Predictors of Rate of Cognitive and Functional Decline in Patients with Amnestic Mild Cognitive Impairment

Amnestic Mild Cognitive Impairment (MCI) is a known risk factor for conversion to Alzheimer’s disease (AD). Although substantial research has been conducted on the general profile of amnestic MCI subjects and predictors of conversion to AD, the research on predictors of rate of decline has been less comprehensive and studied. The present study sought to fill the gaps in this portion of research by systematically and comprehensively examining predictors of rate of decline in a longitudinal sample of individuals with MCI. Specifically, this study identified predictors of rate of cognitive and functional decline, including age, genetic vulnerability, baseline cognitive performance, baseline functional ability, and baseline neuropsychiatric severity. Participants with single or multi-domain aMCI (N = 151) were assessed at baseline and for a mean of 1.32 follow-up visits (mean interval from baseline to last follow-up = 1.61 years). Results showed that carriers of the ApoE ε4 allele declined more quickly on all three dementia severity measures, but not on instrumental activities of daily living (iADL) functioning, compared to non-carriers. Older individuals declined more rapidly on iADL functioning (but not in dementia severity). Participants with average baseline iADL ratio scores declined more quickly compared to participants with above or below average baseline iADL ratio scores. Participants with lower Executive Functions composite scores at baseline declined more quickly on dementia severity measures but more slowly on iADL functioning. In addition, lower Memory composite scores at baseline predicted faster decline on iADL functioning only. Greater memory impairment severity (operationalized as the number of memory scores in the impaired range) at baseline predicted faster decline on the MMSE in particular. Contrary to hypotheses, those with lower levels of depression at baseline declined more rapidly on dementia severity measures compared to those with higher levels of depression. Identifying potential predictors of rate of decline from amnestic MCI to AD could be clinically meaningful for prognostic purposes, understanding risk and protective factors, as well as guiding future treatments and clinical trials that could aim to target and delay progression among those patients who are particularly vulnerable to more quickly convert to AD.