Logopenic primary progressive aphasia (LPA) is often associated with Alzheimer's disease (AD) pathology. However, few studies have compared cortical atrophy patterns in LPA and AD and their association with cognitive performance.
Objective
To identify atrophy patterns specific to LPA and determine whether those patterns relate to deficits in specific cognitive domains.
Methods
Electronic health records from 2014–2024 were retrospectively reviewed to identify patients with LPA who had undergone MRI and neuropsychological (NP) examinations. Patients with LPA (n = 26) were matched in terms of age, sex, education, and symptom duration to patients with amnestic mild cognitive impairment (aMCI; n = 13). Logistic regression was used to assess group differences in MRI measures of cortical volume and thickness. Cluster analysis was used to identify patterns of atrophy that were associated with specific cognitive domains.
Results
The LPA group performed significantly worse than the aMCI group on NP measures assessing verbal learning, attention/working memory, language, and executive functioning (p < 0.05). Compared to the aMCI group, the LPA group demonstrated both smaller and thinner cortex in the left lateral aspect of the superior temporal gyrus, superior temporal sulcus, and fusiform gyrus (p < 0.05), with the left superior temporal sulcus providing the most accurate measure of discrimination. Severity of language related cognitive deficits was not associated with a specific cluster in the LPA group.
Conclusions
Patients with LPA demonstrate specific patterns of cortical atrophy that are distinguishable from atrophy due to aMCI and may be useful for diagnostic purposes.
Gorno-TempiniMLHillisAEWeintraubS, et al.Classification of primary progressive aphasia and its variants. Neurology2011; 76: 1006–1014.
2.
MesulamMWicklundAJohnsonN, et al.Alzheimer and frontotemporal pathology in subsets of primary progressive aphasia. Ann Neurol2008; 63: 709–719.
3.
BergeronDGorno-TempiniMLRabinoviciGD, et al.Prevalence of amyloid-β pathology in distinct variants of primary progressive aphasia. Ann Neurol2018; 84: 729–740.
4.
McKhannGMKnopmanDSChertkowH, et al.The diagnosis of dementia due to Alzheimer's disease: recommendations from the National Institute on Aging-Alzheimer's Association workgroups on diagnostic guidelines for Alzheimer's disease. Alzheimers Dement2011; 7: 263–269.
5.
Gorno-TempiniMLBrambatiSMGinexV, et al.The logopenic/phonological variant of primary progressive aphasia. Neurology2008; 71: 1227–1234.
6.
RabinoviciGDJagustWJFurstAJ, et al.Abeta amyloid and glucose metabolism in three variants of primary progressive aphasia. Ann Neurol2008; 64: 388–401.
7.
RogalskiECobiaDHarrisonTM, et al.Progression of language decline and cortical atrophy in subtypes of primary progressive aphasia. Neurology2011; 76: 1804–1810.
8.
RohrerJDCasoFMahoneyC, et al.Patterns of longitudinal brain atrophy in the logopenic variant of primary progressive aphasia. Brain Lang2013; 127: 121–126.
9.
ButtsAMMachuldaMMMartinP, et al.Temporal cortical thickness and cognitive associations among typical and atypical phenotypes of Alzheimer's disease. J Alzheimers Dis Rep2022; 6: 479–491.
10.
LeytonCEHodgesJRPiguetO, et al.Common and divergent neural correlates of anomia in amnestic and logopenic presentations of Alzheimer's disease. Cortex2017; 86: 45–54.
11.
OssenkoppeleRCohn-SheehyBILa JoieR, et al.Atrophy patterns in early clinical stages across distinct phenotypes of Alzheimer's disease. Hum Brain Mapp2015; 36: 4421–4437.
12.
MadhavanAWhitwellJLWeigandSD, et al.FDG PET and MRI in logopenic primary progressive aphasia versus dementia of the Alzheimer's type. PLoS One2013; 8: e62471.
13.
RamananSMarstallerLHodgesJR, et al.Understanding the neural basis of episodic amnesia in logopenic progressive aphasia: a multimodal neuroimaging study. Cortex2020; 125: 272–287.
14.
FunayamaMNakagawaYNakajimaA, et al.Dementia trajectory for patients with logopenic variant primary progressive aphasia. Neurol Sci2019; 40: 2573–2579.
15.
de la SablonnièreJTastevinMLavoieM, et al.Longitudinal changes in cognition, behaviours, and functional abilities in the three main variants of primary progressive aphasia: a literature review. Brain Sci2021; 11: 1209.
16.
OsherJEWicklundAHRademakerA, et al.The mini-mental state examination in behavioral variant frontotemporal dementia and primary progressive aphasia. Am J Alzheimers Dis Other Demen2007; 22: 468–473.
17.
NhoKRisacherSLCranePK, et al.Voxel and surface-based topography of memory and executive deficits in mild cognitive impairment and Alzheimer's disease. Brain Imaging Behav2012; 6: 551–567.
18.
DickersonBCBakkourASalatDH, et al.The cortical signature of Alzheimer's disease: regionally specific cortical thinning relates to symptom severity in very mild to mild AD dementia and is detectable in asymptomatic amyloid-positive individuals. Cereb Cortex2009; 19: 497–510.
19.
ColemanMMKeithCMWilhelmsenK, et al.Surface-based correlates of cognition along the Alzheimer's continuum in a memory clinic population. Front Neurol2023; 14: 1214083.
20.
WinKTPlutaJYushkevichP, et al.Neural correlates of verbal episodic memory and lexical retrieval in logopenic variant primary progressive aphasia. Front Neurosci2017; 11: 330.
21.
RogalskiECobiaDHarrisonTM, et al.Anatomy of language impairments in primary progressive aphasia. J Neurosci2011; 31: 3344–3350.
22.
Gorno-TempiniMLDronkersNFRankinKP, et al.Cognition and anatomy in three variants of primary progressive aphasia. Ann Neurol2004; 55: 335–346.
23.
JackCRJr.BennettDABlennowK, et al.NIA-AA Research framework: toward a biological definition of Alzheimer's disease. Alzheimers Dement2018; 14: 535–562.
24.
AlbertMSDeKoskySTDicksonD, et al.The diagnosis of mild cognitive impairment due to Alzheimer's disease: recommendations from the National Institute on Aging-Alzheimer's Association workgroups on diagnostic guidelines for Alzheimer's disease. Alzheimers Dement2011; 7: 270–279.
25.
MesulamMM. Primary progressive aphasia and the left hemisphere language network. Dement Neurocogn Disord2016; 15: 93–102.
BenedictRHBSchretlenDGroningerL, et al.Hopkins verbal learning test – revised: normative data and analysis of inter-form and test-retest reliability. Clin Neuropsychol1998; 12: 43–55.
KaplanEGoodglassHWeintraubS. Boston naming test. 2nd Ed. Austin, TX: Pro-Ed, 2001.
30.
BenedictRH. Brief visuospatial memory test - revised: professional manual. Odessa, FL: Psychological Assessment Resources, 1997.
31.
DelisDCKaplanEKramerJH. Delis–Kaplan executive function system. San Antonio: The Psychological Corporation, 2001.
32.
RosenbergAÖhlund-WistbackaUHallA, et al.β-amyloid, tau, neurodegeneration classification and eligibility for anti-amyloid treatment in a memory clinic population. Neurology2022; 99: e2102–e2113.
33.
DestrieuxCFischlBDaleA, et al.Automatic parcellation of human cortical gyri and sulci using standard anatomical nomenclature. Neuroimage2010; 53: 1–15.
34.
AugustinackJCHuberKEStevensAA, et al.Predicting the location of human perirhinal cortex, brodmann's area 35, from MRI. Neuroimage2013; 64: 32–42.
35.
FischlBStevensAARajendranN, et al.Predicting the location of entorhinal cortex from MRI. Neuroimage2009; 47: 8–17.
36.
The MathWorks Inc. MATLAB version: 9.13.0 (R2022b). Natick, MA: The MathWorks Inc, 2022.
37.
BenjaminiYHochbergY. On the adaptive control of the false discovery rate in multiple testing with independent statistics. J Educ Behav Stat2000; 25: 60–83.
38.
YoudenWJ. Index for rating diagnostic tests. Cancer1950; 3: 32–35.
39.
DiCiccioTJEfronB. Bootstrap confidence intervals. Stat Sci1996; 11: 189–228.
40.
RousseeuwPJ. Silhouettes: a graphical aid to the interpretation and validation of cluster analysis. J Comput Appl Math1987; 20: 53–65.
41.
MendezMFMonserrattLHLiangLJ, et al.Neuropsychological similarities and differences between amnestic Alzheimer's disease and its non-amnestic variants. J Alzheimers Dis2019; 69: 849–855.
42.
MagninEChopardGFerreiraS, et al.Initial neuropsychological profile of a series of 20 patients with logopenic variant of primary progressive aphasia. J Alzheimers Dis2013; 36: 799–808.
43.
ButtsAMMachuldaMMDuffyJR, et al.Neuropsychological profiles differ among the three variants of primary progressive aphasia. J Int Neuropsychol Soc2015; 21: 429–435.
