Narrative impairment, white matter damage and CSF biomarkers in the Alzheimer's disease spectrum.

Claudia Drummond,Marina Carneiro Monteiro,Jorge Moll,Felipe Kenji Sudo,Fernanda Tovar-Moll,Andrea Silveira De Souza,Naima Assuncao,Ivanei Bramati,Ricardo De Oliveira-Souza,Bart Vanderboght,Natalia Oliveira,Rochele Paz Fonseca,Paulo Mattos,Gabriel Coutinho,Alina Teldeschi,Carlos Otavio Brandao

doi:10.18632/aging.102391

Abstract

Background: Narrative discourse (ND) refers to one’s ability to verbally reproduce a sequence of temporally and logically-linked events. Impairments in ND may occur in subjects with Amnestic Mild Cognitive Impairment (aMCI) and Alzheimer’s Disease (AD), but correlates across this function, neuroimaging and cerebrospinal fluid (CSF) AD biomarkers remain understudied.Objectives: We sought to measure correlates among ND, Diffusion Tensor Imaging (DTI) indexes and AD CSF biomarkers in patients within the AD spectrum.Results: Groups differed in narrative production (NProd) and comprehension. aMCI and AD presented poorer inference abilities than controls. AD subjects were more impaired than controls and aMCI regarding WB (p<0.01). ROIs DTI assessment distinguished the three groups. Mean Diffusivity (MD) in the uncinate, bilateral parahippocampal cingulate and left inferior occipitofrontal fasciculi negatively correlated with NProd. Changes in specific tracts correlated with T-tau/Aβ1-42 ratio in CSF.Conclusions: AD and aMCI patients presented more ND impairments than controls. Those findings were associated with changes in ventral language-associated and in the inferior parahippocampal pathways. The latest were correlated with biomarkers’ levels in the CSF.Methods: AD (N=14), aMCI (N=31) and Control (N=39) groups were compared for whole brain (WB) and regions of interest (ROI) DTI parameters, ND and AD CSF biomarkers.

Highlights

Ancillary methods for assessing cognitive impairment within the continuum of Alzheimer’s Disease (AD) have enabled substantial progress in the understanding of the pathophysiology of the disease, which may contribute to the development of strategies for prevention, early diagnosis and disease-modifying treatment [1]
Measurable indicators of AD pathology comprise an array of clinical, biochemical and neuroimaging factors, such as: (1) changes in structural MRI; (2) abnormalities in the white matter (WM) integrity evidenced by Diffusion Tensor Imaging (DTI) [2]; (3) regional glucose metabolic reduction, as measured by 2-[18F]-fluoro-2deoxy-d-glucose PET (FDG-PET) [3]; (4) cortical amyloid load demonstrated through the Carbon-11labelled Pittsburgh compound B (11 C-PiB) PET [3]; (5) molecular alterations of the brain [4,5,6] and (6) cognitive deficits indicated by neuropsychological assessment [7,8,9]
Mean scores on the Mini-Mental State Examination (MMSE) were significantly lower for AD subjects compared to controls and Amnestic Mild Cognitive Impairment (aMCI) groups; no differences were found for this variable between controls and aMCI

Summary

Introduction

Ancillary methods for assessing cognitive impairment within the continuum of Alzheimer’s Disease (AD) have enabled substantial progress in the understanding of the pathophysiology of the disease, which may contribute to the development of strategies for prevention, early diagnosis and disease-modifying treatment [1]. Measurable indicators of AD pathology comprise an array of clinical, biochemical and neuroimaging factors, such as: (1) changes in structural MRI (hippocampal and entorhinal cortex atrophy, for example); (2) abnormalities in the white matter (WM) integrity evidenced by Diffusion Tensor Imaging (DTI) [2]; (3) regional glucose metabolic reduction, as measured by 2-[18F]-fluoro-2deoxy-d-glucose PET (FDG-PET) [3]; (4) cortical amyloid load demonstrated through the Carbon-11labelled Pittsburgh compound B (11 C-PiB) PET [3]; (5) molecular alterations of the brain (metabolomics, oxidative stress, beta-amyloid processing, tau-protein pathology and insulin signaling) [4,5,6] and (6) cognitive deficits indicated by neuropsychological assessment [7,8,9] In this respect, recent evidence suggested that combining results from different categories of AD markers may improve the accuracy for both the detection of dementia and for the prediction of cognitive decline in subjects with Mild Cognitive Impairment (MCI) [10,11,12,13,14]. Methods: AD (N=14), aMCI (N=31) and Control (N=39) groups were compared for whole brain (WB) and regions of interest (ROI) DTI parameters, ND and AD CSF biomarkers

Objectives

Methods

Results

Conclusion