TY - JOUR
T1 - Handedness and language learning disability differentially distribute in progressive aphasia variants
AU - Miller, Zachary A.
AU - Mandelli, Maria Luisa
AU - Rankin, Katherine P.
AU - Henry, Maya L.
AU - Babiak, Miranda C.
AU - Frazier, Darvis T.
AU - Lobach, Iryna V.
AU - Bettcher, Brianne M.
AU - Wu, Teresa Q.
AU - Rabinovici, Gil D.
AU - Graff-Radford, Neill R.
AU - Miller, Bruce L.
AU - Gorno-Tempini, Maria Luisa
N1 - Funding Information:
This work was supported by National Institutes of Health (grants P50AG023501, P01AG019724, T32 AG23481, DHS 04-35516, 1 R01 NS050915-05A1, P50AG16574) and its contents are solely the responsibility of the authors and do not necessarily represent the official views of the National Institute on Aging or NIH. Additional funds include the Consortium for Frontotemporal Dementia Research and the Tau Research Consortium.
PY - 2013/11
Y1 - 2013/11
N2 - Primary progressive aphasia is a neurodegenerative clinical syndrome that presents in adulthood with an isolated, progressive language disorder. Three main clinical/anatomical variants have been described, each associated with distinctive pathology. A high frequency of neurodevelopmental learning disability in primary progressive aphasia has been reported. Because the disorder is heterogeneous with different patterns of cognitive, anatomical and biological involvement, we sought to identify whether learning disability had a predilection for one or more of the primary progressive aphasia subtypes. We screened the University of California San Francisco Memory and Aging Center's primary progressive aphasia cohort (n = 198) for history of languagerelated learning disability as well as hand preference, which has associations with learning disability. The study included logopenic (n = 48), non-fluent (n = 54) and semantic (n = 96) variant primary progressive aphasias. We investigated whether the presence of learning disability or non-right-handedness was associated with differential effects on demographic, neuropsychological and neuroimaging features of primary progressive aphasia. We showed that a high frequency of learning disability was present only in the logopenic group (X 2 = 15.17, P< 0.001) and (X2 = 11.51, P< 0.001) compared with semantic and nonfluent populations. In this group, learning disability was associated with earlier onset of disease, more isolated language symptoms, and more focal pattern of left posterior temporoparietal atrophy. Non-right-handedness was instead over-represented in the semantic group, at nearly twice the prevalence of the general population (X2 = 6.34, P = 0.01). Within semantic variant primary progressive aphasia the right-handed and non-right-handed cohorts appeared homogeneous on imaging, cognitive profile, and structural analysis of brain symmetry. Lastly, the non-fluent group showed no increase in learning disability or non-right-handedness. Logopenic variant primary progressive aphasia and developmental dyslexia both manifest with phonological disturbances and posterior temporal involvement. Learning disability might confer vulnerability of this network to earlyonset, focal Alzheimer's pathology. Left-handedness has been described as a proxy for atypical brain hemispheric lateralization. As non-right-handedness was increased only in the semantic group, anomalous lateralization mechanisms might instead be related to frontotemporal lobar degeneration with abnormal TARDBP. Taken together, this study suggests that neurodevelopmental signatures impart differential trajectories towards neurodegenerative disease.
AB - Primary progressive aphasia is a neurodegenerative clinical syndrome that presents in adulthood with an isolated, progressive language disorder. Three main clinical/anatomical variants have been described, each associated with distinctive pathology. A high frequency of neurodevelopmental learning disability in primary progressive aphasia has been reported. Because the disorder is heterogeneous with different patterns of cognitive, anatomical and biological involvement, we sought to identify whether learning disability had a predilection for one or more of the primary progressive aphasia subtypes. We screened the University of California San Francisco Memory and Aging Center's primary progressive aphasia cohort (n = 198) for history of languagerelated learning disability as well as hand preference, which has associations with learning disability. The study included logopenic (n = 48), non-fluent (n = 54) and semantic (n = 96) variant primary progressive aphasias. We investigated whether the presence of learning disability or non-right-handedness was associated with differential effects on demographic, neuropsychological and neuroimaging features of primary progressive aphasia. We showed that a high frequency of learning disability was present only in the logopenic group (X 2 = 15.17, P< 0.001) and (X2 = 11.51, P< 0.001) compared with semantic and nonfluent populations. In this group, learning disability was associated with earlier onset of disease, more isolated language symptoms, and more focal pattern of left posterior temporoparietal atrophy. Non-right-handedness was instead over-represented in the semantic group, at nearly twice the prevalence of the general population (X2 = 6.34, P = 0.01). Within semantic variant primary progressive aphasia the right-handed and non-right-handed cohorts appeared homogeneous on imaging, cognitive profile, and structural analysis of brain symmetry. Lastly, the non-fluent group showed no increase in learning disability or non-right-handedness. Logopenic variant primary progressive aphasia and developmental dyslexia both manifest with phonological disturbances and posterior temporal involvement. Learning disability might confer vulnerability of this network to earlyonset, focal Alzheimer's pathology. Left-handedness has been described as a proxy for atypical brain hemispheric lateralization. As non-right-handedness was increased only in the semantic group, anomalous lateralization mechanisms might instead be related to frontotemporal lobar degeneration with abnormal TARDBP. Taken together, this study suggests that neurodevelopmental signatures impart differential trajectories towards neurodegenerative disease.
KW - Alzheimer's disease
KW - Case control study
KW - Dementia aphasia
KW - Frontotemporal dementia
KW - Risk factors in epidemiology
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U2 - 10.1093/brain/awt242
DO - 10.1093/brain/awt242
M3 - Article
C2 - 24056533
AN - SCOPUS:84884156173
SN - 0006-8950
VL - 136
SP - 3461
EP - 3473
JO - Brain
JF - Brain
IS - 11
ER -