Discrete Relationships between Spatiotemporal Gait Characteristics and Domain-Specific Neuropsychological Performance in Midlife.

Midlife risk factors such as type 2 diabetes mellitus (T2DM) confer a significantly increased risk of cognitive impairment in later life with executive function, memory, and attention domains often affected first. Spatiotemporal gait characteristics are emerging as important integrative biomarkers of neurocognitive function and of later dementia risk. We examined 24 spatiotemporal gait parameters across five domains of gait previously linked to cognitive function on usual-pace, maximal-pace, and cognitive dual-task gait conditions in 102 middle-aged adults with (57.5 ± 8.0 years; 40% female) and without (57.0 ± 8.3 years; 62.1% female) T2DM. Neurocognitive function was measured using a neuropsychological assessment battery. T2DM was associated with significant changes in gait phases and rhythm domains at usual pace, and greater gait variability observed during maximal pace and dual tasks. In the overall cohort, both the gait pace and rhythm domains were associated with memory and executive function during usual pace. At maximal pace, gait pace parameters were associated with reaction time and delayed memory. During the cognitive dual task, associations between gait variability and both delayed memory/executive function were observed. Associations persisted following covariate adjustment and did not differ by T2DM status. Principal components analysis identified a consistent association of slower gait pace (step/stride length) and increased gait variability during maximal-pace walking with poorer memory and executive function performance. These data support the use of spatiotemporal gait as an integrative biomarker of neurocognitive function in otherwise healthy middle-aged individuals and reveal discrete associations between both differing gait tasks and gait domains with domain-specific neuropsychological performance. Employing both maximal-pace and dual-task paradigms may be important in cognitively unimpaired populations with risk factors for later cognitive decline-with the aim of identifying individuals who may benefit from potential preventative interventions.

Peripheral Inflammation and Cognitive Performance in Middle-Aged Adults With and Without Type 2 Diabetes: Results From the ENBIND Study.

Midlife Type 2 Diabetes Mellitus (T2DM) is associated with a greater risk of dementia in later life. Peripheral inflammation and its impact on cognition is proposed as one of the pathological mechanisms mediating this link. However, studies have primarily focused on older individuals with established cognitive impairment and a long duration of T2DM. Importantly, knowledge of which individuals with midlife T2DM who are at greatest risk of later cognitive decline is lacking. We examined the cross-sectional relationship between serum levels of 8 pro-inflammatory markers (IL-1ß, IL-6, TNF-α, IL-8, MCP-1, CXCL10, IL-12p70, CRP) and performance on a detailed neuropsychological assessment battery in middle-aged adults with uncomplicated T2DM (N = 89; 52 ± 8.1 years, 47% female) and matched healthy controls (N = 50; 52 ± 8.3 years, 59% female). Linear regression was used to analyze associations between serum markers and cognitive performance in the overall cohort, followed by a T2DM∗protein concentration interaction analysis to identify any T2DM-specific effects. We observed a significant T2DM-specific association between serum TNF-α levels and scores on the Paired Associates Learning (PAL) task (ß: -3.16, SE: 1.32, p = 0.01, Std. Beta: -0.94), a task with significant working memory demands previously implicated in T2DM-related cognitive dysfunction. However, this did not persist on controlling for multiple testing. We provide exploratory evidence for a significant T2DM-specific relationship between serum TNF-α and memory performance. These findings require further replication and longitudinal analysis with the aim of selecting-out individuals with midlife T2DM at risk of future cognitive decline for potential preventative interventions.