An investigation of PreMCI: subtypes and longitudinal outcomes

To investigate the clinical features and rates of progression of conditions that are not considered to be normal, but do not fulfill criteria for mild cognitive impairment (MCI).

We longitudinally evaluated 269 elderly subjects who did not meet formal criteria for MCI at baseline but had: (1) a clinical history suggesting MCI without neuropsychological deficits (PreMCI-Clinical); or (2) neuropsychological deficits on one or more memory measures in conjunction with a negative clinical examination (amnestic PreMCI-NP) or were normal on both neuropsychological and clinical examination.

The rate of progression to MCI or dementia over an average of 2- to 3 years was 3.7% for no cognitive impairment subjects, whereas it was significantly greater for all PreMCI subtypes (22.0% for PreMCI-Clinical, 38.9% for amnestic PreMCI-NP subjects with two or more memory impairments). Among PreMCI subjects as a whole, lower baseline scores on object memory and category fluency tests were the best predictors of progression to MCI or dementia. Cardiovascular risk factors, Parkinsonian symptoms, and hippocampal atrophy were not associated with progression.

Distinct PreMCI subtypes defined on the basis of clinical and neuropsychological evaluations were found to have distinct characteristics, but both subtypes demonstrated elevated risk for progression to MCI or dementia. Despite the lack of evidence of clinical impairment, subjects with neuropsychological deficits in two memory domains were particularly at increased risk for progression of their deficits.