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FRIMED2-FRIPRO forskerprosjekt, medisin og helse

Set to change - Early factors influencing neurocognitive plasticity and aging and the role of beta-amyloid and epigenetics: a twin study

Alternative title: Innstilt på endring – Tidlige innflytelser på nevrokognitiv plastisitet og aldring og rollen til amyloid og epigenetikk: en tvillingstudie

Awarded: NOK 12.0 mill.

Project Number:

301395

Application Type:

Project Period:

2020 - 2026

Location:

Subject Fields:

People`s brains and cognitive functions change through life. Still, brain and cognitive function in old age can be predicted from how we functioned when we were young. The critical question raised in this project is whether we are neurodevelopmentally set to change through life in certain ways. If so, which early life factors are important for shaping brain characteristics and cognition into adulthood and old age, what is the relative contribution of genetic and environmental influences, and how do these factors work to affect epigenetic changes, amyloid burden (indexing Alzheimer pathology) and brain and cognitive changes with advancing age? Our objective is to test whether and how early life environmental factors and genetics influence neurocognitive plasticity, epigenetics, amyloid burden and brain and cognitive age change through life. In this project, we will estimate amyloid burden in 200 older twins by Flutemetamol (18F) Positron Emission Tomography (PET), and run a five-year follow-up assessment of brain and cognitive changes in 300 younger and older twins. This adds a critical component to a larger program of research recently funded through an ERC consolidator grant, where data collection started primo 2019. 400 twins receive a cognitive intervention, including navigation training with true locomotion by bicycling in a virtual reality environment. All undergo repeated testing and multi-modal brain scanning four times over 2.5 years through periods of intervention and rest. The results will be linked to existing information from the Norwegian Twin Registry on early factors such as birth weight. Inclusion of PET scans and longer follow-up examinations will provide a unique opportunity for new insights into the arguably most highly regarded biomarker for cognitive decline and Alzheimer?s Disease, as well as how a series of early and later factors work to affect longitudinal age changes in brain and cognition over several years.

Cognitive function in old age can be predicted from how you functioned as young, even though there are substantial age changes. The objective is to test whether and how early environmental factors and genetics impact neurocognitive plasticity, epigenetics, amyloid burden and brian and cognitive age changes across several years. A major risk factor for cognitive decline and Alzheimer’s disease is accumulation of beta-amyloid (Abeta) in the brain. Abeta accumulation starts long before detectable cognitive decline and is hypothesized to restrict plasticity. The heritability of plasticity and Abeta accumulation, and the relative importance of environmental, genetic and epigenetic influences are unknown. Neurocognitive plasticity, i.e. changes in brain and cognition in response to environmental demands over time, shows huge individual variability, for unknown reasons. We seek to identify pathways for neurodevelopmental origins of functional variation through life. We include younger and older adult mono- (MZ) and dizygotic twins (total n = 400), with varying degrees of prenatal environmental variance, as indexed by extent of discordance in birth weight (BW). BW discordance in MZ twins enables disentangling early environmental and genetic influences on neurocognitive plasticity, epigenetics, amyloid burden and neurocognitive age changes across several years. A novel ecologically valid memory intervention is employed, utilizing navigation with true locomotion and prospective memory in virtual reality. Twins will be assessed with brain MRI, cognitive, health and epigenetic measures at multiple time points spread across 5 years, including before and after a 10 weeks intervention in a AB/BA crossover design. Brain amyloid scans will be obtained midway in the follow-up period. This will reveal how early environment and genetics influence epigenetics, neurocognitive plasticity, amyloid burden and brain and cognitive age change longitudinally, and possible lifestyle mediators.

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Funding scheme:

FRIMED2-FRIPRO forskerprosjekt, medisin og helse