Modifying the minimum criteria for diagnosing amnestic MCI to improve prediction of brain atrophy and progression to Alzheimer\u2019s disease

Eero Vuoksimaa,Linda K Mcevoy,William S Kremen,Carol E Franz,Dominic Holland

doi:10.1007/s11682-018-0019-6

Abstract

Mild cognitive impairment (MCI) is a heterogeneous condition with variable outcomes. Improving diagnosis to increase the likelihood that MCI reliably reflects prodromal Alzheimer’s Disease (AD) would be of great benefit for clinical practice and intervention trials. In 230 cognitively normal (CN) and 394 MCI individuals from the Alzheimer’s Disease Neuroimaging Initiative, we studied whether an MCI diagnostic requirement of impairment on at least two episodic memory tests improves 3-year prediction of medial temporal lobe atrophy and progression to AD. Based on external age-adjusted norms for delayed free recall on the Rey Auditory Verbal Learning Test (AVLT), MCI participants were further classified as having normal (AVLT+, above −1 SD, n = 121) or impaired (AVLT -, −1 SD or below, n = 273) AVLT performance. CN, AVLT+, and AVLT- groups differed significantly on baseline brain (hippocampus, entorhinal cortex) and cerebrospinal fluid (amyloid, tau, p-tau) biomarkers, with the AVLT- group being most abnormal. The AVLT- group had significantly more medial temporal atrophy and a substantially higher AD progression rate than the AVLT+ group (51% vs. 16%, p < 0.001). The AVLT+ group had similar medial temporal trajectories compared to CN individuals. Results were similar even when restricted to individuals with above average (based on the CN group mean) baseline medial temporal volume/thickness. Requiring impairment on at least two memory tests for MCI diagnosis can markedly improve prediction of medial temporal atrophy and conversion to AD, even in the absence of baseline medial temporal atrophy. This modification constitutes a practical and cost-effective approach for clinical and research settings.

Highlights

The pathological process in Alzheimer’s disease (AD) begins long before the onset of dementia (Braak et al 2011; Jack et al 2010) making early detection a primary concern
cognitively normal (CN) participants were older (P < .05) and had higher American National Adult Reading Test (ANART) scores (P < .001) than those with mild cognitive impairment (MCI) but educational level did not differ between these two groups (P = .14)
The Auditory Verbal Learning Test (AVLT) was treated as an external predictor despite the fact that AVLT scores sometimes conflicted with the core clinical criteria for diagnosis

Summary

Introduction

The pathological process in Alzheimer’s disease (AD) begins long before the onset of dementia (Braak et al 2011; Jack et al 2010) making early detection a primary concern. To aid in early detection, mild cognitive impairment (MCI) has been introduced as a prodromal stage of AD. Improvement in MCI diagnosis is needed to ensure that those with MCI are at increased risk of progressing to AD. Individuals with MCI are at elevated risk for developing dementia, there is substantial variation in progression rates across studies (Langa and Levine 2014). Amyloid and tau biomarkers are used to support a diagnosis of AD in research studies, and the National Institute on AgingAlzheimer’s Association (NIA-AA) framework recommends inclusion of these biomarkers for earlier identification

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