1. Atrophy patterns in early clinical stages across distinct phenotypes of Alzheimer's disease
- Author
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Ossenkoppele, Rik, Cohn-Sheehy, Brendan I, La Joie, Renaud, Vogel, Jacob W, Möller, Christiane, Lehmann, Manja, van Berckel, Bart NM, Seeley, William W, Pijnenburg, Yolande A, Gorno-Tempini, Maria L, Kramer, Joel H, Barkhof, Frederik, Rosen, Howard J, van der Flier, Wiesje M, Jagust, William J, Miller, Bruce L, Scheltens, Philip, and Rabinovici, Gil D
- Subjects
Biological Psychology ,Psychology ,Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD) ,Aging ,Brain Disorders ,Dementia ,Alzheimer's Disease ,Neurosciences ,Neurodegenerative ,Biomedical Imaging ,Clinical Research ,Eye Disease and Disorders of Vision ,Acquired Cognitive Impairment ,2.1 Biological and endogenous factors ,Aetiology ,Neurological ,Age of Onset ,Aged ,Alzheimer Disease ,Animals ,Aphasia ,Primary Progressive ,Atrophy ,Cerebral Cortex ,Female ,Humans ,Male ,Middle Aged ,Nerve Net ,Phenotype ,Syndrome ,Alzheimer's disease ,magnetic resonance imaging ,posterior cortical atrophy ,logopenic variant primary progressive aphasia ,early-onset dementia ,default mode network ,language ,memory ,vision ,atrophy ,voxel-based morphometry ,Cognitive Sciences ,Experimental Psychology ,Biological psychology ,Cognitive and computational psychology - Abstract
Alzheimer's disease (AD) can present with distinct clinical variants. Identifying the earliest neurodegenerative changes associated with each variant has implications for early diagnosis, and for understanding the mechanisms that underlie regional vulnerability and disease progression in AD. We performed voxel-based morphometry to detect atrophy patterns in early clinical stages of four AD phenotypes: Posterior cortical atrophy (PCA, "visual variant," n=93), logopenic variant primary progressive aphasia (lvPPA, "language variant," n=74), and memory-predominant AD categorized as early age-of-onset (EOAD, 65 years, n=114). Patients with each syndrome were stratified based on: (1) degree of functional impairment, as measured by the clinical dementia rating (CDR) scale, and (2) overall extent of brain atrophy, as measured by a neuroimaging approach that sums the number of brain voxels showing significantly lower gray matter volume than cognitively normal controls (n=80). Even at the earliest clinical stage (CDR=0.5 or bottom quartile of overall atrophy), patients with each syndrome showed both common and variant-specific atrophy. Common atrophy across variants was found in temporoparietal regions that comprise the posterior default mode network (DMN). Early syndrome-specific atrophy mirrored functional brain networks underlying functions that are uniquely affected in each variant: Language network in lvPPA, posterior cingulate cortex-hippocampal circuit in amnestic EOAD and LOAD, and visual networks in PCA. At more advanced stages, atrophy patterns largely converged across AD variants. These findings support a model in which neurodegeneration selectively targets both the DMN and syndrome-specific vulnerable networks at the earliest clinical stages of AD.
- Published
- 2015