Today, I review, link to, and excerpt from The diagnosis of mild cognitive impairment due to Alzheimer’s disease: Recommendations from the National Institute on Aging-Alzheimer’s Association workgroups on diagnostic guidelines for Alzheimer’s disease [PubMed Abstract] [Full-Text HTML] [Full-Text PDF]. Alzheimers Dement. 2011 May;7(3):270-9. doi: 10.1016/j.jalz.2011.03.008. Epub 2011 Apr 21.
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- Abstract
- 1. Introduction
- 2. Core clinical criteria for the diagnosis of MCI
- 3. MCI—Research criteria incorporating biomarkers
- 4. Proposed terminology for classifying individuals with “MCI due to AD” with varying levels of certainty
- Acknowledgments
- Footnotes
- References
Abstract
The National Institute on Aging and the Alzheimer’s Association charged a workgroup with the task of developing criteria for the symptomatic predementia phase of Alzheimer’s disease (AD), referred to in this article as mild cognitive impairment due to AD. The workgroup developed the following two sets of criteria: (1) core clinical criteria that could be used by healthcare providers without access to advanced imaging techniques or cerebrospinal fluid analysis, and (2) research criteria that could be used in clinical research settings, including clinical trials. The second set of criteria incorporate the use of biomarkers based on imaging and cerebrospinal fluid measures. The final set of criteria for mild cognitive impairment due to AD has four levels of certainty, depending on the presence and nature of the biomarker findings. Considerable work is needed to validate the criteria that use biomarkers and to standardize biomarker analysis for use in community settings.
Keywords: Mild cognitive impairment, AD dementia, Diagnosis 1. Introduction
The National Institute on Aging and the Alzheimer’s Association convened a working group to revise the diagnostic criteria for the symptomatic predementia phase of Alzheimer’s disease (AD). Details of the selection and the charge to the working group are outlined in the Introduction to the revised criteria for AD that accompanies this article [1]. The present article summarizes the recommendations of the working group.
The working group was assembled because of growing consensus in the field that there is a phase of AD when individuals experience a gradually progressive cognitive decline that results from the accumulation of AD pathology in the brain. When the cognitive impairment is sufficiently great, such that there is interference with daily function, the patient is diagnosed with AD dementia. The dementia phase of AD is the topic of a separate working group report [2]. It is important to note that, as AD is a slow, progressive disorder, with no fixed events that define its onset, it is particularly challenging for clinicians to identify transition points for individual patients. Thus, the point at which an individual transitions from the asymptomatic phase to the symptomatic predementia phase [3], or from the symptomatic predementia phase to dementia onset, is difficult to identify [2]. Moreover, there is greater diagnostic uncertainty earlier in the disease process. It is, nevertheless, important to incorporate this continuum of impairment into clinical and research practice.
- 2.McKhann GM, Knopman DS, Chertkow H, Hyman BT, Jack CR, Jr, Kawas CH, et al. The diagnosis of dementia due to Alzheimer’s disease: recommendations from the National Institute on Aging–Alzheimer’s Association workgroups on diagnostic guidelines for Alzheimer’s disease. Alzheimers Dement. 2011;7:263–9. doi: 10.1016/j.jalz.2011.03.005. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 3.Sperling RA, Aisen PS, Beckett LA, Bennett DA, Craft S, Fagan AM, et al. Towards defining the preclinical stages of Alzheimer’s disease: recommendations from the National Institute on Aging–Alzheimer’s Association workgroups on diagnostic guidelines for Alzheimer’s disease. Alzheimers Dement. 2011;7:280–92. doi: 10.1016/j.jalz.2011.03.003. [DOI] [PMC free article] [PubMed] [Google Scholar]
In these recommendations, we use the term “mild cognitive impairment (MCI) due to AD” to refer to the symptomatic predementia phase of AD. This degree of cognitive impairment is not normal for age and, thus, constructs such as age-associated memory impairment and age-associated cognitive decline do not apply. From this perspective, MCI due to AD can be considered as a subset of the many causes of cognitive impairment that are not dementia (CIND), including impairments resulting from head trauma, substance abuse, or metabolic disturbance [4].
Thus, the concept of “MCI due to AD” is used throughout this article to reflect the fact that the ultimate focus of these criteria is to identify those symptomatic but nondemented individuals whose primary underlying pathophysiology is AD. Similar to AD dementia, MCI due to AD cannot be currently diagnosed by a laboratory test, but requires the judgment of a clinician. Thus, MCI is a syndrome defined by clinical, cognitive, and functional criteria [5,6]. Also, similar to AD dementia, etiologies in addition to AD pathophysiological processes may coexist in an individual who meets the criteria for MCI due to AD. Nevertheless, similar to the criteria proposed by the International Working Group of Dubois et al [7], these criteria assume that it is possible to identify those individuals with AD pathophysiological processes as the likely primary cause of their progressive cognitive dysfunction [8–10].
2. Core clinical criteria for the diagnosis of MCI
In this section, we outline the core clinical criteria for individuals with MCI. In considering the specifics of this clinical and cognitive syndrome, it is important to emphasize, as noted earlier in the text, that sharp demarcations between normal cognition and MCI and between MCI and dementia are difficult, and clinical judgment must be used to make these distinctions.
2.1. MCI—Criteria for the clinical and cognitive syndrome
2.1.1. Concern regarding a change in cognition
There should be evidence of concern about a change in cognition, in comparison with the person’s previous level. This concern can be obtained from the patient, from an informant who knows the patient well, or from a skilled clinician observing the patient.
2.1.2. Impairment in one or more cognitive domains
There should be evidence of lower performance in one or more cognitive domains that is greater than would be expected for the patient’s age and educational background. If repeated assessments are available, then a decline in performance should be evident over time. This change can occur in a variety of cognitive domains, including memory, executive function, attention, language, and visuospatial skills. An impairment in episodic memory (i.e., the ability to learn and retain new information) is seen most commonly in MCI patients who subsequently progress to a diagnosis of AD dementia. (See the section on the cognitive characteristics later in the text for further details).
2.1.3. Preservation of independence in functional abilities
Persons with MCI commonly have mild problems performing complex functional tasks which they used to perform previously, such as paying bills, preparing a meal, or shopping. They may take more time, be less efficient, and make more errors at performing such activities than in the past. Nevertheless, they generally maintain their independence of function in daily life, with minimal aids or assistance. It is recognized that the application of this criterion is challenging, as it requires knowledge about an individual’s level of function at the current phase of their life. However, it is noteworthy that this type of information is also necessary for the determination of whether a person is demented.
2.1.4. Not demented
These cognitive changes should be sufficiently mild that there is no evidence of a significant impairment in social or occupational functioning. It should be emphasized that the diagnosis of MCI requires evidence of intraindividual change. If an individual has only been evaluated once, change will need to be inferred from the history and/or evidence that cognitive performance is impaired beyond what would have been expected for that individual. Serial evaluations are of course optimal, but may not be feasible in a particular circumstance.
2.2. Cognitive characteristics of MCI
It is important to determine whether there is objective evidence of cognitive decline, and if so, the degree of this decline in the reports by the individual and/or an informant. Cognitive testing [results of a Google search] is optimal for objectively assessing the degree of cognitive impairment for an individual. Scores on cognitive tests for individuals with MCI [link is to Cognitive Tests and Performance Validity Tests] are typically 1 to 1.5 standard deviations below the mean for their age and education matched peers on culturally appropriate normative data (i.e., for the impaired domain(s), when available). It is emphasized that these ranges are guidelines and not cutoff scores.
2.2.1. Cognitive assessment
As noted earlier in the text, impairment in episodic memory (i.e., the ability to learn and retain new information) is most commonly seen in MCI patients who subsequently progress to a diagnosis of AD dementia. Research studies have shown that there are a variety of episodic memory tests that are useful for identifying those MCI patients who have a high likelihood of progressing to AD dementia within a few years. These tests share the characteristic that they assess both immediate and delayed recall, so that it is possible to determine retention over a delay. Many, although not all, of the tests that have proven useful in this regard are word-list learning tests with multiple trials. Such tests reveal the rate of learning over time, as well as the maximum amount acquired over the course of the learning trials. They are also useful for demonstrating that the individual is, in fact, paying attention to the task on immediate recall, which then can be used as a baseline to assess the relative amount of material retained on delayed recall. Examples of such tests include (but are not limited to): the Free and Cued Selective Reminding Test, the Rey Auditory Verbal Learning Test, and the California Verbal Learning Test. Other episodic memory measures include: immediate and delayed recall of a paragraph such as the Logical Memory I and II of the Wechsler Memory Scale Revised (or other versions) and immediate and delayed recall of nonverbal materials, such as the Visual Reproduction subtests of the Wechsler Memory Scale-Revised I and II.
Because other cognitive domains can be impaired among individuals with MCI, it is important to examine domains in addition to memory. These include: executive functions (e.g., set-shifting, reasoning, problem-solving, planning), language (e.g., naming, fluency, expressive speech, and comprehension), visuospatial skills, and attentional control (e.g., simple and divided attention). Many validated clinical neuropsychological measures are available to assess these cognitive domains, including (but not limited to): the Trail Making Test (executive function), the Boston Naming Test, letter and category fluency (language), figure copying (spatial skills), and digit span forward (attention). If formal cognitive testing is not feasible, then cognitive function can be assessed using a variety of simple, informal techniques. For example, the clinician can ask a patient to learn a street address and to recall it after a delay interval of a few minutes (e.g., John Brown, 42 Market Street, Chicago). Alternatively, the clinician can ask the patient to name three objects (e.g., a pen, a paper clip, and a dollar bill), place them in different locations around the room and subsequently ask the patient to recall the names of the objects and their locations, again after a brief delay. These types of approaches are relatively easy to perform during an office visit, and will yield informative results. It is important, however, for clinicians to recognize that these informal tests will likely be insensitive to subtle cognitive dysfunction during the early stages of MCI, and will often yield normal performance. In addition, these approaches typically do not assess cognitive domains beyond memory.
Finally, it must be recognized that atypical clinical presentations of AD may arise, such as the visual variant of AD (involving posterior cortical atrophy) or the language variant (sometimes called logopenic aphasia), and these clinical profiles are also consistent with MCI due to AD.
2.2.2. Summary of clinical and cognitive evaluation
The initiation of a clinical and cognitive evaluation typically includes a cognitive concern expressed by the patient, an informant, or a clinician observing the patient’s performance. Cognitive decline can be documented by means of the history from the patient, preferably corroborated by an informant, or on the basis of observation by the clinician. Ideally, if serial assessments are available, they would be preferable, but in the setting of a single evaluation, this information is inferred from the history. The patient’s cognition is assessed and found to be outside the normal range of function for the patient’s age and educational background, but not sufficiently impaired to constitute dementia. The impairment can involve one or more cognitive domains. The clinician determines whether memory is prominently impaired, or whether the impairments in other cognitive domains predominate, such as spatial or language impairment. Typically, memory is the most common domain involved among patients who subsequently progress to AD dementia, as noted earlier in the text. There is generally mild functional impairment for complex tasks, but basic activities of daily living should be preserved, and the person should not meet criteria for dementia. It should be noted that the clinical syndrome, as summarized in this section and Table 1, is almost identical to the one previously described by Petersen et al [5,6,11].
Table 1.
Summary of clinical and cognitive evaluation for MCI due to AD
Establish clinical and cognitive criteria Cognitive concern reflecting a change in cognition reported by patient or informant or clinician (i.e., historical or observed evidence of decline over time) Objective evidence of Impairment in one or more cognitive domains, typically including memory (i.e., formal or bedside testing to establish level of cognitive function in multiple domains) Preservation of independence in functional abilities Not demented Examine etiology of MCI consistent with AD pathophysiological process Rule out vascular, traumatic, medical causes of cognitive decline, where possible Provide evidence of longitudinal decline in cognition, when feasible Report history consistent with AD genetic factors, where relevant Abbreviations: AD, Alzheimer’s disease; MCI, mild cognitive impairment.
