Prodromal posterior cortical atrophy: clinical, neuropsychological, and radiological correlation

Chan, Lung Tat Andrew; Lynch, Whitney; May, Mary De; Horton, Jonathan C.; Miller, Bruce L.; Rabinovici, Gil D.

doi:10.1080/13554794.2013.860176

Cited by 13 publications

(7 citation statements)

References 48 publications

(85 reference statements)

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“…Alternatively, the neurodegenerative process may already be too advanced in a clinical population to investigate the sites of earliest atrophy, even at the prodromal stage, and requires subjects in preclinical stages of AD. For example, [Chan et al, ] described a cognitively normal research volunteer who developed a PCA syndrome and showed isolated atrophy in the visual association cortex at baseline. This and the present finding of greater extent of atrophy in language and visual areas in PCA and lvPPA compared with posterior DMN regions hints towards earlier involvement of syndrome‐specific off‐DMN regions, but does not rule out initial posterior DMN onset or neurodegenerative processes occurring in parallel.…”

Section: Discussionmentioning

confidence: 99%

Atrophy patterns in early clinical stages across distinct phenotypes of Alzheimer's disease

Ossenkoppele

Cohn‐Sheehy

Joie

et al. 2015

Human Brain Mapping

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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) and late age-of-onset (LOAD, >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.

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Section: Discussionmentioning

confidence: 99%

Atrophy patterns in early clinical stages across distinct phenotypes of Alzheimer's disease

Ossenkoppele

Cohn‐Sheehy

Joie

et al. 2015

Human Brain Mapping

Self Cite

205

174

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“…Our results are partly concordant with recent findings that APOE‐ε4 carriers show different brain activity during scene perception (Shine, Hodgetts, Postans, Lawrence, & Graham, 2015), and anatomically match previously reported cases of AD‐related visuoperceptual deficits (Chan et al., 2015) and studies of posterior cortical atrophy (Crutch et al., 2012; Migliaccio et al., 2012). …”

Section: Discussionmentioning

confidence: 99%

Functional brain network centrality is related to APOE genotype in cognitively normal elderly

et al. 2018

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IntroductionAmyloid plaque deposition in the brain is an early pathological change in Alzheimer's disease (AD), causing disrupted synaptic connections. Brain network disruptions in AD have been demonstrated with eigenvector centrality (EC), a measure that identifies central regions within networks. Carrying an apolipoprotein (APOE)‐ε4 allele is a genetic risk for AD, associated with increased amyloid deposition. We studied whether APOE‐ε4 carriership is associated with EC disruptions in cognitively normal individuals.MethodsA total of 261 healthy middle‐aged to older adults (mean age 56.6 years) were divided into high‐risk (APOE‐ε4 carriers) and low‐risk (noncarriers) groups. EC was computed from resting‐state functional MRI data. Clusters of between‐group differences were assessed with a permutation‐based method. Correlations between cluster mean EC with brain volume, CSF biomarkers, and psychological test scores were assessed.ResultsDecreased EC in the visual cortex was associated with APOE‐ε4 carriership, a genetic risk factor for AD. EC differences were correlated with age, CSF amyloid levels, and scores on the trail‐making and 15‐object recognition tests.ConclusionOur findings suggest that the APOE‐ε4 genotype affects brain connectivity in regions previously found to be abnormal in AD as a sign of very early disease‐related pathology. These differences were too subtle in healthy elderly to use EC for single‐subject prediction of APOE genotype.

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“…whether the disease starts in the DMN and spreads into specific networks outside the DMN or vice versa. A small number of studies that have assessed changes over time in different AD variants suggest that atrophy is initially concentrated in regions outside the DMN (which is particularly apparent in cases of prodromal PCA (Chan, et al, 2015, Kennedy, et al, 2012), and later spreads more widely across the brain, indicating that these different clinical variants of AD might converge anatomically over time (Chan, et al, 2015, Cho, et al, 2013, Kennedy, et al, 2012, Lehmann, et al, 2012, Leyton, et al, 2013, Rohrer, et al, 2013). However, these studies are often based on small sample sizes and include patients that were relatively advanced, therefore providing limited information about the early stages.…”

Section: Discussionmentioning

confidence: 99%

Loss of functional connectivity is greater outside the default mode network in nonfamilial early-onset Alzheimer's disease variants

Lehmann

Madison

Ghosh

et al. 2015

Neurobiology of Aging

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The common and specific involvement of brain networks in clinical variants of Alzheimer’s disease (AD) is not well understood. We performed task-free (“resting-state”) functional imaging in 60 non-familial AD patients, including 20 early-onset AD (EOAD, age at onset <65 years, amnestic/dysexecutive deficits), 24 logopenic aphasia (lvPPA, language deficits) and 16 posterior cortical atrophy patients (PCA, visual deficits), as well as 60 healthy controls. Seed-based connectivity analyses were conducted to assess differences between groups in 3 default mode network (DMN) components (anterior, posterior and ventral) and four additional non-DMN networks: left and right executive-control, language and higher visual networks. Significant decreases in connectivity were found across AD variants compared with controls in the non-DMN networks. Within the DMN components, patients showed higher connectivity in the anterior DMN, in particular in lvPPA. No significant differences were found for the posterior and ventral DMN. Our findings suggest that loss of functional connectivity is greatest in networks outside the DMN in early-onset and non-amnestic AD variants, and may thus be a better biomarker in these patients.

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Prodromal posterior cortical atrophy: clinical, neuropsychological, and radiological correlation

Cited by 13 publications

References 48 publications

Atrophy patterns in early clinical stages across distinct phenotypes of Alzheimer's disease

Atrophy patterns in early clinical stages across distinct phenotypes of Alzheimer's disease

Functional brain network centrality is related to APOE genotype in cognitively normal elderly

Loss of functional connectivity is greater outside the default mode network in nonfamilial early-onset Alzheimer's disease variants

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