title: 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.
authors.affiliation: University of Kentucky College of Medicine, Department of Neurology, 740 S. Limestone, Suite B-101, Lexington, KY 40536, United States. Electronic address: amelia.anderson@uky.edu.
authors.forename: Amelia J
authors.initials: AJ
authors.lastname: Anderson-Mooney
authors.affiliation: University of Kentucky College of Medicine, Department of Neurology and Sanders-Brown Center on Aging, 800 S. Limestone, Room 312, Lexington, KY 40536, United States. Electronic address: fascom@uky.edu.
authors.forename: Frederick A
authors.initials: FA
authors.lastname: Schmitt
authors.affiliation: University of Kentucky, Department of Molecular & Biomedical Pharmacology and Sanders-Brown Center on Aging, 800 S. Limestone, Room 203, Lexington, KY 40536, United States. Electronic address: Elizabeth.Head@uky.edu.
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Head
authors.affiliation: University of California - Irvine School of Medicine, Department of Pediatrics, Bldg 2 3rd Floor Rt 81, 101 The City Drive, Mail Code: 4482, Orange, CA 92668, United States. Electronic address: itlott@uci.edu.
authors.forename: Ira T
authors.initials: IT
authors.lastname: Lott
authors.affiliation: University of Florida College of Medicine, Department of Neurology, Room L3-100, McKnight Brain Institute, 1149 Newell Drive, Gainesville, FL 32611, United States. Electronic address: heilman@neurology.ufl.edu.
authors.forename: Kenneth M
authors.initials: KM
authors.lastname: Heilman
mesh_terms: D000375:Aging; D000544:Alzheimer Disease / Q000473:pathology / Q000503:physiopathology* / Q000523:psychology; D003071:Cognition; D003072:Cognition Disorders / Q000473:pathology / Q000503:physiopathology* / Q000523:psychology; D004314:Down Syndrome / Q000473:pathology / Q000503:physiopathology* / Q000523:psychology; D020235:Gait Apraxia / Q000473:pathology / Q000503:physiopathology*; D006801:Humans; D009422:Nervous System Diseases; D011788:Quality of Life; D012306:Risk; D066127:White Matter / Q000473:pathology
keywords: Alzheimer’s disease; Cerebrovascular disease; Down syndrome; Dyspraxia; Gait; White matter