NORDSTROM,* M. VIITANEN,~ AND J. S~F *Karolinska Institute, Department of Psychiatry at S:t G6ran’s Hospital, and TDepartment of Geriatric Medicine at Huddinge Hospital, Stockholm, Sweden L.O.
Twenty-five elderly subjects were examined with brain magnetic resonance imaging (MRI). The subjects were divided into two groups: those with Mini-Mental State Examination (MMSE) scores above 25, and those subjects with MMSE scores between 18 and 24. The degree of white matter abnormalities (WMA) (expressed as relative volumes) as well as the presence of cerebrovascular risk factors were evaluated in the two groups. We found that a) subjects with low MMSE scores had significantly larger relative volumes of WMA than the subjects with higher scores, b) a significant correlation (r, = 0.53, p c O.OO!J) between MMSE scores and the relative volume of WMA was also established, and c) a weak significant correlation (r, = -0.51, p c 0.05) between arterial blood pressure and WMA was found in the subjects with high MMSE scores. Besides these findings no other correlations between the presence of cerebrovascular risk factors and WMA were found in any of the groups. Keywords: MRI; White matter abnormalities; Dementia; Cerebrovascular risk factors; Cognitive; Normal controls.
often selected by advertisements or from among relatives of demented patients, and sometimes they have been selected from patients referred for a brain MRI examination with no pathological findings. In a recent study a group of “successfully aged” persons were examined with brain MRI scans and it was found that less than 8% showed WMA. The group of patients were, however, not representative for “normally aged” persons, because those with arteriosclerosis and other diseases were excluded. Also, they showed very high intellectual and cognitive functions.’ In order to study further the occurrence and degree of WMA in “normally” aged subjects, we have studied a different group of elderly people. These subjects were randomly selected from a larger group participating in a population study aiming to investigate the frequency of dementia and mental illnesses in elderly living in a central part of Stockholm. We also aimed to evaluate if there was a correlation between the degree of WMA and cognitive functions as well as between the degree of WMA and cerebrovascular risk factors.
INTRODUCTION Magnetic resonance imaging (MRI) is highly sensitive in detecting abnormalities in the cerebral white matter. These alterations are usually demonstrated as focal areas of increased signal intensity on T2-weighted images. The abnormalities are often found in the deep cerebral white matter and in the basal ganglia. The MRI technique has been widely used in the study of dementia and many reports have discussed white matter abnormalities (WMA) in relation to different types of dementia.lm3 The degree of WMA increases with age4y5and whether these changes are a part of a normal aging process or if they are important for the development of dementia has not been fully elucidated. When studying WMA in normal aging the selection of subjects is crucial. A review article by Drayer reports that several studies have shown WMA from 30 to 80% in normal populations.6 There is a lot of discrepancy about the frequency in WMA observed in different studies. This might be due in part to different ways of selecting study participants. Subjects are
RECENED 10/8/91; ACCEPTED3/24/92. Please address all correspondence to L.O. Wahlund, De-
partment of Psychiatry, S:t G6rans Hospital, Box 12500, S-11281 Stockholm, 859
Sweden.
Magnetic Resonance Imaging0 Volume 10, Number 6, 1992
860
SUBJECTS AND METHODS In a parish in the central part of Stockholm all persons older than 75 years were examined to investigate the incidence of psychiatric disorders and dementia in elderly. This population consisted of 2,369 subjects. All the subjects were interviewed and the degree of cognitive impairments were established using the MiniMental State Examination (MMSE).’ A total of 364 were found to score 25) 86 1 Fern 77 2 Fern 3 81 Fern 85 4 Fern 84 5 Fern 6 Male 92 85 7 Male 79 8 Fern 77 9 Fern 81 10 Fern 83 11 Fern Male 82 12 Male 77 13 79 14 Fern 81 Male 15 lOF/5M 82 f 4
Stroke
-
-
+ -
-
+ + 3+/12-
+ 1+/14-
Blood glucose level
7.2 6.4 4.6 21 .d;bM) 6.0 6.2 5.1 6.8 6.2 4.9 5.0 5.2 5.1 4.1 6.7 + 4
Syst. BP
Diast. BP
MMSE
WMA
160 150 140 160 160 120 190 200 160 160 135 120 175 170 150 157 f 22
80 80 75 75 80 60 100 90 85 90 80 70 110 80 70 82 f 12
28 28 26 26 29 29 27 26 29 27 26 29 30 28 30 28 f 1
+ f
135 170 140 180 135 140 120 140 115 NI 142 f 21
80 85 80 80 75 80 75 80 75 NI 79 f 3
20 21 23 21 22 22 23 22 21 20 21 * 1
f f f f -
6+/9-
(Mean f SD) Patients 16 17 18 19
(MMSE scores 18-24) Fern 86 Fern 83 Fern 85 Fern 81
+ -
20 21
Fern Male
81 91
+ -
22 23
Fern Male
77 77
+ +
24 25 Fern 8F/2M
84 77 82 f 5
l& 5+/4-
+ NI 1+/9-
5.6 4.8 8.0 5.8 5.6 4.3 3.9 4.6 4.6 NI 5.2 + 1.2
-F + + + + + + + -
8+/2-
The following cerebrovascular risk factors were noted: History of ischemic heart disease (myocardial infarction, atria1 fibrillation, angina pectoris, congestive heart disease) or stroke. Moreover, blood glucose level and arterial blood pressure, as well as scores from the Mini-Mental State Examination (MMSE) test, are also given. The presence of white matter abnormalities (WMA) is also noted. DM: diabetes mellitus, NI: no information.
Quantitative estimation of white matter abnormalities 0 L.O. WAHLUND
sidered: 1) ischemic heart disease, 2) history of stroke, 3) diabetes mellitus, 4) arterial blood pressure, and 5) level of blood glucose. These risk factors as well as the MMSE scores are presented in Table 1. Magnetic Resonance Imaging The MRI examinations were performed with a low field magnetic resonance imager operating at 0.02 T (Acutscan 110, Instrumentarium Corp.). The brains were scanned with 12 (10 mm) transaxial slices with no gap between. A mid-sagittal image was used as localizer and the transaxial slices were positioned according to the CA-CP line. A highly 7”-weighted pulse sequence (SE 2300/130) was selected to get an optimal contrast between abnormalities in the white matter and brain tissue. Periventricular WMA were sometimes difficult to separate from the cerebrovascular fluid (CSF) on the Tz-weighted images. In these cases we used a mixed T,/T, pulse sequence (SR 500/60) to obtain a good separation between CSF and WMA. Area and Volume Measurements From the 12 slices, 8 were selected for volume measurements. The first and lowest slice was the one imaging the optic nerve and the next seven, more cranial slices were used for the volume measurements. After transferring the images to an image processor (GOP300, Struer-Vision AB) the volume estimations were made in the following way: In each slice the areas of increased signal intensity (white matter abnormalities) were detected and manually outlined by one of the authors (GAL) with a paint function in the image processor, and the areas of the WMA were calculated. This was done without knowing the MMSE scores or other clinical data of the subjects. The volume of the WMA was calculated as the area of WMA multiplied by the slice thickness (10 mm). The degree of WMA was expressed as a relative volume (a quotient between the sum of the volume(s) of the WMA and the intracranial volume from the 8 selected slices). The brain was divided into six regions as shown in Fig. 1 A-E, the regions were designated as follows: A. Left and right frontal areas (L Fr and R Fr) (Including periventricular and non-periventricular WMA); B. Left and right lateral areas (including centrum semiovale) (L L and R L); and C. Left and right posterior areas (L P and R P) (Including periventricular and non-periventricular WMA).
861
ET AL.
StatisticalAnalysis All group comparisons were made using MannWhitney U-test and x2-test, correlations were evaluated using Spearman’s rank correlation coefficient. RESULTS
Clinical data as well as the presence of brain WMA in the “patients” and “controls” are shown in Table 1. We did not find any statistically significant differences in systolic or diastolic blood pressure between the “patients” and “controls.” Nor were there any differences in the level of blood-glucose. The frequency of ischemit risk factors was not significantly different in the “patients” (6/9) as compared to the “controls” (5/15), although the “controls” had a fewer frequency of ischemit risk factors. A statistically significant (p < 0.05, x2) higher frequency of WMA was found in the “patients” (S/10) than among the “controls” (6/15). The relative volumes of WMA are presented in Table 2. We found that the “patients” had significantly larger WMA volumes in the right and left frontal areas as well as in the right and left posterior areas compared to the “controls.” Also the relative volumes of WMA in the whole brain were significantly larger in the “patients” than in the “controls.” When comparing the volumes of WMA in the posterior and anterior parts of the brains we found that there were slightly more WMA in the posterior regions than in the anterior in both groups (“patients”, 1.67 f 3.12, 0.73 + 0.95 and “controls”, 0.14 + 0.23, 0.1 + 0.17). However, the differences were not statistically significant. There were no differ-
Table 2. Volumes of white matter abnormalities in six brain-regions, in the hemispheres and in the whole brain
Brain area Frontal left Frontal right Lateral left Lateral right Posterior left Posterior right Left hemisphere Right hemisphere Total brain
Patients (n = 10) 0.37 0.37 0.08 0.21 0.71 0.99 1.50 1.53 3.0
-+ 0.60 If: 0.50 rf: 0.1 f 0.42 * 1.12 + 2.03 f 2.53 * 2.50 f 4.99
Controls (n = 15) 0.05 0.05 0.02 0.01 0.09 0.05 0.19
* 0.10 zk 0.1 f 0.05 z!c0.03 f 0.15 f 0.10 f 0.28
0.12 * 0.18 0.31 Ik 0.44
P
