Result card

  • CUR3: What is the natural course of the Alzheimer’s disease (AD) and the Mild Cognitive Impairment (MCI)?

What is the natural course of the Alzheimer’s disease (AD) and the Mild Cognitive Impairment (MCI)?

Authors: Antonio Migliore, Tapani Keranen, Sinikka Sihvo

Internal reviewers: Kristian Lampe

The major issue with MCI is that subjects with this disorder may progress to dementia in higher proportions than do cognitively normal people. A challenge in assessing the outcome of MCI – as in the case of the incidence and prevalence of MCI – is the non-uniform criteria applied in the diagnosis of the disorder. Furthermore, the symptomatology in the subjects is variable and in addition to Alzheimer’s disease, MCI may appear in patients with other neurodegenerative disorders such as Parkinson’s disease an also in  cerebrovascular disorders. According to a meta-analysis of eight studies that examined the risk of  dementia or Alzheimer’s disease annual conversion rate (ACR) to dementia was 13.8 (95% 8.44–22.6), higher in subjects with MCI compared to healthy controls {56}. However, most of the individuals with MCI may not develop dementia. Studies report a wide variation in the risk of conversion after a one year follow-up (10.2 to 33.6%, median 19.0%), and after two years conversion frequency has varied from 9.8 to 36.3% (median 18.6%) {81}. A meta-analysis, based on the data of 41 studies with at least three years of follow-up concluded that about 30% of the MCI patients convert to dementia within 5 years after the diagnosis of MCI, and that the cumulative conversion rate to dementia in subjects followed up 5 years or more may not exceed 38% {56}. In general, population based studies show lower conversion rates of MCI to dementia: in the meta-analysis, the proportion of MCI subjects with conversion to dementia was 39.2% in the clinic based studies and 21.9% in community studies {56}. The ACR of MCI to dementia varies 2% to 31% across the studies {9}. Meta-analysis of community based studies reported an ACR of MCI to Alzheimer type dementia to be 6.9% (95% CI 4.1–10.4%) {56}. Several predictive factors for the risk of conversion from MCI to dementia have been identified. Multivariate analyses have shown that at baseline lower Mini Mental State Examination (MMSE), diastolic blood pressure, BMI {66}, ApoE ԑ4 allele {22}, temporal lobe /hippocampal volume in MRI {33} {37} {80}, abnormal FDG- or BIB PET {44} as well as CSF concentration of TAU and ApoE ԑ4 {33} {50} {54} {80} predict the risk of conversion to dementia. According to the meta-analysis of follow-ups studies, the ACR to dementia is similar in subjects with amnestic MCI and multiple-domain MCI (11.7% and 12.2%, respectively) and higher than in subjects with non-amnestic MCI {56}. Assessment of the risk of mortality associated with MCI is difficult due to limited number of population based studies as well as due to varying criteria for the diagnosis of MCI {34}. However, several studies have reporter increased mortality in subjects with MCI compared with cognitively non-impaired controls with hazard ratios varying from 1.2 to 2.2 {34} {35} {39} {83}. The mortality may be higher in subjects with multiple-domain amnestic MCI compared to those with single-domain amnestic MCI {39}. AD is characterized by insidious onset and progressive deterioration of cognitive function, functional abilities, behavior and mood. The progression varies inter-individually. Several scales are being used in clinical practice for the assessment of the severity of cognitive and functional decline in dementia. Most commonly used are MMSE, Clinical Dementia Rating (CDR), and Global Deterioration scale (GDS) {38} {68}. For clinical assessment and treatment consideration purposes, AD dementia is categorized as mild (MMSE 18–26, GDS 3–4, CDR 0.5–1), moderate (MMSE 10–22, GDS 4–6, CDR 1–2), and severe (MMSE 0–2, GDS 6–7, CDR 2–3). The decline in MMSE scores varies between 2.6 and 4.5 points in various studies, slower in community based studies than in clinic based surveys {1}. Some studies have suggested a non-linear decline in cognition in AD so that the progression is slower in patients with mild disease and on the other hand in severe disease but faster in patients with moderate disease {19} {57}. Functional decline is a prerequisite for the diagnosis of dementia and it is manifested already in early AD dementia. With the progression of cognitive symptoms in AD, social and occupational functioning continue to deteriorate {40}. Also behavioral and psychic symptoms correlate with the severity of cognitive deficits {47} {57}. Functional decline in patients with AD eventually leads to institutionalization. It has been estimated that approximately 50% of the demented patients of Northern Europe and North America are in institutionalized care but the percentage is lower in Southern European countries {1}.

The mortality risk in patients with AD is 1.5 to 5-fold compared with cognitively normal subjects {78}. Median survival time in AD ranges from 3.3 to 11.7 years {78}, and the annual mortality rate is 5.95% (95% CI 4.56–7.34) {18}. Predictive factors for mortality in patients with AD are age, male sex, increased disease severity and functional impairment {78}.

Migliore A et al. Result Card CUR3 In: Migliore A et al. Health Problem and Current Use of the Technology In: Jefferson T, Cerbo M, Vicari N [eds.]. Use of Intravenous immunoglobulins for Alzeheimer’s disease including Mild Cognitive Impairment [Core HTA], Agenas - Agenzia nazionale per i servizi sanitari regionali ; 2015. [cited 2 December 2022]. Available from: