Searching for Primary Predictors of Conversion from Mild Cognitive Impairment to Alzheimer’s Disease: A Multivariate Follow-Up Study

Abstract

Recent proposals of diagnostic criteria within the healthy aging-Alzheimer's disease (AD) continuum stressed the role of biomarker information. More importantly, such information might be critical to predict those mild cognitive impairment (MCI) patients at a higher risk of conversion to AD. Usually, follow-up studies utilize a reduced number of potential markers although the conversion phenomenon may be deemed as multifactorial in essence. In addition, not only biological but also cognitive markers may play an important role. Considering this background, we investigated the role of cognitive reserve, cognitive performance in neuropsychological testing, hippocampal volumes, APOE genotype, and magnetoencephalography power sources to predict the conversion to AD in a sample of 33 MCI patients. MCIs were followed up during a 2-year period and divided into two subgroups according to their outcome: The "stable" MCI group (sMCI, 21 subjects) and the "progressive" MCI group (pMCI, 12 subjects). Baseline multifactorial information was submitted to a hierarchical logistic regression analysis to build a predictive model of conversion to AD. Results indicated that the combination of left hippocampal volume, occipital cortex theta power, and clock drawing copy subtest scores predicted conversion to AD with a 100% of sensitivity and 94.7% of specificity. According to these results it might be suggested that anatomical, cognitive, and neurophysiological markers may be considered as "first order" predictors of progression to AD, while APOE or cognitive reserve proxies might play a more secondary role.

Biomagnetic biomarkers for dementia: A pilot multicentre study with a recommended methodological framework for magnetoencephalography

“…Validation of these measures on an independent data set would indicate the utility in obtaining a clinically valid biomarker. Brain network connectivity measures are key markers of disease; neural networks are particularly vulnerable to neural dysfunction even in preclinical disease [23] and abnormalities can index disease severity [24,25] and predict conversion from MCI to AD [26,27]. We show patterns of functional connectivity within frequency bands, comparable with previous research: In frontal regions, connectivity was enhanced in the theta band, but diminished in the alpha band, and connectivity to posterior regions was reduced in both bands (broadband enhancement was probably dominated by slow frequency bands).…”

“…Artifact-related components were removed. MEG data were segmented into 4-second epochs and filtered using a 2000th order FIR band-pass filter with a Hanning window into five bands (with 2 seconds of real data padding added either side): for source analysis: broad band (2-45 Hz), and for connectivity analysis: theta (4-8 Hz), alpha (8-12 Hz), beta (12)(13)(14)(15)(16)(17)(18)(19)(20)(21)(22)(23)(24)(25)(26)(27)(28)(29)(30), and gamma (30)(31)(32)(33)(34)(35)(36)(37)(38)(39)(40)(41)(42)(43)(44)(45). The data were coregistered to the T1-weighted MRI and the forward model calculated using a realistic single shell head [11].…”

Revolution of Alzheimer Precision Neurology. Passageway of Systems Biology and Neurophysiology

“…For example, the combination of genetic data, such as the APOE polymorphism characterization with MEG resting state analysis has revealed promising in identifying MCI subjects at high risk of conversion to AD dementia as well as asymptomatic subjects at high risk of developing significant cognitive deterioration [408]. Multifactorial characterization of MCI subjects, including neuropsychological assessment, structural and functional brain measures, APOE genotyping, demonstrated very high sensitivity and specificity for predicting conversion to AD [409]. …”

<b><i>APOE</i></b> ε4 Genotype and Cognitive Reserve Effects on the Cognitive Functioning of Healthy Elders

“…Considering previous investigations that highlighted the role of educational attainment as a sensitive estimate of CR, this proxy was measured as years of formal education (range 1–25 years), and obtained by questioning participants or caregivers (see [21]).…”

“…In order to evaluate the global cognitive and functional status of the participants, all of them were screened by a set of standardized tests (for a review of the protocol, see [21]). Additionally, participants underwent an extensive neuropsychological assessment to explore their cognitive functioning by using the following tests: direct and inverse digit span test (DDS and IDS, Wechsler Memory Scale III, WMS-III) [22], immediate and delayed recall (IR and DR, WMS-III) [22], phonemic and semantic fluency (PhF and SF, controlled oral word association test) [23], ideomotor praxis of Barcelona test [24], visual object and space perception test (VOSP) [25], Boston naming test (BNT) [26], and trail-making test (TMT), parts A and B (TMT-A and TMT-B) [27].…”