Atrophy progression in semantic dementia with asymmetric temporal involvement: A tensor-based morphometry study
Introduction
Semantic dementia (SD) is the variant of frontotemporal lobar degeneration (FTLD) characterized by progressive loss of conceptual knowledge (semantic memory) and anterior temporal lobe atrophy (Hodges et al., 1992, Neary et al., 1998). Asymmetrical hemispheric involvement is common in SD, with patients most often showing greater left than right temporal atrophy (Chan et al., 2001a, Chan et al., 2001b, Galton et al., 2001, Gorno-Tempini et al., 2004a, Gorno-Tempini et al., 2004b, Mummery et al., 2000, Rosen et al., 2002). The clinical syndrome associated with this pattern of predominantly left temporal involvement (‘left temporal lobe variant’, LTLV) corresponds to the classic description of SD, and is characterized by progressive naming, word comprehension and object recognition deficits (Hodges et al., 1992, Neary et al., 1998). On the other hand, when atrophy is greater in the right temporal lobe (‘right temporal lobe variant’, RTLV), patients often present with a different clinical syndrome where behavioral disturbances, such as personality changes, loss of empathy and compulsions, are prominent (Edwards-Lee et al., 1997, Gorno-Tempini et al., 2004a, Gorno-Tempini et al., 2004b, Miller et al., 1993, Perry et al., 2001). Language deficits are less evident in RTLV at presentation, and semantic memory impairment is often limited to the categories of people, smells, or food (Evans et al., 1995, Gainotti et al., 2003, Gorno-Tempini et al., 2004a, Gorno-Tempini et al., 2004b, Joubert et al., 2006, Thompson et al., 2004).
Later in the course of the disease, RTLV and LTLV become more difficult to distinguish. Seeley et al. (2005) performed a retrospective analysis of the clinical evolution of SD patients presenting with asymmetrical temporal atrophy. The study showed that, within three years of onset, the RTLV and LTLV clinical syndromes began to overlap. Specifically, whilst presenting symptoms progressed, LTLV patients also developed a behavioral syndrome, while RTLV cases also showed a more generalized semantic and language impairment. The anatomical basis of this progressive clinical merging of RTLV and LTLV has not yet been investigated.
Objective and automated mapping of tissue loss over time can be achieved using specifically designed neuroimaging MRI techniques, such as tensor-based morphometry (TBM) (Leow et al., 2006). In TBM volume changes are inferred from the non-linear deformation field required to warp two serial MRI scans. This technique has proven useful for tracking progression of atrophy in various neurodegenerative diseases (Chan et al., 2001a, Chan et al., 2001b, Fox et al., 2000, Fox et al., 2001, Fox et al., 1999, Fox and Freeborough, 1997, Freeborough et al., 1996, Kipps et al., 2005, Leow et al., 2006, Studholme et al., 2001). A TBM-like approach has been applied to serial scans of classic SD patients and has shown progression of atrophy in the temporal lobes (Cardenas and Studholme, 2004, Whitwell et al., 2004), but longitudinal neuroimaging studies of patients with predominant right or left temporal atrophy are still lacking.
The aim of this longitudinal neuroimaging study was to identify patterns of regional atrophy progression in LTLV and RTLV in the first year following diagnosis. TBM, as implemented in the Statistical Parametric Mapping software (SPM2), was used to obtain and compare maps of gray matter contraction over time in LTLV and RTLV patients and controls. Based on previous clinical evidence, we hypothesize that, as disease progresses, atrophy changes will include the temporal lobe least affected at presentation and the ventromedial frontal regions.
Section snippets
Subjects
MR images were obtained at presentation (Time 1) and at one-year follow-up (Time 2) from 19 right-handed SD patients (mean age 62.1 ± 6.0 years, 12 males, 7 females) and 25 healthy controls (mean age 64.8 ± 6.9 years, 9 males, 16 females). All patients were evaluated at UCSF Memory and Aging Center by a team of clinicians with expertise in neurodegenerative diseases, including a behavioral neurologist, a neuropsychologist, a nurse, and a psychiatrist. Only cases for which a consensus diagnosis of
LTLV and RTLV neuropsychological performance
At presentation, LTLV and RTLV patients showed comparable CDR and MMSE scores suggesting borderline functional status (see Table 1). Consistently with SD diagnosis, when compared to normal controls, both LTLV and RTLV showed deficits in language (phonemic and category fluency, and naming test) and behavior (Neuropsychiatric Inventory), in the context of fairly intact visuospatial (Modified Rey-Osterrieth Copy), working memory (Digit Backward) and executive (Modified Trials) abilities. LTLV
Discussion
We used tensor-based morphometry to map the progression of gray matter atrophy in patients with anatomically defined left (LTLV) or right (RTLV) temporal lobe variants of semantic dementia (SD) over a one-year period from initial diagnosis. In both variants, results showed gray matter contraction in the temporal lobe most affected at presentation, but also significant changes in the least affected side. This finding provides the anatomical substrate of the clinical overlap between the two
Conflicts of interest
None.
Acknowledgments
The study was supported by the National Institute of Neurological Disorders and Stroke (R01 NS050915), the State of California (DHS 04-35516), the National Institute on Aging (P50 AG03006, P01 AG019724), the John Douglas French Alzheimer's Foundation, the McBean Foundation, the Sandler Foundation, the Alzheimer's Disease Research Center of California (03-75271 DHS/ADP/ARCC), the Larry Hillblom Foundation (grant #2002/2F) and the Koret Foundation (grant 99-0102). We thank patients and their
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