Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress
Clinical Collections
Advances in Alzheimer’s

Keynote webinar | Spotlight on medication adherence

LIVE: Thursday 27th June 2024, 18:00-19:30 (CEST)
Join our expert panel to discover why you need to understand the drivers of non-adherence in your patients, and how you can optimize medication adherence in your clinics to drastically improve patient outcomes.
ADVANCED SEARCH
Log in
Top
Alzheimer's Research & Therapy
Published in: Alzheimer's Research & Therapy 1/2023

Open Access 01-12-2023 | Aphasia | Research

The neural substrates of transdiagnostic cognitive-linguistic heterogeneity in primary progressive aphasia

Authors: Siddharth Ramanan, Ajay D. Halai, Lorna Garcia-Penton, Alistair G. Perry, Nikil Patel, Katie A. Peterson, Ruth U. Ingram, Ian Storey, Stefano F. Cappa, Eleonora Catricala, Karalyn Patterson, James B. Rowe, Peter Garrard, Matthew A. Lambon Ralph

Published in: Alzheimer's Research & Therapy | Issue 1/2023

Login to get access

Abstract

Background

Clinical variants of primary progressive aphasia (PPA) are diagnosed based on characteristic patterns of language deficits, supported by corresponding neural changes on brain imaging. However, there is (i) considerable phenotypic variability within and between each diagnostic category with partially overlapping profiles of language performance between variants and (ii) accompanying non-linguistic cognitive impairments that may be independent of aphasia magnitude and disease severity. The neurobiological basis of this cognitive-linguistic heterogeneity remains unclear. Understanding the relationship between these variables would improve PPA clinical/research characterisation and strengthen clinical trial and symptomatic treatment design. We address these knowledge gaps using a data-driven transdiagnostic approach to chart cognitive-linguistic differences and their associations with grey/white matter degeneration across multiple PPA variants.

Methods

Forty-seven patients (13 semantic, 15 non-fluent, and 19 logopenic variant PPA) underwent assessment of general cognition, errors on language performance, and structural and diffusion magnetic resonance imaging to index whole-brain grey and white matter changes. Behavioural data were entered into varimax-rotated principal component analyses to derive orthogonal dimensions explaining the majority of cognitive variance. To uncover neural correlates of cognitive heterogeneity, derived components were used as covariates in neuroimaging analyses of grey matter (voxel-based morphometry) and white matter (network-based statistics of structural connectomes).

Results

Four behavioural components emerged: general cognition, semantic memory, working memory, and motor speech/phonology. Performance patterns on the latter three principal components were in keeping with each variant’s characteristic profile, but with a spectrum rather than categorical distribution across the cohort. General cognitive changes were most marked in logopenic variant PPA. Regardless of clinical diagnosis, general cognitive impairment was associated with inferior/posterior parietal grey/white matter involvement, semantic memory deficits with bilateral anterior temporal grey/white matter changes, working memory impairment with temporoparietal and frontostriatal grey/white matter involvement, and motor speech/phonology deficits with inferior/middle frontal grey matter alterations.

Conclusions

Cognitive-linguistic heterogeneity in PPA closely relates to individual-level variations on multiple behavioural dimensions and grey/white matter degeneration of regions within and beyond the language network. We further show that employment of transdiagnostic approaches may help to understand clinical symptom boundaries and reveal clinical and neural profiles that are shared across categorically defined variants of PPA.
Appendix
Available only for authorised users
Literature
1.
Gorno-Tempini ML, Hillis AE, Weintraub S, Kertesz A, Mendez M, Cappa SF, et al. Classification of primary progressive aphasia and its variants. Neurology. 2011;76(11):1006–14.PubMedPubMedCentralCrossRef
2.
3.
Hodges JR, Patterson K. Semantic dementia: a unique clinicopathological syndrome. Lancet Neurol. 2007;6(11):1004–14.PubMedCrossRef
4.
Snowden J, Goulding PJ, David N. Semantic dementia: a form of circumscribed cerebral atrophy. Behav Neurol. 1989;2(3):167–82.CrossRef
5.
6.
Gorno-Tempini ML, Brambati SM, Ginex V, Ogar J, Dronkers NF, Marcone A, et al. The logopenic/phonological variant of primary progressive aphasia. Neurology. 2008;71(16):1227–34.PubMedPubMedCentralCrossRef
7.
Ingram RU, Halai AD, Pobric G, Sajjadi S, Patterson K, Lambon Ralph MA. Graded, multidimensional intra- and intergroup variations in primary progressive aphasia and post-stroke aphasia. Brain. 2020;143(10):3121–35.PubMedPubMedCentralCrossRef
8.
Sajjadi SA, Patterson K, Arnold RJ, Watson PC, Nestor PJ. Primary progressive aphasia: a tale of two syndromes and the rest. Neurology. 2012;78(21):1670–7.PubMedPubMedCentralCrossRef
9.
Watanabe H, Hikida S, Ikeda M, Mori E. Unclassified fluent variants of primary progressive aphasia: distinction from semantic and logopenic variants. Brain Commun. 2022;4(3):fcac015.PubMedPubMedCentralCrossRef
10.
Harris JM, Saxon JA, Jones M, Snowden JS, Thompson JC. Neuropsychological differentiation of progressive aphasic disorders. J Neuropsychol. 2019;13(2):214–39.PubMedCrossRef
11.
Mesulam MM, Wieneke C, Thompson C, Rogalski E, Weintraub S. Quantitative classification of primary progressive aphasia at early and mild impairment stages. Brain. 2012;135(Pt 5):1537–53.PubMedPubMedCentralCrossRef
12.
Wilson SM, Henry ML, Besbris M, Ogar JM, Dronkers NF, Jarrold W, et al. Connected speech production in three variants of primary progressive aphasia. Brain. 2010;133(Pt 7):2069–88.PubMedPubMedCentralCrossRef
13.
Vonk JM, Jonkers R, Hubbard HI, Gorno-Tempini ML, Brickman AM, Obler LK. Semantic and lexical features of words dissimilarly affected by non-fluent, logopenic, and semantic primary progressive aphasia. J Int Neuropsychol Soc. 2019;25(10):1011–22.PubMedPubMedCentralCrossRef
14.
Dalton SGH, Shultz C, Henry ML, Hillis AE, Richardson JD. Describing phonological paraphasias in three variants of primary progressive aphasia. Am J Speech Lang Pathol. 2018;27(1S):336–49.PubMedPubMedCentralCrossRef
15.
Leyton CE, Savage S, Irish M, Schubert S, Piguet O, Ballard KJ, et al. Verbal repetition in primary progressive aphasia and Alzheimer’s disease. J Alzheimers Dis. 2014;41(2):575–85.PubMedCrossRef
16.
Croot K, Ballard K, Leyton CE, Hodges JR. Apraxia of speech and phonological errors in the diagnosis of nonfluent/agrammatic and logopenic variants of primary progressive aphasia. J Speech Lang Hear Res. 2012;55(5):S1562–72.PubMedCrossRef
17.
Sajjadi SA, Patterson K, Tomek M, Nestor PJ. Abnormalities of connected speech in the non-semantic variants of primary progressive aphasia. Aphasiology. 2012;26(10):1219–37.CrossRef
18.
Knibb JA, Woollams AM, Hodges JR, Patterson K. Making sense of progressive non-fluent aphasia: an analysis of conversational speech. Brain. 2009;132(Pt 10):2734–46.PubMedPubMedCentralCrossRef
19.
Migliaccio R, Boutet C, Valabregue R, Ferrieux S, Nogues M, Lehéricy S, et al. The brain network of naming: a lesson from primary progressive aphasia. PLoS ONE. 2016;11(2):e0148707.PubMedPubMedCentralCrossRef
20.
Ramanan S, Roquet D, Goldberg ZL, Hodges JR, Piguet O, Irish M, et al. Establishing two principal dimensions of cognitive variation in logopenic progressive aphasia. Brain communications. 2020;2(2):fcaa125.PubMedPubMedCentralCrossRef
21.
Catricalà E, Santi GC, Polito C, Conca F, Esposito V, Caminiti SP, et al. Comprehensive qualitative characterization of linguistic performance profiles in primary progressive aphasia: a multivariate study with FDG-PET. Neurobiol Aging. 2022;120:137–48.PubMedCrossRef
22.
Enderby P, Crow E. Frenchay Aphasia Screening Test: validity and comparability. Disabil Rehabil. 1996;18(5):238–40.PubMedCrossRef
23.
Swinburn K, Porter G, Howard D. Comprehensive aphasia test. 2004.
24.
Azuar C, Leger A, Arbizu C, Henry-Amar F, Chomel-Guillaume S, Samson Y. The Aphasia Rapid Test: an NIHSS-like aphasia test. J Neurol. 2013;260(8):2110–7.PubMedPubMedCentralCrossRef
25.
Clark HM, Utianski RL, Duffy JR, Strand EA, Botha H, Josephs KA, et al. Western aphasia battery-revised profiles in primary progressive aphasia and primary progressive apraxia of speech. Am J Speech Lang Pathol. 2020;29(1S):498–510.PubMedCrossRef
26.
Rogalski E, Cobia D, Harrison TM, Wieneke C, Weintraub S, Mesulam MM. Progression of language decline and cortical atrophy in subtypes of primary progressive aphasia. Neurology. 2011;76(21):1804–10.PubMedPubMedCentralCrossRef
27.
Mesulam MM. Slowly progressive aphasia without generalized dementia. Ann Neurol. 1982;11(6):592–8.PubMedCrossRef
28.
Ulugut H, Stek S, Wagemans LE, Jutten RJ, Keulen MA, Bouwman FH, et al. The natural history of primary progressive aphasia: beyond aphasia. J Neurol. 2022;269(3):1375–85.PubMedCrossRef
29.
Bozeat S, Lambon Ralph MA, Patterson K, Garrard P, Hodges JR. Non-verbal semantic impairment in semantic dementia. Neuropsychologia. 2000;38(9):1207–15.PubMedCrossRef
30.
Macoir J, Lavoie M, Laforce R Jr, Brambati SM, Wilson MA. Dysexecutive symptoms in primary progressive aphasia: beyond diagnostic criteria. J Geriatr Psychiatry Neurol. 2017;30(3):151–61.PubMedCrossRef
31.
Ramanan S, Marstaller L, Hodges JR, Piguet O, Irish M. Understanding the neural basis of episodic amnesia in logopenic progressive aphasia: a multimodal neuroimaging study. Cortex. 2020;125:272–87.PubMedCrossRef
32.
Watson CL, Possin K, Allen IE, Hubbard HI, Meyer M, Welch AE, et al. Visuospatial functioning in the primary progressive aphasias. J Int Neuropsychol Soc. 2018;24(3):259–68.PubMedCrossRef
33.
Kamath V, Sutherland ER, Chaney G-A. A meta-analysis of neuropsychological functioning in the logopenic variant of primary progressive aphasia: comparison with the semantic and non-fluent variants. J Int Neuropsychol Soc. 2020;26(3):322–30.PubMedCrossRef
34.
Ramanan S, Flanagan E, Leyton CE, Villemagne VL, Rowe CC, Hodges JR, et al. Non-verbal episodic memory deficits in primary progressive aphasias are highly predictive of underlying amyloid pathology. J Alzheimer’s Dis. 2016;51(2):367–76.CrossRef
35.
Ramanan S, Foxe D, El-Omar H, Ahmed RM, Hodges JR, Piguet O, et al. Evidence for a pervasive autobiographical memory impairment in Logopenic Progressive Aphasia. Neurobiol Aging. 2021;108:168–78.PubMedCrossRef
36.
Foxe D, Leyton CE, Hodges JR, Burrell JR, Irish M, Piguet O. The neural correlates of auditory and visuospatial span in logopenic progressive aphasia and Alzheimer’s disease. Cortex. 2016;83:39–50.PubMedCrossRef
37.
Conca F, Esposito V, Giusto G, Cappa SF, Catricala E. Characterization of the logopenic variant of Primary Progressive Aphasia: a systematic review and meta-analysis. Ageing Res Rev. 2022;82:101760.PubMedCrossRef
38.
Ramanan S, Irish M, Patterson K, Rowe JB, Gorno-Tempini ML, Lambon Ralph MA. Understanding the multidimensional cognitive deficits of logopenic variant primary progressive aphasia. Brain. 2022.
39.
Owens TE, Machulda MM, Duffy JR, Strand EA, Clark HM, Boland S, et al. Patterns of Neuropsychological dysfunction and cortical volume changes in Logopenic Aphasia. J Alzheimers Dis. 2018;66(3):1015–25.PubMedPubMedCentralCrossRef
40.
Brown JA, Deng J, Neuhaus J, Sible IJ, Sias AC, Lee SE, et al. Patient-tailored, connectivity-based forecasts of spreading brain atrophy. Neuron. 2019;104(5):856-68 e5.PubMedPubMedCentralCrossRef
41.
Mandelli ML, Vilaplana E, Brown JA, Hubbard HI, Binney RJ, Attygalle S, et al. Healthy brain connectivity predicts atrophy progression in non-fluent variant of primary progressive aphasia. Brain. 2016;139(Pt 10):2778–91.PubMedPubMedCentralCrossRef
42.
Seeley WW, Crawford RK, Zhou J, Miller BL, Greicius MD. Neurodegenerative diseases target large-scale human brain networks. Neuron. 2009;62(1):42–52.PubMedPubMedCentralCrossRef
43.
Collins JA, Montal V, Hochberg D, Quimby M, Mandelli ML, Makris N, et al. Focal temporal pole atrophy and network degeneration in semantic variant primary progressive aphasia. Brain. 2017;140(2):457–71.PubMedCrossRef
44.
Bonakdarpour B, Hurley RS, Wang AR, Fereira HR, Basu A, Chatrathi A, et al. Perturbations of language network connectivity in primary progressive aphasia. Cortex. 2019;121:468–80.PubMedPubMedCentralCrossRef
45.
Mesulam MM, Rogalski EJ, Wieneke C, Hurley RS, Geula C, Bigio EH, et al. Primary progressive aphasia and the evolving neurology of the language network. Nat Rev Neurol. 2014;10(10):554–69.PubMedPubMedCentralCrossRef
46.
Schwindt GC, Graham NL, Rochon E, Tang-Wai DF, Lobaugh NJ, Chow TW, et al. Whole-brain white matter disruption in semantic and nonfluent variants of primary progressive aphasia. Hum Brain Mapp. 2013;34(4):973–84.PubMedCrossRef
47.
Galantucci S, Tartaglia MC, Wilson SM, Henry ML, Filippi M, Agosta F, et al. White matter damage in primary progressive aphasias: a diffusion tensor tractography study. Brain. 2011;134(10):3011–29.PubMedPubMedCentralCrossRef
48.
Agosta F, Ferraro PM, Canu E, Copetti M, Galantucci S, Magnani G, et al. Differentiation between subtypes of primary progressive aphasia by using cortical thickness and diffusion-tensor MR imaging measures. Radiology. 2015;276(1):219–27.PubMedCrossRef
49.
Acosta-Cabronero J, Patterson K, Fryer TD, Hodges JR, Pengas G, Williams GB, et al. Atrophy, hypometabolism and white matter abnormalities in semantic dementia tell a coherent story. Brain. 2011;134(Pt 7):2025–35.PubMedCrossRef
50.
Mahoney CJ, Malone IB, Ridgway GR, Buckley AH, Downey LE, Golden HL, et al. White matter tract signatures of the progressive aphasias. Neurobiol Aging. 2013;34(6):1687–99.PubMedPubMedCentralCrossRef
51.
Catani M, Mesulam MM, Jakobsen E, Malik F, Martersteck A, Wieneke C, et al. A novel frontal pathway underlies verbal fluency in primary progressive aphasia. Brain. 2013;136(Pt 8):2619–28.PubMedPubMedCentralCrossRef
52.
Powers JP, McMillan CT, Brun CC, Yushkevich PA, Zhang H, Gee JC, et al. White matter disease correlates with lexical retrieval deficits in primary progressive aphasia. Front Neurol. 2013;4:212.PubMedPubMedCentralCrossRef
53.
Luo C, Makaretz S, Stepanovic M, Papadimitriou G, Quimby M, Palanivelu S, et al. Middle longitudinal fascicle is associated with semantic processing deficits in primary progressive aphasia. Neuroimage Clin. 2020;25:102115.PubMedCrossRef
54.
D’Anna L, Mesulam MM, de ThiebautSchotten M, Dell’Acqua F, Murphy D, Wieneke C, et al. Frontotemporal networks and behavioral symptoms in primary progressive aphasia. Neurology. 2016;86(15):1393–9.PubMedPubMedCentralCrossRef
55.
Agosta F, Galantucci S, Canu E, Cappa SF, Magnani G, Franceschi M, et al. Disruption of structural connectivity along the dorsal and ventral language pathways in patients with nonfluent and semantic variant primary progressive aphasia: a DT MRI study and a literature review. Brain Lang. 2013;127(2):157–66.PubMedCrossRef
56.
Jeurissen B, Leemans A, Tournier JD, Jones DK, Sijbers J. Investigating the prevalence of complex fiber configurations in white matter tissue with diffusion magnetic resonance imaging. Hum Brain Mapp. 2013;34(11):2747–66.PubMedCrossRef
57.
Dell’Acqua F, Tournier JD. Modelling white matter with spherical deconvolution: how and why? NMR Biomed. 2019;32(4):e3945.PubMedCrossRef
58.
Patel N, Peterson KA, Ingram RU, Storey I, Cappa SF, Catricala E, et al. A “Mini Linguistic State Examination” to classify primary progressive aphasia. Brain Commun. 2022;4(2):fcab299.PubMedCrossRef
59.
Peterson KA, Jones PS, Patel N, Tsvetanov KA, Ingram R, Cappa SF, et al. Language disorder in progressive supranuclear palsy and corticobasal syndrome: neural correlates and detection by the MLSE screening tool. Front Aging Neurosci. 2021;13:675739.PubMedPubMedCentralCrossRef
60.
Matias-Guiu JA, Pytel V, Hernandez-Lorenzo L, Patel N, Peterson KA, Matias-Guiu J, et al. Spanish version of the mini-linguistic state examination for the diagnosis of primary progressive aphasia. J Alzheimers Dis. 2021;83(2):771–8.PubMedCrossRef
61.
Catricalà E, Polito C, Presotto L, Esposito V, Sala A, Conca F, et al. Neural correlates of naming errors across different neurodegenerative diseases: An FDG-PET study. Neurology. 2020;95(20):e2816–30.PubMedCrossRef
62.
Bruffaerts R, Schaeverbeke J, De Weer A-S, Nelissen N, Dries E, Van Bouwel K, et al. Multivariate analysis reveals anatomical correlates of naming errors in primary progressive aphasia. Neurobiol Aging. 2020;88:71–82.PubMedCrossRef
63.
Budd MA, Kortte K, Cloutman L, Newhart M, Gottesman RF, Davis C, et al. The nature of naming errors in primary progressive aphasia versus acute post-stroke aphasia. Neuropsychology. 2010;24(5):581.PubMedPubMedCentralCrossRef
64.
Hsieh S, Schubert S, Hoon C, Mioshi E, Hodges JR. Validation of the Addenbrooke’s Cognitive Examination III in frontotemporal dementia and Alzheimer’s disease. Dement Geriatr Cogn Disord. 2013;36(3–4):242–50.PubMedCrossRef
65.
Leyton CE, Hornberger M, Mioshi E, Hodges JR. Application of Addenbrooke’s cognitive examination to diagnosis and monitoring of progressive primary aphasia. Dement Geriatr Cogn Disord. 2010;29(6):504–9.PubMedCrossRef
66.
Schilling K, Janve V, Gao Y, Stepniewska I, Landman BA, Anderson AW. Comparison of 3D orientation distribution functions measured with confocal microscopy and diffusion MRI. Neuroimage. 2016;129:185–97.PubMedCrossRef
67.
Dhollander T, Clemente A, Singh M, Boonstra F, Civier O, Duque JD, et al. Fixel-based analysis of diffusion MRI: methods, applications, challenges and opportunities. Neuroimage. 2021;241:118417.PubMedCrossRef
68.
Savard M, Pascoal TA, Servaes S, Dhollander T, Iturria-Medina Y, Kang MS, et al. Impact of long-and short-range fibre depletion on the cognitive deficits of fronto-temporal dementia. Elife. 2022;11.
69.
Mito R, Raffelt D, Dhollander T, Vaughan DN, Tournier J-D, Salvado O, et al. Fibre-specific white matter reductions in Alzheimer’s disease and mild cognitive impairment. Brain. 2018;141(3):888–902.PubMedCrossRef
70.
Murley AG, Coyle-Gilchrist I, Rouse MA, Jones PS, Li W, Wiggins J, et al. Redefining the multidimensional clinical phenotypes of frontotemporal lobar degeneration syndromes. Brain. 2020;143(5):1555–71.PubMedPubMedCentralCrossRef
71.
Ramanan S, El-Omar H, Roquet D, Ahmed RM, Hodges JR, Piguet O, et al. Mapping behavioural, cognitive and affective transdiagnostic dimensions in frontotemporal dementia. Brain Commun. 2023;5(1):fcac344.PubMedPubMedCentralCrossRef
72.
Fan JM, Gorno-Tempini ML, Dronkers NF, Miller BL, Berger MS, Chang EF. Data-Driven, Visual framework for the characterization of aphasias across stroke, post-resective, and neurodegenerative disorders over time. Front Neurol. 2020;11:616764.PubMedPubMedCentralCrossRef
73.
Butler RA, Lambon Ralph MA, Woollams AM. Capturing multidimensionality in stroke aphasia: mapping principal behavioural components to neural structures. Brain. 2014;137(Pt 12):3248–66.PubMedPubMedCentralCrossRef
74.
Cornblath EJ, Robinson JL, Irwin DJ, Lee EB, Lee VM, Trojanowski JQ, et al. Defining and predicting transdiagnostic categories of neurodegenerative disease. Nat Biomed Eng. 2020;4(8):787–800.PubMedPubMedCentralCrossRef
75.
Ding J, Chen K, Liu H, Huang L, Chen Y, Lv Y, et al. A unified neurocognitive model of semantics language social behaviour and face recognition in semantic dementia. Nat Commun. 2020;11(1):2595.PubMedPubMedCentralCrossRef
76.
Verdi S, Marquand AF, Schott JM, Cole JH. Beyond the average patient: how neuroimaging models can address heterogeneity in dementia. Brain. 2021;144(10):2946–53.PubMedPubMedCentralCrossRef
77.
78.
Tournier JD, Smith R, Raffelt D, Tabbara R, Dhollander T, Pietsch M, et al. MRtrix3: a fast, flexible and open software framework for medical image processing and visualisation. Neuroimage. 2019;202:116137.PubMedCrossRef
79.
Avants BB, Tustison N, Song G. Advanced normalization tools (ANTS). Insight j. 2009;2(365):1–35.
80.
Schilling KG, Blaber J, Hansen C, Cai L, Rogers B, Anderson AW, et al. Distortion correction of diffusion weighted MRI without reverse phase-encoding scans or field-maps. PLoS ONE. 2020;15(7):e0236418.PubMedPubMedCentralCrossRef
81.
82.
Cordero-Grande L, Christiaens D, Hutter J, Price AN, Hajnal JV. Complex diffusion-weighted image estimation via matrix recovery under general noise models. Neuroimage. 2019;200:391–404.PubMedCrossRef
83.
Kellner E, Dhital B, Kiselev VG, Reisert M. Gibbs-ringing artifact removal based on local subvoxel-shifts. Magn Reson Med. 2016;76(5):1574–81.PubMedCrossRef
84.
Andersson JLR, Graham MS, Zsoldos E, Sotiropoulos SN. Incorporating outlier detection and replacement into a non-parametric framework for movement and distortion correction of diffusion MR images. Neuroimage. 2016;141:556–72.PubMedCrossRef
85.
Andersson JLR, Sotiropoulos SN. An integrated approach to correction for off-resonance effects and subject movement in diffusion MR imaging. Neuroimage. 2016;125:1063–78.PubMedCrossRef
86.
Tustison NJ, Avants BB, Cook PA, Zheng Y, Egan A, Yushkevich PA, et al. N4ITK: improved N3 bias correction. IEEE Trans Med Imaging. 2010;29(6):1310–20.PubMedPubMedCentralCrossRef
87.
Dhollander T, Raffelt D, Connelly A. Unsupervised 3-tissue response function estimation from single-shell or multi-shell diffusion MR data without a co-registered T1 image. ISMRM Workshop on Breaking the Barriers of Diffusion MRI. 2016.
88.
Dhollander T, Connelly A. A novel iterative approach to reap the benefits of multi-tissue CSD from just single-shell (+b=0) diffusion MRI data. ISMRM 24th Annual Meeting & Exhibition. 2016.
89.
Dhollander T, Tabbara R, Rosnarho-Tornstrand J, Tournier JD, Raffelt D, Connelly A. Multi-tissue log-domain intensity and inhomogeneity normalisation for quantitative apparent fibre density. ISMRM. 2021.
90.
Fornito A, Zalesky A, Breakspear M. The connectomics of brain disorders. Nat Rev Neurosci. 2015;16(3):159–72.PubMedCrossRef
91.
92.
Tzourio-Mazoyer N, Landeau B, Papathanassiou D, Crivello F, Etard O, Delcroix N, et al. Automated anatomical labeling of activations in SPM using a macroscopic anatomical parcellation of the MNI MRI single-subject brain. Neuroimage. 2002;15(1):273–89.PubMedCrossRef
93.
R Core Team. R language and environment for statistical computing. Austria: R Foundation for Statistical Computing; 2022.
94.
The MathWorks Inc. MATLAB. 7.10.0 ed. Natick, MA. 2010.
95.
Ballabio D. A MATLAB toolbox for Principal Component Analysis and unsupervised exploration of data structure. Chemometr Intell Lab Syst. 2015;149:1–9.CrossRef
96.
Ilin A, Raiko T. Practical approaches to principal component analysis in the presence of missing values. J Mach Learn Res. 2010;11:1957–2000.
97.
Tipping ME, Bishop CM. Probabilistic principal component analysis. J R Stat Soc. 1999;61(3):611–22.CrossRef
98.
Jolliffe I. Principal component analysis. Encyclopedia of statistics in behavioral science. 2005.
99.
Smith SM, Nichols TE. Threshold-free cluster enhancement: addressing problems of smoothing, threshold dependence and localisation in cluster inference. Neuroimage. 2009;44(1):83–98.PubMedCrossRef
100.
Zalesky A, Fornito A, Bullmore ET. Network-based statistic: identifying differences in brain networks. Neuroimage. 2010;53(4):1197–207.PubMedCrossRef
101.
Baggio HC, Abos A, Segura B, Campabadal A, Garcia-Diaz A, Uribe C, et al. Statistical inference in brain graphs using threshold-free network-based statistics. Hum Brain Mapp. 2018;39(6):2289–302.PubMedPubMedCentralCrossRef
102.
103.
Ingram RU, Halai AD, Pobric G, Sajjadi S, Patterson K, Lambon Ralph MA. Graded, multidimensional intra- and intergroup variations in primary progressive aphasia and post-stroke aphasia. Brain. 2020.
104.
Leyton CE, Hodges JR, McLean CA, Kril JJ, Piguet O, Ballard KJ. Is the logopenic-variant of primary progressive aphasia a unitary disorder? Cortex. 2015;67:122–33.PubMedCrossRef
105.
Matias-Guiu JA, Diaz-Alvarez J, Cuetos F, Cabrera-Martin MN, Segovia-Rios I, Pytel V, et al. Machine learning in the clinical and language characterisation of primary progressive aphasia variants. Cortex. 2019;119:312–23.PubMedCrossRef
106.
Husain M. Transdiagnostic neurology: neuropsychiatric symptoms in neurodegenerative diseases. Brain. 2017;140(6):1535–6.PubMedCrossRef
107.
Kamath V, Sutherland ER, Chaney GA. A meta-analysis of neuropsychological functioning in the logopenic variant of primary progressive aphasia: comparison with the semantic and non-fluent variants. J Int Neuropsychol Soc. 2019:1–9.
108.
Humphreys GF, Jackson RL, Lambon Ralph MA. Overarching principles and dimensions of the functional organization in the inferior parietal cortex. Cereb Cortex. 2020;30(11):5639–53.PubMedPubMedCentralCrossRef
109.
Humphreys GF, Lambon Ralph MA. Fusion and fission of cognitive functions in the human parietal cortex. Cereb Cortex. 2015;25(10):3547–60.PubMedCrossRef
110.
Ramanan S, Bellana B. A domain-general role for the angular gyrus in retrieving internal representations of the external world. J Neurosci. 2019;39(16):2978–80.PubMedPubMedCentralCrossRef
111.
Ramanan S, Piguet O, Irish M. Rethinking the role of the angular gyrus in remembering the past and imagining the future: the contextual integration model. Neuroscientist. 2018;24(4):342–52.PubMedCrossRef
112.
Igelstrom KM, Graziano MSA. The inferior parietal lobule and temporoparietal junction: A network perspective. Neuropsychologia. 2017;105:70–83.PubMedCrossRef
113.
Krishnan K, Machulda MM, Whitwell JL, Butts AM, Duffy JR, Strand EA, et al. Varying degrees of temporoparietal hypometabolism on FDG-PET reveal amyloid-positive logopenic primary progressive aphasia is not a homogeneous clinical entity. J Alzheimers Dis. 2017;55(3):1019–29.PubMedPubMedCentralCrossRef
114.
Mazzeo S, Polito C, Lassi M, Bagnoli S, Mattei M, Padiglioni S, et al. Loss of speech and functional impairment in Alzheimer’s disease-related primary progressive aphasia: predictive factors of decline. Neurobiol Aging. 2022;117:59–70.PubMedCrossRef
115.
Tetzloff KA, Duffy JR, Clark HM, Strand EA, Machulda MM, Schwarz CG, et al. Longitudinal structural and molecular neuroimaging in agrammatic primary progressive aphasia. Brain. 2018;141(1):302–17.PubMedCrossRef
116.
Wilson SM, Galantucci S, Tartaglia MC, Gorno-Tempini ML. The neural basis of syntactic deficits in primary progressive aphasia. Brain Lang. 2012;122(3):190–8.PubMedPubMedCentralCrossRef
117.
Lambon Ralph MA, Jefferies E, Patterson K, Rogers TT. The neural and computational bases of semantic cognition. Nat Rev Neurosci. 2017;18(1):42–55.CrossRef
118.
119.
Catricala E, Conca F, Fertonani A, Miniussi C, Cappa SF. State-dependent TMS reveals the differential contribution of ATL and IPS to the representation of abstract concepts related to social and quantity knowledge. Cortex. 2020;123:30–41.PubMedCrossRef
120.
Catricala E, Della Rosa PA, Plebani V, Vigliocco G, Cappa SF. Abstract and concrete categories? Evidences from neurodegenerative diseases. Neuropsychologia. 2014;64:271–81.PubMedCrossRef
121.
Conca F, Borsa VM, Cappa SF, Catricala E. The multidimensionality of abstract concepts: a systematic review. Neurosci Biobehav Rev. 2021;127:474–91.PubMedCrossRef
122.
Jefferies E, Lambon Ralph MA. Semantic impairment in stroke aphasia versus semantic dementia: a case-series comparison. Brain. 2006;129(Pt 8):2132–47.PubMedCrossRef
123.
Funayama M, Nakagawa Y, Yamaya Y, Yoshino F, Mimura M, Kato M. Progression of logopenic variant primary progressive aphasia to apraxia and semantic memory deficits. BMC Neurol. 2013;13:158.PubMedPubMedCentralCrossRef
124.
Lukic S, Mandelli ML, Welch A, Jordan K, Shwe W, Neuhaus J, et al. Neurocognitive basis of repetition deficits in primary progressive aphasia. Brain Lang. 2019;194:35–45.PubMedPubMedCentralCrossRef
125.
126.
Baddeley A. Working memory: looking back and looking forward. Nat Rev Neurosci. 2003;4(10):829–39.PubMedCrossRef
127.
Smith EE, Jonides J, Marshuetz C, Koeppe RA. Components of verbal working memory: evidence from neuroimaging. Proc Natl Acad Sci U S A. 1998;95(3):876–82.PubMedPubMedCentralCrossRef
128.
Eikelboom WS, Janssen N, Jiskoot LC, van den Berg E, Roelofs A, Kessels RPC. Episodic and working memory function in Primary Progressive Aphasia: a meta-analysis. Neurosci Biobehav Rev. 2018;92:243–54.PubMedCrossRef
129.
Ogar JM, Dronkers NF, Brambati SM, Miller BL, Gorno-Tempini ML. Progressive nonfluent aphasia and its characteristic motor speech deficits. Alzheimer Dis Assoc Disord. 2007;21(4):S23-30.PubMedCrossRef
130.
Josephs KA, Duffy JR, Strand EA, Whitwell JL, Layton KF, Parisi JE, et al. Clinicopathological and imaging correlates of progressive aphasia and apraxia of speech. Brain. 2006;129(Pt 6):1385–98.PubMedCrossRef
131.
Clark DG, Charuvastra A, Miller BL, Shapira JS, Mendez MF. Fluent versus nonfluent primary progressive aphasia: a comparison of clinical and functional neuroimaging features. Brain Lang. 2005;94(1):54–60.PubMedCrossRef
132.
Ash S, Evans E, O’Shea J, Powers J, Boller A, Weinberg D, et al. Differentiating primary progressive aphasias in a brief sample of connected speech. Neurology. 2013;81(4):329–36.PubMedPubMedCentralCrossRef
133.
134.
Halai AD, Woollams AM, Lambon Ralph MA. Using principal component analysis to capture individual differences within a unified neuropsychological model of chronic post-stroke aphasia: Revealing the unique neural correlates of speech fluency, phonology and semantics. Cortex. 2017;86:275–89.PubMedPubMedCentralCrossRef
135.
Roncero C, Kniefel H, Service E, Thiel A, Probst S, Chertkow H. Inferior parietal transcranial direct current stimulation with training improves cognition in anomic Alzheimer’s disease and frontotemporal dementia. Alzheimers Dement (N Y). 2017;3(2):247–53.PubMedCrossRef
136.
de Aguiar V, Rofes A, Wendt H, Ficek BN, Webster K, Tsapkini K. Treating lexical retrieval using letter fluency and tDCS in primary progressive aphasia: a single-case study. Aphasiology. 2022;36(3):353–79.CrossRef
137.
Taylor-Rubin C, Croot K, Nickels L. Speech and language therapy in primary progressive aphasia: a critical review of current practice. Expert Rev Neurother. 2021;21(4):419–30.PubMedCrossRef
138.
Gallee J, Volkmer A. Role of the speech-language therapist/pathologist in primary progressive aphasia. Neurol Clin Pract. 2023;13(4):e200178.PubMedCrossRef
Metadata
Title
The neural substrates of transdiagnostic cognitive-linguistic heterogeneity in primary progressive aphasia
Authors
Siddharth Ramanan
Ajay D. Halai
Lorna Garcia-Penton
Alistair G. Perry
Nikil Patel
Katie A. Peterson
Ruth U. Ingram
Ian Storey
Stefano F. Cappa
Eleonora Catricala
Karalyn Patterson
James B. Rowe
Peter Garrard
Matthew A. Lambon Ralph
Publication date
01-12-2023
Publisher
BioMed Central
Keyword
Aphasia
Published in
Alzheimer's Research & Therapy / Issue 1/2023
Electronic ISSN: 1758-9193
DOI
https://doi.org/10.1186/s13195-023-01350-2

Other articles of this Issue 1/2023

Alzheimer's Research & Therapy 1/2023 Go to the issue

Research

Feasibility and therapeutical potential of local intracerebral encapsulated cell biodelivery of BDNF to AppNL−G−F knock-in Alzheimer mice

Research

Home-based transcranial alternating current stimulation (tACS) in Alzheimer’s disease: rationale and study design

Research

Alzheimer’s polygenic risk scores, APOE, Alzheimer’s disease risk, and dementia-related blood biomarker levels in a population-based cohort study followed over 17 years

Review

Blood and CSF chemokines in Alzheimer’s disease and mild cognitive impairment: a systematic review and meta-analysis

Research

A biomarker-validated time scale in years of disease progression has identified early- and late-onset subgroups in sporadic Alzheimer’s disease

Research

Long-term effects of immunotherapy with a brain penetrating Aβ antibody in a mouse model of Alzheimer’s disease