Mild cognitive impairment vs. mild cognitive dysfunctions: validation with a nomothetic network approach

Aim:No studies have examined whether interactions between the apolipoprotein E4 (ApoE4) allele and peripheral biomarkers, hypertension, and type 2 diabetes mellitus (T2DM) may impact the neurocognitive, behavioral, and social dysfunctions in amnestic mild cognitive impairment (aMCI) and Alzheimer's disease (AD).We aimed to clinically define and biologically validate a subgroup of aMCI subjects who take up an intermediate position between controls and AD patients. Methods:In 61 healthy controls, 60 subjects with aMCI, and 60 AD patients, we measured the features of aMCI/AD using the Consortium to Establish a Registry for Alzheimer's Disease (CERAD).A composite BIORISK score was computed using the ApoE4 allele, serum folate, albumin, white blood cells, fasting blood glucose, atherogenic index of plasma, T2DM, and hypertension.Results: Clustering and nearest neighbor analyses were unable to validate the aMCI subgroup.We constructed two z unit-based composite scores, the first indicating overall burden of cognitive, social, and behavioral deterioration (OBD) and the second reflecting the interactions among ApoE4, all other biomarkers, hypertension, and T2DM (BIORISK).We found that 40.2% of the variance in the OBD score was explained by BIORISK, ApoE4, age, and education.The OBD index was used to construct three subgroups (normal, medium, and high OBD) with the medium group (n = 45) showing mild cognitive dysfunctions (MCD) in memory, language, orientation, and ADL.People with MCD show OBD and BIORISK scores that are significantly different from controls and AD. Conclusion:Petersen's aMCI criteria cannot be validated and should be replaced by the more restrictive, biologically validated MCD class.