The prevalence of MCI and its subtypes varies greatly from one study to another, ranging from 3% to around 17% of elderly people (> 65 years).8
These data largely depend on the diagnostic criteria used and on the type of cohort studied (longitudinal follow‐up of cohorts or memory clinic cohorts). Early studies included amnestic MCI, whereas the more recent studies refer to the wider concept of MCI. Epidemiological studies suggest that the progression of MCI is heterogeneous, and may be reversible, stable or progress to dementia.8,9,10,11,12
Dementia thus usually corresponds to the Alzheimer type.13,14,15
Studies also maintain the heterogeneity of the associated factors. Cerebrovascular factors or psychiatric disorders in particular are commonly observed.
The criteria corresponding to memory problems and absence of repercussions on daily life may be too restrictive, resulting in the underestimation of the prevalence of MCI.16
Lastly, a low positive predictive value of the subtypes of MCI has been recently reported, suggesting that the subtype classification of MCI is of limited clinical relevance.17
The diagnosis of MCI and its subtypes, however, was based on psychometric definitions and not in combination with clinical judgement.
Neuropsychological aspects of the classification of MCI are currently the most poorly defined. Objective cognitive impairment must be diagnosed on the basis of evidence, but no limits have been proposed or should be strictly applied on an individual basis. The diagnosis is made by the doctor. Evaluation by a neuropsychological expert may complete the clinical procedure. Emphasis has recently been placed on the importance of both the doctor's role and clinical judgement.5
The choice of evaluation method varies greatly from one study to another, depending on the type of population analysed (patients originating from specialist consultations or cohorts) and also on the objectives of the study. “All‐purpose” consensus‐based or reference batteries currently do not exist. Measures that were used previously, although imperfect, are those with which neuropsychologists and physicians are more familiar, and the ones most commonly used. The absence of a cut‐off gives rise to a possible overlap between the scores obtained by the so‐called normal people and those obtained by people with MCI. Longitudinal follow‐up of cognitive performance may be more effective and may sometimes prove vital in defining the cognitive status of a person. Some people will regain normal cognitive function, some will remain stable and some will undergo a more or less rapid progression of symptoms (fast and slow decliners). The following predictive criteria have been isolated: age > 77 years, initial Mini Mental State Examination (MMS) < 28, increased impairment of free recall, gradual decline in improvement by indexing, poor performance on the clock test, decline in mental flexibility and sensitivity to interference, and presence of the apolipoprotein E, e4 allele.5,18
The predictive importance of memory decline seen during tests repeated over 2 years, rather than an isolated measurement, has been emphasised.19
The recently described concept of both cognitive and functional decline may be vital in identifying people with MCI at high risk of progression to dementia.20
The concept of MCI was described relatively recently and neuropathological data are still limited. The information provided by cohort studies such as the Religious Order Study will perhaps be the most important findings over the next few years.21
In this study, postmortem examination is systematically carried out, irrespective of cognitive status or cause of death. Neuropathological findings are correlated with results of periodic cognitive evaluation. The clinical and neuropathological criteria distinguishing normal elderly people from those with Alzheimer's disease are, however, still debated. Where should the limit be in terms of neuropathology: should it be qualitative or purely quantitative?22
Most neuropathological data support the concept of a continuum between normal ageing and dementia. MCI may represent a transitional neuropathological condition. Degenerative lesions are also observed in so‐called normal people. Moreover, despite the limited number of published cases, aetiological heterogeneity with respect to vascular lesions and other neurodegenerative disease is apparent.23
Biomarkers are the most widely studied indicators of the existence of specific lesions found in Alzheimer's disease. The essential component of senile plaque is the β amyloid protein and that of neurofibrillary degeneration is hyperphosphorylated τ protein. Numerous studies have been carried out on these pathological proteins, which are potential markers owing to their relationship with the characteristic lesions. Identification of potential biomarkers was focused primarily on analysis of CSF, access to which is limited in standard medical practice with patients with MCI. Nevertheless, three markers (total τ protein, hyperphosphorylated τ protein and amyloid β42 protein) make it possible to distinguish, with adequate sensitivity, patients with incipient Alzheimer's disease or symptomatic Alzheimer's disease in the initial stages from patients undergoing normal ageing or those with depression or Parkinson's disease. Specificity is much lower with regard to other degenerative forms of dementia, such as Lewy body dementia or frontotemporal dementia.24
Moreover, the combination of variables, including genetic data (eg, apolipoprotein E), could accurately predict Alzheimer's disease in people with MCI better than each of the variables individually.25
Although morphological brain imaging is part of the systematic diagnostic procedure for dementia, it is not currently essential for MCI. The diagnostic criteria for MCI are based solely on clinical evaluation. The difficulties in defining the limits of this concept and the need to characterise its different subtypes may necessitate the wider use of imaging in the future.
Brain imaging essentially makes it possible to identify the early stages of Alzheimer's disease, characterising one of the aetiopathogenic subgroups of MCI. This stage of progression is diagnosed by the different localisation of abnormalities in morphological and functional imaging. Different regions may be selected as targets. The entorhinal and hippocampo‐amygdala regions are of greater interest in volumetric analysis, whereas the temporoparietal cortical and posterior cingulate regions are more important in functional imaging.25,26,27,28,29,30
This separation of the morphological and metabolic effects of the lesions may be explained by the existence of compensatory mechanisms that are particularly active in the hippocampus. These compensate for loss of neurones and maintain relative metabolism in this region. The early changes observed in the posterior association cortex are related to a deafferentation mechanism.31
Moreover, positron emission tomography may, in the future, prove to be the most effective tool in detecting microglial activation, regional deposition of β amyloid protein and neurofibrillary tangles.32,33