CN111415745A - Calculation method for prompting Alzheimer disease risk of elderly men by androgen - Google Patents

Abstract

The invention provides a calculation method for androgen to prompt the risk of Alzheimer's Disease (AD) in elderly men. By constructing an equation model, fitting the ROC curve, and calculating the diagnostic cutoff value, the amnestic mild recognition is obtained. Laboratory reference values for androgens for amnestic Mild Cognitive Impairm (aMCI). Specific steps: Referring to the results of univariate analysis comparing aMCI with cognitive normal, select statistically significant variables for further multivariate logistic regression analysis, obtain independent predictors of aMCI, and construct equations. The present invention has high predictive value, suggesting a possible risk of aMCI.

Description

A method for calculating androgen-indicated Alzheimer's disease risk in older men

technical field

The invention relates to a risk calculation method, in particular to a calculation method for androgen prompting the risk of Alzheimer's disease in elderly men.

Background technique

The world's first internationally recognized diagnostic criteria for Alzheimer's Disease (AD) were the NINCDS-ADRDA diagnostic criteria published by the National Association of Neurology and Language Disorders, Stroke and Alzheimer's Disease and Related Disorders in 1984. Over the past 30 years, with the improvement of people's understanding of AD disease and the ability to detect its pathophysiological process, the concept of the clinical spectrum of the disease has undergone tremendous changes. AD diagnostic criteria have also been continuously updated and improved, after four NINCDS-ADRDA criteria (1984) - IWG criteria (2007, 2010) - NIA-AA criteria (2011) - IWG2 criteria (2014) stage. Regardless of the NIA-AA criteria or the IWG criteria, there is a consensus on the concept of AD as a continuous disease process including preclinical, pre-dementia, and dementia stages, and biomarkers have been incorporated into their respective diagnostic criteria. The preclinical asymptomatic stage of AD and the pre-dementia stage of mild cognitive impairment (Mild Cognitive Impairment, MCI) are all classified into AD, which greatly moves the diagnosis of AD forward, and only mild neuronal damage is required. However, the target population with sufficient functional compensation has great therapeutic value and research significance.

Biomarkers that have been added to the above diagnostic criteria to show pathological features of AD include cerebrospinal fluid Aβ42, total tau (T-tau) protein and phosphorylated tau (P-tau) protein concentrations, brain amyloid deposition (PETamyloid-PE) and deoxyglucose metabolism PET (FDG-PET) and brain atrophy visible on MRI. Although NIA-AA also proposed a double standard for clinical and research use in AD diagnosis, clinical diagnosis of AD can still be completed in the absence of cerebrospinal fluid and molecular PET. However, in the clinical diagnosis of AD, in the absence of biomarker support, only relying on clinical symptoms for diagnosis will reduce the specificity of diagnosis; although the inclusion of biomarkers increases the specificity of diagnosis, it has been Most of the detection of biomarkers added to the diagnostic criteria is complicated, invasive and expensive, not suitable for clinical promotion, and difficult to apply on a large scale. Therefore, there is an urgent need to find diagnostic markers with high sensitivity and specificity that can be easily obtained, and blood biomarkers are the first choice.

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 changes in reproductive hormones and the hypothalamic-pituitary-gonadal axis increase the risk of AD. Therefore, whether the level of androgen in peripheral blood can be used as one of the biomarkers for the early diagnosis of AD is worth exploring in depth, which type of androgen has the highest predictive value and what is the reference cutoff value is the focus of our research.

SUMMARY OF THE INVENTION

The purpose of the present invention is to provide a method for calculating the risk of Alzheimer's disease in elderly men prompted by androgen.

Technical scheme of the present invention:

A method for calculating androgen-induced AD risk in elderly men. By constructing an equation model, fitting the ROC curve, and calculating the diagnostic cutoff value, the androgen of amnestic Mild Cognitive Impairm (aMCI) was obtained. Laboratory reference value.

Preferably, the specific steps are: referring to the results of the univariate analysis comparing aMCI and cognitive normality, select statistically significant variables for further multivariate logistic regression analysis, obtain independent predictors of aMCI, and construct an equation; log the regression equation Logit (P) is taken as the joint predictor L, the ROC curve is made with the joint predictor L as the test variable, and the probability value AUC value is obtained; Logit(P) is taken as the joint predictor L=-22.43+0.95age-2.84education-FT, so The age is the age; the education is the educational level; the FT is the free testosterone in the peripheral blood.

Preferably, the Yuden Index, the maximum YI method is used to formulate the diagnostic cutoff Cut Off value, where YI=sensitivity + specificity-1; then the external verification method is used to make the ROC curve with the verification model L' as the test variable, Obtain the validation probability value AUC value and the maximum method to formulate the diagnostic cutoff value Cut Off value and compare with the model.

Preferably, the AUC values of the fitted model L and the validation model L' are both >0.7, indicating that the FT value has a moderate diagnostic value for aMCI in elderly men; the cut-off value of L' is 4.91, which means that when The risk of aMCI was considered when education-FT≥4.91, that is, FT≤0.95age-2.84education-27.34.

Preferably, the classification of aMCI and cognitive normality adopts the cognitive function detection application scale.

Preferably, the cognitive function testing application scale includes the Mini Mental State Scale MMSE, Montreal Cognitive Function Assessment Scale MoCA, Auditory Word Test VALT, Digit Span Test DST, Wiring Test TMT, Boston Naming Test BNT, animal Verbal Fluency AFT, Clock Drawing Test CDT, Clinical Dementia Rating Scale CDR, Geriatric Depression Scale GDS, Activities of Daily Living Scale ADL and Hachinski Ischemia Rating Scale.

Preferably, the application of the cognitive function detection application scale in aMCI:

②一般认知功能正常MMSE≥24分，CDR＝0.5且CDR 记忆≥0.5；③日常生活能力完整或仅轻度受损ADL≤26分；④Hachinski缺血评分量表<4分，GDS>11分。① There is objective memory impairment inconsistent with age MoCA ≤ 24 points, after adjusting for age and education level

② Normal cognitive function MMSE≥24 points, CDR=0.5 and CDR memory≥0.5; ③ADL≤26 points with complete or only mild impairment of daily living ability; ④Hachinski ischemia score <4 points, GDS>11 points .

Preferably, the inclusion and exclusion criteria for AD:

Inclusion criteria: (1) males aged ≥ 65 years; (2) meeting the NIA-AA clinical diagnostic criteria for AD: ① patients or insiders complained of memory impairment or confirmed the existence of objective impairment inconsistent with age through neuropsychological tests Including memory function, executive function, and visuospatial function. At the onset of the disease, any cognitive function is mainly impaired, and memory function is no longer emphasized; ②The patient's daily living ability and work ability are affected; ③The inability to use delirium or mental disorder To explain the symptoms of patients; 4) Insidious onset, symptoms appear gradually over months or years; 5) Exclude other causes of dementia; (3) Voluntary participation;

Exclusion criteria: (1) those suffering from depression and other mental illnesses; (2) those who are drug or alcohol dependent; (3) those with severe visual and auditory impairment who cannot complete the cognitive test.

Preferably, the inclusion and exclusion criteria for aMCI:

Inclusion criteria: (1) males aged ≥ 65 years; (2) meeting the criteria reported by Petersen in 2004 and the National Institute of Aging and Alzheimer's Disease Institute NIA-AA: ① patients or insiders complained of memory impairment; ②Confirmed the existence of objective memory impairment inconsistent with age through neuropsychological tests; ③Generally normal cognitive function; ④Complete or only mild impairment of activities of daily living; ⑤No dementia; (3) Voluntary participation;

Exclusion criteria: (1) other types of cognitive impairment or systemic diseases that cause cognitive impairment; (2) patients with intracranial space-occupying lesions that cause cognitive impairment; (3) mental illnesses such as depression (4) Those who are drug or alcohol dependent; (5) Those with severe visual and auditory impairment who cannot complete the cognitive test.

Preferably, the inclusion and exclusion criteria of cognitively normal persons:

Inclusion criteria: (1) males aged ≥ 65 years; (2) normal cognitive function; (3) daily living ability is not affected; (4) voluntary participation;

Exclusion criteria: (1) cancer patients or other systemic diseases; (2) severe visual and auditory impairment, unable to complete cognitive testing.

Beneficial effects of the present invention:

The invention shows high predictive value, and the serum FT value has predictive value for aMCI risk, can be used as a reference biomarker for evaluating AD, and at the same time proposes a reference boundary value that is helpful for clinical diagnosis.

Description of drawings

FIG. 1 is a ROC curve diagram of aMCI predicted by FT formula according to an embodiment of the present invention.

FIG. 2 is a ROC curve diagram for verifying the prediction effect of the FT formula on aMCI according to an embodiment of the present invention.

Detailed ways

1 material

1.1 Research objects

1.1.1 Sources of research subjects

From March to July 2018 and March to July 2019, 4 community health service centers were randomly selected in each main urban area of Shijiazhuang City, Hebei Province. Men were the subjects of the study, and their physical health, mental status, and cognitive function were assessed. A total of 2062 people cooperated and completed the cognitive function test, including 1665 people with normal cognition, 290 people with aMCI, and 65 people with AD. 576 of these people received blood sampling for experimental purposes, including 243 with normal cognition, 271 with aMCI, and 62 with AD.

The study was approved by the Ethics Committee of Hebei Medical University, and written informed consent was obtained from each subject.

1.1.2 Inclusion and exclusion criteria of study subjects

Inclusion and exclusion criteria for cognitively normal:

Inclusion criteria: (1) males aged ≥ 65 years; (2) normal cognitive function; (3) unaffected activities of daily living; (4) voluntary participation.

Exclusion criteria: (1) cancer patients or other systemic diseases; (2) severe visual and auditory impairment, unable to complete cognitive testing.

Inclusion and exclusion criteria for aMCI:

Inclusion criteria: (1) males aged ≥ 65 years; (2) meeting the criteria reported by Petersen in 2004 and the National Institute of Aging and Alzheimer's Disease Association (NIA-AA): ① patients or insiders complained of memory 2) Objective memory impairment consistent with age confirmed by neuropsychological tests; 3) Normal cognitive function in general; 4) Complete or only mild impairment of activities of daily living; 5) No dementia. (3) Voluntary participation.

Exclusion criteria: (1) other types of cognitive impairment or systemic diseases that cause cognitive impairment; (2) patients with intracranial space-occupying lesions that cause cognitive impairment; (3) mental illnesses such as depression (4) Those who are drug or alcohol dependent; (5) Those with severe visual and auditory impairment who cannot complete the cognitive test.

Inclusion and exclusion criteria for AD:

Inclusion criteria: (1) males aged ≥ 65 years; (2) meeting the NIA-AA clinical diagnostic criteria for AD: ① patients or insiders complained of memory impairment or confirmed the existence of objective impairment inconsistent with age through neuropsychological tests (memory function, executive function, visuospatial function, etc.), at the onset of the disease, any one of the cognitive functions is mainly damaged, and the memory function is no longer emphasized; ② the patient's daily living ability and work ability are affected; ③ unable to use Delirium or mental disorder to explain the patient's symptoms; ④ insidious onset, symptoms appear gradually over months or years; ⑤ exclusion of other causes of dementia. (3) Voluntary participation.

Exclusion criteria: (1) those suffering from depression and other mental illnesses; (2) those who are drug or alcohol dependent; (3) those with severe visual and auditory impairment who cannot complete the cognitive test.

1.2 Main instruments and reagents

1.2.1 The main instruments and equipment are shown in Table 1-1

Table 1-1

1.2.2 The main reagents and consumables are shown in Table 1-2

Table 1-2

2 methods

2.1 Research content

2.1.1 Demographic data: name, age, educational level, etc.

2.1.2 Cognitive Function Test Application Scale:

(1) Mini-Mental State Inventory (MMSE): It was compiled by Folstein et al. in 1975, with a total of 10 items, involving six cognitive functions of orientation, memory, attention, calculation, language and visual space. The total score reflects the overall cognitive function. The total score is between 0 and 30 points. The higher the total score, the better the overall cognitive function. When the education level is less than 7 years, the total score will add 1 point. A score of 30 indicates normal cognition, and a total score of less than or equal to 27 indicates cognitive impairment.

(2) Montreal Cognitive Function Assessment (MoCA): It was developed by Canadian scholars Nasreddine et al. on the basis of MMSE in 2004, and more targeted assessment of patients' executive function and visuospatial structural skills. The total score also reflects the overall cognitive function. The total score is between 0 and 30 points. The higher the total score, the better the overall cognitive function. When the education level is less than 7 years, the total score will add 1 point. A score of -30 indicates normal cognition, and a total score less than or equal to 24 indicates cognitive impairment.

(3) Auditory Vocabulary Test (VALT): compiled according to the methods and principles of California Vocabulary Learning Test and Hong Kong Vocabulary Learning Test, and used to test the memory function of the elderly. It consists of 15 words, which can be divided into 5 semantic categories, with 3 words in each category. Under the condition that the research subjects need to be recalled in advance, the researcher clearly reads out 15 randomly presented words at the speed of one word per second. Then the research subjects immediately recalled 15 words, and learned to recall three times in a row. The average number of words recalled three times was recorded as the "short-term recall" score. After about 20 minutes of other tests, the research subjects were asked to recall the words just now. 15 words, the number of recalled words this time is recorded as the "delayed recall" score, and then recalled again using the category cue as a clue, the number of recalled words this time is recorded as the "cue recall" score, and finally is recognition, research The subject needs to judge whether the 30 words read out by the researcher have been learned or not based on their memory. The number of words recalled this time is recorded as the "recognized recall" score. The higher the recall score each time, the better the memory.

(4) Digit Span Test (DST): It mainly evaluates the patient's attention and working memory. It is divided into two parts: forward digit test and reverse digit test. Numbers, the research subjects were asked to say the numbers read by the researcher forward or backward respectively. When two tests of the same length failed, the test was over, and the highest score of success before the end of the recording was the score of this test. (5) Tethering Test (TMT): It was originally developed by Partington in 1938 and was widely used in the detection of executive function of the elderly. Later, considering the large gap in English proficiency among the elderly in my country, the TMT was modified. , TMT-A requires the research subjects to connect the 25 numbers (1-25) on the paper in order, TMT-B is to include the numbers in the black and white circles, and the research subjects are required to connect the lines in numerical order at the same time The two graphics should be arranged alternately (such as white circle 1-black circle 1-white circle 2-black circle 2-white circle 3 and so on), the result is represented by the time-consuming number of the connection, the longer the time-consuming, the execution function the worse.

(6) Boston Naming Test (BNT): It is one of the commonly used scales used to detect language function, requiring the research subjects to name 30 line drawings. The sensitivity of BNT to identify cognitive impairment is high, the sensitivity of identifying MCI is 61%, and the sensitivity of identifying mild to moderate AD is 79% and 95%, respectively, which is a reliable basis for AD diagnosis. The number of line drawings correctly spoken by the subjects was recorded as a BNT score.

(7) Animal Word Fluency (AFT): It mainly tests the semantic fluency of the research subjects, and asks the subjects to say as many names of animals as possible within 1 minute. Impairment of word fluency can be manifested in the early stages of AD, which is one of the important neuropsychological tools for the early diagnosis of AD. The number of animals named within 1 minute was recorded as the AFT score.

(8) Clock Drawing Experiment (CDT): a simple and easy-to-operate screening tool for evaluating visuospatial ability and executive function. This experiment adopts the rule of thirds, which is 1 point for correctly drawing a circular dial, 1 point for marking all numbers in the correct position, 1 point for 11:10 on the pointer.

(9) Clinical Dementia Rating Scale (CDR): published by Professor Hughes in 1982, the overall evaluation is obtained by evaluating the cognitive function and social life ability of the research subjects, mainly used for the classification and longitudinal changes of dementia severity assessment. According to the score of 0, 0.5, 1, 2 and 3, the subjects can be divided into no dementia, suspected dementia, mild dementia, moderate dementia and severe dementia.

(10) Geriatric Depression Scale (GDS): Created by Briink et al. in 1982, it is a depression screening scale specially used for the elderly, which can more sensitively reflect the unique somatic symptoms of elderly depressed patients, with a score of less than or equal to 10 A score of 11-20 indicates mild depression, a score of 21-25 indicates moderate depression, and a score of 26-30 indicates severe depression.

(11) Activities of Daily Living Scale (ADL): It was jointly compiled by American Lawton and Brody in 1969, including the Physical Self-care Scale and the Instrumental Activities of Daily Living Scale, which can provide a detailed and accurate understanding of the daily living ability of the research subjects. , when the score is greater than or equal to 26 points, it indicates that daily life is obviously affected, and it is widely used in scientific research work.

(12) Hachinski ischemia scale: When patients have memory loss, cognitive impairment on objective assessment, and reduced ability of daily living, this scale is usually used to distinguish vascular cognitive impairment from AD. Out of 12 points, vascular cognitive impairment can be considered when the score is greater than or equal to 4 points. The higher the score, the greater the possibility of vascular cognitive impairment.

(13) Comprehensive application of cognitive scales in the diagnosis of aMCI

②一般认知功能正常(MMSE≥24分，CDR＝0.5且CDR 记忆≥0.5)；③日常生活能力完整或仅轻度受损(ADL≤26分)；④Hachinski缺血评分量表<4分，GDS>11分。① There is objective memory impairment inconsistent with age (MoCA ≤ 24 points, after adjusting for age and education level

② Normal cognitive function (MMSE≥24 points, CDR=0.5 and CDR memory≥0.5); ③ Complete or only mild impairment of daily living activities (ADL≤26 points); ④Hachinski ischemia score <4 points, GDS>11 points.

2.1.3 Collection and processing of blood samples

Step 1: From 7:30am to 9:30am, on an empty stomach, 10ml of peripheral blood was drawn from the cubital vein, and a non-anticoagulated closed blood collection tube was placed. If severe hemolysis, lipemia, or turbidity occurred during sample collection, the sample was discarded.

Step 2: Centrifugation: rotate speed 3000rpm, time 10min, take the upper serum and distribute it in cryopreservation tubes, store in -80℃ refrigerator for future use, avoid repeated freezing and thawing.

Step 3: The samples should not be stored at room temperature for more than 8 hours after collection; if the samples are not processed within 8 hours, they should be placed in a refrigerator at 2-8°C; if they need to be stored for more than 48 hours, they should be frozen at -80°C . Place at room temperature for 10 min before use, shake gently to mix.

2.1.4 Specimen detection method

(1) Chemiluminescence method

①The detection of TT, SHBG, FSH and LH adopts chemiluminescence method, and the steps are as follows:

②Take out the sample from the -80℃ refrigerator, leave it at room temperature for 10min, and mix well;

③ Enter the test request screen from the main menu;

④Set a position on the sample rack for each sample, input the sample information and the name of the test to be detected;

⑤Put the sample tube into the set position in the sample rack;

⑥Press the run key to start the detection;

⑦ Automatically calculate the test results and make records.

(2) enzyme-linked immunosorbent assay

FT, DHT, DHEA and DHEA-S were detected by enzyme-linked immunosorbent assay. The steps are as follows:

①Take out the sample from the -80℃ refrigerator, leave it at room temperature for 10min, and mix well;

②Place the coated plate with the number of samples required for the experiment on the plate rack;

③ Add 20 μL of standard, quality control and sample to the corresponding microwells;

④ Add 100 μL of enzyme conjugate to each microwell, mix for 10s, and mix thoroughly;

⑤ 37 ℃ for 60 minutes;

⑥ Discard the reaction solution in the well, add 300 μL washing solution to each well, wash the plate 3 times, and pat dry on absorbent paper;

⑦ Add 100 μL of substrate solution to each microwell, and incubate at room temperature for 15 min in the dark;

⑧ Add 100 μL of stop solution to each microwell to stop the reaction;

⑨ Read the OD value at 450±10nm of the microplate reader within 10min after adding the stop solution.

2.2 Statistical methods

By constructing an equation model, fitting the ROC curve, and calculating the cutoff value, the laboratory reference value of androgen for the diagnosis of aMCI was obtained. Specific steps: refer to the results of univariate analysis comparing aMCI and NC, select statistically significant variables for further multivariate logistic regression analysis, obtain independent predictors of aMCI, and construct equations. Take the regression equation Logit(P) as the joint predictor L, and use L as the test variable to make the ROC curve to obtain the AUC value. The Cut Off value was determined by the Yuden Index, YI maximum method, YI=sensitivity+specificity-1. After that, the external verification method is used to make the ROC curve with L' as the test variable, and the verification AUC value and Cut Off value are obtained and compared with the model.

3 Experimental results

3.1 Multivariate logistic regression analysis for predicting aMCI risk

In the univariate analysis, it was found that there were differences in age, education level, FT and DHT between the NC group and the aMCI group. Therefore, the above 4 variables were used as independent variables, and Logitical regression analysis was performed, and it was found that only age, education level and FT entered in the end. equation. The result is that when the age is greater than 65 years old, the equation is Logit(P)=-1.660+0.070 age-0.210 education level-0.074FT, Table 2-1.

3.2 ROC curve and CUT OFF value for predicting aMCI risk

Take Logit(P) as the joint predictor L=-22.43+0.95age-2.84education-FT. The area under the curve of L was 0.722, and the cut-off value was 6.63. The specific results are shown in Table 2-2 and Figure 1. External validation of the constructed equation showed that the area under the curve for L' was 0.712 with a cutoff value of 4.91. Table 2-2 and Figure 2.

The use of substances in peripheral blood as biomarkers for AD diagnosis is a hot spot in AD research. In order to identify a marker as a diagnostic criterion for AD, it is necessary to formulate a corresponding diagnostic cut-off value and examine its sensitivity and accuracy as a predictive value. ROC analysis is currently recognized as the best method to measure the quality of diagnostic information and diagnostic decisions. It is a compromise between sensitivity and specificity corresponding to different thresholds. The diagnostic cutoff value (Cut Off value) was determined by the maximum method of the Youden Index (YI), YI=sensitivity+specificity-1. So far, many studies have used youden's index and ROC curve to detect the early predictive value of biomarkers such as Aβ, tau protein, miRNA and other markers for AD. The ROC curve is favored by many researchers because of its unique advantages. The ROC curve adopts an easily interpretable scale to give a more intuitive visual impression, and the sensitivity and specificity of different cut-off point values reflected by the curve are independent of the prevalence. .

The AUC value of the area under the ROC curve is a common indicator used to evaluate the pros and cons of a binary classification model. The value of AUC ranges between 0.5 and 1. The closer the AUC is to 1.0, the higher the authenticity of the detection method and the better the effect of the model; when it is equal to 0.5, the authenticity is the lowest and has no diagnostic value. Using the biological marker Aβ to predict the effect of AD alone, it was found that the AUC value was concentrated between 0.7-0.9, and the AUC value even exceeded 0.9 in the study using the specific and Aβ-binding technology, showing a high predictive value. . MiRNAs also have moderate predictive value for early screening of AD (0.79, 0.786, 0.82, 0.879), but the combined prediction of multiple miRNAs can significantly increase the prediction accuracy, hsa-miR-191, hsa-miR-101, hsa- The AUC value of miR-103 and hsa-miR-222 to distinguish MCI from healthy group reached 0.962, showing high predictive value.

Due to the close relationship between androgen and AD in elderly men, this study fitted the ROC curve using peripheral blood FT to diagnose aMCI in elderly men and performed external validation. The AUC values of the fitted model L and the validation model L' are both >0.7, indicating that the FT value has a moderate diagnostic value for aMCI in elderly men. The threshold value of L' is 4.91, which means that aMCI risk is considered when -22.43+0.95age-2.84education-FT≥4.91, that is, FT≤0.95age-2.84education-27.34. For example, in a 70-year-old man with 9 years of education, peripheral blood FT values were measured, and when FT ≤ 13.6 pg/mL, it suggested that there may be a risk of aMCI.

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.

Images