Gait patterns associated with thyroid function: The Rotterdam Study

Gait is an important health indicator and poor gait is strongly associated with disability and risk of falls. Thyroid dysfunction is suggested as a potential determinant of gait deterioration, but this has not been explored in a population-based study. We therefore investigated the association of thyroid function with gait patterns in 2645 participants from the Rotterdam Study with data available on TSH (thyroid-stimulating hormone), FT4 (free thyroxine) and gait, without known thyroid disease or dementia. The primary outcome was Global gait (standardized Z-score), while secondary outcomes included gait domains (Rhythm, Variability, Phases, Pace, Base of support, Tandem, Turning) and velocity. Gait was assessed by electronic walkway. Multivariable regression models revealed an inverted U-shaped association of TSH (p < 0.001), but no association of FT4 concentrations with Global gait (p = 0.2). TSH levels were positively associated with Base of support (p = 0.01) and followed an inverted U-shaped curve with Tandem (p = 0.002) and velocity (p = 0.02). Clinical and subclinical hypothyroidism were associated with worse Global gait than euthyroidism (β = −0.61; CI = −1.03, −0.18; p = 0.004 and β = −0.13; CI = −0.26, −0.00; p = 0.04, respectively). In euthyroid participants, higher thyroid function was associated with worse gait patterns. In conclusion, both low and high thyroid function are associated with alterations in Global gait, Tandem, Base of support and velocity

Lipopolysaccharide-binding protein and future Parkinson's disease risk: a European prospective cohort

INTRODUCTION: Lipopolysaccharide (LPS) is the outer membrane component of Gram-negative bacteria. LPS-binding protein (LBP) is an acute-phase reactant that mediates immune responses triggered by LPS and has been used as a blood marker for LPS. LBP has recently been indicated to be associated with Parkinson's disease (PD) in small-scale retrospective case-control studies. We aimed to investigate the association between LBP blood levels with PD risk in a nested case-control study within a large European prospective cohort. METHODS: A total of 352 incident PD cases (55% males) were identified and one control per case was selected, matched by age at recruitment, sex and study center. LBP levels in plasma collected at recruitment, which was on average 7.8 years before diagnosis of the cases, were analyzed by enzyme linked immunosorbent assay. Odds ratios (ORs) were estimated for one unit increase of the natural log of LBP levels and PD incidence by conditional logistic regression. RESULTS: Plasma LBP levels were higher in prospective PD cases compared to controls (median (interquartile range) 26.9 (18.1-41.0) vs. 24.7 (16.6-38.4) µg/ml). The OR for PD incidence per one unit increase of log LBP was elevated (1.46, 95% CI 0.98-2.19). This association was more pronounced among women (OR 2.68, 95% CI 1.40-5.13) and overweight/obese subjects (OR 1.54, 95% CI 1.09-2.18). CONCLUSION: The findings suggest that higher plasma LBP levels may be associated with an increased risk of PD and may thus pinpoint to a potential role of endotoxemia in the pathogenesis of PD, particularly in women and overweight/obese individuals

Towards early disease modification of Parkinson’s disease: a review of lessons learned in the Alzheimer field

Parkinson’s disease (PD) research is beginning to focus on early disease modification and prevention. The therapeutic pipeline includes a growing range of pharmacological interventions that could theoretically intervene with the underlying disease process. It is hoped that applying such interventions in a very early stage of the disease pathology, before the onset of motor symptoms or during its early stages, may prevent or delay further disease progression. To identify people in this early disease stage, criteria for ‘prodromal PD’ have been proposed—describing people with one or more specific features that jointly constitute a variably increased risk of developing clinically manifest PD. Here, we aim to draw lessons from the field of Alzheimer’s research, which has followed a similar strategy over the last decade, including the expansion of the disease label to ‘prodromal’ stages. Importantly, none of the large and costly randomized-controlled trials aiming to slow down or prevent Alzheimer’s dementia by targeting the alleged disease pathology, i.e., amyloid-β aggregation, resulted in detectable clinical effects. Lack of sufficiently robust phase 2 trial results before moving to phase 3 studies, suboptimal participant selection, insensitive outcomes, a too narrow target focus, and trial design flaws contributed to this disappointing outcome. We discuss the various similarities between these Alzheimer’s and PD approaches, and review the design of prevention or early disease modification trials for both diseases including the potential for immunotherapy. Finally, we offer considerations to optimize the design of such trials in PD, benefiting from the lessons learned in Alzheimer’s prevention research