White matter hyperintensity burden predicts cognitive but not motor decline in Parkinson's disease: results from the Ontario Neurodegenerative Diseases Research Initiative.

BACKGROUND AND PURPOSE: The pathophysiology of Parkinson's disease (PD) negatively affects brain network connectivity, and in the presence of brain white matter hyperintensities (WMHs) cognitive and motor impairments seem to be aggravated. However, the role of WMHs in predicting accelerating symptom worsening remains controversial. The objective was to investigate whether location and segmental brain WMH burden at baseline predict cognitive and motor declines in PD after 2 years. METHODS: Ninety-eight older adults followed longitudinally from Ontario Neurodegenerative Diseases Research Initiative with PD of 3-8 years in duration were included. Percentages of WMH volumes at baseline were calculated by location (deep and periventricular) and by brain region (frontal, temporal, parietal, occipital lobes and basal ganglia + thalamus). Cognitive and motor changes were assessed from baseline to 2-year follow-up. Specifically, global cognition, attention, executive function, memory, visuospatial abilities and language were assessed as were motor symptoms evaluated using the Movement Disorder Society Unified Parkinson's Disease Rating Scale Part III, spatial-temporal gait variables, Freezing of Gait Questionnaire and Activities Specific Balance Confidence Scale. RESULTS: Regression analysis adjusted for potential confounders showed that total and periventricular WMHs at baseline predicted decline in global cognition (p < 0.05). Also, total WMH burden predicted the decline of executive function (p < 0.05). Occipital WMH volumes also predicted decline in global cognition, visuomotor attention and visuospatial memory declines (p < 0.05). WMH volumes at baseline did not predict motor decline. CONCLUSION: White matter hyperintensity burden at baseline predicted cognitive but not motor decline in early to mid-stage PD. The motor decline observed after 2 years in these older adults with PD is probably related to the primary neurodegenerative process than comorbid white matter pathology.

Intermittent feeding alters sensitivity to changes in reward value.

The influence of binge-like feeding schedules on subsequent food-related behavior is not well understood. We investigated the effect of repeated cycles of restriction and refeeding on two food-related behaviors; goal-directed responding for a palatable food reward and sensory-specific satiety. Hungry rats were trained to perform two instrumental actions for two distinct food outcomes and were then subjected to repeated cycles of restricted and unrestricted access to their maintenance chow for 30-days or were maintained on food restriction. Goal-directed control was then assessed using specific satiety-induced outcome devaluation. Rats were given 1 h access to one of theoutcomes and were then immediately given a choice between the two actions. Rats maintained on restriction responded more for the valued than the devalued reward but rats with a history of restriction and refeeding failed to show this effect. Importantly, all rats showed sensory-specific satiety when offered a choice between the two foods, indicating that pre-feeding selectively reduced the value of the pre-fed food. By contrast, sensory-specific satiety was not observed in rats with a history of intermittent feeding when the foods were offered sequentially. These results indicate that, similar to calorically dense diets, intermittent feeding patterns can impair the performance of goal-directed actions as well as the ability to reject a pre-fed food when it is offered alone.

Association of Dual-Task Gait Cost and White Matter Hyperintensity Burden Poststroke: Results From the ONDRI.

BACKGROUND: Acute change in gait speed while performing a mental task [dual-task gait cost (DTC)], and hyperintensity magnetic resonance imaging signals in white matter are both important disability predictors in older individuals with history of stroke (poststroke). It is still unclear, however, whether DTC is associated with overall hyperintensity volume from specific major brain regions in poststroke. METHODS: This is a cohort study with a total of 123 older (69 ± 7 years of age) participants with history of stroke were included from the Ontario Neurodegenerative Disease Research Initiative. Participants were clinically assessed and had gait performance assessed under single- and dual-task conditions. Structural neuroimaging data were analyzed to measure both, white matter hyperintensity (WMH) and normal appearing volumes. Percentage of WMH volume in frontal, parietal, occipital, and temporal lobes as well as subcortical hyperintensities in basal ganglia + thalamus were the main outcomes. Multivariate models investigated associations between DTC and hyperintensity volumes, adjusted for age, sex, years of education, global cognition, vascular risk factors, APOE4 genotype, residual sensorimotor symptoms from previous stroke and brain volume. RESULTS: There was a significant positive global linear association between DTC and hyperintensity burden (adjusted Wilks' λ = .87, P = .01). Amongst all WMH volumes, hyperintensity burden from basal ganglia + thalamus provided the most significant contribution to the global association (adjusted ß = .008, η2 = .03; P = .04), independently of brain atrophy. CONCLUSIONS: In poststroke, increased DTC may be an indicator of larger white matter damages, specifically in subcortical regions, which can potentially affect the overall cognitive processing and decrease gait automaticity by increasing the cortical control over patients' locomotion.

Motor and Cognitive Trajectories Before Dementia: Results from Gait and Brain Study.

OBJECTIVES: To compare the trajectories of motor and cognitive decline in older adults who progress to dementia with the trajectories of those who do not. To evaluate the added value of measuring motor and cognitive decline longitudinally versus cross-sectionally for predicting dementia. DESIGN: Prospective cohort study with 5 years of follow-up. SETTING: Clinic based at a university hospital in London, Ontario, Canada. PARTICIPANTS: Community-dwelling participants aged 65 and older free of dementia at baseline (N=154). MEASUREMENTS: We evaluated trajectories in participants' motor performance using gait velocity and cognitive performance using the MoCA test twice a year for 5 years. We ascertained incident dementia risk using Cox regression models and attributable risk analyses. Analyses were adjusted using a time-dependent covariate. RESULTS: Overall, 14.3% progressed to dementia. The risk of dementia was almost 7 times as great for those whose gait velocity declined (hazard ratio (HR)=6.89, 95% confidence interval (CI)=2.18-21.75, p=.001), more than 3 times as great for those with cognitive decline (HR=3.61, 95% CI=1.28-10.13, p=.01), and almost 8 times as great in those with combined gait velocity and cognitive decline (HR=7.83, 95% CI=2.10-29.24, p=.002), with an attributable risk of 105 per 1,000 person years. Slow gait at baseline alone failed to predict dementia (HR=1.16, 95% CI=0.39-3.46, p=.79). CONCLUSION: Motor decline, assessed according to serial measures of gait velocity, had a higher attributable risk for incident dementia than did cognitive decline. A decline over time of both gait velocity and cognition had the highest attributable risk. A single time-point assessment was not sufficient to detect individuals at high risk of dementia.