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Type 2 Diabetes Mellitus (T2DM) in midlife is associated with a greater risk of dementia in later life. Both gait speed and spatiotemporal gait characteristics have been associated with later cognitive decline in community-dwelling older adults. Thus, the assessment of gait characteristics in uncomplicated midlife T2DM may be important in selecting-out those with T2DM at greatest risk of later cognitive decline. We assessed the relationship between Inertial Motion Unit (IMUs)-derived gait characteristics and cognitive function assessed via Montreal Cognitive Assessment (MoCA)/detailed neuropsychological assessment battery (CANTAB) in middle-aged adults with and without uncomplicated T2DM using both multivariate linear regression and a neural network approach. Gait was assessed under (i) normal walking, (ii) fast (maximal) walking and (iii) cognitive dual-task walking (reciting alternate letters of the alphabet) conditions. Overall, 138 individuals were recruited (n = 94 with T2DM; 53% female, 52.8 ± 8.3 years; n = 44 healthy controls, 43% female, 51.9 ± 8.1 years). Midlife T2DM was associated with significantly slower gait velocity on both slow and fast walks (both p < 0.01) in addition to a longer stride time and greater gait complexity during normal walk (both p < 0.05). Findings persisted following covariate adjustment. In analyzing cognitive performance, the strongest association was observed between gait velocity and global cognitive function (MoCA). Significant associations were also observed between immediate/delayed memory performance and gait velocity. Analysis using a neural network approach did not outperform multivariate linear regression in predicting cognitive function (MoCA) from gait velocity. Our study demonstrates the impact of uncomplicated T2DM on gait speed and gait characteristics in midlife, in addition to the striking relationship between gait characteristics and global cognitive function/memory performance in midlife. Further studies are needed to evaluate the longitudinal relationship between midlife gait characteristics and later cognitive decline, which may aid in selecting-out those with T2DM at greatest-risk for preventative interventions.

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-1β, 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 (β: −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.

Summary: Background: Coronaviruses are known to precipitate disorders of smell and taste function. With the emerging global coronavirus disease (CoVID19) pandemic due to the severe acute respiratory syndrome coronavirus 2, early reports suggested that smell and taste dysfunction were clinical features of CoVID19. Our study aimed to investigate the prevalence of smell and taste disturbances in a cohort of CoVID19 positive patients who were isolated at home and being medically managed through telephone consultation. Methods: This was a retrospective cross-sectional study conducted at St. James’s Hospital Dublin, an urban 850 bed tertiary referral centre. 46 out of 50 CoVID19 positive patients, managed through a telephone clinic from the hospital infectious disease department, were assessed for olfactory and gustatory function loss. Results: The median age of participants was 36.5 years (interquartile range (IQR) 27 - 48) and 19 (41%) were male. The majority (31; 67%) never smoked and 17 (37%) reported co-morbidities. Approximately half of patients reported some degree of smell (22; 48%) or taste (25; 54%) function loss. 13 patients (28%) reported a complete loss of sense of smell, 8 (17%) reported a complete loss of sense of taste and 7 (15%) reported simultaneous total loss of both. The median age of patients with any degree of smell disturbance was significantly lower than patients without (median 30.5 years (IQR 24 – 43.25) versus 41 years (IQR 28.25 – 52.75), p = 0.025). The median age of patients with any degree of taste disturbance was lower than those without, but did not reach statistical significance (median 34 years (IQR 24 - 45) versus 40 years (IQR 27.5 – 52.5) p = 0.174). Conclusion: Smell or taste dysfunction were present in our defined subgroup of patients. Further research is required in different population cohorts to build the evidence base for smell and taste dysfunction as clinical indicators of CoVID19 disease and to assess if these symptoms persist after disease resolution.