General introduction 23 1 dementia, dementia has multiple aetiologies. With this shift, the concept of MCI has also changed. From a prodromal or predementia concept of ‘… a transitional period between normal ageing and the diagnosis of clinically probable very early AD, and this transitional zone has been described using a variety of terms such as mild cognitive impairment’ (Petersen, 2004) towards a more descriptive intermediate functional state to ‘define the grey area between intact cognitive functioning and clinical dementia’ (Petersen et al., 2014). With the emancipation of other aetiologies besides AD that can cause cognitive impairment, the criteria of MCI were also adapted. From primarily memory-focused criteria towards ‘a condition in which individuals demonstrate cognitive impairment with minimal impairment of instrumental activities of daily living’ (Petersen et al., 2018). Most importantly ‘it can also be secondary to other disease processes i.e., other neurologic, neurodegenerative, systemic, or psychiatric disorders’ (Petersen et al., 2018). With this shift, both cognitive and functional abilities must be considered in the evaluation of MCI (Winblad et al., 2004). In turn, these adaptations initiated further specification of the MCI. This involves differentiating between amnestic (aMCI) or non-amnestic (naMCI) disorder and with or without multiple domains. This results in four subtypes: aMCI (single or multiple domains), naMCI (single or multiple domains) (Petersen, 2004). Although MCI is less AD-focused, AD is still a frequently suspected probable cause. This is reflected in new subtypes like ‘MCI due to AD’ or ‘MCI supported with biomarkers’, although they are mainly created for research purposes (on early interventions for AD) (Mattsson et al., 2009). One reason for this is that not all patients with MCI develop dementia. Even more, there is substantial literature that 20% (up to 55% are reported) revert to normal cognition, 40% remain stable, and 40% convert to dementia. By creating subgroups of MCI, studies attempt to predict who is at a higher risk of developing dementia (Visser and Verhey, 2008). Although the percentages of reverting and converting differ substantially in the literature, it is acknowledged that people with MCI have a significantly higher risk of progressing to dementia than agematched controls (Alexopoulos et al., 2006; Petersen et al., 2018). This difference in conversion rate as well as the prevalence and incidence that vary across studies is most likely due to the differences in study populations, as incidence increases with age and the type of patient (Visser and Verhey, 2008; Bermejo-Pareja et al., 2021) — 5% to 15% for the annual conversion rate to dementia compared to 1–2% for controls, resulting in a five to ten times higher conversion rate. Cumulative dementia incidence was 14.9% in individuals with MCI older than age 65 years, during following 2 years. MCI prevalence was 6.7% for ages 60–64, 8.4% for 65–69, 10.1% for 70–74, 14.8% for 75–79, and 25.2% for 80–84 (Petersen et al., 2018).
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