The Impact of Parental Longevity on Brain Health - and the Influence of Physical Functions and Genetics

Parent Grant (R01AG062659) Specific Aims: Trajectories and modifiable risk factors of brain, gait, and cognitive decline in aging and pre-dementia ABSTRACT: Clinical gait abnormalities are present in about 35% of community-dwelling older adults in the US, and accelerated gait decline is associated with many adverse physical and cognitive outcomes - including falls, disability, cognitive decline, and dementia. Such outcomes not only reduce the quality of life of affected individuals, their families, and friends, but also leads to increased health care costs. Our research aims to understand the interrelationship between brain aging, gait decline, cognitive decline, and dementia – and will guide future development of interventions for maintaining gait and cognition in aging and early dementia. Accelerated gait decline is associated with an increased risk for cognitive decline, Alzheimer’s disease, and related dementias (1-9). A common explanation of such associations is that gait and cognition rely on shared neural substrates that are affected by both normal and dementia-related aging (10-13). Yet, the neural substrates that link gait, cognition, and dementia are not well-understood. A better understanding of these neural substrates – and how they are influenced by potentially modifiable risk factors of dementia such as poor social networks or support (14, 15) – is important for developing effective therapies for maintaining gait and cognition in aging and early dementia. We propose to compare trajectories of functional and structural brain changes, gait decline and cognitive decline in older adults who are cognitively normal, and those in the early stages of cognitive decline. Aim 1: Compare trajectories of functional and structural brain aging, gait decline and cognitive decline. H.1a: Functional and structural brain changes, mainly in supplementary motor area, insula, and PFC, precede (are steeper or have earlier change points than) gait and cognitive decline. H.1b: Functional brain changes related to gait and cognitive decline precede structural brain changes. Aim 2: Examine the influence of MCR on functional and structural brain changes, gait, and cognitive decline. H.2: Trajectories of functional and structural brain changes, mainly in supplementary motor area, insula, and PFC, are steeper/have earlier change points in those with MCR than non-MCR. Aim 3: Examine the role of social networks on functional and structural brain changes, gait, and cognitive decline. H.3: Trajectories of functional and structural brain changes, mainly in insula and PFC, gait and cognitive decline are steeper/have earlier change points in those with small social networks than large social networks.