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Identifying cognitive and neurological markers of prodromal dementia: A novel, targeted functional connectivity approach

Funder: UK Research and InnovationProject code: 2929132
Funded under: ESRC

Identifying cognitive and neurological markers of prodromal dementia: A novel, targeted functional connectivity approach

Description

Advances in medical and social care has resulted in greater life-expectancy and an increasingly aging population across communities (1). However, dementia syndromes pose a significant risk to the life-expectancy, health, and wellbeing of aging communities, as well as their families (2, 3). Dementia syndromes include many neurodegenerative disorders characterised by progressive cognitive decline over and above normal aging, such as Alzheimer's disease and frontotemporal dementia. An estimated 50 million people are currently living with dementia, projected to increase to 152 million by 2050 (4). No cure currently exists but promising interventions have been developed to slow progression (5) and prevent dementia in the prodromal stages (6). Therefore, accurate and reliable methods of detecting dementia syndromes in their prodromal stages is paramount. As well as memory deficits (7), individuals in the prodromal stages of many dementia syndromes exhibit language deficits (8, 9, 10). However, these language deficits are diverse and the underlying cognitive mechanisms remain unclear. Central to theories of language comprehension and production is the view that language is represented hierarchically (11). Words are grouped into phrases that are embedded in higher-order phrases, allowing us to form hierarchical dependencies between parts of a sentence despite intervening information (12). Anaphora, that is the use of a word to refer to another, is one such example where successful interpretation is dependent on forming hierarchical dependencies between non-adjacent words. A recent study found individuals with prodromal dementia were impaired producing anaphoric sentences that allow coreference compared to healthy controls (13). For example, "He triggered the alarm when the ambassador saw the intruder", where 'he' could refer to 'the ambassador' or someone else in the discourse. This may suggest that individuals with prodromal dementia have difficulties tracking multiple hierarchical dependencies in language. However, no research has yet evaluated this cognitive mechanism in this population. Recent research has also aimed to identify reliable biological markers of the prodromal stages of dementia. Dementia is characterised by progressive neurodegeneration, causing atrophy and deterioration of functional networks in the brain (14). Functional connectivity is a suitable candidate to detect early stages of dementia, as deterioration of functional connectivity precedes structural changes (15). Synchronous neural activity is thought to facilitate the activation and coordination of

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