Clinical Concept Heterogeneity of Mild Cognitive Impairment

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MCI was proposed as a nosological entity referring to elderly people with mild cognitive deficit but no dementia. In the first criteria for MCI, which were proposed by Petersen et al in 1997 [20] and 1999 [14], the emphasis was on the compulsory presence of memory problems and memory disorders, implying that cases of MCI represented a fairly uniform group of subjects. The criteria for MCI included as follows: memory complaints of the subject (corroborated by an informant), objective memory disorders considering age, absence of other cognitive disorders, intact basic activities of daily living, and absence of dementia. This concept of MCI made it possible to define a group of patients at high risk of developing dementia, particularly Alzheimer-type dementia. This definition of MCI, however, has been criticized for being tautological: in fact when the concept of MCI is restricted to memory disorder only, defined on the basis of tests generally used for the early diagnosis of AD, it probably leads to the identification of people at a high risk of progression to AD.

As studies of nondemented cognitively impaired individuals expanded, it also became clear that there were considerable numbers of subjects whose memory impairment was the predominant but not the only cognitive problem that could be seen. Many individuals with mild cognitive impairment that evolved to AD were slightly impaired also in domains such as language or executive functions in addition to memory. Likewise, individuals were found whose primary cognitive impairment was in domains other than memory (e.g. spatial skill or attention).

The different clinical presentations of patients commonly observed in clinical contexts led Petersen et al to propose an extension of the concept in 2001 [21], and in 2004 [22], considering a syndrome-type classification, based on the clinical evaluation and associated to different outcomes. Based on whether predominant memory impairment was present or not, two primary subtypes were delineated: amnestic and non-amnestic MCI [22]. The revised criteria also acknowledged the possibility that more than one cognitive domain might be impaired within each of these subtypes (e.g. amnestic MCI, single or multiple domains impaired). These revised criteria are conceptually similar to CIND concept, as they include a broad range of cognitive deficits caused by multiple etiologies. In this context, the original clinical criteria for MCI were clearly focused on amnestic MCI, and it was demonstrated that amnestic MCI subjects (single or multiple domain impaired) are at increased risk of progressing to AD over time, whereas single-domain non-memory MCI, characterized by impairment of a cognitive domain other than memory, are thought to be the transitional phase between normal aging and other dementias such as vascular dementia, Frontotemporal Lobar Degeneration, Lewy body dementia and focal atrophy, or psychiatric disorders such as depression.

Another important source of heterogeneity in MCI clinical concept, both in its severity and nature, is the setting in which subjects are studied: the broader is the inclusion in a study, the higher is the probability to include individuals with less severe underlying disease: studies emerging from memory clinics in tertiary care settings report the highest proportion of individuals who progress to AD over time [23], whereas studies that recruit broadly from community are likely to have much lover rates of conversion to AD on follow-up [24].

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