MRI Visual Ratings of Brain Atrophy and White Matter Hyperintensities across the Spectrum of Cognitive Decline Are Differently Affected by Age and Diagnosis.

Hanneke F M Rhodius-Meester,Philip Scheltens,Marije R Benedictus,Majon Muller,Frederik Barkhof,Mike P Wattjes,Wiesje M Van Der Flier

doi:10.3389/fnagi.2017.00117

Abstract

Aim: To assess the associations of age and diagnosis with visual ratings of medial temporal lobe atrophy (MTA), parietal atrophy (PA), global cortical atrophy (GCA), and white matter hyperintensities (WMH) and to investigate their clinical value in a large memory clinic cohort.Methods: We included 2,934 patients (age 67 ± 9 years; 1,391 [47%] female; MMSE 24 ± 5) from the Amsterdam Dementia Cohort (1,347 dementia due to Alzheimer's disease [AD]; 681 mild cognitive impairment [MCI]; 906 controls with subjective cognitive decline). We analyzed the effect of age, APOE e4 and diagnosis on visual ratings using linear regression analyses. Subsequently, we compared diagnostic and predictive value in three age-groups (<65 years, 65–75 years, and >75 years).Results: Linear regression analyses showed main effects of age and diagnosis and an interaction age*diagnosis for MTA, PA, and GCA. For MTA the interaction effect indicated steeper age effects in MCI and AD than in controls. PA and GCA increased with age in MCI and controls, while AD patients have a high score, regardless of age. For WMH we found a main effect of age, but not of diagnosis. For MTA, GCA and PA, diagnostic value was best in patients <65 years (optimal cut-off: ≥1). PA and GCA only discriminated in patients <65 years and MTA in patients <75 years. WMH did not discriminate at all. Taking into account APOE did not affect the identified optimal cut-offs. When we used these scales to predict progression in MCI using Cox proportional hazard models, only MTA (cut-off ≥2) had any predictive value, restricted to patients >75 years.Conclusion: Visual ratings of atrophy and WMH were differently affected by age and diagnosis, requiring an age-specific approach in clinical practice. Their diagnostic value seems strongest in younger patients.

Highlights

The current diagnostic criteria for mild cognitive impairment (MCI) and dementia due to Alzheimer’s disease (AD) advise to apply biomarkers such as MRI features, to identify patients with AD pathology (Dubois et al, 2007, 2014; Albert et al, 2011; McKhann et al, 2011)
The aim of our study was to explore the effect of age on the diagnostic value of visual ratings of medial temporal lobe atrophy (MTA), parietal atrophy (PA), global cortical atrophy (GCA), and white matter hyperintensities (WMH) for discriminating controls from AD and for predicting progression to dementia in MCI in a very large memory clinic cohort
Patients with AD were more often female, more often APOE e4 carrier, had the lowest mini mental state examination (MMSE) score and highest MTA, PA, and GCA compared to controls and MCI

Summary

Introduction

The current diagnostic criteria for mild cognitive impairment (MCI) and dementia due to Alzheimer’s disease (AD) advise to apply biomarkers such as MRI features, to identify patients with (underlying) AD pathology (Dubois et al, 2007, 2014; Albert et al, 2011; McKhann et al, 2011). Studies demonstrating discriminatory value of atrophy, such as medial temporal lobe atrophy (MTA), parietal atrophy (PA) and global cortical atrophy (GCA) in AD, often use automatic quantitative MRI analysis (van de Pol et al, 2006; Sluimer et al, 2008; Henneman et al, 2009a; Trzepacz et al, 2014). These analyses are time consuming hard to apply in daily clinical practice. Since these studies used patients with a mean age of 75, it remains uncertain what the optimal cut-off in younger patients would be

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