ADNI-subject-Info

生物标记物

β-淀粉样蛋白

β-淀粉样蛋白（amyloid β-protein，Aβ）分子量约4kDa，由β淀粉样前体蛋白(β-amyloid precursor protein,APP)水解而来，由细胞分泌，在细胞基质沉淀聚积后具有很强的神经毒性作用。

Aβ 对神经元的作用与其状态有关。溶解状态的 Aβ 在短时间内可促使神经突生长，提高神经元的存活率，而沉积状态的 Aβ 对神经元呈现相反的作用，引起与阿尔茨海默病相似的病理变化———神经突退缩和神经元变性，最显著地改变发生在衰老的哺乳类动物大脑 。

• CSF Aβ：即脑脊液（CSF）中β-淀粉样蛋白（Aβ）检测量

综合目前研究结果，至少可以推测 AD 发病早期血浆 Aβ42 的减低反映了淀粉样蛋白在脑内的沉积。与血液学结果相同，AD 患者脑脊液 Aβ42 普遍减低。综合目前包括 2 000 余患者及健康对照的数十个临床研究发现，50% 的 AD患者中存在 Aβ42 的减低，其诊断 AD 的敏感性及特异性在 80%~90% 之间 ，各年龄段的健康对照中 Aβ42 绝对浓度均高于 500 pg/mL。由于脑脊液 Aβ 水平存在每日显著波动，故今后或许有必要将这一因素加以考虑以提高标准性。

脑脊液中Aβ水平出现异常可比认知能力下降的发现提前好几年，同阿尔茨海默病的情况相呼应，后者的病理性淀粉样蛋白同样早于临床症状多年。尤其，脑脊液Aβ水平“正常”的患者5年内发展为痴呆的风险很低。

Tau蛋白

Tau蛋白为含磷酸基蛋白，正常成熟脑中Tau蛋白分子含2～3个磷酸基。而阿尔茨海默症（老年痴呆症）患者脑的Tau蛋白则异常过度磷酸化，每分子Tau蛋白可含5～9个磷酸基，并丧失正常生物功能。

• CSF TAU

在神经变性过程中，tau 蛋白和水溶性磷酸化 tau 蛋白 (phosphorylated tau protein, p-tau) 可通过病变神经元的细胞膜进入脑脊液中，故定量测定脑脊液中上述两种物质水平有助于神经退行性疾病的诊断，目前已是较为成熟的生物学标记物。研究显示，中重度 AD 患者脑脊液中 tau 蛋白水平较正常对照明显升高，且这一指标的升高早于临床痴呆症状的出现，提示其可用于 AD 的预测。

AD患者血浆、脑脊液（CSF）中Tau蛋白测定可用酶联免疫吸附法（ELISA），研究表明AD患者CSF中Tau蛋白水平比同龄正常及非神经疾病患者组均显著增高。用CSF中Tau蛋白含量增高诊断AD，其敏感性为82%，特异性达70%。如同时测出CSF中Tau蛋白水平增加及β-AP42水平降低，对AD诊断的特异性可达70%～90%。

• CSF PTAU：脑脊液 磷酸化TAU

在阿尔茨海默病发病机制中，Aβ异常沉积被认为是神经元变性的上游反应；tau 蛋白过磷酸化则为 Aβ神经毒性的下游反应，脑脊液总 tau 蛋白和（或）磷酸化 tau 蛋白表达升高提示神经元死亡。

APOE4

NPAPOE – Apolipoprotein-E 载脂蛋白E – 1=e3,e3; 2=e3,e4; 3= e3,e2; 4=e4,e4; 5=e4,e2; 6=e2,e2; 9=Missing/Unknown/Not Assessed

有些基因或环境因素仍可能是罹患此病的危险因子。最著名的基因危险因子是载脂蛋白E（APOE）的ε4等位基因[45][46]，约有40%到80%的病患带有至少一个APOEε4等位基因[46]，其中异型合子的个体罹患风险增加3倍，而同型合子则增加15倍[40]。然而，环境或基因造成的影响并不一定会完全表现出来。举例来说，不同于其他族群，部分尼日利亚族群罹患阿尔茨海默病的几率和发病年龄与其是否带有APOEε4没有相关[47][48]。

现有数据证实携带 ApoEε4 等位基因者由 MCI进展至 AD 的风险较高。但对于 AD 的诊断和鉴别诊断，ApoE 基因型的敏感性与特异性均不高，提示其不适于用作预测 MCI 向 AD 进展的诊断性指标，其基因型测定亦不推荐用作AD 的常规临床检测或非 AD 患者的预测性检查 ；但由于 ApoEε4等位基因可影响脑脊液中主要 AD 生物学标记物如Aβ、tau、p-tau 等的水平，故在 AD 的研究方面仍有其潜在价值。

ApoE 蛋白在 AD 患者血液中的浓度变化目前尚存在争议，综合现有相关研究，其升高 、减低或与对照无显著差异均有报道。而ApoEε3 和 ApoEε4 杂合子中两种血浆蛋白比值也与AD 的诊断无相关性。由于上述结果的异质性，ApoE 蛋白水平目前尚不推荐用于诊断性试验。而ApoEε4 等位基因并非发生 AD 的必要条件或充分条件，也不能单独用以诊断 AD。

参考

* 阿尔茨海默病相关核心生物标志物研究进展 2014年1月
* 脑脊液生物学标志物在阿尔茨海默病早期诊断中的作用 2014年4月
* ADNI Biostatistics FROM HELP & FAQS

显影剂

FDG

氟代脱氧葡萄糖是2-脱氧葡萄糖的氟代衍生物。其完整的化学名称为2-氟-2-脱氧-D-葡萄糖，通常简称为18F-FDG或FDG。FDG最常用于正电子发射断层扫描（PET）类的医学成像设备：FDG分子之中的氟选用的是属于正电子发射型放射性同位素的氟-18（fluorine-18，F-18，18F，18氟），从而成为18F-FDG（氟-[18F]脱氧葡糖）。在向病人（患者，病患）体内注射FDG之后，PET扫描仪可以构建出反映FDG体内分布情况的图像。接着，核医学医师或放射医师对这些图像加以评估，从而作出关于各种医学健康状况的诊断。

AV45

针对阿尔茨海默病两大核心标志物的检测（Aβ和 tau 蛋白）而开发的淀粉样蛋白显像剂 AV⁃45 已正式通过美国食品与药品管理局（FDA）批准

Florbetapir（18F）（商品名AMYViD;也称为florbetapir-fluor-18或18F-AV-45）是一种含有放射性核素氟-18的PET扫描放射性药物化合物，于2012年被FDA批准作为阿尔茨海默病的诊断工具。[1] [2] [3] [4] 与匹兹堡化合物B（ Pittsburgh compound B，PiB）一样，Florbetapir与β-淀粉样蛋白结合，但是氟-18的半衰期为109.75分钟，而PiB的放射性半衰期为20分钟。 Wong等人。 研究发现，较长的生命使示踪剂在AD患者的大脑中积累得更多，特别是在已知与β-淀粉样沉积物相关的区域。

临床信息

临床痴呆评分框Clinical Dementia Rating Sum of Boxes, CDRSB

临床痴呆评定或CDR是用于量化痴呆症状严重性（即其“阶段”）的数字量表。医疗专业人员在六个方面评估患者的认知和功能表现：记忆，方向， 评判和解决问题，社区事务，家庭和爱好以及个人护理。 将这些中的每一个中的得分组合以获得0到3的综合得分。

Composite Rating 综合评级	Symptoms 症状
0	none
0.5	very mild
1	mild
2	moderate
3	severe

CDR被认为能够识别非常轻微的损伤，但其缺点包括管理所需的时间，最终依赖于主观评估，以及相对无法随时间捕捉变化。虽然评估最终具有主观性，但最近的研究表明，评估者的可靠性非常高。因此，CDR似乎是评估和分期痴呆的可靠而有效的工具。

认知评估量化表

The Alzheimer’s Disease Assessment Scale–Cognitive Subscale (ADAS-Cog)

ADAS11

ADAS13

ADASQ4

Summary of ADAS-cog tasks

Task	Description	Scoring
Word Recall	A list of 10 words is read by the subject, and then the subject is asked to verbally recall as many of the words as possible. Three trials of reading and recalling are performed.	Mean number of words not recalled across the three trials; scoring range is 0 to 10.
Naming Objects and Fingers	The subject is asked to name the fingers of their dominant hand as well as twelve objects: flower (plastic), bed (doll house furniture), whistle, pencil, rattle, mask, scissors, comb, wallet, harmonica, stethoscope, and tongs.	The number of fingers and objects correctly named; scoping range is 0 to 4.
Commands	The subject is asked to perform commands that involve one to five steps. For example, the two-step command is to “Point to the ceiling, then to the floor.”	Scored from 0 to 5 based on the largest number of steps that are correctly performed (score is 0 if five step command is correctly performed).
Constructional Praxis	The subject is shown four geometric forms (circle, two overlapping rectangles, rhombus, cube) and asked to copy them on a piece of paper.	Scored from 0 to 5 based on the number of correctly drawn forms.
Ideational Praxis	The subject is asked to pretend to send a letter to themselves: fold letter, put letter in envelope, seal envelope, address envelope, and put a stamp on the envelope.	Scored from 0 to 5 based on difficulty of performing the five components.
Orientation	The subject is asked the date, month, year, day of the week, season, time of day, place, and person.	The number of correct responses; scoring range is 0 to 8.
Word Recognition	The subject reads twelve words aloud, and then these twelve words are randomly shuffled with twelve new words, and the subject is asked whether they have previously seen each of the twenty-four words. Three trials are performed.	Mean number of correct responses across the three trials; scoring range is 0 to 12.
Language	After the administration of the Word Recall task (Q1) ten minutes of open-ended conversation occur between the test administrator and subject, before the remainder of the tasks are presented. These ten minutes of conversation are used to assess language ability.	Quality of speech is given a global rating by the administrator that ranges from 0 to 5.
Comprehension of Spoken Language	This task also relies on the ten minutes of open-ended conversation. The administrator provides an assessment of how well the subject can understand speech.	The administrator provides a score from 0 to 5.
Word Finding Difficulty	During the aforementioned open-ended conversation, the administrator assesses how much difficulty the subject has in finding desired words.	The administer provides a score from 0 to 5.
Remembering Test Instructions	The administrator provides an assessment according to the number of times that the subject needed to be reminded of instructions for the Word Recognition task.	The administrator provides a score from 1 to 5.

简易精神状态检查表MMSE

简易精神状态量表或称简易精神状态检查表(Mini-Mental State Examination，MMSE)由Folstein(1975)等人编制，是最具影响的标准化智力状态检查工具之一，其作为认知障碍检查方法，可以用于阿尔茨海默病的筛查，简单易行。检查表详情

听觉言语学习测试

Rey Auditory Verbal Learning Test (RAVLT)

RAVLT_immediate

RAVLT_learning

RAVLT_forgetting

RAVLT_perc_forgetting

逻辑记忆 - 延迟调用LDELTOTAL

Rey听觉言语学习测试（RAVLT）评估各种各样的功能：短期听觉 - 言语记忆（short-term auditory-verbal memory），学习速度（rate of learning），学习策略（learning strategies），追溯和主动干扰（retroactive, and proactive interference），存在过程中混淆的混乱（presence of confabulation of confusion in memory processes），信息的保留（retention of information）， 学习和检索之间的差异（differences between learning and retrieval）。

参与者将获得在五个不同试验中重复的15个不相关单词的列表，并被要求重复。 给出了15个不相关单词的另一个列表，并且客户端必须再次重复15个单词的原始列表，然后在30分钟后再次重复。 该程序需要大约10至15分钟（不包括30分钟的间隔）。

RAVLT评估口头学习和记忆。 审查员以每秒一个的速度朗读15个单词的列表。 然后要求参与者重复他/她能记住的列表中的所有单词。 该程序共进行五次。 然后，审查员提供15个单词的第二个列表，允许参与者只有一次尝试召回这个新列表。 紧随其后，要求参与者记住第一个列表中尽可能多的单词。 在延迟20分钟后，再次要求参与者从第一个列表中回忆尽可能多的单词。 然后，参与者读取单词列表并询问每个单词是否来自第一个列表。 事实证明，RAVLT在评估言语学习和记忆方面很有用，包括主动抑制，追溯抑制，保留，编码与检索和主观组织。

日常认知测试参与者报告

• Everyday Cognition - Participant Self-Report

记忆 EcogPtMem (1…4)

1. Remembering a few shopping items without a list.
2. Remembering things that happened recently (such as recent outings, events in the news).
3. Recalling conversations a few days later.
4. Remembering where I have placed objects.
5. Repeating stories and/or questions.
6. Remembering the current date or day of the week.
7. Remembering I have already told someone something.
8. Remembering appointments, meetings, or engagements.

语言 EcogPtLang (1…4)

1. Forgetting the names of objects.
2. Verbally giving instructions to others.
3. Finding the right words to use in conversations.
4. Communicating thoughts in a conversation.
5. Following a story in a book or on TV.
6. Understanding the point of what other people are trying to say.
7. Remembering the meaning of common words.
8. Describing a program I have watched on TV.
9. Understanding spoken directions or instructions.

行动 EcogPtVisspat (1…4)

1. Following a map to find a new location.
2. Reading a map and helping with directions when someone else is driving.
3. Finding my car in a parking lot.
4. Finding my way back to a meeting spot in the mall or other location.
5. Finding my way around a familiar neighborhood.
6. Finding my way around a familiar store.
7. Finding my way around a house visited many times.

计划性思考 EcogPtPlan (1…4)

1. Planning a sequence of stops on a shopping trip.
2. The ability to anticipate weather changes and plan accordingly (i.e., bring a coat or umbrella)
3. Developing a schedule in advance of anticipated events.
4. Thinking things through before acting.
5. Thinking ahead.

器官 EcogPtOrgan (1…4)

1. Keeping living and work space organized.
2. Balancing the checkbook without error.
3. Keeping financial records organized.
4. Prioritizing tasks by importance.
5. Keeping mail and papers organized.
6. Using an organized strategy to manage a medication schedule involving multiple medications.

协同注意力 EcogPtDivatt (1…4)

1. The ability to do two things at once.
2. Returning to a task after being interrupted.
3. The ability to concentrate on a task without being distracted by external things in the environment.
4. Cooking or working and talking at the same time.

合计 EcogPtTotal (1…4)

日常认知测试研究报告

记忆 EcogSPMem (1…4)

1. Remembering a few shopping items without a list.
2. Remembering things that happened recently (such as recent outings, events in the news).
3. Recalling conversations a few days later.
4. Remembering where he/she has placed objects.
5. Repeating stories and/or questions.
6. Remembering the current date or day of the week.
7. Remembering he/she has already told someone something.
8. Remembering appointments, meetings, or engagements.

语言 EcogSPLang (1…4)

1. Forgetting the names of objects.
2. Verbally giving instructions to others.
3. Finding the right words to use in conversations.
4. Communicating thoughts in a conversation.
5. Following a story in a book or on TV.
6. Understanding the point of what other people are trying to say.
7. Remembering the meaning of common words.
8. Describing a program he/she has watched on TV.
9. Understanding spoken directions or instructions.

行为 EcogSPVisspat (1…4)

1. Following a map to find a new location.
2. Reading a map and helping with directions when someone else is driving.
3. Finding one’s car in a parking lot.
4. Finding my way back to a meeting spot in the mall or other location.
5. Finding his/her way around a familiar neighborhood.
6. Finding his/her way around a familiar store.
7. Finding his/her way around a house visited many times.

计划性思考 EcogSPPlan (1…4)

1. Planning a sequence of stops on a shopping trip.
2. The ability to anticipate weather changes and plan accordingly (i.e., bring a coat or umbrella)
3. Developing a schedule in advance of anticipated events.
4. Thinking things through before acting.
5. Thinking ahead.

器官 EcogSPOrgan (1…4)

1. Keeping living and work space organized.
2. Balancing the checkbook without error.
3. Keeping financial records organized.
4. Prioritizing tasks by importance.
5. Keeping mail and papers organized.
6. Using an organized strategy to manage a medication schedule involving multiple medications.

协同注意力 EcogSPDivatt (1…4)

1. The ability to do two things at once.
2. Returning to a task after being interrupted.
3. The ability to concentrate on a task without being distracted by external things in the environment.
4. Cooking or working and talking at the same time.

合计 EcogSPTotal (1…4)

MRI场强 FLDSTRENG

• Field Strength: 1.5=1.5T MRI;3=3T MRI

DIGITSCOR

• Digit Symbol Substitution

mPACCdigit

• ADNI modified Preclinical(临床前) Alzheimer’s Cognitive Composite 认知综合症 (PACC) with Digit Symbol Substitution

线索B- mPACCtrailsB

• ADNI modified Preclinical Alzheimer’s Cognitive Composite (PACC) with Trails B

MOCA