Ocal, Dilek; (2023) "Am I The Right Way Up?" Multisensory Disturbances in Posterior Cortical Atrophy and Typical Alzheimer’s Disease. Doctoral thesis (Ph.D), UCL (University College London).

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Abstract

The cognitive and neuroanatomical underpinnings of Alzheimer's disease (AD)-related postural disturbances remain unclear, yet they significantly impact those living with the disease. Stabilising the body in an upright orientation depends on convergent multisensory information and a widespread network of brain regions. Understanding how this interplay is affected by neurodegeneration and is impacted within different AD phenotypes is critical for identifying fall risk factors and optimising fall prevention strategies. In this thesis, I will investigate the ability to stabilise the body in an upright orientation and its modulation by visual information in typical memory-led AD (tAD) and posterior cortical atrophy (PCA) - a neurodegenerative syndrome characterised by predominant occipitoparietal atrophy and visuospatial and visuoperceptual processing deficits. To achieve this, I will assess the cognitive and neuroanatomical correlates of perception of verticality and upright postural control with and without vision using behavioural, neuropsychological and neuroanatomical measures (voxel-based morphometry; tract-based spatial statistics). I will provide evidence that impairments in the perceived vertical without visual cues are associated with diffuse white matter changes in both patient groups and with poorer visuoperceptual skills and hippocampal atrophy in the PCA group. I will show that both patient groups exhibit greater deviations from the Earth's vertical in the presence of visual orientation cues and that these are correlated with projection and association fibre abnormalities in the tAD group. I will also demonstrate that the moderating effects of visual information on perturbation-evoked postural responses are smaller in PCA and that the resulting response increases are accompanied by thalamo-occipital atrophy and diffuse white matter changes. By providing insight into the cognitive and neuroanatomical correlates of postural disorientation and instability in PCA and tAD, these findings shed light on the impact of neurodegeneration on multisensory integration and highlight the importance of trans-syndromic and syndrome-specific sensory vulnerabilities in AD-related postural disturbances.

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