Dataset Information

Within-patient correspondence of amyloid-? and intrinsic network connectivity in Alzheimer's disease.

ABSTRACT: There is striking overlap between the spatial distribution of amyloid-? pathology in patients with Alzheimer's disease and the spatial distribution of high intrinsic functional connectivity in healthy persons. This overlap suggests a mechanistic link between amyloid-? and intrinsic connectivity, and indeed there is evidence in patients for the detrimental effects of amyloid-? plaque accumulation on intrinsic connectivity in areas of high connectivity in heteromodal hubs, and particularly in the default mode network. However, the observed spatial extent of amyloid-? exceeds these tightly circumscribed areas, suggesting that previous studies may have underestimated the negative impact of amyloid-? on intrinsic connectivity. We hypothesized that the known positive baseline correlation between patterns of amyloid-? and intrinsic connectivity may mask the larger extent of the negative effects of amyloid-? on connectivity. Crucially, a test of this hypothesis requires the within-patient comparison of intrinsic connectivity and amyloid-? distributions. Here we compared spatial patterns of amyloid-?-plaques (measured by Pittsburgh compound B positron emission tomography) and intrinsic functional connectivity (measured by resting-state functional magnetic resonance imaging) in patients with prodromal Alzheimer's disease via spatial correlations in intrinsic networks covering fronto-parietal heteromodal cortices. At the global network level, we found that amyloid-? and intrinsic connectivity patterns were positively correlated in the default mode and several fronto-parietal attention networks, confirming that amyloid-? aggregates in areas of high intrinsic connectivity on a within-network basis. Further, we saw an internetwork gradient of the magnitude of correlation that depended on network plaque-load. After accounting for this globally positive correlation, local amyloid-?-plaque concentration in regions of high connectivity co-varied negatively with intrinsic connectivity, indicating that amyloid-? pathology adversely reduces connectivity anywhere in an affected network as a function of local amyloid-?-plaque concentration. The local negative association between amyloid-? and intrinsic connectivity was much more pronounced than conventional group comparisons of intrinsic connectivity would suggest. Our findings indicate that the negative impact of amyloid-? on intrinsic connectivity in heteromodal networks is underestimated by conventional analyses. Moreover, our results provide first within-patient evidence for correspondent patterns of amyloid-? and intrinsic connectivity, with the distribution of amyloid-? pathology following functional connectivity gradients within and across intrinsic networks.

SUBMITTER: Myers N

PROVIDER: S-EPMC4065018 | biostudies-literature | 2014 Jul

REPOSITORIES: biostudies-literature

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Within-patient correspondence of amyloid-β and intrinsic network connectivity in Alzheimer's disease.

Myers Nicholas N Pasquini Lorenzo L Göttler Jens J Grimmer Timo T Koch Kathrin K Ortner Marion M Neitzel Julia J Mühlau Mark M Förster Stefan S Kurz Alexander A Förstl Hans H Zimmer Claus C Wohlschläger Afra M AM Riedl Valentin V Drzezga Alexander A Sorg Christian C

Brain : a journal of neurology 20140426 Pt 7

There is striking overlap between the spatial distribution of amyloid-β pathology in patients with Alzheimer's disease and the spatial distribution of high intrinsic functional connectivity in healthy persons. This overlap suggests a mechanistic link between amyloid-β and intrinsic connectivity, and indeed there is evidence in patients for the detrimental effects of amyloid-β plaque accumulation on intrinsic connectivity in areas of high connectivity in heteromodal hubs, and particularly in the ...[more]

PMID: 24771519

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Project description:BackgroundAmyloid-beta (Aβ) has a dose-response relationship with cognition in healthy adults. Additionally, the levels of functional connectivity within and between brain networks have been associated with cognitive performance in healthy adults. Aiming to explore potential synergistic effects, we investigated the relationship of inter-network functional connectivity, Aβ burden, and memory decline among healthy individuals and individuals with preclinical, prodromal, or clinical Alzheimer's disease.MethodsIn this longitudinal cohort study (ADNI2), participants (55-88 years) were followed for a maximum of 5 years. We included cognitively healthy participants and patients with mild cognitive impairment (with or without elevated Aβ) or Alzheimer's disease. Associations between memory decline, Aβ burden, and connectivity between networks across the groups were investigated using linear and curvilinear mixed-effects models.ResultsWe found a synergistic relationships between inter-network functional connectivity and Aβ burden on memory decline. Dose-response relationships between Aβ and memory decline varied as a function of directionality of inter-network connectivity across groups. When inter-network correlations were negative, the curvilinear mixed-effects models revealed that higher Aβ burden was associated with greater memory decline in cognitively normal participants, but when inter-network correlations were positive, there was no association between the magnitude of Aβ burden and memory decline. Opposite patterns were observed in patients with mild cognitive impairment. Combining negative inter-network correlations with Aβ burden can reduce the required sample size by 88% for clinical trials aiming to slow down memory decline.ConclusionsThe direction of inter-network connectivity provides additional information about Aβ burden on the rate of expected memory decline, especially in the preclinical phase. These results may be valuable for optimizing patient selection and decreasing study times to assess efficacy in clinical trials.

Dataset Information

Within-patient correspondence of amyloid-? and intrinsic network connectivity in Alzheimer's disease.

Publications

Within-patient correspondence of amyloid-β and intrinsic network connectivity in Alzheimer's disease.

Similar Datasets

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