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FRIMEDBIO-Fri prosj.st. med.,helse,biol

Lifespan Memory Imaging Redux – Can Change in Activity Reconfigurations Be an Early Marker of Future Memory Decline?

Alternative title: Livsløpshukommelse avbildet på ny - kan endring i aktivitetsrekonfigurering være en tidlig markør for framtidig hukommelsessvikt?

Awarded: NOK 8.0 mill.

Memory abilities decline in normal aging and particularly in Alzheimer’s disease (AD), at great personal and societal costs. Using repeated measures of brain activity while we remember, I aim to predict early in adulthood who will show memory decline and who will maintain good function. A major cause of memory decline is likely the buildup of the protein tau combined with loss of brain cells in the temporal lobes (TL). We urgently need earlier markers to detect signs of brain dysfunction preceding memory decline. There are indications that deviations in how the brain processes memory information exist prior to cell loss. If we can detect these deviations years before memory decline, this would be a tremendously valuable tool. As tau builds up in TL over years, I hypothesize that the memory activity will be affected early, before substantial levels of tau, and cell loss. I have access to a unique sample (n=554) scanned with magnetic resonance imaging (MRI) 6 years ago, with various risks for developing AD dementia as indexed by the protein beta-amyloid and genetic factors. These participants will be followed up with an extensive MRI examination measuring memory activation, structure, and a range of different indices related to memory networks. The participants will undergo thorough experimental testing of memory and other mental process, and 50 persons will perform molecular brain imaging to measure tau. Brain activity will be analyzed with novel tools allowing prediction of individual memory alterations, also in persons from external samples provided by collaborators. I measure activity related to memories with contextual detail, the most age-sensitive memory process, dependent on the TL. I hypothesize that a reduced ability of networks to change their activity architecture, will be an early marker for later memory decline. Contributions from tau, beta-amyloid, brain structure, and genetic risk factors can provide insights into the underlying causal factors.

Memory abilities decline in normal aging and Alzheimer’s disease (AD), at great personal and societal costs. Using longitudinal imaging of brain activity, the objective is to predict early who will show memory decline and who will maintain good function as they age. A major cause of memory decline is likely the accumulation of tau proteins combined with atrophy of the medial temporal lobe (MTL). We urgently need earlier markers to detect subtle signs of brain dysfunction preceding memory decline. There are indications that deviations in how the brain processes memory information exist prior to accelerated atrophy. If we can detect these deviations years before memory decline is seen, this would be a tremendously valuable tool. As tau builds up in MTL over years, slowly disturbing neuronal processes, I hypothesize that the functioning will be affected early, before substantial levels of tau and atrophy. I have access to a unique sample (n=554) scanned with magnetic resonance imaging (MRI) 6 years ago, with various risks for developing AD dementia as indexed by beta-amyloid (Abeta) and genetic factors. These participants will be brought back and followed up with an extensive MRI examination measuring memory activation, microstructure, atrophy and a range of different indices related to functional and structrual networks. The participants will also undergo thorough experimental cognitive testing, and 50 persons will be scanned using positron emission tomography to quantify the load of tau. Data will be analysed with novel tools allowing prediction of individual memory alterations, also in single persons from external samples. I measure network activity related to source memory, the most age-sensitive memory process and dependent on the MTL. I hypothesize that a reduced ability of networks to reconfigure will be an early marker for later memory decline. Interactions with tau, beta-amyloid, structural change, and genetic risk factors can provide mechanistic insights.

Funding scheme:

FRIMEDBIO-Fri prosj.st. med.,helse,biol

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