Dataset Information

Joint associations of ?-amyloidosis and cortical thickness with cognition.

ABSTRACT: In 1164 cognitively unimpaired persons, aged 50-95 years, from the population-based Mayo Clinic Study of Aging, we examined the relationships of baseline cognition and cognitive changes across the full range of cortical thickness of an Alzheimer signature region of interest and global ?-amyloid levels measured by Pittsburgh compound B positron emission tomography (PIB PET) standardized uptake value ratio (SUVR). In machine-learning models accounting for both biomarkers simultaneously, worsening biomarker values were additive and associated with lower baseline global cognition and greater subsequent decline in global cognition. Associations between Alzheimer's disease signature cortical thickness or PIB PET ?-amyloid SUVR and baseline cognition were mainly linear. Lower Alzheimer's disease signature cortical thickness values across the entire range of thickness predicted future decline in global cognitive scores, demonstrating its close relationship to cognitive functioning. PIB PET ?-amyloid SUVR also predicted cognitive decline across its full range, even when cortical thickness was accounted for. PIB PET ?-amyloid's relationship to cognitive decline was nonlinear, more prominent at lower ?-amyloid levels and less prominent at higher ?-amyloid levels.

SUBMITTER: Knopman DS

PROVIDER: S-EPMC5871603 | biostudies-literature | 2018 May

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Joint associations of β-amyloidosis and cortical thickness with cognition.

Knopman David S DS Lundt Emily S ES Therneau Terry M TM Vemuri Prashanthi P Lowe Val J VJ Kantarci Kejal K Gunter Jeffrey L JL Senjem Matthew L ML Mielke Michelle M MM Machulda Mary M MM Roberts Rosebud O RO Boeve Bradley F BF Jones David T DT Petersen Ronald C RC Jack Clifford R CR

Neurobiology of aging 20180202

In 1164 cognitively unimpaired persons, aged 50-95 years, from the population-based Mayo Clinic Study of Aging, we examined the relationships of baseline cognition and cognitive changes across the full range of cortical thickness of an Alzheimer signature region of interest and global β-amyloid levels measured by Pittsburgh compound B positron emission tomography (PIB PET) standardized uptake value ratio (SUVR). In machine-learning models accounting for both biomarkers simultaneously, worsening ...[more]

PMID: 29471214

Similar Datasets

Project description:ObjectiveTo examine the cross-sectional associations between regional tau, β-amyloid (Aβ), and cortical thickness and neuropsychological function across the preclinical and clinical spectrum of Alzheimer disease (AD).MethodsWe included 106 participants from the Swedish Biomarkers for Identifying Neurodegenerative Disorders Early and Reliably (BioFINDER) study, of whom 33 had preclinical AD (Aβ-positive cognitively normal individuals), 25 had prodromal AD (Aβ-positive mild cognitive impairment), and 48 had probable AD dementia. All underwent [18F]flortaucipir (tau) and structural MRI (cortical thickness), and 88 of 106 underwent [18F]flutemetamol (Aβ) PET. Linear regression models adjusted for age, sex, and education were performed to examine associations between 7 regions of interest and 7 neuropsychological tests for all 3 imaging modalities.ResultsIn preclinical AD, [18F]flortaucipir, but not [18F]flutemetamol or cortical thickness, was associated with decreased global cognition, memory, and processing speed (range standardized β = 0.35-0.52, p < 0.05 uncorrected for multiple comparisons). In the combined prodromal AD and AD dementia group, both increased [18F]flortaucipir uptake and reduced cortical thickness were associated with worse performance on a variety of neuropsychological tests (most regions of interest survived correction for multiple comparisons at p < 0.05), while increased [18F]flutemetamol uptake was specifically associated with lower scores on a delayed recall memory task (p < 0.05 uncorrected for multiple comparisons). The strongest effects for both [18F]flortaucipir and cortical thickness on cognition were found in the lateral and medial parietal cortex and lateral temporal cortex. The effect of [18F]flutemetamol on cognition was generally weaker and less region specific.ConclusionOur findings suggest that tau PET is more sensitive than Aβ PET and measures of cortical thickness for detecting early cognitive changes in preclinical AD. Furthermore, both [18F]flortaucipir PET and cortical thickness show strong cognitive correlates at the clinical stages of AD.

Project description:Early-life education (years of schooling) has been investigated in regards to cognition, health outcomes and mortality. It has been shown to confer cognitive reserve that might lessen the impact of brain pathology and its impact on cognitive and motor functioning in a variety of neurodegenerative diseases and, for instance, to influence electrical activity [Begum, T., Reza, F., Ahmed, I., & Abdullah, J. M. (2014). Influence of education level on design-induced N170 and P300 components of event related potentials in the human brain. J Integr Neurosci, 13(1), 71-88. doi:10.1142/S0219635214500058]. On the other hand, demonstrations of a direct association between education and brain-structural measures have been more equivocal and scant. The current study sought to identify univariate cortical-thickness patterns underlying education and general intelligence after adjusting for age, gender and possible in-scanner movement in 353 individuals aged 40 to 80. We followed up this idea with multivariate analyses as well. For univariate analyses, our analyses yielded no robust associations between education and general intelligence beyond confounding effects of gender, age and extraneous in-scanner movement. A subsequent multivariate analyses showed a relationship between education and regional cortical thickness with a robust pattern of negative as well as positive loadings in several right-sided brain areas, speaking to a subtle but robust distributed effect of education on cortical thickness. Cortical thickness variance that is the residual of this education-related pattern was shown to be positively associated with age and extraneous in-scanner movement. Our study thus presents a complex picture of the association of education with regional cortical thickness: education was associated with a distributed brain-wide pattern of positive as well as negative loadings with unaccounted residuals being larger for older participants. Focal regional associations beyond demographic and age covariates were not identified.

Project description:Cortical thickness is a highly heritable structural brain measurement, and reduced thickness has been associated with schizophrenia, bipolar disorder, and decreased cognitive performance among healthy control individuals. Identifying genes that contribute to variation in cortical thickness provides a means to elucidate some of the biological mechanisms underlying these diseases and general cognitive abilities.To identify common genetic variants that affect cortical thickness in patients with schizophrenia, patients with bipolar disorder, and controls and to test these variants for association with cognitive performance.A total of 597 198 single-nucleotide polymorphisms were tested for association with average cortical thickness in a genome-wide association study. Significantly associated single-nucleotide polymorphisms were tested for their effect on several measures of cognitive performance.Four major hospitals in Oslo, Norway.A total of 1054 case individuals and controls were analyzed in the genome-wide association study and follow-up cognitive study. The genome-wide association study included controls (n = 181) and individuals with DSM-IV -diagnosed schizophrenia spectrum disorder (n = 94), bipolar spectrum disorder (n = 97), and other psychotic and affective disorders (n = 49).Cortical thickness measured with magnetic resonance imaging and cognitive performance as assessed by several neuropsychological tests.Two closely linked genetic variants (rs4906844 and rs11633924) within the Prader-Willi and Angelman syndrome region on chromosome 15q12 showed a genome-wide significant association (P = 1.1 x 10(-8) with average cortical thickness and modest association with cognitive performance (permuted P = .03) specifically among patients diagnosed as having schizophrenia.This genome-wide association study identifies a common genetic variant that contributes to the heritable reduction of cortical thickness in schizophrenia. These results highlight the usefulness of cortical thickness as an intermediate phenotype for neuropsychiatric diseases. Future independent replication studies are required to confirm these findings.

Dataset Information

Joint associations of ?-amyloidosis and cortical thickness with cognition.

Publications

Joint associations of β-amyloidosis and cortical thickness with cognition.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets