Dataset Information

Functional Brain Network Connectivity Patterns Associated With Normal Cognition at Old-Age, Local ?-amyloid, Tau, and APOE4.

ABSTRACT: Background: Integrity of functional brain networks is closely associated with maintained cognitive performance at old age. Consistently, both carrier status of Apolipoprotein E ?4 allele (APOE4), and age-related aggregation of Alzheimer's disease (AD) pathology result in altered brain network connectivity. The posterior cingulate and precuneus (PCP) is a node of particular interest due to its role in crucial memory processes. Moreover, the PCP is subject to the early aggregation of AD pathology. The current study aimed at characterizing brain network properties associated with unimpaired cognition in old aged adults. To determine the effects of age-related brain change and genetic risk for AD, pathological proteins ?-amyloid and tau were measured by Positron-emission tomography (PET), PCP connectivity as a proxy of cognitive network integrity, and genetic risk by APOE4 carrier status. Methods: Fifty-seven cognitively unimpaired old-aged adults (MMSE = 29.20 ± 1.11; 73 ± 8.32 years) were administered 11C Pittsburgh Compound B and 18F Flutemetamol PET for assessing ?-amyloid, and 18F AV-1451 PET for tau. Individual functional connectivity seed maps of the PCP were obtained by resting-state multiband BOLD functional MRI at 3-Tesla for increased temporal resolution. Voxelwise correlations between functional connectivity, ?-amyloid- and tau-PET were explored by Biological Parametric Mapping (BPM). Results: Local ?-amyloid was associated with increased connectivity in frontal and parietal regions of the brain. Tau was linked to increased connectivity in more spatially distributed clusters in frontal, parietal, occipital, temporal, and cerebellar regions. A positive interaction was observable for APOE4 carrier status and functional connectivity with brain regions characterized by increased local ?-amyloid and tau tracer retention. Conclusions: Our data suggest an association between spatially differing connectivity systems and local ?-amyloid, and tau aggregates in cognitively normal, old-aged adults, which is moderated by APOE4. Additional longitudinal studies may determine protective connectivity patterns associated with healthy aging trajectories of AD-pathology aggregation.

SUBMITTER: Quevenco FC

PROVIDER: S-EPMC7075450 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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Functional Brain Network Connectivity Patterns Associated With Normal Cognition at Old-Age, Local β-amyloid, Tau, and APOE4.

Quevenco Frances C FC van Bergen Jiri M JM Treyer Valerie V Studer Sandro T ST Kagerer Sonja M SM Meyer Rafael R Gietl Anton F AF Kaufmann Philipp A PA Nitsch Roger M RM Hock Christoph C Unschuld Paul G PG

Frontiers in aging neuroscience 20200309

<b>Background</b>: Integrity of functional brain networks is closely associated with maintained cognitive performance at old age. Consistently, both carrier status of Apolipoprotein E ε4 allele (APOE4), and age-related aggregation of Alzheimer's disease (AD) pathology result in altered brain network connectivity. The posterior cingulate and precuneus (PCP) is a node of particular interest due to its role in crucial memory processes. Moreover, the PCP is subject to the early aggregation of AD pat ...[more]

PMID: 32210782

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Project description:The advent of tau-targeted positron emission tomography tracers such as flortaucipir (18F-AV-1451, also known as 18F-T807) have made it possible to investigate the sequence of development of tau and amyloid-β in relationship to age, and to the development of cognitive impairment due to Alzheimer's disease. In this study, flortaucipir tau and florbetapir amyloid positron emission tomography were obtained for 217 subjects including 16 young and 58 older cognitively normal subjects, 95 subjects with mild cognitive impairment (Mini-Mental State Examination 24-30) and 48 subjects with clinically-defined possible or probable Alzheimer's disease (Mini-Mental State Examination >10). Images were evaluated visually and quantitatively by regional and voxel-based cortical to cerebellar standard uptake value ratios. For amyloid positron emission tomography positive (Aβ+) subjects, flortaucipir neocortical standard uptake value ratio was significantly higher with more advanced clinical stage (Alzheimer's disease > mild cognitive impairment > older cognitively normal) and was significantly elevated for Aβ+ mild cognitive impairment and Alzheimer's disease subjects relative to the respective Aβ- subjects. In contrast, florbetapir Aβ- older cognitively normal subjects showed an increase in flortaucipir standard uptake value ratios in mesial temporal lobe regions (amygdala, hippocampus/choroid plexus region of interest) compared to younger cognitively normal subjects, but no increased standard uptake value ratios in neocortical regions. Analysis of covariance with planned contrasts showed no differences in regional or composite posterior neocortical flortaucipir standard uptake value ratio as a function of diagnostic group among Aβ- older cognitively normal or clinically diagnosed Alzheimer's disease or mild cognitive impairment subjects. The pattern of flortaucipir distribution among Aβ+ subjects was reminiscent of the cross-sectional distribution of tau reported in post-mortem pathology studies, in that the most commonly affected regions were the inferior and lateral temporal lobes, the same regions where the first signs of increased retention appeared in Aβ+ cognitively normal subjects. However, there was large variability in extent/density of flortaucipir tau binding among Aβ+ subjects. Although high neocortical flortaucipir retention was consistently associated with an Aβ+ florbetapir positron emission tomography scan, not all Aβ+ subjects had elevated flortaucipir standard uptake value ratios. Finally, within the Aβ+ group, increasing levels of flortaucipir tau binding were associated with increased cognitive impairment, as assessed by Mini-Mental State Examination and Alzheimer's Disease Assessment Scale. These results suggest development of tau beyond the mesial temporal lobe is associated with, and may be dependent on, amyloid accumulation. Further, the results are consistent with the hypothesis that cortical tau is associated with cognitive impairment.

Dataset Information

Functional Brain Network Connectivity Patterns Associated With Normal Cognition at Old-Age, Local ?-amyloid, Tau, and APOE4.

Publications

Functional Brain Network Connectivity Patterns Associated With Normal Cognition at Old-Age, Local β-amyloid, Tau, and APOE4.

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