Associations between brain structure and dual decline in gait and cognition.

Dual decline in gait and cognition is associated with an increased risk of dementia, with combined gait and memory decline exhibiting the strongest association. To better understand the underlying pathology, we investigated the associations of baseline brain structure with dual decliners using three serial gait speed and cognitive assessments in memory, processing speed-attention, and verbal fluency. Participants (n=267) were categorized based on annual decline in gait speed and cognitive measures. Lower gray and white matter volume and higher white matter hyperintensity volume increased the risk of being a dual decliner in gait and both the memory and processing speed-attention groups (all p < 0.05). Lower hippocampal volume (p = 0.047) was only associated with dual decline in gait and memory group. No brain structures were correlated with dual decline in gait and verbal fluency. These results suggest that neurodegenerative pathology and white matter hyperintensities are involved in dual decline in gait and both memory and processing speed-attention. Smaller hippocampal volume may only contribute to dual decline in gait and memory.

Cognitive reserve proxies are associated with age-related cognitive decline - Not age-related gait speed decline.

Cognition and gait share brain substrates in aging and dementia. Cognitive reserve (CR) allows individuals to cope with brain pathology and delay cognitive impairment and dementia. Yet, evidence for that CR is associated with age-related cognitive decline is mixed, and evidence for that CR is associated with age-related gait decline is limited. In 1,079 older (M Age = 75.4 years; 56.0% women) LonGenity study participants without dementia at baseline and up to 12 years of annual follow-up (M follow-up = 3.9 years, SD = 2.5 years), high CR inferred from cognitive (education years), physical (number of blocks walked per day; weekly physical activity days), and social (volunteering/working; living with someone) proxies were associated with slower rates of age-related decline in global cognition - not gait speed decline. Thus, cognitive, physical, and social CR proxies are associated with cognitive decline in older adults without dementia. The multifactorial etiology and earlier decline in gait than cognition may render it less modifiable by CR proxies later in life.

Plasma metabolomic signatures of dual decline in memory and gait in older adults.

Older adults experiencing dual decline in memory and gait have greater dementia risk than those with memory or gait decline only, but mechanisms are unknown. Dual decline may indicate specific pathophysiological pathways to dementia which can be reflected by circulating metabolites. We compared longitudinal changes in plasma metabolite biomarkers of older adults with and without dual decline in the Baltimore Longitudinal Study of Aging (BLSA). Participants were grouped into 4 phenotypes based on annual rates of decline in verbal memory and gait speed: no decline in memory or gait, memory decline only, gait decline only, and dual decline. Repeated measures of plasma metabolomics were measured by biocrates p500 kit during the same time of memory and gait assessments. In BLSA, 18 metabolites differed across groups (q-value < 0.05). Metabolites differentially abundant were enriched for lysophosphatidylcholines (lysoPC C18:0,C16:0,C17:0,C18:1,C18:2), ceramides (d18:2/24:0,d16:1/24:0,d16:1/23:0), and amino acids (glycine) classes. Compared to no decline, the dual decline group showed greater declines in lysoPC C18:0, homoarginine synthesis, and the metabolite module containing mostly triglycerides, and showed a greater increase in indoleamine 2,3-dioxygenase (IDO) activity. Metabolites distinguishing dual decline and no decline groups were implicated in metabolic pathways of the aminoacyl-tRNA biosynthesis, valine, leucine and isoleucine biosynthesis, histidine metabolism, and sphingolipid metabolism. Older adults with dual decline exhibit the most extensive alterations in metabolic profiling of lysoPCs, ceramides, IDO activity, and homoarginine synthesis. Alterations in these metabolites may indicate mitochondrial dysfunction, compromised immunity, and elevated burden of cardiovascular and kidney pathology.

Relative Trajectories of Gait and Cognitive Decline in Aging.

BACKGROUND: Gait and cognition decline with advancing age, and presage the onset of dementia. Yet, the relative trajectories of gait and cognitive decline in aging are poorly understood-particularly among those with the motoric cognitive risk (MCR) syndrome. This study compared changes in simple and complex gait performance and cognition, as a function of age and MCR. METHODS: We examined gait and cognitive functions of 1 095 LonGenity study participants (mean age = 75.4 ± 6.7 years) with up to 12 years of annual follow-up. Participants were of Ashkenazi Jewish descent, free of dementia, ambulatory, and had a 12.2% MCR prevalence at baseline. Gait speed was measured at usual pace walking (single-task walking, STW-speed) and walking while talking (WWT-speed). Eleven neuropsychological test scores were examined separately, and as a global cognition composite. Linear mixed-effects models adjusted for baseline sex, education, parental longevity, cognitive impairment, and global health were used to estimate changes in gait and cognition, as a function of age and MCR. RESULTS: STW-speed, WWT-speed, and cognitive tests performance declined in a nonlinear (accelerating) fashion with age. STW-speed declined faster than WWT-speed and cognitive test scores. People with MCR showed faster rates of decline on figure copy and phonemic fluency. CONCLUSIONS: Gait declines at a faster rate than cognition in aging. People with MCR are susceptible to faster decline in visuospatial, executive, and language functions. This study adds important knowledge of trajectories of gait and cognitive decline in aging, and identifies MCR as a risk factor for accelerated cognitive decline.

Mitigating Gait Decline in a Woman With Parkinson's Disease: A Case Report.

Levodopa therapy is the standard pharmacological treatment for Parkinson's disease (PD). However, after an initial period of significant benefit, the effects of levodopa begin to wear off. This results in a reduction in the effect duration and the development of motor complications. We describe the case of a 69-year-old woman presented with a 3-year history of lower back pain and progressive left leg weakness. One year prior to referral for neurological assessment, the patient first noted progressive leg weakness and insufficient strength to rise from a chair. The diagnosis of PD was made after excluding potential neurological disorders. The patient was initially started on oral levodopa, which improved her motor symptoms considerably during the first year. However, dose adjustment and combined pharmacological strategies failed to sufficiently control motor symptoms during the subsequent year. The patient experienced declines in gait ability, clumsiness in the left limbs, and difficulty in performing housework. The patient then sought chiropractic attention. Gait rehabilitation was the major goal in the treatment program for this patient, with the impression of motor complications of PD. The intervention consisted of spinal manipulation, intermittent motorized traction of the lumbar segments, and gait training programs. Following 3 months of the intervention, the patient demonstrated increased muscle strength and improved gait characteristics, as depicted by a gait cyclogram and vertical ground reaction force graphing. The current report illustrates that a multicomponent chiropractic approach may be used as an additional measure to mitigate gait decline in PD patients.

Cognitive and neuroimaging profiles of older adults with dual decline in memory and gait speed.

We previously showed that dual decline in memory and gait speed was associated with an increased risk of dementia compared to memory or gait decline only or no decline. We now characterized cognitive and neuroimaging profiles of dual decliners by comparing longitudinal rates of change in various cognitive domains (n = 664) and brain volumes (n = 391; selected frontal, temporal, parietal, subcortical, and cerebellar areas) in Baltimore Longitudinal Study of Aging participants who experienced age-related dual decline to others. Compared to others, dual decliners had steeper declines in verbal fluency, attention, and sensorimotor function by Pegboard nondominant hand performance. Dual decliners had greater brain volume loss in superior frontal gyrus, superior parietal gyrus, precuneus, thalamus, and cerebellum (all p ≤ 0.01). Participants with age-related dual decline experienced steeper declines in multiple cognitive domains and greater brain volume loss in cognitive, sensorimotor, and locomotion areas. Impaired sensorimotor integration and locomotion are underlying features of dual decline. Whether these features contribute to the increased risk of dementia should be investigated.

Gait kinematics and kinetics are affected more by peripheral arterial disease than by age.

Peripheral arterial disease (PAD) produces abnormal gait and disproportionately affects older individuals. The current study investigated PAD gait biomechanics in younger (<65 yr) and older (>/=65 yr) subjects. The study included 61 patients with PAD (31 younger, age: 57.4 +/- 5.3 yr, and 30 older, age: 71.9 +/- 5.2 yr) and 52 nondisabled age-matched control subjects. Patients with PAD were tested during pain-free walking and compared with control subjects. Joint kinematics and kinetics (torques) were compared using a 2 x 2 analysis of variance (groups: patients with PAD vs control subjects, age: younger vs older). Patients with PAD had significantly increased ankle and decreased hip range of motion during the stance phase as well as decreased ankle dorsiflexor torque compared with control subjects. Gait changes in older individuals are largely constrained to time-distance parameters. Joint kinematics and kinetics are significantly altered in patients with PAD during pain-free walking. Symptomatic PAD produces a consistent ambulatory deficit across ages definable by advanced biomechanical analysis. The most important finding of the current study is that gait, in the absence of PAD and other ambulatory comorbidities, does not decline significantly with age based on advanced biomechanical analysis. Therefore, previous studies must be examined in the context of patients with potential PAD being present in the population, and future ambulatory studies must include PAD as a confounding factor when assessing the gait function of elderly individuals.