THEMED ARTICLE y Alzheimer’s Disease
Review
Mild cognitive impairment Expert Rev. Neurother. 13(11), 1247–1261 (2013)
Craig Gordon1 and Daniel J Martin* 1 ST5 Old Age Psychiatry, NHS Greater Glasgow and Clyde, Glasgow, UK University of Glasgow, MHW, 1055 Great Western Road, Glasgow, UK *Author for correspondence: [email protected]
www.expert-reviews.com
Mild cognitive impairment is the term applied to the cognitive state that lies between normal aging and dementia. There has been significant controversy around describing, defining and characterizing mild cognitive impairment. This review will cover current understanding of the condition and discuss clinical features, research strategies and future directions. KEYWORDS: alzheimers • dementia • early identification • mental health • mild cognitive impairment
The use of MCI as a distinct clinical entity was established by Petersen and colleagues in their 1999 paper ‘Mild Cognitive Impairment: Clinical Characterization and outcome’ [1]. This was not the origin of the name, however, as MCI was originally described in the 1980s by the New York University group [2]. Prior to this a variety of candidate titles were put forward for significant cognitive decline, which does not meet operationalized criteria for dementia [3]. Benign senescent forgetfulness was suggested in 1962 by Kral [4], with numerous others being described in the years following, including aging-associated cognitive decline, age-associated memory impairment, late-life forgetfulness and cognitive impairment, no dementia [5]. Interestingly, each term was replaced by another with associated criteria that were felt to refine the vague nature of the previous terminology [6]. Petersen and colleagues outlined diagnostic criteria for the condition (FIGURE 1), which included abnormal memory for age as demonstrated by performance on cognitive tests at a level of 1.5 SD below age and education matched peers while having general neuropsychological test scores within 0.5 SD [1]. Despite the significant progress of the Peterson and colleagues paper, this definition of MCI was not universally held [7]. The diagnostic criteria were subsequently modified, shifting the emphasis from a specific memory complaint to that of a more general cognitive deficit (FIGURE 2) [8]. As well as broadening the criteria for MCI, further subcategories of the condition were introduced, which could be distinguished, for example, by ascertaining whether or not the patient had solely a memory complaint and determining if more than one cognitive domain
10.1586/14737175.2013.856265
was affected. This led to the subcategories of amnestic mild cognitive impairment (aMCI) and non-amnestic MCI (naMCI), both with single and multiple domain variants. Under this new system, the original term MCI was replaced by aMCI, single domain. The rationale behind this further classification was to address the diversity of potential underlying etiologies. If the clinician could identify the specific type of MCI in their patient they may be able to more accurately predict the underlying pathology [8]. The National Institute on Aging and the US based Alzheimer’s Association created a working group to further clarify diagnostic criteria for MCI occurring specifically due to Alzheimer’s disease (AD) [9]. These criteria do not differ greatly from those outlined earlier, the authors make reference to performance in memory testing, that is, 1.5 SD below the mean, stressing that no specific tests or cutoffs are recommended. However, one key difference is the relaxing of the criterion indicating full independence in activities of daily living (ADLs) [9]. In his 2012 article [10], Morris questions the recent proposed revision to the criteria put forward by Albert and colleagues, stating that by including the following description ‘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’, the distinction between MCI and early stage dementia may become difficult. This criticism is indirectly echoed by Petersen when he states that the distinction between MCI and dementia is whether or not the ability to carry out all ADLs is impaired [11]. Interestingly, this is not a new area of concern,
2013 Informa UK Ltd
ISSN 1473-7175
1247
Review
Gordon & Martin
MCI & its relation to dementia etiologies 1999 Criteria for MCI 1. Subjective memory complaint. 2. Retained independence in activities of daily living. 3. Criteria for dementia must not be met. 4. Abnormal memory for age, typically 1.5 SD below peers. 5. Normal general cognitive function.
Figure 1. 1999 criteria for mild cognitive impairment. Reproduced with permission from [1].
with research already undertaken in an attempt to resolve this issue. For example, a German group explored the ability of 45 MCI patients to perform ADLs as measured using a validated instrument, against that of 30 matched controls [12]. They identified that cases scored significantly lower on the ‘Alzheimer’s disease Cooperative Study scale for ADL in MCI’, which suggests that in MCI as defined by the Mayo criteria, there is an impairment in the ability to manage ADLs independently. The authors suggest that, due to a grading of cognitive ability required for completion of increasingly complex ADLs, it makes logical sense that a more demanding activity, such as managing finances, will be more adversely affected by MCI than a more basic task, for example, dressing oneself [12]. The authors conclude by reasoning that assessment of complex ADLs is valuable in the assessment of MCI. Diagnostic criteria for the condition are still evolving, with the recent development of early MCI (eMCI), late MCI (lMCI) and subjective memory impairment (SMI) being explored in an attempt to identify earlier disease identification [13]. Indeed, the Alzheimer’s Disease Neuroimaging Initiative (ADNI) group, a large body exploring all aspects of AD research, received a ‘Grand Opportunities’ grant to investigate eMCI (defined as cognitive impairment 0.5 SD below the mean), with the hypothesis being that this research would allow them to identify disease presence at the earliest possible stage [14]. Further to this, Jessen and colleagues in a German longitudinal study have examined the outcomes over 6 years for patients who fall into each of the categories of SMI, eMCI and lMCI. They found that there was a stepwise increase in progression to dementia rates with SMI
Review
Mild cognitive impairment Expert Rev. Neurother. 13(11), 1247–1261 (2013)
Craig Gordon1 and Daniel J Martin* 1 ST5 Old Age Psychiatry, NHS Greater Glasgow and Clyde, Glasgow, UK University of Glasgow, MHW, 1055 Great Western Road, Glasgow, UK *Author for correspondence: [email protected]
www.expert-reviews.com
Mild cognitive impairment is the term applied to the cognitive state that lies between normal aging and dementia. There has been significant controversy around describing, defining and characterizing mild cognitive impairment. This review will cover current understanding of the condition and discuss clinical features, research strategies and future directions. KEYWORDS: alzheimers • dementia • early identification • mental health • mild cognitive impairment
The use of MCI as a distinct clinical entity was established by Petersen and colleagues in their 1999 paper ‘Mild Cognitive Impairment: Clinical Characterization and outcome’ [1]. This was not the origin of the name, however, as MCI was originally described in the 1980s by the New York University group [2]. Prior to this a variety of candidate titles were put forward for significant cognitive decline, which does not meet operationalized criteria for dementia [3]. Benign senescent forgetfulness was suggested in 1962 by Kral [4], with numerous others being described in the years following, including aging-associated cognitive decline, age-associated memory impairment, late-life forgetfulness and cognitive impairment, no dementia [5]. Interestingly, each term was replaced by another with associated criteria that were felt to refine the vague nature of the previous terminology [6]. Petersen and colleagues outlined diagnostic criteria for the condition (FIGURE 1), which included abnormal memory for age as demonstrated by performance on cognitive tests at a level of 1.5 SD below age and education matched peers while having general neuropsychological test scores within 0.5 SD [1]. Despite the significant progress of the Peterson and colleagues paper, this definition of MCI was not universally held [7]. The diagnostic criteria were subsequently modified, shifting the emphasis from a specific memory complaint to that of a more general cognitive deficit (FIGURE 2) [8]. As well as broadening the criteria for MCI, further subcategories of the condition were introduced, which could be distinguished, for example, by ascertaining whether or not the patient had solely a memory complaint and determining if more than one cognitive domain
10.1586/14737175.2013.856265
was affected. This led to the subcategories of amnestic mild cognitive impairment (aMCI) and non-amnestic MCI (naMCI), both with single and multiple domain variants. Under this new system, the original term MCI was replaced by aMCI, single domain. The rationale behind this further classification was to address the diversity of potential underlying etiologies. If the clinician could identify the specific type of MCI in their patient they may be able to more accurately predict the underlying pathology [8]. The National Institute on Aging and the US based Alzheimer’s Association created a working group to further clarify diagnostic criteria for MCI occurring specifically due to Alzheimer’s disease (AD) [9]. These criteria do not differ greatly from those outlined earlier, the authors make reference to performance in memory testing, that is, 1.5 SD below the mean, stressing that no specific tests or cutoffs are recommended. However, one key difference is the relaxing of the criterion indicating full independence in activities of daily living (ADLs) [9]. In his 2012 article [10], Morris questions the recent proposed revision to the criteria put forward by Albert and colleagues, stating that by including the following description ‘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’, the distinction between MCI and early stage dementia may become difficult. This criticism is indirectly echoed by Petersen when he states that the distinction between MCI and dementia is whether or not the ability to carry out all ADLs is impaired [11]. Interestingly, this is not a new area of concern,
2013 Informa UK Ltd
ISSN 1473-7175
1247
Review
Gordon & Martin
MCI & its relation to dementia etiologies 1999 Criteria for MCI 1. Subjective memory complaint. 2. Retained independence in activities of daily living. 3. Criteria for dementia must not be met. 4. Abnormal memory for age, typically 1.5 SD below peers. 5. Normal general cognitive function.
Figure 1. 1999 criteria for mild cognitive impairment. Reproduced with permission from [1].
with research already undertaken in an attempt to resolve this issue. For example, a German group explored the ability of 45 MCI patients to perform ADLs as measured using a validated instrument, against that of 30 matched controls [12]. They identified that cases scored significantly lower on the ‘Alzheimer’s disease Cooperative Study scale for ADL in MCI’, which suggests that in MCI as defined by the Mayo criteria, there is an impairment in the ability to manage ADLs independently. The authors suggest that, due to a grading of cognitive ability required for completion of increasingly complex ADLs, it makes logical sense that a more demanding activity, such as managing finances, will be more adversely affected by MCI than a more basic task, for example, dressing oneself [12]. The authors conclude by reasoning that assessment of complex ADLs is valuable in the assessment of MCI. Diagnostic criteria for the condition are still evolving, with the recent development of early MCI (eMCI), late MCI (lMCI) and subjective memory impairment (SMI) being explored in an attempt to identify earlier disease identification [13]. Indeed, the Alzheimer’s Disease Neuroimaging Initiative (ADNI) group, a large body exploring all aspects of AD research, received a ‘Grand Opportunities’ grant to investigate eMCI (defined as cognitive impairment 0.5 SD below the mean), with the hypothesis being that this research would allow them to identify disease presence at the earliest possible stage [14]. Further to this, Jessen and colleagues in a German longitudinal study have examined the outcomes over 6 years for patients who fall into each of the categories of SMI, eMCI and lMCI. They found that there was a stepwise increase in progression to dementia rates with SMI
