Dataset Information

The association between tau PET and retrospective cortical thinning in clinically normal elderly.

ABSTRACT: Tau pathology has been associated with neuronal loss at autopsy, but the temporal evolution of tau pathology and atrophy remains unclear. Here, we investigate the association between cross-sectional AV-1451-PET as a marker of tau pathology and cortical thickness cross-sectionally. We also investigated retrospective rates of cortical thinning over the three years preceding the AV-1451 scan in a clinically normal cohort of 103 older adults from the Harvard Aging Brain Study. Tau measurements were Geometric Transfer Matrix partial volume corrected standardized uptake value ratios (SUVRs) with a cerebellar gray reference region. Thirty-four FreeSurfer-defined cortical regions of interest (ROIs) were used for both thickness and AV-1451 in each hemisphere, with seven additional volumetric ROIs. We examined "local" relationships between AV-1451 and cortical thickness in the same ROI, as well as inferior temporal AV-1451 and all thickness ROIs. All models included baseline age and sex, both interacting with time in retrospective longitudinal models, as covariates. Cross-sectional models controlled for the number of days between the two scans. Cross-sectional local comparisons revealed significant associations between elevated AV-1451 and thinner cortical ROIs predominantly in temporal regions, while analyses associating inferior temporal AV-1451 with all cortical ROIs showed a widespread pattern of significant relationships, which was strongest in temporal and parietal cortices. In our retrospective longitudinal analyses, we saw significant relationships in temporal and parietal regions. Significant local relationships were seen in right superior temporal, middle temporal, temporal pole, and fusiform, as well as the left cuneus and banks of the left superior temporal sulcus. Significant relationships between inferior temporal AV-1451 and faster thinning were observed in right temporal regions (middle temporal and fusiform) and bilateral parahippocampal cortices. We observed significant negative relationships between local and inferior temporal AV-1451 signal and both cross-sectional cortical thickness and rates of thinning in lateral and medial temporal regions. This is an important early step toward elucidating the relationship between tau pathology and retrospective longitudinal atrophy in aging and preclinical AD.

SUBMITTER: LaPoint MR

PROVIDER: S-EPMC5772972 | biostudies-literature | 2017 Aug

REPOSITORIES: biostudies-literature

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The association between tau PET and retrospective cortical thinning in clinically normal elderly.

LaPoint Molly R MR Chhatwal Jasmeer P JP Sepulcre Jorge J Johnson Keith A KA Sperling Reisa A RA Schultz Aaron P AP

NeuroImage 20170522

Tau pathology has been associated with neuronal loss at autopsy, but the temporal evolution of tau pathology and atrophy remains unclear. Here, we investigate the association between cross-sectional AV-1451-PET as a marker of tau pathology and cortical thickness cross-sectionally. We also investigated retrospective rates of cortical thinning over the three years preceding the AV-1451 scan in a clinically normal cohort of 103 older adults from the Harvard Aging Brain Study. Tau measurements were ...[more]

PMID: 28545932

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Project description:Neurofibrillary tau tangles are a hallmark pathology of Alzheimer's disease (AD) and are more closely associated with AD-related cortical atrophy and symptom severity than amyloid-beta (Aβ). However, studies regarding the effect of tau on longitudinal cortical thinning, particularly in healthy aging and preclinical AD, have been limited in number due to the relatively recent introduction of in vivo PET tracers for imaging tau pathology. Here, we investigate [18F]-flortaucipir (FTP, a marker of paired helical filament tau) PET as a predictor of atrophy in healthy aging and preclinical AD. We examine longitudinal structural MRI brain imaging data, retrospectively and prospectively relative to FTP imaging, using piecewise linear mixed-effect models with time centered at each participant's FTP-PET session. Participants include 111 individuals from the Harvard Aging Brain Study who underwent at least three MRI sessions over an average of 4.46 years and one FTP-PET at the approximate midpoint of the observation period. Our primary analyses focus on inferior temporal (IT) FTP standardized uptake value ratios and longitudinal FreeSurfer defined cortical regions of interest. Relationships were also explored using other regional FTP measures (entorhinal, composite, and local), within high and low Pittsburgh compound-B (PiB) PET groups, and with longitudinal subcortical volume. Strong associations between IT FTP and cortical thinning were found, most notably in temporal, midline, and prefrontal regions, with stronger effects generally observed in the prospective as compared to retrospective time frame. Significant differences between prospective and retrospective rates of thinning were found in the inferior and middle temporal gyri, cingulate areas, as well as pars orbitalis such that higher IT FTP was associated with greater prospective rates of thinning. Within the high PiB group, significant differences between prospective and retrospective rates of thinning were similarly observed. However, no consistent pattern of tau-related change in cortical thickness within the low PiB group was discerned. These results provide support for the hypothesis that tau pathology is a driver of future atrophy as well as provide additional evidence for tau-PET as an effective AD biomarker for interventional clinical trials.

Project description:BackgroundThe alterations in cortical morphology, such as cortical thinning, observed in psychotic disorder, may be the outcome of interacting genetic and environmental effects. It has been suggested that urban upbringing may represent a proxy environmental effect impacting cortical thickness (CT). Therefore, the current study examined whether the association between group as a proxy genetic variable (patients with psychotic disorder [high genetic risk], healthy siblings of patients [intermediate risk] and healthy control subjects [average risk]) and CT was conditional on different levels of the childhood urban environment and whether this was sex-dependent.MethodsT1-weighted MRI scans were acquired from 89 patients with a psychotic disorder, 95 non-psychotic siblings of patients with psychotic disorder and 87 healthy control subjects. Freesurfer software was used to measure CT. Developmental urban exposure was classified as low, medium, and high, reflecting the population density and the number of moves between birth and the 15th birthday, using data from the Dutch Central Bureau of Statistics and the equivalent database in Belgium. Multilevel regression analyses were used to examine the association between group, sex, and urban upbringing (as well as their interactions) and cortical CT as the dependent variable.ResultsCT was significantly smaller in the patient group compared to the controls (B = -0.043, p <0.001), but not in the siblings compared to the controls (B = -0.013, p = 0.31). There was no main effect of developmental urbanicity on CT (B = 0.001, p = 0.91). Neither the three-way group × urbanicity × sex interaction (?2 = 3.73, p = 0.16), nor the two-way group × urbanicity interaction was significant (?2 = 0.51, p = 0.77).ConclusionThe negative association between (familial risk for) psychotic disorder and CT was not moderated by developmental urbanicity, suggesting that reduced CT is not the outcome of familial sensitivity to the proxy environmental factor 'urban upbringing'.

Dataset Information

The association between tau PET and retrospective cortical thinning in clinically normal elderly.

Publications

The association between tau PET and retrospective cortical thinning in clinically normal elderly.

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