A Multifactor Approach to Mild Cognitive Impairment

Taha Qarni, BHSc; Arash Salardini, MD


Semin Neurol. 2019;39(2):179-187. 

In This Article

Mild Cognitive Impairment as a Prodromal Stage of Neurodegenerative Dementias

The natural history of MCI is heterogeneous.[19–22] There are three possible outcomes:

  1. Reversion to normal aging: In approximately 16% of individuals with MCI, cognition reverts to normal in a year.[22] The predictors of reversions are less severe symptoms, an absence of apolipoprotein E4 (ApoE4), absence of involvement of episodic memory problems, and attribution to a medical or psychiatric condition. Most of this group of patients either had a one-time insult from which they recovered, or they had reduced cognitive reserve combined with a low level subacute condition.

  2. Stability: About 34% of individuals with MCI are cognitively stable at the end of 3 years after diagnosis. Predictors of stability include better neuropsychological test results (especially in speed of mentation and memory recall), younger age at diagnosis, and an absence of ApoE4.[23] Patients belonging to this category either had a single-phase damage to the brain or, more likely, have staved off progression to dementia via cognitive reserve or other less well understood mechanisms.

  3. Progression to dementia: Every year, approximately 10 to 15% of individuals with MCI convert to dementia, mostly Alzheimer's disease (AD).[19,24,25] The rate of progression is higher in individuals who are positive for amyloid, tau, or ApoE4.[5,6,25–27]

Seen in this light, MCI may be seen as an intermediate clinical or pathological stage before the onset of dementia. The current paradigm governing our thinking regarding neurodegenerative diseases comes from work done in the Mayo Clinic by Jack et al.[28] According to this model, neuropathological lesions accumulate for many years, sometimes decades, before an individual becomes symptomatic with a neurodegenerative dementia. In this way, one can imagine an intermediary pathological stage of disease where the patient has deviated from normal aging but is not yet demented.