High amyloid burden is associated with fewer specific words during spontaneous speech in individuals with subjective cognitive decline

Sander C.J. Verfaillie*, Jurriaan Witteman, Rosalinde E.R. Slot, Ilanah J. Pruis, Lieke E.W. Vermaat, Niels D. Prins, Niels O. Schiller, Mark van de Wiel, Philip Scheltens, Bart N.M. van Berckel, Wiesje M. van der Flier, Sietske A.M. Sikkes

*Corresponding author for this work

Research output: Contribution to JournalArticleAcademicpeer-review


Self-perceived word-finding difficulties are common in aging individuals as well as in Alzheimer's Disease (AD). Language and speech deficits are difficult to objectify with neuropsychological assessments. We therefore aimed to investigate whether amyloid, an early AD pathological hallmark, is associated with speech-derived semantic complexity. We included 63 individuals with subjective cognitive decline (age 64 ± 8, MMSE 29 ± 1), with amyloid status (positron emission tomography [PET] scans n = 59, or Aβ1-42 cerebrospinal fluid [CSF] n = 4). Spontaneous speech was recorded using three open-ended tasks (description of cookie theft picture, abstract painting and a regular Sunday), transcribed verbatim and subsequently, linguistic parameters were extracted using T-scan computational software, including specific words (content words, frequent, concrete and abstract nouns, and fillers), lexical complexity (lemma frequency, Type-Token-Ratio) and syntactic complexity (Developmental Level scale). Nineteen individuals (30%) had high levels of amyloid burden, and there were no differences between groups on conventional neuropsychological tests. Using multinomial regression with linguistic parameters (in tertiles), we found that high amyloid burden is associated with fewer concrete nouns (ORmiddle (95%CI): 7.6 (1.4–41.2), ORlowest: 6.7 (1.2–37.1)) and content words (ORlowest: 6.3 (1.0–38.1). In addition, we found an interaction for education between high amyloid burden and more abstract nouns. In conclusion, high amyloid burden was modestly associated with fewer specific words, but not with syntactic complexity, lexical complexity or conventional neuropsychological tests, suggesting that subtle spontaneous speech deficits might occur in preclinical AD.

Original languageEnglish
Pages (from-to)184-192
Number of pages9
Early online date7 May 2019
Publication statusPublished - Aug 2019
Externally publishedYes


Research of the VUmc Alzheimer center is part of the neurodegeneration research program of the Amsterdam Neuroscience. The VUmc Alzheimer Center is supported by Alzheimer Nederland and Stichting VUmc Fonds. Wiesje van der Flier is recipient of a research grant for the SCIENCe project from Gieske-Strijbis Fonds. Sander Verfaillie and Rosalinde Slot are supported by a research grant from Gieske-Strijbis Fonds. Sietske Sikkes is supported by grants from JPND and Zon-MW. [ 18 F]florbetapir PET scans were made possible by Avid Radiopharmeuticals Inc., a wholly owned subsidiary of Eli Lilly and Company (NYSE: LLY). [ 18 F]florbetaben PET scans were performed in the context of a research grant by Piramal Neuroimaging. SCJV, JW, RERS, IP, LEWV, NOS, MvdW, BNMvB report no disclosures. NDP serves on the advisory board of Boehringer Ingelheim and Probiodrug, and on the DSMB of Abbvie's M15–566 trial; has provided consultancy services for Sanofi, Takeda, and Kyowa Kirin Pharmaceutical Development; receives research support from Alzheimer Nederland (project number WE.03–2012-02); and is CEO and co-owner of the Alzheimer Research Center, Amsterdam, the Netherlands. PS has received grant support for the institution Alzheimer Center, VU University Medical Center from GE Healthcare and MERCK; has received speaker's fees paid to the institution Alzheimer Center, VU University Medical Center, from Lilly, GE Healthcare, and Roche; and serves as editor in chief of Alzheimer's Research and Therapy. SAMS provided consultancy services in the past 2 years for Nutricia and Takeda; all fees were paid to her institution. WMVdF has received research funding and speaker honorarium from Boehringer Ingelheim; research programs have been funded by ZonMW, NWO, EU-FP7, Alzheimer Nederland, CardioVasculair Onderzoek Nederland, stichting Dioraphte, Gieskes-Strijbis fonds, Boehringer Ingelheim, Piramal Neuroimaging, Roche BV, Janssen Stellar, and Combinostics; and all funding is paid to her institution.

FundersFunder number
Alzheimer Nederland and Stichting VUmc Fonds
Cardiovasculair Onderzoek Nederland
DSMB of AbbvieWE.03–2012-02
Gieske-Strijbis Fonds
Janssen Stellar
Piramal Neuroimaging
Roche BV
Eli Lilly and Company
Boehringer Ingelheim
EU Joint Programme – Neurodegenerative Disease Research
Nederlandse Organisatie voor Wetenschappelijk Onderzoek
Alzheimer Nederland


    • Alzheimer's disease
    • Amyloid burden
    • Early diagnosis
    • Linguistics
    • Preclinical AD
    • Spontaneous speech
    • Subjective cognitive decline


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