Anatomically Standardized Detection of MRI Atrophy Patterns in Early-Stage Alzheimer's Disease.

Lukas Lenhart,Reinhold Schmidt,Peter Dal Bianco,Gerhard Ransmayr,Michaela Wagner,Stephan Seiler,Christoph Scherfler,Thomas Potrusil,Georg Goebel,Thomas Benke,Lukas Pirpamer

doi:10.3390/brainsci11111491

Abstract

MRI studies have consistently identified atrophy patterns in Alzheimer’s disease (AD) through a whole-brain voxel-based analysis, but efforts to investigate morphometric profiles using anatomically standardized and automated whole-brain ROI analyses, performed at the individual subject space, are still lacking. In this study we aimed (i) to utilize atlas-derived measurements of cortical thickness and subcortical volumes, including of the hippocampal subfields, to identify atrophy patterns in early-stage AD, and (ii) to compare cognitive profiles at baseline and during a one-year follow-up of those previously identified morphometric AD subtypes to predict disease progression. Through a prospectively recruited multi-center study, conducted at four Austrian sites, 120 patients were included with probable AD, a disease onset beyond 60 years and a clinical dementia rating of ≤1. Morphometric measures of T1-weighted images were obtained using FreeSurfer. A principal component and subsequent cluster analysis identified four morphometric subtypes, including (i) hippocampal predominant (30.8%), (ii) hippocampal-temporo-parietal (29.2%), (iii) parieto-temporal (hippocampal sparing, 20.8%) and (iv) hippocampal-temporal (19.2%) atrophy patterns that were associated with phenotypes differing predominately in the presentation and progression of verbal memory and visuospatial impairments. These morphologically distinct subtypes are based on standardized brain regions, which are anatomically defined and freely accessible so as to validate its diagnostic accuracy and enhance the prediction of disease progression.

Highlights

Alzheimer’s disease (AD) is a progressive neurodegenerative disorder with the insidious onset of memory decline and the subsequent impairment of multiple cognitive domains
The first component highly loaded on the following MRI parameters: the volumes of the entire hippocampus and the hippocampal subfields including the subiculum, the CA3, the CA4/dentate gyrus and the CA1-2 transition zones (L = 0.43, Table 1)
In agreement with large multicenter cohorts as the Alzheimer’s Disease Neuroimaging Initiative (ADNI) or European community founded AddNeuroMed consortium, this study revealed, in a newly and prospectively recruited cohort at four Austrian sites, that AD is an umbrella term for morphologically distinct subgroups that differ as to their cognitive phenotype

Summary

Introduction

Alzheimer’s disease (AD) is a progressive neurodegenerative disorder with the insidious onset of memory decline and the subsequent impairment of multiple cognitive domains. AD typically originates in the medial temporal lobes, which include the hippocampus, and spreads to the association cortices [1]. Three subtypes were recently described and termed as (i) typical AD that has generally balanced NFT counts in the hippocampus and the medial temporal lobe, including the association cortices, respectively, (ii) limbic-predominant AD presenting with NFT accumulations predominantly in the hippocampus, and (iii) hippocampal-sparing AD showing NFT counts predominantly in the association cortex [2]. Individuals with the hippocampal-sparing subtype of AD were associated with a younger age at onset, shorter disease duration, rapid progression and the presence of a non-amnestic syndrome compared to those with typical AD. Limbic-predominant AD was typically associated with late disease onset, slower disease progression and an amnestic syndrome [2,5–8]

Objectives

Methods

Results

Conclusion