Connected speech as a marker of disease progression in autopsy-proven Alzheimer's disease.

Samrah Ahmed,Peter Garrard,Anne-Marie F Haigh,Celeste A De Jager

doi:10.1093/brain/awt269

Abstract

Although an insidious history of episodic memory difficulty is a typical presenting symptom of Alzheimer’s disease, detailed neuropsychological profiling frequently demonstrates deficits in other cognitive domains, including language. Previous studies from our group have shown that language changes may be reflected in connected speech production in the earliest stages of typical Alzheimer’s disease. The aim of the present study was to identify features of connected speech that could be used to examine longitudinal profiles of impairment in Alzheimer’s disease. Samples of connected speech were obtained from 15 former participants in a longitudinal cohort study of ageing and dementia, in whom Alzheimer’s disease was diagnosed during life and confirmed at post-mortem. All patients met clinical and neuropsychological criteria for mild cognitive impairment between 6 and 18 months before converting to a status of probable Alzheimer’s disease. In a subset of these patients neuropsychological data were available, both at the point of conversion to Alzheimer’s disease, and after disease severity had progressed from the mild to moderate stage. Connected speech samples from these patients were examined at later disease stages. Spoken language samples were obtained using the Cookie Theft picture description task. Samples were analysed using measures of syntactic complexity, lexical content, speech production, fluency and semantic content. Individual case analysis revealed that subtle changes in language were evident during the prodromal stages of Alzheimer’s disease, with two-thirds of patients with mild cognitive impairment showing significant but heterogeneous changes in connected speech. However, impairments at the mild cognitive impairment stage did not necessarily entail deficits at mild or moderate stages of disease, suggesting non-language influences on some aspects of performance. Subsequent examination of these measures revealed significant linear trends over the three stages of disease in syntactic complexity, semantic and lexical content. The findings suggest, first, that there is a progressive disruption in language integrity, detectable from the prodromal stage in a subset of patients with Alzheimer’s disease, and secondly that measures of semantic and lexical content and syntactic complexity best capture the global progression of linguistic impairment through the successive clinical stages of disease. The identification of disease-specific language impairment in prodromal Alzheimer’s disease could enhance clinicians’ ability to distinguish probable Alzheimer’s disease from changes attributable to ageing, while longitudinal assessment could provide a simple approach to disease monitoring in therapeutic trials.

Highlights

One of the most important clinical clues to a diagnosis of probable Alzheimer’s disease is an insidious history of learning and memory difficulties, often noticed by others, and sufficient to impact on performance of day-to-day activities (McKhann et al, 1984; Dubois et al, 2007)
Much attention has been paid to the evolution of language change over the course of Alzheimer’s disease, as both retrospective analyses of written and spoken language dating from presymptomatic periods (Snowdon et al, 1996; Garrard et al, 2005; van Velzen and Garrard, 2008), and prospective cohort studies of ageing populations (Forbes-McKay and Venneri, 2005; Oulhaj et al, 2009), have shown that subtle changes in language and communication ability may be apparent years or even decades before either a patient or his/her closest associates becomes aware of any symptoms of cognitive deterioration
Performance on the Mini-Mental State Examination and all subtests of the CAMCOG other than those relating to comprehension, perception and calculation were significantly lower in the mild cognitive impairment group than those of control subjects, but the mean score was still above the dementia cut-off of 80/107 points

Summary

Introduction

One of the most important clinical clues to a diagnosis of probable Alzheimer’s disease is an insidious history of learning and memory difficulties, often noticed by others, and sufficient to impact on performance of day-to-day activities (McKhann et al, 1984; Dubois et al, 2007). Much attention has been paid to the evolution of language change over the course of Alzheimer’s disease, as both retrospective analyses of written and spoken language dating from presymptomatic periods (Snowdon et al, 1996; Garrard et al, 2005; van Velzen and Garrard, 2008), and prospective cohort studies of ageing populations (Forbes-McKay and Venneri, 2005; Oulhaj et al, 2009), have shown that subtle changes in language and communication ability may be apparent years or even decades before either a patient or his/her closest associates becomes aware of any symptoms of cognitive deterioration Translation of these striking observations into simple and specific markers of language change in Alzheimer’s disease could have far-reaching clinical consequences. The identification of disease-specific language abnormalities in patients with prodromal Alzheimer’s disease, or mild cognitive impairment (Petersen et al, 1999; Gauthier et al, 2006), would enhance clinicians’ ability to distinguish probable Alzheimer’s disease from the more benign effects of ageing on cognition, while longitudinal assessment could provide readily obtainable markers of disease progression

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