Gait dyspraxia as a clinical marker of cognitive decline in Down syndrome: A review of theory and proposed mechanisms

Abstract

Down syndrome (DS) is the most common genetic cause of intellectual disability in children. With aging, DS is associated with an increased risk for Alzheimer's disease (AD). The development of AD neuropathology in individuals with DS can result in further disturbances in cognition and behavior and may significantly exacerbate caregiver burden. Early detection may allow for appropriate preparation by caregivers. Recent literature suggests that declines in gait may serve as an early marker of AD-related cognitive disorders; however, this relationship has not been examined in individuals with DS. The theory regarding gait dyspraxia and cognitive decline in the general population is reviewed, and potential applications to the population with individuals with DS are highlighted. Challenges and benefits in the line of inquiry are discussed. In particular, it appears that gait declines in aging individuals with DS may be associated with known declines in frontoparietal gray matter, development of AD-related pathology, and white matter losses in tracts critical to motor control. These changes are also potentially related to the cognitive and functional changes often observed during the same chronological period as gait declines in adults with DS. Gait declines may be an early marker of cognitive change, related to the development of underlying AD-related pathology, in individuals with DS. Future investigations in this area may provide insight into the clinical changes associated with development of AD pathology in both the population with DS and the general population, enhancing efforts for optimal patient and caregiver support and propelling investigations regarding safety/quality of life interventions and disease-modifying interventions.

Gait and postural control patterns and rehabilitation in Down syndrome: a systematic review

“…Ligament laxity, hypotonia and cognitive delay presented by DS directly influence the development of compensatory strategies in the movement and postural control 9,49,50) . During childhood, the considerable variability of gait parameters 2,11,37) can be explained by the incomplete maturation of the locomotor system.…”

“…Down syndrome (DS) has been widely studied in the field of physical rehabilitation with the aim of identifying the relationship between motor characteristics and the impairment of functional performance [1][2][3][4][5][6][7] . The main features of DS are delayed neuropsychomotor development, global muscle hypotonia and ligament laxity, that result in an average of two years for gait acquisition 8) and in compromised cognitive functions 6,9,10) . Motor abnormalities often lead to the development of abnormal postural control, resulting in instability and an impaired gait pattern, with an increased energy expenditure and reduced performance [11][12][13] .…”

Neuronal overexpression ofDYRK1A/minibrainalters motor decline, neurodegeneration and synaptic plasticity inDrosophila

“…People with DS have impaired motor skills which are evident from childhood and are caused by abnormal development of the nervous system [3,4]. Later, in middle age, they undergo faster agedependent motor decline, which is an early marker of future dementia, comorbidities and mortality, and is likely caused by histopathological changes in the brain [7,8]. The life expectancy of people with DS is about 28 years shorter than the general population [9].…”

“…Individuals with DS almost invariably develop Alzheimer's disease (AD)-like symptoms (AD-DS). These include progressive dementia after 40 years of age, the onset of amyloid plaques, neurofibrillary tangles and neurodegeneration after 10 -20 years [5,6], faster age-dependent motor decline that is an early marker for the onset of cognitive decline and health deterioration [7,8], and a shorter mean life expectancy by approximately 28 years [9]. Currently there is no treatment for DS or AD; our understanding of the mechanisms of the disorder is incomplete and this hampers the development of effective therapies.…”

Sex differences in the gait kinematics of patients with Down syndrome: A preliminary report

“…DS is a chromosomal aneuploidy that produces disruptions in various body systems, including musculoskeletal function, and delayed neuropsychomotor development (2). In particular, ligament laxity, osteoporosis, and muscle hypotonia in the lower limbs critically affect postural control and mobility (3)(4)(5): gait function is characterized by reduced speed, reduced step length and increased step width, balance…”