Abstract
Objective: To determine whether single nucleotide polymorphisms (SNPs) of the cholinergic system and quantitative parameters of postural control are associated in healthy older adults. This is a cross-sectional analysis from the TREND study.Methods: All participants performed a static postural control task for 30 s on a foam pad in semitandem stance and eyes closed. We analyzed mean power frequency (MPF), area, acceleration, jerk, and velocity from a mobile sensor worn at the lower back using a validated algorithm. Genotypes of four SNPs in genes involved in the cholinergic system (SLC5A7, CHAT, BCHE, CHRNA4) were extracted from the NeuroX chip. All participants present a normal neurological examination and a Minimental state examination score >24.Results: Four hundred and seventy seven participants were included. Mean age was 69 years, 41% were female. One SNP of the cholinergic pathway was significantly associated with a quantitative postural control parameter. The minor allele of rs6542746 in SLC5A7 was associated with lower MPF (4.04 vs. 4.22 Hz; p = 3.91 × 10-4). Moreover, the following associations showed trends toward significance: minor allele of rs6542746 in SLC5A7 with higher anteroposterior acceleration (318 vs. 287 mG; p = 0.005), and minor allele of rs3810950 in CHAT with higher mediolateral acceleration [1.77 vs. 1.65 log(mG); p = 0.03] and velocity [1.83 vs. 1.74 log(mm/s); p = 0.019]. Intraindividual occurrence of rs6542746 and rs3810950 minor alleles was dose-dependently related with lower MPF (p = 0.004).Conclusion: This observational study suggests an influence of SNPs of the cholinergic pathway on postural control in older adults.
Highlights
Postural instability is a common and disabling feature of older adults
Evidence has become consistent that degeneration of cholinergic neurons in the pedunculopontine nucleus (PPN) -one of the three main sources of acetylcholine supply in the brain- plays a central role in impaired postural control (Lee et al, 2000; Bohnen et al, 2009; Kucinski and Sarter, 2015)
Supporting the cholinergic relevance in postural control, several studies (Bohnen et al, 2009; Karachi et al, 2010; Rochester et al, 2012; Muller et al, 2013) indicate that degeneration of the cholinergic part of the PPN plays a central role in impaired postural control and gait dysfunction in Parkinson disease (PD) and other degenerative diseases
Summary
Postural instability is a common and disabling feature of older adults. One in three adults aged 65 and older will fall at least once a year (Frenklach et al, 2009). Evidence has become consistent that degeneration of cholinergic neurons in the pedunculopontine nucleus (PPN) -one of the three main sources of acetylcholine supply in the brain- plays a central role in impaired postural control (Lee et al, 2000; Bohnen et al, 2009; Kucinski and Sarter, 2015). Supporting the cholinergic relevance in postural control, several studies (Bohnen et al, 2009; Karachi et al, 2010; Rochester et al, 2012; Muller et al, 2013) indicate that degeneration of the cholinergic part of the PPN plays a central role in impaired postural control and gait dysfunction in Parkinson disease (PD) and other degenerative diseases. We did not find data about degeneration of this system in association with age and postural control in the “healthy” older population
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