Mild Cognitive Impairment: Prodromal Alzheimer's Disease or Something Else?

Abstract

The majority of mild cognitive impairment (MCI) studies use baseline and one follow-up measurement to determine the clinical course of the disorder. This report of MCI clinical course is based on the a statistical evaluation of multiple neurocognitive tests over a 60 month period in elderly normal and MCI cohorts. The data includes serial informant-based measures (Clinical Dementia Rating [CDR]) and a comprehensive battery of neuropsychological tests analyzed by two different regression methods. Twenty-nine elderly participants entered the study as neurocognitively normal; 26 remained normal, 2 progressed to MCI, and 1 progressed to dementia. Eighty-three participants entered the study as multiple domain MCI cases; 10 became normal, 46 remained MCI, and 27 progressed to dementia. Three of the 27 demented died with full necropsies performed (one case was progressive supranuclear palsy and two confirmed Alzheimer’s disease with severe cerebral amyloid angiopathy (CAA)). Without serial measures, 1 in 8 MCI could be misclassified as “stable MCI” despite reverting to normal. The stable MCI cohorts did not benefit from practice effects though the normal subjects did. Applying Classification and Regression Tree (CART) analysis enabled prediction of the endpoint status of participants from baseline values with 78.6% accuracy. The fluctuating cognitive status of the multiple domain MCI cases implies a remitting pathologic process with elements of recovery consistent with a progressive microvasculopathy such as CAA.

Short-term practice effects in mild cognitive impairment: Evaluating different methods of change

“…But when practice effects have been observed in MCI, they were most robust on memory measures (Duff et al, 2007; Machulda et al, 2013; Yan & Dick, 2006). The absence of practice effects on the processing speed tests would also be supportive of existing studies that have failed to find improvements in patients with MCI (Britt et al, 2011; Cooper et al, 2004; Darby et al, 2002; Schrijnemaekers et al, 2006). These seemingly discrepant findings might be expected given the meta-analysis of Calamia et al (2012), who noted that practice effects vary depending on multiple factors, including the types of cognitive domains and tests examined.…”

“…Perhaps not surprisingly, findings of practice effects in patients with mild cognitive impairment (MCI) have been equivocal. For example, some studies have reported an absence of practice effects in MCI on various cognitive measures across various retest intervals (Britt et al, 2011; Cooper, Lacritz, Weiner, Rosenberg, & Cullum, 2004; Darby, Maruff, Collie, & McStephen, 2002; Schrijnemaekers, de Jager, Hogervorst, & Budge, 2006). Conversely, others have reported improvements on repeated testing in these patients (Duff et al, 2007; Mathews et al, 2014; Yan & Dick, 2006), and that patients with MCI who do not show practice effects tend to have worse outcomes than those that do show improvements on retesting (Duff et al, 2011; Hassenstab et al, 2015; Machulda et al, 2013).…”

Altered Serum Iron and Copper Homeostasis Predicts Cognitive Decline in Mild Cognitive Impairment

“…Subjects were enrolled in the study from a community-based recruitment as previously reported [9, 10]. Briefly, individuals with subjective memory complaints were screened and those classified as MCI or early AD were enrolled in the study.…”

Diagnostic transitions in mild cognitive impairment by use of simple Markov models

“…Thus, in a study with a serial testing strategy, Britt et al . () observed that 12.4% of the multiple domain MCI patients in their sample reverted to normal cognitive functioning. This proportion is similar to that obtained by Forlenza et al .…”

“…In comparison, the proportion of transitions to normal cognitive function is lower in multi-domain MCI. Thus, in a study with a serial testing strategy, Britt et al (2011) observed that 12.4% of the multiple domain MCI patients in their sample reverted to normal cognitive functioning. This proportion is similar to that obtained by Forlenza et al (2009) for a multiple domain MCI group (15%).…”