WO2022186275A1 - アルツハイマー型認知症判定装置、アルツハイマー型認知症判定方法、およびプログラム - Google Patents
アルツハイマー型認知症判定装置、アルツハイマー型認知症判定方法、およびプログラム Download PDFInfo
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- A—HUMAN NECESSITIES
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- A61B5/00—Measuring for diagnostic purposes; Identification of persons
- A61B5/40—Detecting, measuring or recording for evaluating the nervous system
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Definitions
- the present invention relates to an Alzheimer's dementia determination device, an Alzheimer's dementia determination method, and a program.
- This application claims priority based on 63/156,936 filed in the United States on March 5, 2021 and Japanese Patent Application No. 2021-178089 filed in Japan on October 29, 2021, The contents of which are incorporated herein.
- Alzheimer's dementia In recent years, the number of dementia patients has increased. About half of dementias are of the Alzheimer's type. No complete preventive or radical cure for Alzheimer's dementia has been found, and it takes about 10 to 20 years for the initial symptoms to appear. There are many. Therefore, early detection and early treatment of Alzheimer's dementia have become important issues.
- MMSE Mini-Mental State Examination
- Non-Patent Document 1 A method of analyzing the relevance of is proposed (see Non-Patent Document 1).
- Non-Patent Document 1 it is difficult to definitively distinguish between sleep in elderly people with Alzheimer's disease and non-Alzheimer's disease. For this reason, instability remains in determining Alzheimer's dementia based only on the number of hours of sleep and the number of times a person wakes up.
- the present invention has been made in view of the above problems, and an Alzheimer's type dementia determination device that can distinguish between Alzheimer's type dementia patients and healthy subjects with less burden on the test subject.
- An object is to provide an Alzheimer's dementia determination method and a program.
- an apparatus for determining Alzheimer's disease includes an acquisition unit that acquires information about heart rate, and a first an estimating unit, a second estimating unit that estimates a non-circadian heart rate rhythm that is a rhythm different from the circadian rhythm of the heart rate, a signal amplitude of the estimated circadian rhythm of the heart rate, and an estimated a determination unit that determines whether or not the person has Alzheimer's dementia based on the signal amplitude of the non-circadian rhythm of the heart rate.
- an apparatus for determining Alzheimer's disease includes an acquisition unit that acquires information on heart rate, and an estimation unit that estimates a circadian rhythm of heart rate from the information on heart rate. and a determination unit that determines whether or not the person has Alzheimer's dementia based on the sine wave component and the cosine wave component of the estimated circadian rhythm signal of the heart rate.
- an apparatus for determining Alzheimer's disease includes an acquisition unit that acquires information about heart rate, and a first An estimation unit and a determination unit that determines whether or not the person has Alzheimer's dementia based on the estimated sine wave component of the signal of the circadian rhythm of the heart rate.
- an acquisition unit acquires information about a heart rate
- a first estimation unit obtains an estimate of the heart rate from the information about the heart rate.
- estimating a circadian rhythm a second estimating unit estimating a non-circadian rhythm of heart rate that is a rhythm different from the circadian rhythm of heart rate, and a determination unit estimating the estimated circadian rhythm of heart rate Based on the signal amplitude and the estimated signal amplitude of the non-circadian rhythm of the heart rate, it is determined whether or not the person has Alzheimer's dementia.
- an acquisition unit acquires information about a heart rate
- an estimation unit uses the information about the heart rate to determine the circadian rhythm of the heart rate. is estimated, and the determination unit determines whether or not the person has Alzheimer's dementia based on the sine wave component and the cosine wave component of the estimated circadian rhythm signal of the heart rate.
- an acquisition unit acquires information about a heart rate
- a first estimation unit obtains an estimate of the heart rate from the information about the heart rate.
- a circadian rhythm is estimated, and a determination unit determines whether or not the person has Alzheimer's dementia based on the sine wave component of the estimated circadian rhythm signal of the heart rate.
- a program causes a computer to acquire information about a heart rate, estimate a circadian rhythm of the heart rate from the information about the heart rate, and estimating a non-circadian heart rate rhythm that is a rhythm, and based on the estimated signal amplitude of the circadian rhythm of the heart rate and the estimated signal amplitude of the non-circadian rhythm of the heart rate, Alzheimer's type Determine whether or not the person has dementia.
- a program causes a computer to acquire information about heart rate, estimate a circadian rhythm of heart rate from the information about heart rate, and estimate the heart rate Based on the sine wave component and the cosine wave component of the circadian rhythm signal, it is determined whether or not the person has Alzheimer's dementia.
- a program causes a computer to acquire information about heart rate, estimate a circadian rhythm of heart rate from the information about heart rate, and estimate the heart rate Based on the sine wave component of the circadian rhythm signal, it is determined whether or not the person has Alzheimer's dementia.
- Alzheimer's type dementia patients and healthy subjects can be distinguished from each other with little burden on the test subject.
- FIG. 3 is a diagram showing an example of melatonin secretion levels in healthy elderly people and Alzheimer's disease patients. It is a figure which shows the structural example of the dementia determination apparatus which concerns on 1st Embodiment. It is a figure which shows the example of estimated circadian rhythmicity fCR (t) estimated by fitting, and estimated non-circadian rhythmicity fNCR (t).
- FIG. 4 is an enlarged view of the sleeping hours of FIG. 3;
- FIG. 4 is a diagram for explaining a calculation method of heart rate data, estimated heart rate f k (t) for 24 hours, and ak average; It is a flow chart of a processing procedure of a dementia determination device concerning a 1st embodiment.
- FIG. 1 is an image diagram of a mat-type sensor system, and an image diagram of where the sensor is used on a subject.
- FIG. FIG. 10 is a diagram showing the accumulation of predicted amplitude ratios rp of circadian rhythms for each data for each subject group.
- FIG. 4 is a diagram showing determination results using predicted amplitude ratios rp of sine waves and cosine waves of circadian rhythms and non-circadian rhythms according to the first embodiment;
- FIG. 10 is a diagram for explaining an estimation method in the case of 8 to 40 hours; It is a figure which shows the structural example of the dementia determination apparatus which concerns on 2nd Embodiment.
- FIG. 4 is a diagram for explaining examples of stable heart rate and unstable heart rate; It is a flow chart of a processing procedure of a dementia determination device concerning a 2nd embodiment. It is a figure which shows the example of the evaluation result by 2nd Embodiment.
- FIG. 4 is a diagram showing an example of unstable ratios of sine waves and cosine waves of Alzheimer's dementia patients, healthy young people, healthy middle-aged people, and healthy elderly people. It is a figure for demonstrating the technique of 3rd Embodiment. It is a figure which shows the structural example of the dementia determination apparatus which concerns on 3rd Embodiment. It is a flowchart of the processing procedure of the dementia determination apparatus which concerns on 3rd Embodiment. It is a figure which shows the example of the evaluation result by 3rd Embodiment.
- each embodiment the subject's heart rate is used to estimate the circadian rhythm, and based on the estimated circadian rhythm, Alzheimer's dementia and healthy elderly people are distinguished.
- the circadian rhythm is a body clock represented by sleep/wake, and has a cycle of about 24 hours.
- FIG. 1 is a diagram showing an example of melatonin secretion levels in healthy elderly people and Alzheimer's type dementia patients.
- Graph g1 is the amount of melatonin secreted by healthy elderly people at each hour
- graph g2 is the amount of melatonin secreted by Alzheimer's dementia patients.
- the horizontal axis is time (hour)
- the vertical axis is Melatonin secretion (pg/ml).
- healthy elderly people have a stable circadian rhythm based on melatonin secretion.
- Alzheimer's type dementia patients do not clearly express the circadian rhythm based on melatonin secretion (that is, are unstable), and their melatonin secretion is lower than that of healthy elderly people.
- This is a disorder of the rhythm of abnormal melatonin secretion, which is one of the symptoms of Alzheimer's dementia, and is a circadian rhythm disorder.
- a circadian rhythm disorder develops, the circadian rhythm becomes unstable, and the circadian nature of the biorhythm of core body temperature is lost.
- the heart rate is similarly circadian (see Reference 1, for example).
- rhythm disturbances due to circadian rhythm disturbances would disrupt the biorhythm of the heart rate, resulting in a lack of circadian characteristics.
- the confirmation result will be described later. Therefore, in the embodiment, Alzheimer's dementia is determined based on the circadian rhythm that appears in the heart rate.
- a circadian rhythm with a period of about 24 hours and a non-circadian rhythm that is a biorhythm other than the circadian rhythm (not with a 24-hour period) used for comparison with this circadian rhythm.
- a ratio of circadian rhythm amplitude/non-circadian rhythm amplitude is calculated from the estimated amplitude, and Alzheimer's dementia is determined based on the calculated ratio.
- FIG. 2 is a diagram showing a configuration example of the dementia determination device according to this embodiment.
- the dementia determination device 1 includes an acquisition unit 11 , a first estimation unit 13 , a second estimation unit 14 , a determination unit 15 , a storage unit 16 and an output unit 17 .
- a biological information measurement device 2 is connected to the dementia determination device 1 at the time of measurement.
- the biological information measuring device 2 is, for example, a mat-type sensor, a smartwatch equipped with a sensor for detecting biological information, or a wearable terminal equipped with a sensor for detecting biological information.
- the biological information measuring device 2 measures at least data about the heart rate during sleep of the subject, and outputs the measured data to the dementia determination device 1 .
- the biological information measuring device 2 is, for example, a mat-type sensor will be described.
- the heart rate data is bio-vibration data.
- the dementia determination device 1 and the biological information measurement device 2 are connected by wire or wirelessly.
- the biological information measurement device 2 includes a communication unit or an interface for data output with the dementia determination device 1 .
- the acquisition unit 11 acquires data related to heart rate (hereinafter referred to as "heart rate data") from the biological information measurement device 2.
- the first estimation unit 13 estimates the circadian rhythm of the heart rate (hereinafter referred to as "circadian rhythm") from the heart rate data.
- the second estimation unit 14 estimates a non-circadian rhythm of heart rate (hereinafter referred to as "non-circadian rhythm”), which is a rhythm different from the circadian rhythm of heart rate, from the heart rate data.
- non-circadian rhythm a non-circadian rhythm of heart rate
- the determination unit 15 determines whether or not the person has Alzheimer's dementia based on the ratio between the estimated signal amplitude of the circadian rhythm of the heart rate and the estimated signal amplitude of the non-circadian rhythm of the heart rate. do.
- the storage unit 16 stores mathematical expressions, threshold values, etc. used by the determination unit 15 .
- the storage unit 16 may store data relating to heart rate during sleep.
- the output unit 17 outputs the determination result determined by the determination unit 15 to an external device.
- the external device is, for example, an image display device, a printing device, a personal computer, a tablet terminal, a smart phone, a dedicated terminal, or the like.
- the output unit 17 has a communication unit or an interface.
- the first estimator 13 and the second estimator 14 perform maximum likelihood estimation of the heart rate using, for example, Real-time Sleep Stage Estimation (RSSE) (see reference 2).
- RSSE performs maximum likelihood estimation of the heart rate, which is represented by a trigonometric function consisting of a plurality of frequency components, with respect to the subject's biological vibration data during sleep obtained from the biological information measuring device 2 .
- RSSE is a method of estimating six stages of sleep (awakening, REM sleep, non-REM sleep 1 to 4) from the obtained estimated heart rate.
- the first estimator 13 and the second estimator 14 estimate the coefficient al,i and the constant term C based on the heart rate data during sleep, and output the estimated heart rate f(t).
- the likelihood function used for maximum likelihood estimation is defined by the following equation (2) using the heart rate raw data HR(t) at time t.
- the first term 1/T ⁇ t 1 T ⁇ HR(t) ⁇ f(t) ⁇ 2 fits the estimated heart rate f(t) to HR(t).
- ⁇ is the weighting of the second term, and is 1.0, for example.
- N represents the total number of parameters to be estimated and is
- the first estimating unit 13 and the second estimating unit 14 modify the cycle group L used for estimating the estimated heart rate f(t) into a circadian cycle group and a non-circadian rhythm cycle group. Estimate the amplitude.
- L CR circadian rhythm cycle group
- L NCR non-circadian rhythm cycle group
- L NCR is defined as, for example, ⁇ 12.5, 12, 11.5 ⁇ [hours], that is, around 12 hours.
- the LCR described above is only an example, and may be ⁇ 26, 25, 24, 23, 22 ⁇ or ⁇ 24.5, 24, 23.5 ⁇ , for example.
- the L NCR described above is an example, and may be ⁇ 13, 12.5, 12, 11.5, 11 ⁇ or ⁇ 12.25, 12, 11.75 ⁇ , for example.
- the reasons for using 12 hours as the period of the non-circadian rhythm are the following reasons I to III.
- Reason I The period of the circadian rhythm does not always fall within the range of 23 to 25 hours depending on the person, and it may be less than 23 hours. This is because there is a risk that Reason II: Using a period shorter than 12 hours facilitates estimation of complex heart rate fluctuations and may interfere with amplitude estimation.
- Reason III As long as the method uses the circadian rhythm amplitude ratio, it is desirable to avoid using waves with periodically different properties. For example, defining non-circadian rhythms such as ultradian rhythms (biological rhythms with a period of about 90 minutes) as non-circadian rhythms is easy to explain medically, but the periodic nature is very different. It's for.
- L CR and L NCR are set as L in Equation (1) to obtain estimated heart rates f CR (t) and f NCR (t) of circadian and non-circadian rhythms as in Equation (4) below.
- FIG. 3 is a diagram showing an example of estimated circadian rhythm f CR (t) and estimated non-circadian rhythm f NCR (t).
- Graph g10 is heart rate (g11) and estimated circadian rhythm f CR (t)
- graph g20 is heart rate (g11) and estimated circadian rhythm f NCR (t).
- the subject's sleep time is between approximately 23:30 and 6:30.
- Heart rate data is acquired during this sleep period.
- the absolute value amplitude ratios of sine waves and cosine waves of circadian rhythms and non-circadian rhythms, which will be described later, are calculated using heart rate data in the range (g12) actually measured during sleeping hours.
- the predicted amplitude ratio of sine waves and cosine waves of circadian and non-circadian rhythms is estimated in a range of about 24 hours or about 12 hours (g13) using heart rate data actually measured during sleep hours.
- the predicted amplitude ratio is the ratio between the amplitude of the circadian rhythm and the amplitude of the non-circadian rhythm estimated using the heartbeat data acquired during sleep.
- the estimated circadian rhythm f CR (t) in the graph g10 is estimated as the following equation (5)
- the estimated non-circadian rhythm f NCR (t) in the graph g20 is estimated as the following equation (6).
- FIG. 4 is an enlarged view of the sleeping hours of FIG.
- a graph g30 is the heart rate data and the estimated heart rate f CR (t) in the period group L CR of the circadian rhythm.
- a graph g40 is the heart rate data and the estimated heart rate f NCR (t) in the periodic group L NCR of the non-circadian rhythm.
- the vertical axis is heart rate and the horizontal axis is time.
- Line g11 indicates heart rate data
- line g32 indicates estimated heart rate f CR (t) consisting of waves of L NCR cycle group
- line g32 indicates estimated heart rate f NCR (t) consisting of waves of L NCR cycle group t).
- the determination unit 15 determines the circadian rhythm/non-circadian rhythm from the estimated heart rate f CR (t) and the estimated heart rate f NCR (t).
- the amplitudes of each rhythm are calculated as a CR and a NCR .
- the amplitude of the circadian rhythm will be referred to as “amplitude aCR” in the specification.
- the amplitude of the non-circadian rhythm is referred to as "amplitude a NCR " in the specification.
- the determination unit 15 calculates the ratio r between the amplitude of the circadian rhythm and the amplitude of the non-circadian rhythm as shown in the following equation (7).
- the following formula (8) is obtained by calculating the average absolute value of the coefficients al and i of all waves without distinguishing between sine and cosine waves of Lk.
- the absolute value amplitude ratio of the circadian rhythm of the circadian rhythm amplitude a CR and the non-circadian rhythm amplitude a NCR is defined as r A (ratio by absolute average).
- r A ratio by absolute average
- the expression (8) is referred to as "average a k " in the specification.
- the absolute value amplitude ratio of the circadian rhythm r A is calculated as the average ak as the absolute average value of the coefficients l and i of all waves, both sinusoidal and non-sinusoidal.
- FIG. 5 is a diagram for explaining a method of calculating the heart rate data, the estimated 24-hour heart rate f k (t), and the average a k .
- the vertical axis represents heart rate
- the horizontal axis represents time
- line g31 represents heart rate data
- line g32 represents transition of estimated heart rate f k (t) for one day.
- a predicted amplitude ratio of the circadian rhythm amplitude a CR and the non-circadian rhythm amplitude a NCR is defined as r P (ratio by predicted amplitude).
- the determination unit 15 determines that the absolute value amplitude ratio r A and the predicted amplitude ratio r P of the two circadian rhythms are smaller than the threshold value of 1.0 as the anxiety point of the circadian rhythm.
- the circadian rhythm is determined to be stable if the absolute value amplitude ratio r A and the predicted amplitude ratio r P of the two circadian rhythms are each greater than the threshold value of 1.0.
- the determination unit 15 determines that the circadian rhythm is evaluated as unstable with two amplitude ratios as Alzheimer's dementia. This is because the characteristics of stability and instability of the circadian rhythm differ depending on the calculation method of the amplitude a CR and the amplitude a NCR . .
- the characteristics of each circadian rhythm amplitude ratio are as follows.
- the absolute value amplitude ratio r A has the characteristic that the amplitude is calculated ignoring the phase information of each wave by using the wave coefficient a l,i as the absolute value for the amplitude ratio calculation. Therefore, for example, when the amplitude of f k (t) is low, all the coefficients a l,i are low, or the final amplitude is low due to the cancellation of waves (positive and negative coefficients). It is possible to distinguish between On the other hand, the predicted amplitude ratio r P is characterized by looking at the amplitude of the estimated heart rate f k (t).
- FIG. 6 is a flowchart of the processing procedure of the dementia determination device according to this embodiment.
- Step S1 The acquisition unit acquires heart rate data during sleep.
- Step S2 The determination unit 15 sets a threshold r amp of the amplitude ratio.
- Step S3 The first estimation unit 13 estimates the circadian rhythm from the heart rate data.
- Step S4 The second estimation unit 14 estimates the non-circadian rhythm from the heart rate data.
- Step S5 The determination unit 15 calculates the signal amplitude of the estimated circadian rhythm.
- Step S6 The determination unit 15 calculates the signal amplitude of the estimated non-circadian rhythm.
- Step S7 The determination unit 15 calculates a predicted amplitude ratio, which is a ratio between the signal amplitude of the circadian rhythm and the signal amplitude of the non-circadian rhythm.
- Step S8 The determination unit 15 determines whether or not the predicted amplitude ratio is equal to or greater than a threshold r amp (for example, the threshold r amp is 1.0). If the determination unit 15 determines that the predicted amplitude ratio is equal to or greater than the threshold r amp (step S8; YES), the process proceeds to step S9. If the determination unit 15 determines that the predicted amplitude ratio is less than the threshold r amp (step S8; NO), the process proceeds to step S10.
- a threshold r amp for example, the threshold r amp is 1.0
- Step S9 The determination unit 15 determines that the subject is healthy. After processing, the determination unit 15 terminates the processing.
- Step S10 The determination unit 15 determines that the patient has Alzheimer's disease. After processing, the determination unit 15 terminates the processing.
- the Alzheimer's type dementia determination rate for each of the two absolute value amplitude ratios r A and the predicted amplitude ratio r P and the overall Alzheimer's type dementia determination rate for the two amplitude ratios (r A ⁇ r P ) verified the effectiveness of the two determination methods.
- the threshold value was set to 1.0.
- the evaluation was approved by the ethics committee of the organization to which the inventors belong, and all subjects signed a consent form.
- FIG. 7 is an image diagram of the mat-type sensor system and an image diagram of where the sensor is used on the subject.
- An image diagram g200 is an image diagram of a mat-type sensor system, which includes a sensor, a data transmitter, and the like.
- An image g210 is an image of where the sensor is used on the subject.
- the mat-type sensor is installed, for example, under the bed mat, at a position corresponding to the upper body of the subject, for example.
- FIG. 8 is a diagram showing the accumulation of the predicted amplitude ratio r p of the circadian rhythm for each data for each subject group.
- the horizontal axis is the circadian rhythm amplitude ratio
- the vertical axis is cumulative (0 to 100%).
- line g251 represents Alzheimer's type dementia patients
- line g252 represents healthy elderly people
- line g253 represents healthy middle-aged people
- line g254 represents healthy young people.
- the point on each cumulative line represents one piece of data
- a line g255 represents the set threshold value of 1.0, and the points on the left side of this line (ratio values are lower than 1.0) are data determined as Alzheimer's type dementia patients. That is, the accumulation of the intersections of the line of each subject group and the line g255 is the determination rate of Alzheimer's dementia at the threshold of 1.0.
- the correct answer rate of the evaluation by the absolute value amplitude ratio r A of the sine wave and cosine wave of the circadian rhythm and non-circadian rhythm is 100.0% for patients with Alzheimer's disease, 16.7% for healthy elderly people, and 16.7% for healthy people. 71.4% of the elderly and 80.0% of the young. According to this evaluation method, Alzheimer's type dementia patients can be determined.
- FIG. 9 is a diagram showing determination results using predicted amplitude ratios r P of sine waves and cosine waves of circadian rhythms and non-circadian rhythms according to the present embodiment.
- the correct answer rate of determination using the predicted amplitude ratio r P of sine waves and cosine waves of circadian and non-circadian rhythms was 82.4% for Alzheimer's disease patients and 82.4% for healthy elderly people. 83.3%, healthy middle-aged people 92.9%, and healthy young people 100.0%.
- Alzheimer's dementia patients in the case of determination using the predicted amplitude ratio of sine waves and cosine waves of circadian rhythm and non-circadian rhythm, Alzheimer's dementia patients, healthy elderly people and healthy middle-aged people Since elderly people and healthy young people are separated by a threshold value of 1.0, even elderly people can be separated into Alzheimer-type dementia patients and healthy people.
- Alzheimer's dementia determination using the predicted amplitude ratio of sine waves and cosine waves of circadian and non-circadian rhythms was highly accurate.
- the circadian rhythm and the non-circadian rhythm are estimated simultaneously using the following equation (10), the amplitude of the circadian rhythm and the amplitude of the non-circadian rhythm are estimated, and the evaluation is performed based on the ratio of the amplitudes.
- the first term is the circadian rhythm and the second term is the specific circadian rhythm.
- circadian rhythm and non-circadian rhythm are estimated simultaneously using equation (10), circadian rhythm amplitude and non-circadian rhythm amplitude are estimated, and circadian rhythm amplitude and non-circadian rhythm amplitude are estimated. Instead of the amplitude, the evaluation may be based on the average of the coefficients of the sine wave sin and cosine wave cos.
- circadian rhythm and non-circadian rhythm are estimated simultaneously using equation (10), and instead of the amplitude of circadian rhythm and the amplitude of non-circadian rhythm, the coefficient of the composite wave of sine wave sin and cosine wave cos is You may make it evaluate based on.
- the following equations (11) and (12) are used to simultaneously estimate the circadian rhythm and the non-circadian rhythm for, for example, 8 to 40 hours.
- the evaluation may be made based on the average of the coefficients of the sine wave sin and cosine wave cos. Specifically, the coefficient of the ratio of the average a CR (equation (11)) and the average a NCR (equation (12)) is taken as the absolute average of the wave coefficients.
- N(L, 24H, 1.0) is the value of the normal distribution f (L) with an average of 24 hours and a variance of 1.0.
- FIG. 10 is a diagram for explaining the estimation method for 8 to 40 hours.
- the horizontal axis is time, and the vertical axis is the value of the normal distribution f (L) with a variance of 1.
- Line g271 is a normal distribution with mean 24 hours and variance 1.0 (N(24H, 1.0)), and line g272 is mean 24 hours and variance 1.0 (max-N(24H , 1.0)).
- the amplitude is calculated using the data for one cycle of the wave according to the following equation (15).
- the first estimating unit 13 estimates the circadian rhythm of the heart rate from the heart rate
- the second estimating unit 14 estimates the circadian rhythm of the heart rate, which is a rhythm different from the circadian rhythm of the heart rate.
- the circadian rhythm is estimated
- the determination unit 15 determines whether Alzheimer's dementia is present based on the estimated signal amplitude of the circadian rhythm of the heart rate and the signal amplitude of the estimated non-circadian rhythm of the heart rate. determined whether or not
- the present embodiment it is possible to distinguish Alzheimer's type dementia patients from healthy subjects with less burden on the test subject.
- the evaluation results show that the rate of misjudgment of healthy subjects is low, and the rate of Alzheimer's dementia is high in the month in which the progression of Alzheimer's dementia in Alzheimer's dementia patients is suspected to be significant.
- heart rate data as an example of biometric information
- the biological information may be pulse rate data, for example.
- "information about heart rate” corresponds to "heart rate data” or "pulse rate data”.
- the ratio of the amplitude of the circadian rhythm and the amplitude of the non-circadian rhythm is compared with the threshold, but the present invention is not limited to this.
- the determination unit 15 may compare the amplitude of the circadian rhythm, the amplitude of the non-circadian rhythm, the difference, and the threshold value, and distinguish between the Alzheimer's type dementia patient and the healthy subject based on the comparison result.
- ⁇ Second embodiment> In the first embodiment, an example in which a threshold (for example, 1.0) is used for determination has been described, but in this embodiment, an example in which no threshold is used for determination will be described.
- the circadian rhythm instability ratio estimated from the heart rate is calculated, and whether or not the subject has Alzheimer's dementia is determined based on the calculated value of the instability ratio.
- the sine wave instability ratio is the ratio between the sum of the absolute values of the coefficients of the sine wave components of the circadian rhythm of the heart rate and the sum of the coefficients of the estimated sine wave components of the circadian rhythm of the heart rate. is.
- the instability ratio of the cosine wave is the ratio of the sum of the absolute values of the coefficients of the cosine wave components of the circadian rhythm of the heart rate to the sum of the coefficients of the estimated cosine wave components of the circadian rhythm of the heart rate. is. Note that the unstable ratio does not have to be the sum, and may be obtained by total multiplication, for example.
- FIG. 11 is a diagram showing a configuration example of a dementia determination device according to this embodiment.
- dementia determination device 1A includes acquisition unit 11 , first estimation unit 13 (estimation unit), determination unit 15A, storage unit 16 , and output unit 17 .
- a biological information measurement device 2 is connected to the dementia determination device 1A at the time of measurement.
- the first estimation unit 13 estimates the circadian rhythm from the heart rate data.
- the determination unit 15A calculates the unstable ratio R of the circadian rhythm, and determines whether or not the subject has Alzheimer's dementia based on the calculated unstable ratio R.
- FIG. 12 is a diagram for explaining an example of stable heart rate and unstable heart rate.
- Graph g300 is an example of measured heart rate data of a healthy subject showing a stable circadian rhythm.
- Graph g310 is an example of measured heart rate data of an Alzheimer's disease patient showing an unstable circadian rhythm.
- the horizontal axis is time and the vertical axis is heart rate.
- Lines g301 and g311 are actually measured values, and lines g302 and g312 are estimated heart rate f(t) for one day.
- the estimated heart rate f(t) of the graph g300 can be expressed by the following equation (16), and the estimated heart rate f(t) of the graph g310 can be expressed by the following equation (17).
- the heart rate gradually decreases and finally increases, and the estimated heart rate f(t) indicates a stable circadian rhythm, as shown in graph g300.
- the sine wave coefficient a l,S and the cosine wave coefficient a l,C have the same sign and are sufficiently large, as shown in Equation (16).
- the heart rate repeatedly increases and decreases in a certain short period of time, and the estimated heart rate f(t) shows an unstable circadian rhythm. , and the amplitude of the estimated heart rate f(t) is small compared to graph g300.
- the coefficients a l,i become positive and negative, and the waves cancel each other out, and the amplitude of the estimated heart rate f(t) becomes It's getting smaller.
- the estimated stability of the circadian rhythm is evaluated with the numerical value R calculated as in the following equation (18).
- R i is calculated using the absolute value of the ratio.
- R i is calculated by the absolute value of the ratio of (i) the absolute value of the coefficient a l ,i included in the denominator and (ii) the simple sum of the coefficient a l,i included in the denominator.
- i is s (sine wave) or c (cosine wave).
- R is the average of Rs of the sine wave and Rc of the cosine wave.
- R is not limited to the average of R s of the sine wave and R c of the cosine wave, and may be, for example, a weighted average obtained by multiplying the R s of the sine wave.
- the coefficients tend to have the same sign and the two sums are expected to have the same value. That is, Ri is expected to be 1.0.
- the determination unit 15A determines that the coefficient is stable.
- the determination unit 15A determines that the coefficients cancel each other and are unstable.
- R is the average of R0 of the sine wave and R1 of the cosine wave. Therefore, when the Alzheimer's dementia patient has a stable circadian rhythm when R is 1.0, the determining unit 15A determines that the patient is a non-Alzheimer's dementia patient. Then, when R exceeds 1.0, the circadian rhythm of the heart rate is unstable, so the determining unit 15A determines that the patient is an Alzheimer's type dementia patient.
- FIG. 13 is a flowchart of the processing procedure of the dementia determination device according to this embodiment.
- Step S1 The acquisition unit acquires heart rate data during sleep.
- Step S2 The first estimation unit 13 estimates the circadian rhythm from the heart rate data.
- Step S101 The determination unit 15A calculates the instability ratio R of the waves of the circadian rhythm.
- Step S102 The determination unit 15A determines whether or not the instability ratio is 1.0. If the determination unit 15A determines that the instability ratio is 1.0 (step S102; YES), the process proceeds to step S103. When the determination unit 15A determines that the instability ratio is not 1.0 (step S102; NO), the process proceeds to step S104.
- Step S103 The determination unit 15A determines that the subject is healthy. After the processing, the determination unit 15A terminates the processing.
- Step S104 The determination unit 15A determines that the patient is an Alzheimer's type dementia patient. After the processing, the determination unit 15A terminates the processing.
- evaluation results Next, an evaluation result example will be described.
- the evaluation was approved by the ethics committee of the organization to which the inventors belong, and all subjects signed a consent form.
- detection accuracy of Alzheimer's dementia was adopted as an evaluation criterion.
- FIG. 14 is a diagram showing an example of evaluation results according to this embodiment.
- the correct answer rate for patients with Alzheimer's disease is 82.4%
- the correct answer rate for healthy elderly people is 66.7%
- the correct answer rate for healthy middle-aged people is 82.4%.
- the correct answer rate of healthy young people was 90.0%.
- whether or not a person has Alzheimer's dementia is determined based on the instability ratio of circadian rhythm waves estimated from heart rate data.
- the present embodiment it is possible to accurately determine whether or not the patient is an Alzheimer's dementia patient.
- the present embodiment has a high Alzheimer's dementia determination rate both in the month in which the progression of Alzheimer's dementia in Alzheimer's dementia patients is suspected to be significant and several months before that month.
- biometric information may be, for example, pulse rate data.
- information about heart rate corresponds to "heart rate data” or "pulse rate data”.
- the determining unit 15A may distinguish between the Alzheimer's type dementia patient and the healthy subject based on the difference between the sum of the absolute values of the coefficients for the instability of the circadian rhythm wave and the sum of the coefficients.
- FIG. 15 is a diagram showing an example of the instability ratio of sine waves and cosine waves for Alzheimer's dementia patients, healthy young people, healthy middle-aged people, and healthy elderly people.
- Table g401 is the instability ratio of sine wave and cosine wave for Alzheimer's dementia patients.
- Table g402 is the sine and cosine instability ratios for healthy young people.
- Table g403 is the instability ratio of sine and cosine waves for healthy middle-aged persons.
- Table g404 is the instability ratio of sine and cosine waves for healthy elderly people.
- the left is the sine wave instability ratio
- the right is the cosine wave instability ratio.
- the hatched columns indicate that the wave instability ratio is greater than 1 (the wave is the point of instability).
- the wave instability ratio of Alzheimer's dementia patients is generally higher than that of healthy subjects.
- the sine wave instability ratio of Alzheimer's dementia patients is greater than the wave instability ratio of healthy subjects. For this reason, in the present embodiment, it is determined whether or not the patient is an Alzheimer's dementia patient using the sine wave instability ratio in the estimated heart rate.
- FIG. 16 is a diagram for explaining the method of this embodiment.
- Table g501 shows the predicted amplitude ratios of circadian and non-circadian rhythms and the instability ratios of sine waves and cosine waves in Alzheimer's dementia patients.
- Table g502 shows the predicted amplitude ratios of circadian and non-circadian rhythms and the instability ratios of sine waves and cosine waves in healthy young people.
- Table g503 shows the predicted amplitude ratios of circadian and non-circadian rhythms and the instability ratios of sine waves and cosine waves in healthy middle-aged people.
- Table g504 shows the predicted amplitude ratios of circadian and non-circadian rhythms and the instability ratios of sine waves and cosine waves of healthy elderly people.
- Tables g501 to g504 the left is the predicted amplitude ratio of circadian and non-circadian rhythms, the middle is the sine wave instability ratio, and the right is the cosine wave instability ratio.
- the hatched columns in the predicted amplitude ratios of circadian and non-circadian rhythms indicate ratios smaller than 1 (waves are unstable), sine waves and cosine waves The hatched column in the instability ratio of is greater than 1 (the wave is unstable). From Tables g501 to g504, it can be seen that the sine wave instability ratio of Alzheimer's dementia patients is particularly greater than that of healthy subjects.
- the determining unit 15C determines that the patient has Alzheimer's disease when the unstable ratio of the coefficients of the sine wave is greater than 1, and when the unstable ratio of the coefficients of the sine wave is 1 Determined to be healthy. Furthermore, in this embodiment, when the unstable ratio of the sine wave coefficient is 1 and the unstable ratio of the cosine wave coefficient is greater than 1, the method of the first embodiment is used for determination.
- FIG. 17 is a diagram showing a configuration example of a dementia determination device according to this embodiment.
- dementia determination device 1C includes acquisition unit 11 , first estimation unit 13B, second estimation unit 14 , determination unit 15C, storage unit 16 , and output unit 17 .
- a biological information measurement device 2 is connected to the dementia determination device 1C at the time of measurement.
- the determination unit 15C determines that the subject is an Alzheimer's disease patient when the unstable ratio of the coefficients of the sine wave is greater than 1, and determines that the subject is healthy when the unstable ratio of the coefficients of the sine wave is 1. . Furthermore, when the unstable ratio of the sine wave coefficient is 1 and the unstable ratio of the cosine wave coefficient is greater than 1, the determination unit 15C determines the ratio of the amplitude of the circadian rhythm to the amplitude of the non-circadian rhythm and the threshold are compared and determined.
- FIG. 18 is a flowchart of the processing procedure of the dementia determination device according to this embodiment.
- Step S201 The acquisition unit 11 acquires heart rate data during sleep.
- Step S202 The determination unit 15C sets a threshold r amp of the amplitude ratio.
- the first estimation unit 13B estimates the circadian rhythm from the heart rate data.
- the second estimation unit 14 estimates the non-circadian rhythm from the heart rate data.
- the determination unit 15C calculates the instability ratio R of the waves of the circadian rhythm.
- the determination unit 15C acquires the sine wave coefficient and the cosine wave coefficient of the circadian rhythm wave. That is, the determination unit 15C determines the ratio of the sum of the estimated sum of the coefficients of the sine wave components of the circadian rhythm of the heart rate to the sum of the estimated sum of the coefficients of the sine wave components of the circadian rhythm of the heart rate. is calculated as the sinusoidal instability ratio R sin . Further, the determining unit 15C determines the ratio of the sum of the estimated sum of the coefficients of the cosine wave component of the circadian rhythm of the heart rate and the sum of the estimated sum of the coefficients of the cosine component of the circadian rhythm of the heart rate. It is calculated as the sinusoidal instability ratio R cos .
- Step S206 The determination unit 15C determines whether or not the coefficient instability ratio R sin of the sine wave is 1.0. If the determination unit 15C determines that the coefficient instability ratio R sin of the sine wave is 1.0 (step S206; YES), the process proceeds to step S210. If the determining unit 15C determines that the sine wave coefficient instability ratio R sin is not 1.0 (step S206; NO), the process proceeds to step S209.
- Step S210 The determination unit 15C determines whether or not the cosine wave coefficient instability ratio R cos is greater than 1.0. If the determination unit 15C determines that the cosine wave coefficient instability ratio R cos is greater than 1.0 (step S210; YES), the process proceeds to step S211. If the determination unit 15C determines that the cosine wave coefficient instability ratio R cos is 1.0 or less (step S216; NO), the process proceeds to step S209.
- Step S211 The determination unit 15C calculates the signal amplitude of the estimated circadian rhythm.
- Step S212 The determination unit 15C calculates the signal amplitude of the estimated non-circadian rhythm.
- Step S213 The determination unit 15C calculates a predicted amplitude ratio, which is a ratio between the signal amplitude of the circadian rhythm and the signal amplitude of the non-circadian rhythm.
- Step S214 The determination unit 15C determines whether or not the predicted amplitude ratio is equal to or greater than a threshold r amp (for example, the threshold r amp is 1.0). If the determination unit 15C determines that the predicted amplitude ratio is equal to or greater than the threshold r amp (step S214; YES), the process proceeds to step S216. If the determination unit 15C determines that the predicted amplitude ratio is less than the threshold r amp (step S214; NO), the process proceeds to step S209.
- a threshold r amp for example, the threshold r amp is 1.0
- Step S209 If the determination unit 15C determines that the instability ratio R sin of the sine wave coefficient is not 1.0 or determines that the predicted amplitude ratio is less than the threshold r amp , the Alzheimer's disease patient It is determined that After the processing, the determination unit 15C terminates the processing.
- Step S216 The determination unit 15C determines that the person is healthy when determining that the ratio is equal to or greater than the threshold. After the processing, the determination unit 15C terminates the processing.
- the determination unit 15C calculates the instability ratio R sin of the sine wave coefficient in the circadian rhythm, and determines whether or not the subject has Alzheimer's dementia based on this value. You may make it In the processing in this case, the acquisition unit acquires the heart rate data, and the determination unit 15C calculates the instability ratio R sin of the sinusoidal wave of the circadian rhythm. Then, the determination unit 15C may determine whether or not the instability ratio of the sine wave coefficient is 1.0. The determining unit 15C may determine that the person is healthy when determining that the instability ratio of the coefficient of the sine wave is 1.0. The determining unit 15C may determine that the patient has Alzheimer's disease when determining that the instability ratio of the sine wave coefficient is not 1.0.
- the acquisition unit 11 acquires information about the heart rate
- the first estimation unit 13B estimates the circadian rhythm of the heart rate from the information about the heart rate
- the determination unit 15C Based on the sine wave component of the signal of the estimated circadian rhythm of the heart rate, it is determined whether or not the person has Alzheimer's dementia.
- the determination unit 15C further uses the cosine wave component of the estimated circadian rhythm signal of the heart rate and the predicted amplitude ratio to determine whether or not the person has Alzheimer's dementia. made it
- evaluation results Next, an evaluation result example will be described.
- the evaluation was approved by the ethics committee of the organization to which the inventors belong, and all subjects signed a consent form.
- FIG. 19 is a diagram showing an example of evaluation results obtained by the method of this embodiment. As shown in FIG. 17, according to this embodiment, the correct answer rate for Alzheimer's dementia patients is maintained at 82.4%, the correct answer rate for healthy elderly people is 83.3%, and the correct answer rate for healthy middle-aged people is 92%. 9%, and the correct answer rate for healthy young people can be improved to 100.0%.
- the unstable ratio of the cosine wave coefficient and the ratio between the signal amplitude of the circadian rhythm and the signal amplitude of the non-circadian rhythm are also used. , to determine whether or not the patient is an Alzheimer's dementia patient.
- biometric information may be, for example, pulse rate data.
- information about heart rate corresponds to "heart rate data” or "pulse rate data”.
- the instability of the wave of the circadian rhythm has been described as the ratio of the coefficients of the sine wave, but the present invention is not limited to this.
- the determining unit 15C discriminates between Alzheimer's type dementia patients and healthy subjects based on the difference between the sum of the absolute values of the coefficients of the sine wave and the sum of the coefficients of the sine wave for the instability of the circadian rhythm wave. You may do so.
- a program for realizing all or part of the functions of the dementia determination device 1 (or 1A, 1B, 1C) in the present invention is recorded on a computer-readable recording medium, and recorded on this recording medium All or part of the processing performed by the dementia determination device 1 (or 1A, 1B, 1C) may be performed by reading the program into the computer system and executing the program.
- the "computer system” referred to here includes hardware such as an OS and peripheral devices.
- the "computer system” includes a WWW system provided with a home page providing environment (or display environment).
- computer-readable recording medium refers to portable media such as flexible discs, magneto-optical discs, ROMs and CD-ROMs, and storage devices such as hard discs incorporated in computer systems.
- computer-readable recording medium means a volatile memory (RAM) inside a computer system that acts as a server or client when a program is transmitted via a network such as the Internet or a communication line such as a telephone line. , includes those that hold the program for a certain period of time.
- RAM volatile memory
- the program may be transmitted from a computer system storing this program in a storage device or the like to another computer system via a transmission medium or by transmission waves in a transmission medium.
- the "transmission medium” for transmitting the program refers to a medium having a function of transmitting information, such as a network (communication network) such as the Internet or a communication line (communication line) such as a telephone line.
- the program may be for realizing part of the functions described above. Further, it may be a so-called difference file (difference program) that can realize the above-described functions in combination with a program already recorded in the computer system.
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Abstract
Description
本願は、2021年 3月 5日に、アメリカ合衆国に出願された63/156,936と、2021年10月29日に、日本に出願された特願2021-178089号に基づき優先権を主張し、その内容をここに援用する。
また、非特許文献1に記載の手法では、決定的にアルツハイマー型認知症と非アルツハイマー型認知症の高齢者睡眠の区別することは難しい。このため、睡眠時間や起床回数だけでは、アルツハイマー型認知症の判定に不安定さが残る。
各実施形態の概要を説明する。各実施形態では、対象者の心拍数を用いて概日リズムを推定し、推定した概日リズムに基づいて、アルツハイマー型認知症と健常高齢者を区別する。なお、概日リズムとは、睡眠・覚醒に代表される体内時計であり、約24時間周期である。
概日リズムに基づいて、アルツハイマー型認知症患者と健常者を区別する原理の概要を説明する。
図1は、健常高齢者とアルツハイマー型認知症患者におけるメラトニン分泌量の一例を示す図である。グラフg1は、健常高齢者の時刻毎のメラトニン分泌量であり、グラフg2は、アルツハイマー型認知症患者のメラトニン分泌量である、グラフg1とg2において、横軸は時刻(時)、縦軸はメラトニン分泌量(pg/ml)である。図1のように、健常高齢者は、メラトニン分泌量に基づく概日リズムが安定している。これに対して、アルツハイマー型認知症患者は、メラトニン分泌量に基づく概日リズムが明確に表れず(すなわち不安定であり)、メラトニン分泌量も健常高齢者より少ない。これは、アルツハイマー型認知症の症状の一つである、メラトニン異常分泌のリズムの乱れであり、概日リズム障害である。
概日リズム障害を発症すると、概日リズムが不安定となり、深部体温の生体リズムの概日性が欠如する。また、心拍数は同じく概日性が見られることが知られている(例えば参考文献1参照)。
本実施形態では、心拍数データから、約24時間周期の概日リズムと、この概日リズムと比較するために用いる概日リズム以外の(24時間周期でない)生体リズムである非概日リズムを最尤推定による三角関数で推定する。そして、本実施形態では、例えば、推定した振幅から概日リズム振幅/非概日リズム振幅の比率(概日リズム振幅比率)を算出し、算出した比率に基づいてからアルツハイマー型認知症を判定する。
図2は、本実施形態に係る認知症判定装置の構成例を示す図である。図2のように、認知症判定装置1は、取得部11、第1推定部13、第2推定部14、判定部15、記憶部16、および出力部17を備える。
認知症判定装置1には、測定時、生体情報測定装置2が接続される。
次に、第1推定部13と第2推定部14が行う処理について説明する。
第1推定部13と第2推定部14は、例えば、Real-time Sleep Stage Estimation(RSSE)(参考文献2参照)を用いて心拍数を最尤推定する。RSSEは、生体情報測定装置2から得られた対象者の睡眠時の生体振動データに対して、複数の周波数成分からなる三角関数で表される心拍数を最尤推定する。そして、RSSEは、得た推定心拍数から6段階(覚醒,レム睡眠,ノンレム睡眠1~4)の睡眠段階を推定する手法である。
約24時間周期である概日リズムの周期群(以下「LCR」と表す)として、LCRを例えば{25,24,23}[時]、すなわち24時間前後で定義する。非概日リズムの周期群(以下「LNCR」と表す)として、LNCRを例えば{12.5,12,11.5}[時]、すなわち12時間前後で定義する。なお、上述したLCRは一例であり、例えば{26,25,24,23,22}や{24.5,24,23.5}等であってもよい。同様に上述したLNCRは一例であり、例えば{13,12.5,12,11.5,11}や{12.25,12,11.75}等であってもよい。
理由I;概日リズムの周期は、人によって23~25時間の範囲に収まるとは限らず、23時間を下回ることもあるため12時間よりも大きい周期を用いると概日リズムとの切り分けが難しくなる恐れがあるためである。
理由II;12時間より小さい周期を用いることは、複雑な心拍数変動の推定を容易にし、振幅推定に支障をきたす可能性があるためである。
理由III;概日リズム振幅比率を用いる手法である以上は、周期的に性質の異なる波の利用は避けるのが望ましい。例えば、ウルトラディアンリズム(約90分周期の生体リズム)のような概日性のないリズムを非概日リズムとするのは、医学的には説明が容易になるものの周期的な性質が大きく異なるためである。
判定部15は、アルツハイマー型認知症の判定に用いる概日リズム振幅比率rを算出するために、推定心拍数fCR(t)、推定心拍数fNCR(t)から概日リズム・非概日リズムそれぞれの振幅をaCR,aNCRとして算出する。以下、明細書中では、概日リズムの振幅を「振幅aCR」という。以下、明細書中では、非概日リズムの振幅を「振幅aNCR」という。
この概日リズムの振幅aCR、非概日リズムの振幅aNCRの予測振幅比率をrP(ratio by Predicted amplitude)とする。
判定部15は、二つの概日リズムの絶対値振幅比率rA,予測振幅比率rPそれぞれで閾値1.0よりも小さいものを概日リズムが不安点と判定する。二つの概日リズムの絶対値振幅比率rA,予測振幅比率rPそれぞれで閾値1.0よりも大きいものを概日リズムが安定と判定する。
絶対値振幅比率rAは、波の係数al,iを絶対値として振幅比率算出に用いることで、各波の位相の情報を無視し振幅を計算する特徴がある。これにより、例えばfk(t)の振幅が低い際に全ての係数al,iが低いためか、それとも波同士の打ち消し合い(正負の係数)が発生することにより最終的な振幅が低いためかの区別が可能である。
これに対して、予測振幅比率rPは、推定心拍数fk(t)の振幅を見ているのが特徴である。
次に、認知症判定装置の処理手順例を説明する。
図6は、本実施形態に係る認知症判定装置の処理手順のフローチャートである。
次に、上述した推定概日リズムと推定非概日リズムの正弦波と余弦波の絶対値振幅比率によるアルツハイマー型認知症の判定と、概日リズムと非概日リズムの正弦波と余弦波の予測振幅比率によるアルツハイマー型認知症の判定とを、被験者のデータを用いて評価した結果を説明する。
図9のように、概日リズムと非概日リズムの正弦波と余弦波の予測振幅比率rPを用いた判定の正答率は、アルツハイマー型認知症患者が82.4%、健常高齢者が83.3%、健常中年者が92.9%、健常若年者が100.0%であった。
このように、概日リズムと非概日リズムの正弦波と余弦波の予測振幅比率を用いたアルツハイマー型認知症判定は、高い精度が得られた。
上述した実施例では、概日リズム(約24時間)と非概日リズム(約12時間)を別々に推定する例を説明したが、これに限らない。また、上述した実施例では、概日リズムの振幅と非概日リズムの振幅を推定する例を説明したが、これに限らない。
例えば、概日リズムと非概日リズムを別々に推定し、概日リズムの振幅と非概日リズムの振幅の代わりに正弦波sinと余弦波cosの係数の平均に基づいて評価するようにしてもよい。
または、概日リズムと非概日リズムを別々に推定し、概日リズムの振幅と非概日リズムの振幅の代わりに正弦波sinと余弦波cosの合成波の係数に基づいて評価するようにしてもよい。
または、式(10)を用いて概日リズムと非概日リズムを同時に推定し、概日リズムの振幅と非概日リズムの振幅の代わりに正弦波sinと余弦波cosの合成波の係数に基づいて評価するようにしてもよい。
第1実施形態では、判定に閾値(例えば1.0)を用いる例を説明したが、本実施形態では、判定に閾値を用いない例を説明する。また、本実施形態では、心拍数から推定した概日リズムの不安定比率を算出し、算出した不安定比率の値に基づいて、対象者がアルツハイマー型認知症であるか否か判定する。なお、正弦波の不安定比率とは、心拍数の概日リズムの正弦波成分の係数の絶対値の和と、推定された心拍数の概日リズムの正弦波成分の係数の和との比率である。また、余弦波の不安定比率とは、心拍数の概日リズムの余弦波成分の係数の絶対値の和と、推定された心拍数の概日リズムの余弦波成分の係数の和との比率である。なお、不安定比率は、総和でなくても良く、例えば総乗算によって求めてもよい。
図11は、本実施形態に係る認知症判定装置の構成例を示す図である。図11のように、認知症判定装置1Aは、取得部11、第1推定部13(推定部)、判定部15A、記憶部16、および出力部17を備える。
認知症判定装置1Aには、測定時、生体情報測定装置2が接続される。
図12は、安定な心拍数と不安定な心拍数の例を説明するための図である。グラフg300は、健常者の測定された心拍数データが安定な概日リズムを示す例である。グラフg310は、アルツハイマー型認知症患者の測定された心拍数データが不安定な概日リズムを示す例である。グラフg300とg310において、横軸は時間、縦軸は心拍数である。また、線g301とg311は実測値であり、線g302とg312は1日の推定心拍数f(t)である。
次に、認知症判定装置の処理手順例を説明する。
図13は、本実施形態に係る認知症判定装置の処理手順のフローチャートである。
次に、評価結果例を説明する。なお、評価において、発明者らが属する組織の倫理委員会により評価が承認され、すべての被験者が同意書に署名している。また、評価では、評価基準として、アルツハイマー型認知症の検出精度(アルツハイマー型認知症患者のアルツハイマー型認知症検出率と健常者の非アルツハイマー型認知症検出率)を採用した。
第2実施形態では、概日リズムの波の不安定さを、推定心拍数の係数に基づいて算出する例を説明した。余弦波は、波の不安定さに敏感であり、健常者に対して誤判定する場合があった。このため、本実施形態では、推定心拍数の正弦波成分を用いて不安定さの判定を行う例を説明する。
推定心拍数fCR(t)は、データ開始時刻以降は睡眠が深くなるにつれて徐々に心拍数が低くなるため、余弦波の係数の変動量が大きい。しかし、データの後半にかけて正弦波の変動量が大きくなった場合は、それまでの余弦波の係数を抑圧つまり打ち消し合いするように更新する傾向がある。この時は、心拍数に概日性の見られる変動があった場合でも不安定と評価される。
このようなときは、概日リズムの不安定さではなく、概日リズムの振幅そのものに着目した方が健常者を正常に判定できる可能性が高い。すなわち、第2実施形態の手法から第1実施形態の手法に切り替えた方が良いということになる。
このため、本実施形態では、第2実施形態の手法の判定を元に、正弦波が安定、余弦波が不安定と評価された場合、第1実施形態の手法の判定へ切り替える。
このため、本実施形態では、推定心拍数において正弦波の不安定比率を用いて、アルツハイマー型認知症患者であるか否かを判定する。
図17は、本実施形態に係る認知症判定装置の構成例を示す図である。図17のように、認知症判定装置1Cは、取得部11、第1推定部13B、第2推定部14、判定部15C、記憶部16、および出力部17を備える。
認知症判定装置1Cには、測定時、生体情報測定装置2が接続される。
図18は、本実施形態に係る認知症判定装置の処理手順のフローチャートである。
次に、評価結果例を説明する。なお、評価において、発明者らが属する組織の倫理委員会により評価が承認され、すべての被験者が同意書に署名している。
Claims (13)
- 心拍数に関する情報を取得する取得部と、
前記心拍数に関する情報から心拍数の概日リズムを推定する第1推定部と、
前記心拍数の概日リズムと異なるリズムである心拍数の非概日リズムを推定する第2推定部と、
推定された前記心拍数の概日リズムの信号振幅と、推定された前記心拍数の非概日リズムの信号振幅とに基づいて、アルツハイマー型認知症であるか否かを判定する判定部と、
を備えるアルツハイマー型認知症判定装置。 - 心拍数に関する情報を取得する取得部と、
前記心拍数に関する情報から心拍数の概日リズムを推定する推定部と、
推定された前記心拍数の概日リズムの信号の正弦波成分と余弦波成分とに基づいて、アルツハイマー型認知症であるか否かを判定する判定部と、
を備えるアルツハイマー型認知症判定装置。 - 心拍数に関する情報を取得する取得部と、
前記心拍数に関する情報から心拍数の概日リズムを推定する第1推定部と、
推定された前記心拍数の概日リズムの信号の正弦波成分に基づいて、アルツハイマー型認知症であるか否かを判定する判定部と、
を備えるアルツハイマー型認知症判定装置。 - 前記判定部は、推定された前記心拍数の概日リズムの信号の余弦波成分と予測振幅比率とを更に用いて、アルツハイマー型認知症であるか否かを判定する、請求項3に記載のアルツハイマー型認知症判定装置。
- 前記判定部は、推定された前記心拍数の概日リズムの信号振幅と、推定された前記心拍数の非概日リズムの信号振幅との比または差と、閾値を比較してアルツハイマー型認知症であるか否かを判定する、
請求項1に記載のアルツハイマー型認知症判定装置。 - 前記判定部は、推定された前記心拍数の概日リズムの係数の絶対値の和と、推定された前記心拍数の概日リズムの係数の和との比または差と、閾値を比較してアルツハイマー型認知症であるか否かを判定する、
請求項2に記載のアルツハイマー型認知症判定装置。 - 前記心拍数の概日リズムと異なるリズムである心拍数の非概日リズムを推定する第2推定部、をさらに備え、
前記判定部は、
推定された前記心拍数の概日リズムの正弦波成分の係数の絶対値の和と、推定された前記心拍数の概日リズムの正弦波成分の係数の和との比とを前記正弦波の不安定比率として算出し、推定された前記心拍数の概日リズムの余弦波成分の係数の絶対値の和と、推定された前記心拍数の概日リズムの余弦成分の係数の和との比とを余弦波の不安定比率として算出し、
前記心拍数の概日リズムの前記正弦波の不安定比率が1より大きい場合に、アルツハイマー型認知症であると判定し、
前記心拍数の概日リズムの前記正弦波の不安定比率が1であり、かつ前記心拍数の概日リズムの前記正弦波の不安定比率が1以下である場合に、健常者であると判定する、
前記心拍数の概日リズムの前記正弦波の不安定比率が1であり、かつ前記心拍数の概日リズムの前記余弦波の不安定比率が1より大きい場合、かつ推定された前記心拍数の概日リズムの信号振幅と、推定された前記心拍数の非概日リズムの信号振幅との比が閾値より小さいである場合に、アルツハイマー型認知症であると判定し、
前記心拍数の概日リズムの前記正弦波の不安定比率が1以下であり、または前記心拍数の概日リズムの前記余弦波の不安定比率が1より大きい場合、かつ推定された前記心拍数の概日リズムの信号振幅と、推定された前記心拍数の非概日リズムの信号振幅との比が閾値以上ある場合に、健常者であると判定する、
請求項4に記載のアルツハイマー型認知症判定装置。 - 取得部が、心拍数に関する情報を取得し、
第1推定部が、前記心拍数に関する情報から心拍数の概日リズムを推定し、
第2推定部が、前記心拍数の概日リズムと異なるリズムである心拍数の非概日リズムを推定し、
判定部が、推定された前記心拍数の概日リズムの信号振幅と、推定された前記心拍数の非概日リズムの信号振幅とに基づいて、アルツハイマー型認知症であるか否かを判定する、
アルツハイマー型認知症判定方法。 - 取得部が、心拍数に関する情報を取得し、
推定部が、前記心拍数に関する情報から心拍数の概日リズムを推定し、
判定部が、推定された前記心拍数の概日リズムの信号の正弦波成分と余弦波成分とに基づいて、アルツハイマー型認知症であるか否かを判定する、
アルツハイマー型認知症判定方法。 - 取得部が、心拍数に関する情報を取得し、
第1推定部が、前記心拍数に関する情報から心拍数の概日リズムを推定し、
判定部が、推定された前記心拍数の概日リズムの信号の正弦波成分に基づいて、アルツハイマー型認知症であるか否かを判定する、
アルツハイマー型認知症判定方法。 - コンピュータに、
心拍数に関する情報を取得させ、
前記心拍数に関する情報から心拍数の概日リズムを推定させ、
前記概日リズムと異なるリズムである心拍数の非概日リズムを推定させ、
推定された前記心拍数の概日リズムの信号振幅と、推定された前記心拍数の非概日リズムの信号振幅とに基づいて、アルツハイマー型認知症であるか否かを判定させる、
プログラム。 - コンピュータに、
心拍数に関する情報を取得させ、
前記心拍数に関する情報から心拍数の概日リズムを推定させ、
推定された前記心拍数の概日リズムの信号の正弦波成分と余弦波成分とに基づいて、アルツハイマー型認知症であるか否かを判定させる、
プログラム。 - コンピュータに、
心拍数に関する情報を取得させ、
前記心拍数に関する情報から心拍数の概日リズムを推定させ、
推定された前記心拍数の概日リズムの信号の正弦波成分に基づいて、アルツハイマー型認知症であるか否かを判定させる、
プログラム。
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