Mild Cognitive Impairment (MCI) is a research term proposed to denote a transitional stage between the cognitive changes of normal ageing and early dementia or Alzheimer’s disease (Winblad et al., 2004; Petersen, 2004). Mild cognitive impairment manifests by presenting as cognitive impairment which is abnormal for age with preserved activities in daily living, but does not meet the criteria for dementia (Gauthier et al., 2006; Petersen, 2007). The memory loss is subtle and formal psychometric testing is needed to measure the decline. This occurs once the patient (or a reliable informant) has complained about their memory. The concept of MCI has
recently emerged as an important clinical entity, which has been proposed for entry into the DSM-V (Petersen and O’Brien, 2006).
Whilst many reports acknowledge MCI as a transitional stage between normal ageing and dementia (e.g., Allegri et al., 2008; Burns and Zaudig, 2002; Mariani et al., 2007; Orgogozo, 2006), not all accept MCI as a risk factor for dementia. Some reports indicate that MCI identifies subjects who already have the disease in the prodrome stage (Morris, 2006). Other reports describe MCI as a predementia stage which inevitably leads to Alzheimer’s disease (e.g., Orgozozo, 2006).
The prevalence of MCI varies considerably and has been reported to be as high as 65% per year (Busse et al., 2006) in different studies. It has been estimated that patients with MCI progress to dementia at inconsistent rates, ranging anywhere from 10% to 15% per year (Luis et al., 2003) compared to healthy elderly who progress to dementia at a rate of 1 to 2%
per annum (Petersen et al., 2001). In a clinical setting, Gabryelewicz et al.
(2007) reported an annual progression rate of 7.3%. The variability in outcome has been attributed to many factors including, age of subjects, inconsistent application of the criteria, use of different tests to define impairment, different follow-up time periods, different entry levels and study setting. All of these factors vary widely between studies (Bondi et al., 2008;
Small et al., 2007).
The working group of Winblad et al. (2004) revised the criteria for MCI to acknowledge non-amnestic presentations which may occur in the preclinical stage (Ribero et al., 2006; Ringman, 2005). The clinical syndrome
of MCI was divided into two broad subtypes: amnestic MCI (aMCI) characterized by the presence of isolated memory impairment, and non-amnestic MCI (naMCI) in which other cognitive functions rather than memory are mostly impaired (Winblad et al., 2004). The general criteria for MCI are provided in Table 3.1.
Table 3.1. General criteria for Mild Cognitive Impairment (MCI) a. Absence of dementia according to DSM-IV or ICD-10
b. Self and/or informant reported cognitive decline c. Impairment on cognitive tasks, and
d. preserved basic activities of daily living or minimal impairment in complex instrumental function
Adapted from Winblad et al. (2004).
Mild cognitive impairment (MCI) was divided further into three categories; i) single non memory domain MCI, with isolated impairment of a cognitive domain other than memory; ii) multiple domain amnestic MCI, characterised by a slight impairment of multiple cognitive domains including memory; and iii) multiple domains non amnestic MCI, with a slight impairment of multiple cognitive domains but without memory deficits (Petersen, 2007).
In terms of risk factors for Alzheimer’s disease, there is consensus that aMCI represents the highest risk subtype and is described as the ‘AD prodrome’ (Gauthier et al., 2006; Lehrner et al., 2005). This supports the hypothesis that isolated memory loss favours a diagnosis of Alzheimer’s
disease (Bowen et al., 1987; Petersen et al., 2001). However, one report indicated that there was no distinction between the two and that amnestic MCI is really just early Alzheimer’s disease (Bruscoli and Lovestone, 2004).
Likewise, some consider mdMCI to represent a more advanced stage of the AD prodrome (Alexopolous et al., 2006) and therefore greater risk. By contrast, the cognitive prognosis of the multiple domains MCI and single domain non-amnestic MCI subtypes appear more varied. These include;
normal ageing, vascular dementia, frontotemporal dementia, dementia with Lewy body dementia, primary progressive aphasia or Alzheimer’s disease (Guarch et al., 2008; Levey et al., 2006; Small et al., 2007).
Mild cognitive impairment is a highly debated concept that has been challenged on several grounds (e.g., Visser, 2007). The primary issue relates to MCI as a risk factor for Alzheimer’s disease. Mild cognitive impairment is perceived to have poor predictive validity for Alzheimer’s disease (e.g., Visser et al., 2006; Whitehouse et al., 2006). Research on MCI has shown that none of the MCI subtypes necessarily progress to Alzheimer’s disease, but many remain stable or even improve their cognitive performance (e.g., Ganguli et al., 2004; Ganguli, 2006; Palmer et al., 2003;
Perri et al., 2007; Visser et al., 2006).
Furthermore, there is no universally accepted approach to the objective identification cognitive impairment or agreement on the degree of objective impairment necessary to constitute decline. There is also confusion on how to define ‘minimal impairment’ or alterations in instrumental activities of daily living (Hodges, 2006). All of these factors
influence outcome. The inclusion of SMC in the criteria that define MCI is also disputed, and this is discussed in Section 3.4.
Despite ongoing controversies, MCI represents a step towards early diagnosis of Alzheimer’s disease and the possibility of earlier therapeutic treatment of symptoms. It provides some indication of the boundary between normal ageing and dementia. Currently, MCI is hindered by the inconsistent application of the criteria, lack of consensus regarding the tests used to measure cognitive impairment and the role of SMC. A consensus on these issues may improve sensitivity and therefore prediction. Also, the issues surrounding memory complaints need to be resolved before MCI can be accepted into the DSM-V as a clinical syndrome. Thus, the challenge which remains for MCI is to consistently identify high-risk individuals with MCI who will progress to a dementia of the Alzheimer’s type and other dementias from those who will not. It is also important to achieve a consensus regarding the criteria included in the diagnosis of MCI (Levey et al., 2006; Touchon, 2006). This will pave the way for the early diagnosis of Alzheimer’s disease and allow identification of subjects with high or ultra high risk. This will enable the development of strategies for early intervention.