Contribution of Brain Imaging to the Understanding Of Gait Disorders in Alzheimer’s Disease

Abstract

Although gait disorders are common in Alzheimer's disease (AD), determining which brain structures and related lesions are specifically involved is a goal yet to be reached. Our objective was to systematically review all published data that examined associations between gait disorders and brain imaging in AD. Of 486 selected studies, 4 observational studies met the selection criteria. The number of participants ranged from 2 to 61 community dwellers (29%-100% female) with prodromal or dementia-stage AD. Quantitative gait disorders (ie, slower gait velocity explained by shorter stride length) were associated with white matter lesions, mainly in the medial frontal lobes and basal ganglia. The nigrostriatal dopamine system was unaffected. Qualitative gait disorders (ie, higher stride length variability) correlated with lower hippocampal volume and function. Gait disorders in AD could be explained by a high burden of age-related subcortical hyperintensities on the frontal-subcortical circuits (nonspecific) together with hippocampal atrophy and hypometabolism (specific).

Association between gait variability and brain ventricle attributes: a brain mapping study

“…Conversely, only few previous studies have addressed the relationships between age-related morphological brain changes and decline in gait performance, and most of them have examined WMH rather than lobar trophism Annweiler et al, 2012a;de Laat et al, 2011;Wolfson et al, 2005). Also, most studies have examined gait parameters relative to motor propulsion (i.e., gait velocity) rather than dynamic regularity of gait (i.e., STV) de Laat et al, 2012;Rosano et al, 2008Rosano et al, , 2012.…”

“…Importantly, while the propulsion component of gait -traditionally explored with gait velocity or step length -has been linked to the trophism and integrity of sensorimotor networks (i.e., basal ganglia, motor cortex and white matter in the corticospinal tract) Rosano et al, 2008), the maintenance of a regular walking pattern is a more complex motor task that may involve different brain regions such as the prefrontal lobes , temporal lobes (Lafleur et al, 2002), precentral gyrus (Gottlieb, 2007) and parietal lobes (Graziano et al, 2002). Brain atrophy has been described while aging in parallel to increase in STV , leading to the assumption that loss of neurons in these different brain regions may explain loss of gait dynamic stability in older adults (Annweiler et al, 2012a). A simple, automatic and reproducible way to explore brain volume reduction is to measure the adjacent sub-volumes of lateral cerebral ventricles for differential changes (Annweiler et al, 2012b;Chance et al, 2003).…”

Gait Variability Can Predict the Risk of Cognitive Decline in Cognitively Normal Older People

“…These neurological conditions may impair cognition as well as gait. In a recent systematic review demonstrating associations between functional and structural cerebral changes and AD-related gait disorders, slower gait speed was associated with white matter lesions mainly in the medial frontal lobes and basal ganglia, whereas higher gait variability was associated with lower hippocampal volume and function [39]. In the present study, even though elderly in the high tertile of gait variability had a normal range of MMSE scores at baseline, they showed poorer performance on memory and executive function already at baseline than those in the midtertile group.…”

Brain health and cognitive and mood disorders in ageing women

“…We have also proposed [28] that this 'immune brain barrier' helps to maintain the brain as an immunologically privileged organ. It is mediated by the expression of the activational response to antigens [29] and the production of the immune-checkpoint proteins, Fas ligand (FasL) and CD40 in microglia, astrocytes, and neurons [55] (Silva unpublished). As activated T cells enter the brain, they may contact processes of the glia limitans or perivascular microglia, thereby receiving an oestrogen-regulated Fas/FasL-mediated death signal [55,56].…”

“…In fact, by the time that these lesions are found by imaging, the involved neurones and glia are well along toward destruction and involved in inflammatory reactions that destroy nearby normal cells and fibres of passage [27][28][29]. With the exception of the hereditary form of early onset Alzheimer's disease, which is an outcome of abnormal lipoproteins, the cause of the above changes in normal brain constituents, the basis of, or inciting factor for, Alzheimer's disease is not yet known [24].…”