CN111415745A - Calculation method for prompting Alzheimer disease risk of elderly men by androgen - Google Patents
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Abstract
The invention provides a method for calculating risk of Alzheimer's Disease (AD) of old men prompted by androgen, which comprises the steps of constructing an equation model, fitting an ROC curve, and calculating a diagnosis threshold value cutoff value to obtain an androgen laboratory reference value of amnesic Mild Cognitive impairment (aMCI). The method comprises the following specific steps: and (3) selecting variables with statistical significance to further perform multi-factor logistic regression analysis by referring to the result of single factor analysis of comparison between the aMCI and the cognitive normal, obtaining an independent prediction factor of the aMCI, and constructing an equation. The invention has high prediction value and prompts possible aMCI risks.
Description
Technical Field
The invention relates to a risk calculation method, in particular to a calculation method for prompting Alzheimer disease risk of old men by androgen.
Background
The first internationally recognized diagnostic criteria for Alzheimer's Disease (AD) in the world was the NINCDS-ADRDA diagnostic criteria published by the national institute of neurologic and linguistic disturbance, stroke and Alzheimer's Disease and related diseases in 1984. Over 30 years, the notion of the clinical spectrum of disease has changed day by day as people understand AD and have improved the ability to detect its pathophysiological processes. AD diagnostic standards are also continuously updated and improved, and pass through 4 stages of NINCDS-ADRDA standard (1984) -IWG standard (2007, 2010) -NIA-AA standard (2011) -IWG 2 standard (2014). Whether the NIA-AA or IWG criteria, there is consensus on the concept of AD as a continuous disease process including preclinical, pre-dementia and dementia, and biological markers are incorporated into the respective diagnostic criteria. The preclinical asymptomatic stage of AD and the Mild Cognitive Impairment stage (MCI) of the prophase of dementia are classified into AD, so that the diagnosis of AD is greatly advanced, and the method has great treatment value and research significance for target people with slight neuron damage but enough function compensation.
The biomarkers that have been added to the above diagnostic criteria to show the pathological features of AD include cerebrospinal fluid a β 42, total tau (T-tau) protein and phosphorylated tau (P-tau) protein concentrations, cerebral amyloid deposits (PETamyloid-PE) and deoxyglucose metabolism PET (FDG-PET), and brain atrophy seen on MRI.
The reduction of sex hormones during aging may play an important role in the development and progression of neurodegenerative diseases, and sex and age dependent reproductive hormones and changes in the hypothalamic-pituitary-gonadal axis increase the risk of AD. Therefore, whether the androgen level in peripheral blood can be used as one of the biomarkers for early diagnosis of AD is worth to deeply study which type of androgen has the highest predictive value and how much the reference threshold value is the focus of our research.
Disclosure of Invention
The invention aims to provide a calculation method for prompting Alzheimer disease risk of old men by using androgen.
The technical scheme of the invention is as follows:
a calculation method for prompting AD risk of elderly men by androgen comprises the steps of constructing an equation model, fitting an ROC curve, and calculating a diagnosis threshold value cutoff value to obtain an androgen laboratory reference value of amnesic Mild cognitive impairment (aMCI).
Preferably, the method specifically comprises the steps of referring to a single-factor analysis result of comparing aMCI with normal cognition, selecting variables with statistical significance, further performing multi-factor logistic regression analysis to obtain independent prediction factors of the aMCI, constructing an equation, taking a regression equation L ogit (P) as a combined prediction factor L, taking the combined prediction factor L as a test variable to make a ROC curve to obtain a probability value AUC (median), taking L ogit (P) as a combined prediction variable L which is-22.43 +0.95age-2.84 reduction-FT, wherein the age is age, the reduction is culture degree, and the FT is free testosterone in peripheral blood.
Preferably, a diagnosis threshold Cut Off value is determined by a Yoden Index, YI maximum method, wherein YI is sensitivity + specificity-1, and then an ROC curve is made by using a verification model L' as a test variable by an external verification method to obtain a verification probability value AUC value and the maximum method diagnosis threshold Cut Off value to be compared with the model.
Preferably, the AUC values of the fitted model L and the validated model L 'are both >0.7, indicating that FT values have a moderate diagnostic value for senile male aMCI, and the cutoff value of L' is 4.91, indicating that aMCI risk is considered when FT ≦ 22.43+0.95age-2.84education-FT ≧ 4.91, i.e., FT ≦ 0.95age-2.84 education-27.34.
Preferably, the classification of acmi from cognitive normal uses the cognitive function test application scale.
Preferably, the cognitive function test application scales include the mini mental state scale MMSE, the montreal cognitive function assessment scale MoCA, the auditory word test VA L T, the numerical breadth test DST, the line test TMT, the boston nomenclature test BNT, the animal word fluency AFT, the bell test CDT, the clinical dementia rating scale CDR, the senile depression scale GDS, the ability to daily live scale AD L, and the Hachinski ischemia score scale.
Preferably, the cognitive function test application scale is applied to acmi:
① there is age-inconsistent objective memory impairment MoCA ≤ 24 points, and the age and education are adjusted
② normal cognitive function with MMSE not less than 24 points, CDR 0.5 and CDR memory not less than 0.5, ③ complete daily life ability or only slight damage AD L not more than 26 points, ④ Hachinski ischemia score scale<4 min, GDS>And 11 minutes.
Preferably, the inclusion and exclusion criteria for AD:
the inclusion criteria are (1) male with age more than or equal to 65 years, (2) the clinical diagnosis criteria of NIA-AA are met, ① patients or lovers mainly complain of memory disorder or confirm the existence of objective damage inconsistent with age through neuropsychological tests, including memory function, executive function and visual space function, and mainly suffer from impaired random cognitive function when starting to avoid emphasizing memory function, ② patients have influence on daily life and working capacity, ③ patients cannot explain symptoms of patients with delirium or mental disorder, ④ patients have disease invigoration, and symptoms gradually appear in months or years, ⑤ excludes dementia caused by other reasons, and (3) the patients voluntarily participate in the diagnosis;
exclusion criteria: (1) patients suffering from mental diseases such as depression; (2) drug or alcohol dependent; (3) and (4) severe visual and auditory disorders, and the cognitive examiners cannot be completed.
Preferably, the inclusion and exclusion criteria for acci:
inclusion criteria (1) male age > 65 years, (2) meeting Petersen report 2004 and the national institute of the aged and Alzheimer's disease Association NIA-AA criteria that ① patients or informed persons complain about memory impairment, [ ② ] confirmed by neuropsychological testing that there was objective memory impairment inconsistent with age, [ ③ ] normal general cognitive function, [ ④ ] complete or only slightly impaired daily living capacity, [ ⑤ ] no dementia, (3) voluntary participation;
exclusion criteria: (1) other types of cognitive disorders or those suffering from systemic diseases that lead to cognitive disorders; (2) those suffering from intracranial space occupying lesions that lead to cognitive impairment; (3) patients suffering from mental diseases such as depression; (4) drug or alcohol dependent; (5) and (4) severe visual and auditory disorders, and the cognitive examiners cannot be completed.
Preferably, the inclusion and exclusion criteria for cognitive normalizers are:
inclusion criteria were: (1) males aged greater than or equal to 65 years old; (2) the cognitive function is normal; (3) the daily life capacity is not affected; (4) voluntary participation;
exclusion criteria: (1) cancer patients or patients with other systemic diseases; (2) severe visual and auditory disorders, and failure to complete cognitive testing.
The invention has the beneficial effects that:
the invention has high prediction value, the serum FT value has prediction value on aMCI risk, and the serum FT value can be used as a reference biomarker for evaluating AD and provides a reference threshold value which is beneficial to clinical diagnosis.
Drawings
FIG. 1 is a ROC plot of FT formula predicted aMCI according to an embodiment of the present invention.
FIG. 2 is a ROC graph illustrating the effect of FT formula on prediction of aMCI according to an embodiment of the present invention.
Detailed Description
1 Material
1.1 study object
1.1.1 sources of study subjects
In 2018, 3 months to 7 months and 2019, 3 months to 7 months, 4 community health service centers are randomly extracted from each main urban area in the Hebei province Shijiazhuang city, and 3000 elderly men aged more than 65 years who are subjected to physical examination by the 4 community health service centers are taken as research objects to evaluate the physical health condition, the mental state and the cognitive function of the elderly men. A total of 2062 persons matched and completed the cognitive function test, among which were recognized normal 1665, acmi 290, and AD 65. These subjects were 576 subjects who had received blood for experimental purposes, among which 243 subjects who were normal, acmi 271 subjects who were normal, and AD 62 subjects who were normal.
The study was approved by the ethical committee of north medical university, hebei, and written informed consent was obtained from each subject.
1.1.2 inclusion and exclusion criteria for study subjects
Inclusion and exclusion criteria for cognitive normality:
inclusion criteria were: (1) males aged greater than or equal to 65 years old; (2) the cognitive function is normal; (3) the daily life capacity is not affected; (4) voluntarily participate in the process.
Exclusion criteria: (1) cancer patients or patients with other systemic diseases; (2) severe visual and auditory disorders, and failure to complete cognitive testing.
Inclusion and exclusion criteria for acmi:
inclusion criteria (1) male age > 65 years, (2) meeting Petersen's 2004 report and national institute of the aged and alzheimer's association (NIA-AA) criteria that ① patients or informed persons complain about memory impairment, ② confirmed by neuropsychological tests that there was objective memory impairment inconsistent with age, ③ general cognitive function was normal, ④ daily life was either intact or only slightly impaired, ⑤ had no dementia, (3) participated voluntarily.
Exclusion criteria: (1) other types of cognitive disorders or those suffering from systemic diseases that lead to cognitive disorders; (2) those suffering from intracranial space occupying lesions that lead to cognitive impairment; (3) patients suffering from mental diseases such as depression; (4) drug or alcohol dependent; (5) and (4) severe visual and auditory disorders, and the cognitive examiners cannot be completed.
Inclusion and exclusion criteria for AD:
the inclusion criteria are (1) male with age more than or equal to 65 years old, (2) the clinical diagnosis criteria of NIA-AA are met, ① patients or lovers mainly complain of memory disorder or confirm the existence of objective damage (memory function, executive function, visual space function and the like) inconsistent with age through neuropsychological tests, any cognitive function is mainly impaired when the patients are ill, the memory function is not emphasized, the daily life capacity and the working capacity of ② patients are affected, ③ cannot explain symptoms of the patients by delirium or mental disorder, ④ causes disease invigoration, the symptoms gradually appear in months or years, and ⑤ excludes dementia caused by other reasons (3) the patients voluntarily participate.
Exclusion criteria: (1) patients suffering from mental diseases such as depression; (2) drug or alcohol dependent; (3) and (4) severe visual and auditory disorders, and the cognitive examiners cannot be completed.
1.2 Main instruments and reagents
1.2.1 Main instruments and Equipment are shown in Table 1-1
TABLE 1-1
1.2.2 Main reagents and consumables are shown in tables 1-2
Tables 1 to 2
2 method
2.1 content of the study
2.1.1 demographic data: name, age, cultural degree, etc.
2.1.2 cognitive function test application scale:
(1) simple mental state scale (MMSE): was compiled in 1975 by Folstein et al and has 10 entries relating to 6 cognitive functions of orientation, memory, attention, computing power, language and visual space. The total score reflects the overall cognitive function, the total score is between 0 and 30, the higher the total score is, the better the overall cognitive function is, when the education degree is less than 7 years, the total score is added with 1, the total score is between 28 and 30, which indicates normal cognition, and the total score is less than or equal to 27, which indicates cognitive disorder.
(2) Montreal cognitive function assessment scale (MoCA): the Canadian scholars Nasreddine et al developed and developed 2004 on the basis of MMSE, and more specifically evaluated the executive function and visual spatial structure skills of the patients. And the total score reflects the overall cognitive function, the total score is between 0 and 30, the higher the total score is, the better the overall cognitive function is, when the education degree is less than 7 years, the total score is added by 1, the total score is between 25 and 30, which indicates normal cognition, and the total score is less than or equal to 24, which indicates cognitive disorder.
(3) The auditory word test (VA L T) is compiled according to a method and a principle of California word learning detection and Hong Kong word learning detection and is used for detecting the memory function of the old, the auditory word test (VA L T) consists of 15 words, can be divided into 5 semantic categories, each category comprises 3 words, under the condition that a research object is prompted to recall in advance, a researcher clearly reads 15 randomly presented words at the speed of one word per second, then the research object recalls the 15 words immediately, the continuous learning and recalling are carried out for 3 times, the average number of 3-time recall words is marked as a short-time recall score, after other tests are carried out for about 20 minutes, the research object recalls the 15 words, the number of the recall words is marked as a delayed recall score, the category prompt is used for recalling again, the number of the recall words is marked as a recall ' cue ' and finally is a recognization, and the research object needs to judge whether 30 read words by the research object are recalled better, the number of the recall words is marked as a ' recall ' and a score ' and recognizes each time.
(4) Digital breadth test (DST): the method mainly evaluates the attention and working memory of a patient, and comprises a forward digital test part and a reverse digital test part, wherein a series of numbers are clearly read by a researcher at the speed of one number per second, a research object is required to speak the numbers read by the researcher in a forward or reverse direction respectively, when 2 tests with the same length fail, the test is finished, and the highest successful score before the record is finished is the score of the test. (5) inline test (TMT): the method is developed and developed by Partington in 1938 and widely applied to detection of mutexecutive functions of the old, then, the connection test is modified by considering that the difference of English level among the old in China is large, a TMT-A requires a research object to connect 25 numbers (1-25) on paper in sequence, a TMT-B comprises the numbers in black circles and white circles, and requires the research object to be alternately arranged while connecting the numbers in sequence (such as white circles 1-black circles 1-white circles 2-black circles 2-white circles 3, and so on), and the result is represented by the number of consumed hours of the connection, and the longer the consumed time is, the worse the mutexecutive function is.
(6) Boston Naming Test (BNT): is one of the common scales for detecting language functions, and requires the research object to name 30 line drawings. BNT has higher sensitivity for recognizing cognitive disorder, while the sensitivity for recognizing MCI is 61 percent, and the sensitivity for recognizing mild and moderate AD is 79 percent and 95 percent respectively, which is a reliable basis for AD diagnosis. The number of correct line drawings spoken by the subject was scored as the score for BNT.
(7) Animal word fluency (AFT): the semantic fluency of the study subjects was mainly examined, requiring the study subjects to speak as many animal names as possible within 1 minute. The impairment of word fluency can be shown in the early stage of AD, and is one of the important neuropsychological tools for early diagnosis of AD. The number of species that were spoken within 1 minute was scored as AFT.
(8) Clock drawing experiment (CDT): a simple and easy-to-operate screening tool for evaluating the visual space ability and the execution function adopts a trisection method, namely, a round dial is correctly drawn for 1 point, all numbers are marked at correct positions for 1 point, and a pointer is 11: score 10 to 1.
(9) Clinical dementia rating scale (CDR): the assessment of cognitive function and social life ability of the study subjects was used to obtain a general assessment, mainly for the assessment of the score and longitudinal variation of dementia severity, published by professor Hughes 1982. Subjects were classified as non-demented, suspect, mild, moderate and severe dementias according to scores of 0, 0.5, 1, 2 and 3.
(10) Senile depression scale (GDS): the screening scale is created by Briink et al in 1982, is a depression screening scale specially used for old people, can more sensitively reflect the specific physical symptoms of senile depressed patients, and has a score of less than or equal to 10 points for normal, 11-20 points for mild depression, 21-25 points for moderate depression and 26-30 points for severe depression.
(11) A daily life capacity scale (AD L) is compiled by L awton and Brody of Americans in 1969, comprises a body life self-care scale and a tool daily life activity scale, can accurately know the daily life capacity of a study object in detail, and is widely applied to scientific research when the score is more than or equal to 26 minutes, which indicates that the daily life is obviously influenced.
(12) Hachinski ischemia score scale: this scale is commonly used to differentiate vascular cognitive disorders from AD when a patient has memory impairment, objective assessment of cognitive impairment, and decreased daily living capacity. The score is 12 points, the score is more than or equal to 4 points, the vascular cognitive disorder can be considered, and the higher the score is, the higher the possibility of the vascular cognitive disorder is.
(13) Comprehensive application of cognitive scale in diagnosing aMCI
① there is age-inconsistent objective memory impairment (MoCA ≦ 24 points, adjusted age and education
② normal cognitive function (MMSE 24 min. or more, CDR 0.5 and CDR memory 0.5), ③ intact or only slightly impaired daily life (AD L min. or less), ④ Hachinski ischemia score scale<4 min, GDS>And 11 minutes.
2.1.3 blood sample Collection and processing
The first step is as follows: in 7: 30-9: 30 am, taking 10ml of peripheral blood from the cubital vein on an empty stomach, and placing a non-anticoagulation closed blood collection tube. If severe hemolysis, lipemia or turbidity occurs during the collection of the sample, the sample is discarded.
The second step is that: centrifuging: rotating at 3000rpm for 10min, collecting upper layer serum, subpackaging in freezing tubes, and storing in-80 deg.C refrigerator for use to avoid repeated freezing and thawing.
The third step: the sample is placed at room temperature for no more than 8 hours after being collected; if the sample is not processed within 8 hours, the sample is required to be placed in a refrigerator at the temperature of 2-8 ℃; if the preservation time is more than 48 hours, the food is frozen and preserved in a refrigerator at the temperature of minus 80 ℃. The mixture was allowed to stand at room temperature for 10min before use, and gently shaken and mixed.
2.1.4 specimen detection method
(1) Chemical luminescence method
① TT, SHBG, FSH, L H are detected by chemiluminescence method, which comprises the following steps:
② taking out the sample from refrigerator at-80 deg.C, standing at room temperature for 10min, and mixing;
③ entering a test requirement screen from a main menu;
④ setting a position on the sample rack for each sample, inputting the sample information and the test name to be detected;
⑤ placing the sample tube in the set position in the sample holder;
⑥ pressing the run key to start the test;
⑦ automatically calculates the test results and makes a record.
(2) Enzyme linked immunosorbent assay
The detection of FT, DHT, DHEA and DHEA-S adopts an enzyme-linked immunosorbent assay, and comprises the following steps:
① taking out the sample from refrigerator at-80 deg.C, standing at room temperature for 10min, and mixing;
② placing the coated plate of the required number of samples on the plate frame;
③ adding standard, quality control and sample into each 20 mu L micro-hole;
④ adding 100 μ L enzyme conjugate into each micro-pore, mixing for 10s, and mixing thoroughly;
⑤ 37 deg.C for 60 min;
⑥ discarding reaction solution in the hole, adding 300 μ L washing solution in each hole, washing the plate for 3 times, and drying on absorbent paper;
⑦ adding 100 μ L substrate solution into each micro-well, incubating for 15min at room temperature in the dark;
⑧ adding 100 mu L stop solution into each micropore to stop the reaction;
⑨ the OD value is read at 450 + -10 nm by a microplate reader 10min after the stop solution is added.
2.2 statistical methods
The method comprises the following steps of establishing an equation model, fitting an ROC curve, calculating a cutoff value, and obtaining an androgen laboratory reference value for diagnosing aMCI, wherein a result of single-factor analysis for comparing aMCI and NC is referred, selecting variables with statistical significance to further perform multi-factor logistic regression analysis, obtaining an independent prediction factor of aMCI, establishing an equation, taking a regression equation L ogit (P) as a combined prediction factor L, taking L as a test variable to make an ROC curve, obtaining an AUC value, establishing a Cut Off value by a Yuden Index and YI maximum method, wherein YI is sensitivity plus specificity-1, and then using L' as a test variable to make an ROC curve, obtaining a verified AUC value and the Cut Off value to be compared with the model.
3 results of the experiment
3.1 Multi-factor logistic regression analysis to predict aMCI Risk
The NC group and the acmi group were found to differ in age, cultural degree, FT and DHT in the one-factor analysis, so the above 4 variables were used as independent variables and subjected to L logistic regression analysis to find that only age, cultural degree and FT entered the equation finally, when the age was over 65 years, the equation was L ogit (p) -1.660+0.070 age-0.210 cultural degree-0.074 FT, table 2-1.
3.2 predicting ROC Curve and CUT OFF value of aMCI Risk
Using L ogit (p) as a joint predictor L ═ 22.43+0.95age-2.84 reduction-FT., ROC curves of 70% of study subjects found L with an area under the curve value of 0.722 and a cutoff value of 6.63, specific results are shown in tables 2-2 and fig. 1, the constructed equations were externally verified, L' with an area under the curve value of 0.712 and a cutoff value of 4.91, tables 2-2 and fig. 2.
The use of substances in peripheral blood as biomarkers for the diagnosis of AD is a hotspot in AD research, and in order to identify a certain marker as a diagnostic standard for AD, a corresponding diagnostic threshold needs to be established, and the sensitivity and accuracy of the marker as a predicted value need to be checked.
The AUC value of the area under the ROC curve is a common index for evaluating the advantages and disadvantages of a binary model, the AUC ranges from 0.5 to 1, the closer the AUC is to 1.0, the higher the authenticity of the detection method is, the lower the authenticity is, and when the AUC is equal to 0.5, the lower the authenticity is, and no diagnostic value is obtained.
Since geriatric male androgens are closely related to AD, the ROC curve for diagnosing geriatric male aMCI using peripheral blood FT was fitted and externally validated, the AUC values for both the fitted model L and the validated model L 'were >0.7, indicating that the FT value has a moderate diagnostic value for geriatric male aMCI, the cutoff value for L' was 4.91, indicating that the risk of aMCI was considered when-22.43 +0.95age-2.84education-FT ≧ 4.91, i.e., FT ≦ 0.95age-2.84 education-27.34. for example, a 70 year old, 9 year educated male tested for peripheral blood FT values, suggesting a possible risk of aMCI when FT ≦ 13.6/m L.
Claims (10)
1. A calculation method for prompting Alzheimer disease risk of old men by androgen is characterized in that an equation model is constructed, an ROC curve is fitted, a diagnosis threshold value cutoff value is calculated, and an androgen laboratory reference value of aMCI is obtained.
2. The method for calculating the risk of Alzheimer's disease in elderly males by androgen stimulation according to claim 1, comprising the steps of selecting statistically significant variables and further performing multi-factor logistic regression analysis with reference to the result of single factor analysis of comparison between aMCI and cognitive normality to obtain independent predictors of aMCI, constructing an equation, using a regression equation L ogit (P) as a combined predictor L, using the combined predictor L as a test variable to make a ROC curve, L-22.43 +0.95age-2.84education-FT, wherein age is age, education is culture degree, and FT is free testosterone in peripheral blood.
3. The method for calculating the risk of Alzheimer's disease in elderly males by using androgen as claimed in claim 2, characterized in that a diagnosis Cut Off value is determined by using a Yoden Index (YI) maximum method, wherein YI is sensitivity + specificity-1, and then an ROC curve is made by using a verification model L' as a test variable by using an external verification method to obtain a verification AUC value and the diagnosis Cut Off value to compare with the model.
4. The method of claim 3, wherein the AUC values of the fitted model L and the validated model L 'are both >0.7, indicating that FT value has a moderate diagnostic value for senile male aMCI, and the cutoff value of L' is 4.91, indicating that aMCI risk is considered when-22.43 +0.95age-2.84 evaluation-FT is greater than or equal to 4.91, namely FT is less than or equal to 0.95age-2.84 evaluation-27.34.
5. The method of claim 1, wherein the classification of aMCI from normal cognition uses a cognitive function test application scale.
6. The method of claim 5, wherein the cognitive function test application scale comprises the SIMS MMSE, the Montreal cognitive function assessment Scale MoCA, the auditory word test VA L T, the numerical breadth test DST, the line test TMT, the Boston naming test BNT, the animal word fluency AFT, the clock test CDT, the clinical dementia assessment Scale CDR, the age Depression Scale GDS, the ability to daily Life Scale AD L, and the Hachinski ischemia score Scale.
7. The method for calculating the risk of Alzheimer's disease in elderly men according to claim 6, wherein the cognitive function test application scale is applied to aMCI;
① there is age-inconsistent objective memory impairment MoCA ≤ 24 points, and the age and education are adjusted
② normal cognitive function with MMSE not less than 24 points, CDR 0.5 and CDR memory not less than 0.5, ③ complete daily life ability or only slight damage AD L not more than 26 points, ④ Hachinski ischemia score scale<4 min, GDS>And 11 minutes.
8. The method of claim 2, wherein the inclusion and exclusion criteria for AD are as follows:
the inclusion criteria are (1) male with age more than or equal to 65 years, (2) the clinical diagnosis criteria of NIA-AA are met, ① patients or lovers mainly complain of memory disorder or confirm the existence of objective damage inconsistent with age through neuropsychological tests, including memory function, executive function and visual space function, and mainly suffer from impaired random cognitive function when starting to avoid emphasizing memory function, ② patients have influence on daily life and working capacity, ③ patients cannot explain symptoms of patients with delirium or mental disorder, ④ patients have disease invigoration, and symptoms gradually appear in months or years, ⑤ excludes dementia caused by other reasons, and (3) the patients voluntarily participate in the diagnosis;
exclusion criteria: (1) patients suffering from mental diseases such as depression; (2) drug or alcohol dependent; (3) and (4) severe visual and auditory disorders, and the cognitive examiners cannot be completed.
9. The method of claim 2, wherein the inclusion and exclusion criteria for acmi are:
the inclusion standard (1) male with age more than or equal to 65 years old, (2) the male meets the standards of ① patients or acquaintances who complain about memory impairment in the 2004 report and NIA-AA of the institute of the national institute of the aged and Alzheimer's disease, ② confirms that the male memory impairment inconsistent with age exists through neuropsychological tests, ③ generally has normal cognitive function, ④ has complete or only slightly impaired daily life capacity, ⑤ has no dementia, and (3) participates in voluntary;
exclusion criteria: (1) other types of cognitive disorders or those suffering from systemic diseases that lead to cognitive disorders; (2) those suffering from intracranial space occupying lesions that lead to cognitive impairment; (3) patients suffering from mental diseases such as depression; (4) drug or alcohol dependent; (5) and (4) severe visual and auditory disorders, and the cognitive examiners cannot be completed.
10. The method of claim 2, wherein the inclusion and exclusion criteria for cognitive normality are as follows:
inclusion criteria were: (1) males aged greater than or equal to 65 years old; (2) the cognitive function is normal; (3) the daily life capacity is not affected; (4) voluntary participation;
exclusion criteria: (1) cancer patients or patients with other systemic diseases; (2) severe visual and auditory disorders, and failure to complete cognitive testing.
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| Publication number | Priority date | Publication date | Assignee | Title |
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| CN114305457A (en) * | 2021-12-28 | 2022-04-12 | 上海仪器仪表研究所 | Senile dementia judging system |
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| US5795883A (en) * | 1993-04-13 | 1998-08-18 | Jenapharm Gmbh | Androgens and anabolic agents |
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