A Two-Study Comparison of Clinical and MRI Markers of Transition from Mild Cognitive Impairment to Alzheimer’s Disease

D P Devanand,Yaakov Stern,Xinhua Liu,Patrick J Brown,Gregory H Pelton,Edward D Huey

doi:10.1155/2012/483469

Abstract

A published predictor model in a single-site cohort study (questionable dementia, QD) that contained episodic verbal memory (SRT total recall), informant report of function (FAQ), and MRI measures was tested using logistic regression and ROC analyses with comparable measures in a second multisite cohort study (Alzheimer's Disease Neuroimaging Initiative, ADNI). There were 126 patients in QD and 282 patients in ADNI with MCI followed for 3 years. Within each sample, the differences in AUCs between the statistical models were very similar. Adding hippocampal and entorhinal cortex volumes to the model containing AVLT/SRT, FAQ, age and MMSE increased the area under the curve (AUC) in ADNI but not QD, with sensitivity increasing by 2% in ADNI and 2% in QD for a fixed specificity of 80%. Conversely, adding episodic verbal memory (SRT/AVLT) and FAQ to the model containing age, Mini Mental State Exam (MMSE), hippocampal and entorhinal cortex volumes increased the AUC in ADNI and QD, with sensitivity increasing by 17% in ADNI and 10% in QD for 80% specificity. The predictor models showed similar differences from each other in both studies, supporting independent validation. MRI hippocampal and entorhinal cortex volumes showed limited added predictive utility to memory and function measures.

Highlights

Mild cognitive impairment (MCI) often represents a transitional state between normal cognition and Alzheimer’s disease (AD) [1, 2]
Adding hippocampal and entorhinal cortex volumes to the model containing Auditory Verbal learning Test (AVLT)/Selective Reminding Test (SRT), Functional Activities Questionnaire (FAQ), age and Mini Mental State Exam (MMSE) increased the area under the curve (AUC) in Alzheimer’s Disease Neuroimaging Initiative (ADNI) but not Questionable Dementia (QD), with sensitivity increasing by 2% in ADNI and 2% in QD for a fixed specificity of 80%
Patients 41–85 years old who presented with subjective memory complaints for clinical evaluation to a Memory Disorders Clinic were eligible if they had a Folstein Mini-Mental State Exam (MMSE) score ≥22 out of 30, memory impairment defined as MMSE recall ≤2/3 objects at 5 minutes or a Selective Reminding Test (SRT) delayed recall score >1 SD below norms, and absence of a consensus diagnosis of dementia made by two experienced raters [3]

Summary

Introduction

Mild cognitive impairment (MCI) often represents a transitional state between normal cognition and Alzheimer’s disease (AD) [1, 2]. Accurate prediction of transition from MCI to AD aids in prognosis and targeting early treatment [3]. Most biomarkers of MCI transition to AD are related to the underlying disease pathology of amyloid plaques and neurofibrillary tangles [6]. Hippocampal and entorhinal cortex atrophy on MRI scan of brain [7], parietotemporal hypometabolism on 18FDG PET [8], increased amyloid uptake using PET [9], and decreased amyloid beta-42 (Aβ42) with increased tau/phospho-tau levels in the cerebrospinal fluid (CSF) [10, 11] each significantly predict transition from MCI to AD. The apolipoprotein E ε4 allele increases AD risk, but is not a strong biomarker of transition from MCI to AD [3]

Methods

Results

Conclusion