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.

The present study adds a lexico-semantic dimension to the linguistic profile based on discourse analysis in typical AD, recently described by the same authors. 2012, 83(11): 1056-1062). The suggestion of differential importance of verb and noun use in the present study may be related to the reduction in syntactic complexity that was reported, using the same set of discourse samples, in the earlier study.

A total of 273 participants (186 with clinical dementia; 87 "normal" controls; mean age 72 years) in a prospective, longitudinal, dementia research study, underwent lumbar puncture (LP), where possible, on an annual basis. Reporting of symptoms after all LP's (n = 541) was 21.6%, the predominant complaints being mild localised back-pain (12.8%) and headache (10.7%). All symptoms were self-limiting. Analysis of headaches after all first LP's (n = 273) revealed an incidence of 14.2% with marked differences between subjects under 60 years of age (33%) and those over 60 years (10.1%), between subjects with "minimal" cerebral atrophy (19.5%) and those with "significant" atrophy (5.6%) and, to a lesser extent, between subjects with no or mild cognitive impairment (20.6%) and those with significant impairment (9.5%). Age under 60 years and lack of significant cerebral atrophy were shown to be independent predictors of headache. Acceptability of LP was high as demonstrated by agreement to a second procedure by 92.2% of eligible subjects. Our results show that LP can be successfully incorporated into research with the elderly.

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