Gait and falls in the memory clinic setting: Neuroimaging as a stepping stone

Abstract

Part I: CSVD as a marker of presence of gait abnormalities and predictor of falls in memory clinic patients. Memory clinic patients not only have cognitive impairment, but also physical performance deficits like gait abnormalities and falls. These clinically relevant deficits can be overlooked in clinical routine, because they are not the reason for referral to the memory clinic. Vigilance for these deficits could be directed by co-occurring medical pathologies that are readily available from the routine clinical work-up, like MRI markers of cerebral small vessel disease (CSVD). Chapter 2 was performed in memory clinic patients with mild cognitive impairment, Alzheimer’s disease (AD) and/or vascular brain injury. White matter hyperintensities (WMH), lacunar infarcts, cerebral microbleeds and total CSVD burden all occurred often. Particularly WMH also co-occurred with clinically relevant impairments in gait, chair stand and mobility. CSVD markers might also improve fall prediction in memory clinic patients, if these markers provide additional predictive value over traditional predictors. Chapter 3 was conducted in memory clinic patients with vascular brain injury. Lacunar infarcts were a univariable predictor of falls. However, they provided limited additional predictive value when added to models including traditional predictors. In general, part I concludes that gait abnormalities and falls occur often in memory clinic patients and should always be checked by clinicians. High burdens of CSVD are associated with physical performance deficits, but provide limited additional value, and therefore primarily serve as an extra warning signal. Part II: the neuronal underpinnings of gait abnormalities and falls in memory clinic patients, zooming in on grey matter atrophy, WMH, and white matter network connectivity. The etiology of gait abnormalities and falls in memory clinic patients is multifactorial. Neuronal underpinnings might include brain injury due to neurodegenerative and vascular pathologies and can now be assessed in detail using novel imaging techniques. First, AD causes grey matter atrophy. Chapter 4 describes that grey matter atrophy, particularly of the basal ganglia and thalamus, is associated with poor gait in AD. Second, CSVD causes WMH. Chapter 5 was conducted in memory clinic patients with vascular brain injury. Strategically located WMH, specifically in the corticospinal tract, were associated with falls, while WMH in other tracts or voxels were not. Yet, WMH volume in this tract was low. Therefore, falls are rather caused by a specific form of WMH that affects multiple tracts. Finally, both AD and CSVD disrupt white matter network connectivity. Chapter 6 wasconducted in memory clinic patients with vascular brain injury. Disrupted regional connectivity of the basal ganglia, thalamus, and prefrontal and posterior regions, was correlated with poor gait, as were global measures of connectivity. In general, part II concludes that gait abnormalities and falls in memory clinic patients have multifactorial neuronal underpinnings. These include injury to multiple brain regions, which compose complex networks covering multiple hierarchical levels of motor control. Disturbances in the highest level involve cortical injury and in the middle level, they comprise subcortical injury. Together, they compromise multiple motor functions and cause gait abnormalities in memory clinic patients.