JP2000139842A - Dementia diagnosing system - Google Patents

Abstract

PROBLEM TO BE SOLVED: To judge dementia with little burden without the danger of the side reaction of medicines by irradiating the eye of a testee with a light, detecting a miosis rate after a prescribed time elapses and judging imbecility in case the miosis rate is smaller than a prescribed value. SOLUTION: The eye of the testee is irradiated with a light from about 50 mm distance by the angle of about 45 deg. in an upper part. That is, a system is constituted of a light source 11, the pupil photographing infrared-ray camera 12 and an image analyzing computer 13 by considering that the light at the pupil becomes the sufficient one. An indication index 14 to be gazed by the testee under photographing is fitted to the infrared-ray camera 12. Then about 600-800 μw light with the wave length of light power meter 520 nm in light strength is irradiated to the pupil. The miosis rate after the prescribed time elapses is detected. Then the detected miosis rate is compared with the prescribed value together with the existence of cerebral cells or the like in a CT image so that presence or absence of dementia is decided. Thus it is decided without the danger of the side reaction of the medicines or the like.

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to a noninvasive diagnostic system for dementia utilizing the fact that miotic responses to light stimuli differ between healthy subjects and demented patients.

[0002]

2. Description of the Prior Art Diagnosis of an elderly man with mild dementia is very difficult. A biopsy of the brain is helpful in determining the pathology of the brain caused by the disease, but only after the patient has died can a definitive diagnosis be obtained. Recently, Alzheimer's disease (AD) has been discovered in some studies, and new technologies are making more accurate diagnosis possible. They are also convenient for monitoring the progress of the disease and will help find effective therapeutics. One of these methods is an eye drop test method that Scinto et al. Is studying, which can diagnose dementia early and easily (LFM Scinto, KR Daffn
er, D. Dressler, BI Ransil, D. Rentz, S. Weintr
aub, M. Mesulam & H. Potter: A Potential noninvasi
ve neurobiological test for Alzheimer's disease, S
cience, 266, 1051/1054 (1994) and WO 96/030.
70 (see Japanese Patent Publication No. Hei 10-503209).

[0003] Vision occurs when an external object forms an image on the retina of the eye, and the image is detected by a photoreceptor and transmitted to the center via the optic nerve. And it is clear that age-related changes occur in vision with aging. Pupil size is regulated by contraction of the pupillary sphincter and dilated pupil. The pupillary sphincter is controlled by the parasympathetic nerve, and the dilated pupil is controlled by the sympathetic nerve. For example, as the light information entering the eye increases, the pupil contracts reflexively, but this information is transmitted through the optic nerve to the central nucleus Edinger-Westphal nucleus, which is located in front of the parasympathetic ganglion of the Edinger-Westphal nucleus. By contracting the pupillary sphincter by reflexively increasing the activity of neurons. In general, the latency of the miotic response to light stimulation increases with age, and the size of the pupil gradually decreases with age from adolescence. Further, both the contraction rate and the divergence rate of the pupil with respect to light are reduced.

Thus, the eye drop test method of Scinto et al. Applied tropicamide (a major component of pupil dilator), which is a synthetic atropine analog, observed changes in the pupil 30 minutes later, and made the drug hypersensitive to the pupil. The purpose of this study is to diagnose Alzheimer's disease based on the differences.

[0005]

However, this method of using drugs has the side effects and risks of drugs, and limits the indication patients. There are also problems such as the measurement time being too long. Accordingly, the present invention provides a new dementia diagnosis system based on the principle of simple, non-invasive, and no side effects in a test and diagnosis system, which utilizes the fact that the rate of change of the pupil and the response time to light stimulation differ between healthy subjects and dementia patients. The purpose is to provide.

[0006]

That is, a first system for diagnosing dementia according to the present invention comprises: a light source for irradiating light to a subject's eye; A miotic ratio detecting means for detecting a miotic ratio to be mimicked, and comparing the miotic ratio detected by the miotic ratio detecting device with a predetermined value. Comprises first determining means for determining that the patient has dementia. Further, a second dementia diagnosis system of the present invention detects a light source for irradiating light to a subject's eye, and a miosis time until the subject's eye is maximally miotic by irradiating light from the light source. A second step of comparing the miosis time detected by the miosis time detection means with a predetermined value and determining that the subject has dementia if the miosis time is longer than a predetermined value; And determining means. Further, the third dementia diagnosis system of the present invention detects a light source for irradiating light to the subject's eye and a miotic ratio at which the subject's eye mimics after a predetermined time after irradiating the light from the light source. Miosis rate detection means, miosis time detection means for irradiating light from the light source to detect miosis time until the subject's eye is maximally miotic, and miosis rate detection means When the miosis rate is smaller than a predetermined value by comparing the miosis rate with a predetermined value, and the miosis time detected by the miosis time detecting means is compared with a predetermined value, and the miosis time is a predetermined value. A third determination unit that determines that the subject has dementia in at least one of the longer cases.

[0007]

According to the system for diagnosing dementia of the present invention, the fact that there is a clear difference in miosis rate and miosis time between a dementia patient such as Alzheimer-type dementia and a healthy elderly person in response to light stimulation is used. Thus, the presence or absence of dementia in the subject can be determined. That is, according to the first system for diagnosing dementia, the miosis rate after a predetermined period of time has elapsed by irradiating light to the subject's eye is compared with a predetermined value (the miosis rate of a healthy person of substantially the same age). If the miosis rate is smaller than a predetermined value, it can be determined that the subject has dementia. According to the second system for diagnosing dementia, the miosis time until the subject's eye is maximally miotic by irradiating light to the subject's eye is set to a predetermined value (the miosis of a healthy person of substantially the same age). The subject can be determined to have dementia if the miosis time is longer than a predetermined value as compared with (time). Further, the third system for diagnosing dementia is configured to be able to detect both the miosis rate and the miosis time, so that either one of them is significantly different from a predetermined value of a healthy person of almost the same age. In some cases, it may be determined as dementia. Further, in this system, when both of them are significantly different from the respective predetermined values, it can be determined that the reliability of the determination of dementia is higher.

[0008]

BRIEF DESCRIPTION OF THE DRAWINGS FIG. 1 is a block diagram showing a system for diagnosing dementia according to the present invention; A. 1. System Configuration FIG. 1 shows a configuration diagram of the system of the present invention. This system irradiates the subject's eye with light from a distance of 50 mm from an angle of 45 ° from the front and a commercially available penlight (trade name: National BF-51) in consideration of sufficient light in the pupil.
1) An improved light source 11 and an infrared camera (CS) placed at a distance of 40 mm from the subject's eyes
3450, TYPE BV6309A3 (TOKYO ELECTRONIC INDUSTRY CO.,
LTD) 12) and a computer (Macintosh 7600) 13 for analyzing images obtained from the infrared camera. Since the pupil diameter changes depending on the distance to the point of gaze, the pupil diameter is fixed to the infrared camera 12, and a presentation index 14, which is a target to be watched by the subject during imaging, is attached. Here, the length of the camera is 175 mm, and the presentation index 14 is arranged at a position 60 mm horizontally behind the camera. An optical power meter (Advantest, TQ) is used to quantitatively measure the light intensity of the light entering the subject's eye.
8210) 15 are also installed. Images captured by the infrared camera 12 are processed by image processing software (Apple video player, MediaGrabber, Graphi
c Processed by Converter 2.9.1) and displayed on the display.

B. Measurement conditions B. 1. Light intensity The light intensity according to the light source state is shown in "Table 1".

[0010]

[Table 1]

As shown in Table 1, the light intensity applied to the pupil is 60 at the wavelength of the optical power meter 520 nm.
It was constant from 0 to 800 μw.

B. 2. Subjects The subjects were 108 subjects shown in the following “Table 2”.

[0013]

[Table 2]

The evaluation of the presence or absence of dementia and the differentiation of dementia include the presence or absence of atrophy of brain cells in CT images, the onset and age of the disease, the manner of progression, symptoms such as current cerebral dysfunction, and the presence or absence of cerebrovascular disease. The results were comprehensively determined based on the history of association with hypertension, arteriosclerosis, etc., the Hasegawa-type simplified intelligence evaluation scale, MMS, and the Miyake-type memorization test. In principle, the subject measured only the left eye (if measurement was impossible due to blindness, surgery, etc., the right eye was measured instead). The subjects wearing contact lenses were measured while wearing them, and the subjects wearing spectacles were measured with the naked eye. C. Measurement Procedure The measurement was first performed with healthy students as subjects to confirm that the system of the present invention was effective irrespective of differences in visual acuity. After confirming the efficacy, the measurement was performed using healthy elderly people and dementia patients as subjects. The flow of a specific measurement procedure for measuring the pupil size and the miosis time is as shown in FIG. That is, the photographing with the infrared camera starts in the state of room light (step 21).
After a second, the light source is turned on (step 22). Then, after the light is irradiated for 5 seconds, the light source is turned off (step 23). The photographing is continued until 5 seconds after the light source is turned off, and the photographing is completed in a total of 15 seconds (step 24). The subject was not required to take a special posture, and was instructed to look at the presented index during the measurement.

D. Analysis method D. 1. Measurement of pupil size Images captured by the infrared camera were captured by a computer, processed, and displayed on the display as processed images. The pupil size was read only in diameter in pixels of this computerized image. The computer processing screen as shown in FIG. 3 was set to 320 × 240 pixels. Since the image processing software can handle an image every 1/30 second, the analysis was performed with this accuracy. FIGS. 3A and 3B show measurement examples of the pupil in the indoor light state and the pupil in the light source on state, respectively.
D. 2. Pupil miosis curve In this way, the pupil diameter is measured for a computer-processed image of the subject's pupil consisting of a total of 150 subjects for 0.03 seconds for 5 seconds, and then the pupil contraction rate is calculated according to the following “Equation 1”. The pupil contraction curve was obtained, an example of which is shown in FIG.
Shown in

[0016]

(Equation 1)

As shown in FIG. 4, in the pupil contraction rate with respect to the light stimulus, the contraction rate (maximum contraction rate) when the pupil is contracted to the minimum is 1 and the light source is turned on. The pupil contraction rate after 5 seconds from the end of the pupil (when the pupil is stable after the light response is completed) is defined as the miotic ratio 2, and the respective miotic ratios are shown in "Equation 2" and "Equation 3". Defined.

[0018]

(Equation 2)

[0019]

(Equation 3)

The miosis time is defined as "the time from turning on the light source until the pupil contracts to the minimum". E. FIG. Measurement results 1. Relationship between visual acuity of normal students and miosis rate The following Table 3 shows the miosis rate 2 with respect to visual acuity of each healthy student. In Table 3, sets A, B, C, and D are those having a visual acuity of 0.5 or less, 0.5 to 1.0, 1.0 or more, and a contact lens wearer, respectively.

[0021]

[Table 3]

From the above "Table 3", as a result of performing the test,
There was no significant difference between the visual acuity groups, and it was confirmed that the measurement results obtained by the diagnostic system of the present invention were constant irrespective of the visual acuity of the subject.

E. 2. Pupil contraction curve of each subject group FIG. 5 shows each pupil contraction curve obtained by plotting the average value of the pupil contraction rate calculated from the computer-processed image for each subject group. From this figure, it can be seen that a dementia patient has a smaller miosis rate and a longer (slower) miosis time than a healthy elderly person. E. FIG. 3. FIG. 6 shows an average miosis rate 1 of each subject group.
As a result of the t-test, the miosis rate 1 between the healthy elderly person and the Alzheimer's type dementia patients and cerebrovascular dementia patients showed a risk rate p <
A significant difference was seen at 0.05. E. FIG. 4. Miosis rate 2 FIG. 7 shows the results of the average miosis rate 2 for each subject group.
As a result of the t-test, a significant difference was found between the healthy elderly person and the Alzheimer-type dementia patient with a miosis rate of 2 at a risk rate of p <0.05. E. FIG. 5. FIG. 8 shows the results of the average miosis time of each subject group. The results of the t-test on the miotic time between healthy elderly people and Alzheimer's dementia patients show that the risk factor p <0.0
1, and the results between healthy elderly and cerebrovascular dementia patients showed a significant difference with a risk factor p <0.05. E. FIG. 6. Differentiation between dementia diseases Alzheimer's type dementia was compared with cerebrovascular dementia and other dementias (sequence dementia of schizophrenia, etc.). No difference was seen. E. FIG. 7. Comparison of healthy elderly people and students Healthy elderly people had lower miosis than students, but no significant difference was observed.

F. Modification of Embodiment In the above embodiment, the microprocessor controls the switching means for switching the light source 11 on and off, the image processing means for performing image processing on an image captured by the infrared camera 12, and the timer according to a program.
The measurement flow shown in FIG. 2 may be advanced.
Further, in the above embodiment, the computer-processed image displayed on the display is analyzed manually,
A pupil area calculating means for calculating a pupil area based on the image data, a calculating means for calculating a miotic ratio, and a calculating means for calculating a miotic time, and a microprocessor of a computer controls the means according to a program. Each step may be sequentially executed, and the parameters obtained by each means may be determined, and the results of the determination may be displayed so as to constitute an automatic diagnosis system controlled by a computer.

[0025]

According to the system for diagnosing dementia of the present invention, the fact that there is a clear difference in miosis rate and miosis time between a dementia patient such as Alzheimer-type dementia and a healthy elderly person in response to light stimulation is used. Thus, the presence or absence of dementia in the subject can be determined. Therefore, this dementia diagnosis system enables early diagnosis of dementia including Alzheimer-type dementia,
Since it is easy to handle and can be diagnosed in a short time, it can be used for general health examinations and the like. It is non-invasive, has no side effects, and does not limit the indications for patients.

[Brief description of the drawings]

FIG. 1 is a schematic diagram showing the configuration of a dementia diagnosis system of the present invention.

FIG. 2 is a flowchart showing a measurement procedure for measuring a pupil size and a miosis time using the dementia diagnosis system of the present invention.

FIGS. 3A and 3B are explanatory diagrams schematically showing measurement examples of a pupil in an indoor light state and a pupil in a light source on state, respectively.

FIG. 4 is a graph showing an example of a pupil miosis curve obtained by calculating a pupil contraction rate from a computer-processed image obtained by using the dementia diagnosis system of the present invention.

FIG. 5 is a graph showing each pupil contraction curve obtained by plotting an average value of pupil contraction rates calculated for each subject group from a computer-processed image obtained using the dementia diagnosis system of the present invention.

FIG. 6 is a bar graph showing an average miosis rate 1 of each subject group.

FIG. 7 is a bar graph showing the average miosis rate 2 of each subject group.

FIG. 8 is a bar graph showing the average miosis time of each subject group.

[Explanation of symbols]

11 ... light source, 12 ... infrared camera, 13 ... computer, 14 ... presentation index, 15 ... optical power meter.

Claims (3)

[Claims] 1. A light source for irradiating light to a subject's eye, a miotic ratio detecting means for detecting a miotic ratio at which the subject's eye contracts after a predetermined time has elapsed after irradiating the light from the light source, A first determination unit that compares the miosis ratio detected by the miosis ratio detection unit with a predetermined value and determines that the subject has dementia when the miosis ratio is smaller than a predetermined value. Dementia diagnostic system. 2. A light source for irradiating light to a subject's eye, a miosis time detecting means for irradiating light from the light source and detecting a miosis time until the subject's eye is maximally miotic. A second determining unit that compares the miotic period detected by the miotic period detecting unit with a predetermined value and determines that the subject has dementia when the miotic period is longer than a predetermined value. Dementia diagnostic system. A light source for irradiating the subject's eye with light; and a miotic ratio detecting means for detecting a miotic ratio of the subject's eye mimicking after a predetermined time from irradiating the light from the light source; A miosis time detecting means for irradiating light from a light source and detecting a miosis time until the subject's eye is maximally miotic, and a miotic rate detected by the miotic rate detecting means and a predetermined value. At least one of a case where the miosis rate is smaller than a predetermined value and a case where the miosis time is longer than a predetermined value by comparing the miosis time detected by the miosis time detecting means with a predetermined value. And a third determining means for determining that the subject has dementia.