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Increased variability in reaction time is associated with amyloid beta pathology at age 70.

ABSTRACT: Introduction:We investigated whether life-course factors and neuroimaging biomarkers of Alzheimer's disease pathology predict reaction time (RT) performance in older adults. Methods:Insight 46 study participants, all born in the same week in 1946 (n = 501; ages at assessment = 69 to 71 years), completed a 2-choice RT task and amyloid beta (A?) positron emission tomography and MR imaging. We tested for associations between task outcomes (RT; error rate; intra-individual variability in RT) and life-course predictors including childhood cognitive ability and education. In a subsample of 406 cognitively normal participants, we investigated associations between task outcomes and biomarkers including A?-positivity. Results:Cognitively normal A?-positive participants had 10% more variable RTs than A?-negative participants, despite having similar mean RTs. Childhood cognitive ability and education independently predicted task performance. Discussion:This study provides novel evidence that A? pathology is associated with poorer consistency of RT in cognitively normal older adults, at an age when dementia prevalence is still very low.

SUBMITTER: Lu K

PROVIDER: S-EPMC7416668 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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Increased variability in reaction time is associated with amyloid beta pathology at age 70.

Lu Kirsty K Nicholas Jennifer M JM James Sarah-Naomi SN Lane Christopher A CA Parker Thomas D TD Keshavan Ashvini A Keuss Sarah E SE Buchanan Sarah M SM Murray-Smith Heidi H Cash David M DM Sudre Carole H CH Malone Ian B IB Coath William W Wong Andrew A Henley Susie M D SMD Fox Nick C NC Richards Marcus M Schott Jonathan M JM Crutch Sebastian J SJ

Alzheimer's & dementia (Amsterdam, Netherlands) 20200810 1

<h4>Introduction</h4>We investigated whether life-course factors and neuroimaging biomarkers of Alzheimer's disease pathology predict reaction time (RT) performance in older adults.<h4>Methods</h4>Insight 46 study participants, all born in the same week in 1946 (n = 501; ages at assessment = 69 to 71 years), completed a 2-choice RT task and amyloid beta (Aβ) positron emission tomography and MR imaging. We tested for associations between task outcomes (RT; error rate; intra-individual variability ...[more]

PMID: 32789161

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Project description:Alzheimer's disease (AD) is a devastating neurodegenerative disorder characterized by initial memory impairments that progress to dementia. In this sense, synaptic dysfunction and loss have been established as the pathological features that best correlate with the typical early cognitive decline in this disease. At the histopathological level, post mortem AD brains typically exhibit intraneuronal neurofibrillary tangles (NFTs) along with the accumulation of amyloid-beta (Abeta) peptides in the form of extracellular deposits. Specifically, the oligomeric soluble forms of Abeta are considered the most synaptotoxic species. In addition, neuritic plaques are Abeta deposits surrounded by activated microglia and astroglia cells together with abnormal swellings of neuronal processes named dystrophic neurites. These periplaque aberrant neurites are mostly presynaptic elements and represent the first pathological indicator of synaptic dysfunction. In terms of losing synaptic proteins, the hippocampus is one of the brain regions most affected in AD patients. In this work, we report an early decline in spatial memory, along with hippocampal synaptic changes, in an amyloidogenic APP/PS1 transgenic model. Quantitative electron microscopy revealed a spatial synaptotoxic pattern around neuritic plaques with significant loss of periplaque synaptic terminals, showing rising synapse loss close to the border, especially in larger plaques. Moreover, dystrophic presynapses were filled with autophagic vesicles in detriment of the presynaptic vesicular density, probably interfering with synaptic function at very early synaptopathological disease stages. Electron immunogold labeling showed that the periphery of amyloid plaques, and the associated dystrophic neurites, was enriched in Abeta oligomers supporting an extracellular location of the synaptotoxins. Finally, the incubation of primary neurons with soluble fractions derived from 6-month-old APP/PS1 hippocampus induced significant loss of synaptic proteins, but not neuronal death. Indeed, this preclinical transgenic model could serve to investigate therapies targeted at initial stages of synaptic dysfunction relevant to the prodromal and early AD.

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Increased variability in reaction time is associated with amyloid beta pathology at age 70.

Publications

Increased variability in reaction time is associated with amyloid beta pathology at age 70.

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