Connected speech as a marker of disease progression in autopsy-proven Alzheimer’s disease
Open accessAbstract
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 claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
Individuals with amnestic AD presentation produce an abundance of generic words, circumlocutions, and few content units.
“Previous studies have shown that individuals with amnestic AD presentation produce an abundance of generic words, circumlocutions, and few content units.”
From Automatic classification of AD pathology in FTD phenotypes using natural speech (2024) · cites this paper as [4]
The Results (Language markers of Alzheimer’s disease progression; page not available) report fewer semantic units and more pronouns in patients with Alzheimer’s disease. The Discussion describes early Alzheimer’s speech as containing many words that convey little information. These passages support the claim about low information content, but they do not establish that patients produce abundant circumlocutions or generic words specifically. (LLM, conf=0.85)
Experimental — accuracy not yet measured
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
Neuropathological stageing of Alzheimer-related changes.
Braak, H., & Braak, E. (1991) · Acta Neuropathologica · doi:10.1007/bf00308809 · Cited by 16,123 · cited 2× · see citing works
“, 1991)], with Braak stage V/VI neurofibrillary tangle density (Braak and Braak, 1991), had been found in all progressors, whereas minimal or no Alzheimer’s disease pathology had been present in control brain tissue.”
BackgroundMild Cognitive Impairment: Clinical Characterization and Outcome
Petersen, R. C., Smith, G. E., Waring, S. C., Ivnik, R. J., Tangalos, E. G., & Kokmen, E. (1999) · Archives of Neurology · doi:10.1001/archneur.56.3.303 · Cited by 8,980 · see citing works
Forbes-McKay, K. E., & Venneri, A. (2005) · Neurological Sciences · doi:10.1007/s10072-005-0467-9 · Cited by 261 · see citing works
Quantitative Analysis of Aphasic Sentence Production: Further Development and New Data
Rochon, E., Saffran, E. M., Berndt, R. S., & Schwartz, M. F. (2000) · Brain and Language · doi:10.1006/brln.1999.2285 · Cited by 260 · see citing works
Giles, E., Patterson, K., & Hodges, J. R. (1996) · Aphasiology · doi:10.1080/02687039608248419 · Cited by 139 · see citing works
Flagged first, then by citations
Research works printed but not linked: 32
- Ahmed S de Jager CA Haigh AM Garrard P Logopenic aphasia in Alzheimer's disease: clinical variant or clinical feature? J Neurol Neurosurg Psychiatry 2012 83 1056 62 22842206
- Ahmed S de Jager CA Haigh AM Garrard P Semantic processing in connected speech at a uniformly early stage of autopsy-confirmed Alzheimer's disease Neuropsychology 2013 27 79 85 23356598
- Albert MS Changes in cognition Neurobiol Aging 2011 32 Suppl 1 S58 63 22078174 PMC3929949
- Almor A Kempler D MacDonald MC Andersen ES Tyler LK Why do Alzheimer patients have difficulty with pronouns? Working memory, semantics, and reference in comprehension and production in Alzheimer's disease Brain Lang 1999 67 202 27 10210631
- Berndt RS Wayland S Rochon E Saffran EM Schwartz MF Quantitative production analysis; a training manual for the analysis of aphasic sentence production 2000 Hove, UK Psychology Press 10764517
- Bondi MW Serody AB Chan AS Eberson-Shumate SC Delis DC Hansen LA Cognitive and neuropathologic correlates of Stroop Color-Word Test performance in Alzheimer's disease Neuropsychology 2002 16 335 43 12146681
- Brookshire RH Nicholas LE Speech sample size and test-retest stability of connected speech measures for adults with aphasia J Speech Hear Res 1994 37 399 407 8028321
- Croisile B Ska B Brabant MJ Duchene A Lepage Y Aimard G Comparative study of oral and written picture description in patients with Alzheimer's disease Brain Lang 1996 53 1 19 8722896
- Dubois B Feldman HH Jacova C Dekosky ST Barberger-Gateau P Cummings J Research criteria for the diagnosis of Alzheimer's disease: revising the NINCDS-ADRDA criteria Lancet Neurol 2007 6 734 46 17616482
- Garrard P Lambon Ralph MA Watson PC Powis J Patterson K Hodges JR Longitudinal profiles of semantic impairment for living and nonliving concepts in dementia of Alzheimer's type J Cogn Neurosci 2001 13 892 909 11595093
- Garrard P Maloney LM Hodges JR Patterson K The effects of very early Alzheimer's disease on the characteristics of writing by a renowned author Brain 2005 128 250 60 15574466
- Gauthier S Reisberg B Zaudig M Petersen RC Ritchie K Broich K Mild cognitive impairment Lancet 2006 367 1262 70 16631882
- Gorno-Tempini ML Brambati SM Ginex V Ogar J Dronkers NF Marcone A The logopenic/phonological variant of primary progressive aphasia Neurology 2008 71 1227 34 18633132 PMC2676989
- Gorno-Tempini ML Hillis AE Weintraub S Kertesz A Mendez M Cappa SF Classification of primary progressive aphasia and its variants Neurology 2011 76 1006 14 21325651 PMC3059138
- Hier DB Hagenlocker K Shindler AG Language disintegration in dementia: effects of etiology and severity Brain Lang 1985 25 117 33 2411334
- Hodges JR Erzinclioglu S Patterson K Evolution of cognitive deficits and conversion to dementia in patients with mild cognitive impairment: a very-long-term follow-up study Dement Geriatr Cogn Disord 2006 21 380 91 16601329
- Locascio JJ Growdon JH Corkin S Cognitive test performance in detecting, staging, and tracking Alzheimer's disease Arch Neurol 1995 52 1087 99 7487561
- McKhann G Drachman D Folstein M Katzman R Price D Stadlan EM Clinical diagnosis of Alzheimer's disease: report of the NINCDS-ADRDA Work Group under the auspices of Department of Health and Human Services Task Force on Alzheimer's disease Neurology 1984 34 939 44 6610841
- Mirra SS Heyman A Mckeel D Sumi SM Crain BJ Brownlee LM The Consortium to Establish a Registry for Alzheimers-Disease (Cerad).2. Standardization of the Neuropathologic Assessment of Alzheimers-Disease Neurology 1991 41 479 86 2011243
- Nicholas M Obler LK Albert ML Helm-Estabrooks N Empty speech in Alzheimer's disease and fluent aphasia J Speech Hear Res 1985 28 405 10 4046581
- Oulhaj A Wilcock GK Smith AD de Jager CA Predicting the time of conversion to MCI in the elderly: role of verbal expression and learning Neurology 2009 73 1436 42 19794124 PMC2882176
- Petersen RC Stevens JC Ganguli M Tangalos EG Cummings JL DeKosky ST Practice parameter: early detection of dementia: mild cognitive impairment (an evidence-based review). Report of the Quality Standards Subcommittee of the American Academy of Neurology Neurology 2001 56 1133 42 11342677
- Ripich DN Terrell BY Patterns of discourse cohesion and coherence in Alzheimer's disease J Speech Hear Disord 1988 53 8 15 3339870
- Rohrer JD Rossor MN Warren JD Alzheimer's pathology in primary progressive aphasia Neurobiol Aging 2012 33 744 52 20580129 PMC3314936
- Roth M Tym E Mountjoy CQ Huppert FA Hendrie H Verma S CAMDEX. A standardised instrument for the diagnosis of mental disorder in the elderly with special reference to the early detection of dementia Br J Psychiatry 1986 149 698 709 3790869
- Rouleau I Salmon DP Butters N Longitudinal analysis of clock drawing in Alzheimer's disease patients Brain Cogn 1996 31 17 34 8790932
- Saffran EM Berndt RS Schwartz MF The quantitative analysis of agrammatic production: procedure and data Brain Lang 1989 37 440 79 2804622
- Snowdon DA Kemper SJ Mortimer JA Greiner LH Wekstein DR Markesbery WR Linguistic ability in early life and cognitive function and Alzheimer's disease in late life. Findings from the Nun Study JAMA 1996 275 528 32 8606473
- Tomoeda CK Bayles KA Longitudinal effects of Alzheimer disease on discourse production Alzheimer Dis Assoc Disord 1993 7 223 36 8305190
- Tomoeda CK Bayles KA Trosset MW Azuma T McGeagh A Cross-sectional analysis of Alzheimer disease effects on oral discourse in a picture description task Alzheimer Dis Assoc Disord 1996 10 204 15 8939280
- Vuorinen E Laine M Rinne J Common pattern of language impairment in vascular dementia and in Alzheimer disease Alzheimer Dis Assoc Disord 2000 14 81 6 10850746
- Wilson SM Henry ML Besbris M Ogar JM Dronkers NF Jarrold W Connected speech production in three variants of primary progressive aphasia Brain 2010 133 2069 88 20542982 PMC2892940
Cited by
Sorted by citations
Linguistic Features Identify Alzheimer’s Disease in Narrative Speech
Fraser, K. C., Meltzer, J. A., & Rudzicz, F. (2015) · Journal of Alzheimer's Disease · doi:10.3233/jad-150520 · Cited by 797 · see citing works
Automatic speech analysis for the assessment of patients with predementia and Alzheimer's disease
König, A., Satt, A., Sorin, A., Hoory, R., Toledo‐Ronen, O., Derreumaux, A., Manera, V., Verhey, F., Aalten, P., Robert, P. H., et al. (2015) · Alzheimer's & Dementia: Diagnosis, Assessment & Disease Monitoring · doi:10.1016/j.dadm.2014.11.012 · Cited by 380 · see citing works
Connected Speech in Neurodegenerative Language Disorders: A Review
Boschi, V., Catricalà, E., Consonni, M., Chesi, C., Moro, A., & Cappa, S. F. (2017) · Frontiers in Psychology · doi:10.3389/fpsyg.2017.00269 · Cited by 362 · see citing works
Mueller, K. D., Hermann, B., Mecollari, J., & Turkstra, L. S. (2018) · Journal of Clinical and Experimental Neuropsychology · doi:10.1080/13803395.2018.1446513 · Cited by 336 · see citing works
Predicting mild cognitive impairment from spontaneous spoken utterances
Asgari, M., Kaye, J., & Dodge, H. (2017) · Alzheimer's & Dementia: Translational Research & Clinical Interventions · doi:10.1016/j.trci.2017.01.006 · Cited by 185 · see citing works
Beltrami, D., Gagliardi, G., Rossini Favretti, R., Ghidoni, E., Tamburini, F., & Calzà, L. (2018) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2018.00369 · Cited by 175 · see citing works
A systematic literature review of automatic Alzheimer’s disease detection from speech and language
Petti, U., Baker, S., & Korhonen, A. (2020) · Journal of the American Medical Informatics Association · doi:10.1093/jamia/ocaa174 · Cited by 168 · see citing works
Dodge, H. H., Zhu, J., Mattek, N. C., Bowman, M., Ybarra, O., Wild, K. V., Loewenstein, D. A., & Kaye, J. A. (2015) · Alzheimer's & Dementia: Translational Research & Clinical Interventions · doi:10.1016/j.trci.2015.01.001 · Cited by 129 · see citing works
Connected speech features from picture description in Alzheimer's disease: a systematic review
Slegers, A., Filiou, R.-P., Montembeault, M., & Brambati, S. M. (2018) · Journal of Alzheimer’s Disease · doi:10.3233/jad-170881 · Cited by 124 · see citing works
Speech and language markers of neurodegeneration: a call for global equity
García, A. M., de Leon, J., Tee, B. L., Blasi, D. E., & Gorno-Tempini, M. L. (2023) · Brain · doi:10.1093/brain/awad253 · Cited by 102 · see citing works
Speech-based automatic and robust detection of very early dementia
Satt, A., Hoory, R., König, A., Aalten, P., & Robert, P. H. (2014) · Interspeech 2014 · doi:10.21437/interspeech.2014-544 · Cited by 76 · see citing works
Severity of Alzheimer’s disease and language features in picture descriptions
Kavé, G., & Dassa, A. (2018) · Aphasiology · doi:10.1080/02687038.2017.1303441 · Cited by 72 · see citing works
Lindsay, H., Tröger, J., & König, A. (2021) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2021.642033 · Cited by 64 · see citing works
Vector-space topic models for detecting Alzheimer's disease
Yancheva, M., & Rudzicz, F. (2016) · Proceedings of the 54th Annual Meeting of the Association for Computational Linguistics (Volume 1: Long Papers) · doi:10.18653/v1/p16-1221 · Cited by 57 · see citing works
Martinc, M., Haider, F., Pollak, S., & Luz, S. (2021) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2021.642647 · Cited by 55 · see citing works
“This heterogeneity seems to be more evident in AD than in specific disorders such as primary progressive aphasia (Ahmed et al., 2013), especially in early stages of AD (Hodges and Patterson, 1995).”
BackgroundMotor speech signature of behavioral variant frontotemporal dementia: Refining the phenotype
Vogel, A. P., Poole, M. L., Pemberton, H., Caverlé, M. W. J., Boonstra, F. M. C., Low, E., Darby, D., & Brodtmann, A. (2017) · Neurology · doi:10.1212/wnl.0000000000004248 · Cited by 49 · see citing works
Two-stage feature selection of voice parameters for early Alzheimer’s disease prediction
Mirzaei, S., El Yacoubi, M., Garcia-Salicetti, S., Boudy, J., Kahindo, C., Cristancho-Lacroix, V., Kerhervé, H., & Rigaud, A.-S. (2018) · IRBM · doi:10.1016/j.irbm.2018.10.016 · Cited by 52 · see citing works
Ostrand, R., & Gunstad, J. (2021) · Journal of Geriatric Psychiatry and Neurology · doi:10.1177/0891988720933358 · Cited by 49 · see citing works
A remote speech-based AI system to screen for early Alzheimer's disease via smartphones
Fristed, E., Skirrow, C., Meszaros, M., Lenain, R., Meepegama, U., Cappa, S., Aarsland, D., & Weston, J. (2022) · Alzheimer's & Dementia: Diagnosis, Assessment & Disease Monitoring · doi:10.1002/dad2.12366 · Cited by 47 · see citing works
Kobayashi, M., Kosugi, A., Takagi, H., Nemoto, M., Nemoto, K., Arai, T., & Yamada, Y. (2019) · Lecture Notes in Computer Science · doi:10.1007/978-3-030-29390-1_4 · Cited by 45 · see citing works
Identifying and Avoiding Confusion in Dialogue with People with Alzheimer's Disease
Chinaei, H., Currie, L. C., Danks, A., Lin, H., Mehta, T., & Rudzicz, F. (2017) · Computational Linguistics · doi:10.1162/coli_a_00290 · Cited by 30 · see citing works
Fristed, E., Skirrow, C., Meszaros, M., Lenain, R., Meepegama, U., Papp, K. V., Ropacki, M., & Weston, J. (2022) · Brain Communications · doi:10.1093/braincomms/fcac231 · Cited by 29 · see citing works
Automated detection of progressive speech changes in early Alzheimer's disease
Robin, J., Xu, M., Balagopalan, A., Novikova, J., Kahn, L., Oday, A., Hejrati, M., Hashemifar, S., Negahdar, M., Simpson, W., et al. (2023) · Alzheimer's & Dementia: Diagnosis, Assessment & Disease Monitoring · doi:10.1002/dad2.12445 · Cited by 21 · see citing works
Automatic classification of AD pathology in FTD phenotypes using natural speech
Cho, S., Olm, C. A., Ash, S., Shellikeri, S., Agmon, G., Cousins, K. A. Q., Irwin, D. J., Grossman, M., Liberman, M., & Nevler, N. (2024) · Alzheimer's & Dementia · doi:10.1002/alz.13748 · Cited by 13 · see citing works
Neurodegenerative Disorders of Speech and Language: Non-language-dominant Diseases
García, A. M., DeLeon, J., & Tee, B. L. (2022) · Encyclopedia of Behavioral Neuroscience, 2nd edition · doi:10.1016/b978-0-12-819641-0.00042-6 · Cited by 10 · see citing works
- Authors
- Ahmed, S., Haigh, A.-M. F., de Jager, C. A., & Garrard, P.
- Affiliations
- St George's, University of London (GB)
- John Radcliffe Hospital (GB)
- Corresponding author
- Garrard, Peter
- Venue
- Brain
- Publisher
- Oxford University Press (OUP)
- Published
- 2013-10-18
- Volume
- 136
- Issue
- 12
- Pages
- 3727-3737
- ISSN
- 0006-8950 (ISSN-L)
- 1460-2156
- PMC
- PMC3859216
- OpenAlex
- W2112224561
- Cited by
- 362
- References
- 5
- Citations by year
- 2026: 35 · 2025: 44 · 2024: 34 · 2023: 39 · 2022: 37 · 2021: 44 · 2020: 47 · 2019: 23 · 2018: 20 · 2017: 16 · 2016: 12 · 2015: 9 · 2014: 2
- FWCI
- 5.45
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- cc-by
- Locations
- Brain (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- St George's Online Research Archive (St George's University of London) (acceptedVersion)
- Funders
- Medical Research Council
- Topics
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Life Sciences › Neuroscience › Cognitive Neuroscience › Neurobiology of Language and Bilingualism
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Keywords
- Alzheimer's disease, connected speech, language impairment, disease progression, mild cognitive impairment, prodromal Alzheimer's disease, syntactic complexity, semantic content, lexical content, speech fluency, longitudinal assessment
- MeSH terms
- Aged, Aged, 80 and over, Alzheimer Disease, Autopsy, Cognition Disorders, Female, Humans, Language Disorders, Language Tests, Longitudinal Studies, Male, Middle Aged, Neuropsychological Tests, Speech, Linear Models, Disease Progression
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
