Neocortical origin and progression of gray matter atrophy in nonamnestic Alzheimer's disease
| Autor: | Laynie Dratch, Jeffrey S. Phillips, Sanjeev N. Vaishnavi, Sharon X. Xie, Corey T. McMillan, David J. Irwin, John Q. Trojanowski, David A. Wolk, Edward B. Lee, Leslie M. Shaw, Carlo Ferrarese, Fulvio Da Re, Murray Grossman |
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| Přispěvatelé: | Phillips, J, Da Re, F, Dratch, L, Xie, S, Irwin, D, Mcmillan, C, Vaishnavi, S, Ferrarese, C, Lee, E, Shaw, L, Trojanowski, J, Wolk, D, Grossman, M |
| Jazyk: | angličtina |
| Rok vydání: | 2018 |
| Předmět: |
Male
0301 basic medicine Aging Pathology Hippocampus Logopenic-variant primary progressive aphasia Neocortex Primary progressive aphasia 0302 clinical medicine tau Gray Matter medicine.diagnostic_test General Neuroscience Middle Aged Alzheimer's disease Corticobasal syndrome Female Braak staging medicine.medical_specialty Frontalvariant Alzheimer's disease Neuropathology Article Temporal lobe 03 medical and health sciences Atrophy Hippocampu Magnetic resonance imaging Alzheimer Disease medicine Humans Aged Retrospective Studies Disease progression business.industry Posterior cortical atrophy medicine.disease Non-amnestic Alzheimer's disease Diffusion Magnetic Resonance Imaging Logistic Models 030104 developmental biology Neurology (clinical) Geriatrics and Gerontology business 030217 neurology & neurosurgery Developmental Biology |
| Popis: | Amnestic Alzheimer’s disease is characterized by early atrophy of the hippocampus and medial temporal lobes before spreading to neocortex. In contrast, non-amnestic Alzheimer’s patients have relative sparing of the hippocampus, but the pattern in which disease spreads is unclear. We examined spreading disease in non-amnestic Alzheimer’s disease using a novel magnetic resonance imaging-based analysis adapted from pathologic staging studies, applied here to cross-sectional imaging data. We selected 240 T1-weighted scans from 129 patients with pathology confirmed by autopsy or cerebrospinal fluid, and atrophy maps were computed relative to 238 scans from 115 elderly controls. For each phenotype, the frequency of atrophy in 116 brain regions was used to infer the anatomical origin of disease and its progression across 4 phases of atrophy. Results from the amnestic cohort were used to determine appropriate parameter settings for the phase assignment algorithm, based on correspondence to Braak pathology staging. Phase 1 regions, which represent the origin of disease, included hippocampus for the amnestic group (comprising 33 scans); left lateral temporal lobe for logopenic-variant primary progressive aphasia (88 scans); occipito-parietal cortex for posterior cortical atrophy (51 scans); temporo-parietal cortex for corticobasal syndrome (31 scans); and fronto-temporal cortex for behavioral/dysexecutive variant Alzheimer’s disease (37 scans). In non-amnestic patients atrophy spread to other neocortical areas in later phases, but the hippocampus exhibited only late-phase atrophy in posterior cortical atrophy and corticobasal syndrome. Region-specific phase values were also associated with regional measures of tau, amyloid-beta, neuronal loss, and gliosis for the subset of patients (n=17) with neuropathology findings; this comparison represented a first validation of the phase assignment algorithm. We subsequently assigned a phase to each patient scan based on the similarity of regional atrophy patterns with atrophy predicted for the corresponding phenotype at each phase. Scan-specific phases were correlated with disease duration as well as global and domain-specific cognition, supporting these phase values as global estimates of patients’ disease progression. Logistic regression models based on spatial overlap with model-predicted atrophy patterns reliably discriminated non-amnestic phenotypes from each other and from amnestic Alzheimer’s disease. The frequency-based phase assignment algorithm employed in the current study thus represents a promising approach for studying the neocortical origin and spread of disease in non-amnestic Alzheimer’s disease. |
| Databáze: | OpenAIRE |
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